Shoshana J. Herzig, MD, MPH

Hall et al. draw attention to the important question of whether some patients may benefit from a naloxone prescription when discharged from the hospital with a short-term opioid prescription for acute pain. Although all members of the working group agreed that naloxone is appropriate in some cases, we were hesitant to recommend this as a standard practice for several reasons.

First, the intent of our Consensus Statement¹ was to synthesize and summarize the areas of consensus in existing guidelines; none of the existing guidelines included in our systematic review make a recommendation for naloxone prescription in the setting of short-term opioid use for acute pain.² We believe that this may relate to the fact that the risk factors for overdose and the threshold of risk above which naloxone would be beneficial have yet to be defined for this population and are likely to differ from those defined in patients using opioids chronically.

Additionally, if practitioners follow the recommendations to limit prescribing for acute pain to the minimum dose and duration of an opioid that was presumably administered in the hospital with an observed response, then the risk of overdose and the potential benefit of naloxone will decrease. Furthermore, emerging data from randomized controlled trials demonstrating noninferiority of nonopioid analgesics in the management of acute pain suggest that we should not so readily presume opioids to be the necessary or the best option.^3-5 Data questioning the benefits of opioids over other safer therapies have particularly important implications for patients in whom the risks are felt to be high enough to warrant consideration of naloxone.

Disclosures

Dr. Herzig reports receiving compensation from the Society of Hospital Medicine for her editorial role in the Journal of Hospital Medicine (unrelated to the present work). None of the other authors have any conflicts of interest to disclose.

Funding

Dr. Herzig is funded by a grant number K23AG042459 from the National Institute on Aging. Dr. Mosher is supported in part by the Department of Veterans Affairs Office of Academic Affiliations and the Office of Research and Development and Health Services Research and Development Service (HSR&D) through the Comprehensive Access and Delivery Research and Evaluation Center (CIN 13-412). The views expressed in this manuscript do not necessarily represent the views of the funding agencies.

Hall et al. draw attention to the important question of whether some patients may benefit from a naloxone prescription when discharged from the hospital with a short-term opioid prescription for acute pain. Although all members of the working group agreed that naloxone is appropriate in some cases, we were hesitant to recommend this as a standard practice for several reasons.

First, the intent of our Consensus Statement¹ was to synthesize and summarize the areas of consensus in existing guidelines; none of the existing guidelines included in our systematic review make a recommendation for naloxone prescription in the setting of short-term opioid use for acute pain.² We believe that this may relate to the fact that the risk factors for overdose and the threshold of risk above which naloxone would be beneficial have yet to be defined for this population and are likely to differ from those defined in patients using opioids chronically.

Additionally, if practitioners follow the recommendations to limit prescribing for acute pain to the minimum dose and duration of an opioid that was presumably administered in the hospital with an observed response, then the risk of overdose and the potential benefit of naloxone will decrease. Furthermore, emerging data from randomized controlled trials demonstrating noninferiority of nonopioid analgesics in the management of acute pain suggest that we should not so readily presume opioids to be the necessary or the best option.^3-5 Data questioning the benefits of opioids over other safer therapies have particularly important implications for patients in whom the risks are felt to be high enough to warrant consideration of naloxone.

Disclosures

Dr. Herzig reports receiving compensation from the Society of Hospital Medicine for her editorial role in the Journal of Hospital Medicine (unrelated to the present work). None of the other authors have any conflicts of interest to disclose.

Funding

Dr. Herzig is funded by a grant number K23AG042459 from the National Institute on Aging. Dr. Mosher is supported in part by the Department of Veterans Affairs Office of Academic Affiliations and the Office of Research and Development and Health Services Research and Development Service (HSR&D) through the Comprehensive Access and Delivery Research and Evaluation Center (CIN 13-412). The views expressed in this manuscript do not necessarily represent the views of the funding agencies.

Hall et al. draw attention to the important question of whether some patients may benefit from a naloxone prescription when discharged from the hospital with a short-term opioid prescription for acute pain. Although all members of the working group agreed that naloxone is appropriate in some cases, we were hesitant to recommend this as a standard practice for several reasons.

First, the intent of our Consensus Statement¹ was to synthesize and summarize the areas of consensus in existing guidelines; none of the existing guidelines included in our systematic review make a recommendation for naloxone prescription in the setting of short-term opioid use for acute pain.² We believe that this may relate to the fact that the risk factors for overdose and the threshold of risk above which naloxone would be beneficial have yet to be defined for this population and are likely to differ from those defined in patients using opioids chronically.

Additionally, if practitioners follow the recommendations to limit prescribing for acute pain to the minimum dose and duration of an opioid that was presumably administered in the hospital with an observed response, then the risk of overdose and the potential benefit of naloxone will decrease. Furthermore, emerging data from randomized controlled trials demonstrating noninferiority of nonopioid analgesics in the management of acute pain suggest that we should not so readily presume opioids to be the necessary or the best option.^3-5 Data questioning the benefits of opioids over other safer therapies have particularly important implications for patients in whom the risks are felt to be high enough to warrant consideration of naloxone.

Disclosures

Dr. Herzig reports receiving compensation from the Society of Hospital Medicine for her editorial role in the Journal of Hospital Medicine (unrelated to the present work). None of the other authors have any conflicts of interest to disclose.

Funding

Dr. Herzig is funded by a grant number K23AG042459 from the National Institute on Aging. Dr. Mosher is supported in part by the Department of Veterans Affairs Office of Academic Affiliations and the Office of Research and Development and Health Services Research and Development Service (HSR&D) through the Comprehensive Access and Delivery Research and Evaluation Center (CIN 13-412). The views expressed in this manuscript do not necessarily represent the views of the funding agencies.

Pain is prevalent among hospitalized patients, occurring in 52%-71% of patients in cross-sectional surveys.^1-3 Opioid administration is also common, with more than half of nonsurgical patients in United States (US) hospitals receiving at least one dose of opioid during hospitalization.⁴ Studies have also begun to define the degree to which hospital prescribing contributes to long-term use. Among opioid-naïve patients admitted to the hospital, 15%-25% fill an opioid prescription in the week after hospital discharge,^5,6 43% of such patients fill another opioid prescription 90 days postdischarge,⁶ and 15% meet the criteria for long-term use at one year.⁷ With about 37 million discharges from US hospitals each year,⁸ these estimates suggest that hospitalization contributes to initiation of long-term opioid use in millions of adults each year.

Additionally, studies in the emergency department and hospital settings demonstrate large variations in prescribing of opioids between providers and hospitals.^4,9 Variation unrelated to patient characteristics highlights areas of clinical uncertainty and the corresponding need for prescribing standards and guidance. To our knowledge, there are no existing guidelines on safe prescribing of opioids in hospitalized patients, aside from guidelines specifically focused on the perioperative, palliative care, or end-of-life settings.

Thus, in the context of the current opioid epidemic, the Society of Hospital Medicine (SHM) sought to develop a consensus statement to assist clinicians practicing medicine in the inpatient setting in safe prescribing of opioids for acute, noncancer pain on the medical services. We define “safe” prescribing as proposed by Aronson: “a process that recommends a medicine appropriate to the patient’s condition and minimizes the risk of undue harm from it.”¹⁰ To inform development of the consensus statement, SHM convened a working group to systematically review existing guidelines on the more general management of acute pain. This article describes the methods and results of our systematic review of existing guidelines for managing acute pain. The Consensus Statement derived from these existing guidelines, applied to the hospital setting, appears in a companion article.

Steps in the systematic review process included: 1) searching for relevant guidelines, 2) applying exclusion criteria, 3) assessing the quality of the guidelines, and 4) synthesizing guideline recommendations to identify issues potentially relevant to medical inpatients with acute pain. Details of the protocol for this systematic review were registered on PROSPERO and can be accessed at https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=71846.

Data Sources and Search Terms

Guideline Inclusion/Exclusion Criteria

We defined guidelines as statements that include recommendations intended to optimize patient care that are informed by a systematic review of evidence and an assessment of the benefits and harm of alternative care options, consistent with the National Academies’ definition.¹¹ To be eligible, guidelines had to be published in English and include recommendations on prescribing opioids for acute, noncancer pain. We excluded guidelines focused on chronic pain or palliative care, guidelines derived entirely from another guideline, and guidelines published before 2010, since such guidelines may contain outdated information.¹² Because we were interested in general principles regarding safe use of opioids for managing acute pain, we excluded guidelines that focused exclusively on specific disease processes (eg, cancer, low-back pain, and sickle cell anemia). As we were specifically interested in the management of acute pain in the hospital setting, we also excluded guidelines that focused exclusively on specific nonhospital settings of care (eg, outpatient care clinics and nursing homes). We included guidelines related to care in the emergency department (ED) given the hospital-based location of care and the high degree of similarity in scope of practice and patient population, as most hospitalized adults are admitted through the ED. Finally, we excluded guidelines focusing on management in the intensive care setting (including the post-anesthesia care unit) given the inherent differences in patient population and management options between the intensive and nonintensive care areas of the hospital.

Guideline Quality Assessment

Guideline Synthesis and Analysis

We extracted recommendations from each guideline related to the following topics: 1) deciding when to use opioids, nonopioid medications, and nonmedication-based pain management modalities, 2) best practices in screening/monitoring/education prior to prescribing an opioid and/or during treatment, 3) opioid selection considerations, including selection of dose, duration, and route of administration, 4) strategies to minimize the risk of opioid-related adverse events, and 5) safe practices on discharge.

Role of the Funding Source

The Society of Hospital Medicine provided administrative and material support for the project, but had no role in the design or execution of the scientific evaluation.

Guideline Quality Assessment

See Table 1 for the AGREE II scaled domain scores, and Appendix Table 1 for the ratings on each individual item within a domain. The range of scaled scores for each of the AGREE II domains were as follows: Scope and purpose 52%-89%, stakeholder involvement 30%-81%, rigor of development 46%-81%, clarity of presentation 59%-72%, applicability 10%-57%, and editorial independence 42%-78%. Overall guideline assessment scores ranged from 4 to 5.33 on a scale from 1 to 7. Three of the guidelines (NICE, ACOEM, and WSAMDG)^16,17,19 were recommended for use without modification by 2 out of 3 guideline appraisers, and one of the guidelines (ACEP)¹⁸ was recommended for use with modification by all 3 appraisers. The guideline by NICE¹⁹ was rated the highest both overall (5.33), and on 4 of the 6 AGREE II domains.

Although the guidelines each included a systematic review of the literature, the NICE¹⁹ and WSAMDG¹⁷ guidelines did not include the strength of recommendations or provide clear links between each recommendation and the underlying evidence base. When citations were present, we reviewed them to determine the type of data upon which the recommendations were based and included this information in Table 2. The majority of the recommendations in Table 2 are based on expert opinion alone, or other guidelines.

Guideline Synthesis and Analysis

Table 2 contains a synthesis of the recommendations related to each of our 5 prespecified content areas. Despite the generally low quality of the evidence supporting the recommendations, there were many areas of concordance across guidelines.

Deciding When to Use Opioids, Nonopioid Medications, and Nonmedication-Based Pain Management Modalities

Three out of 4 guidelines recommended restricting opioid use to severe pain or pain that has not responded to nonopioid therapy,^16-18 2 guidelines recommended treating mild to moderate pain with nonopioid medications, including acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs),^16,17 and 2 guidelines recommended co-prescribing opioids with nonopioid analgesic medications to reduce total opioid requirements and improve pain control.^16,17 Each of these recommendations was supported by at least one randomized controlled trial.

Best Practices in Screening/Monitoring/Education to Occur Prior to Prescribing an Opioid and/or During Treatment

Three guidelines recommended checking prescription drug monitoring programs (PDMPs), all based on expert consensus.^16-18 Only the WSAMDG guideline offered guidance as to the optimal timing to check the PDMP in this setting, specifically recommending to check before prescribing opioids.¹⁷ Two guidelines also recommended helping patients set reasonable expectations about their recovery and educating patients about the risks/side effects of opioid therapy, all based on expert consensus or other guidelines.^17,19

Opioid Selection Considerations, Including Selection of Dose, Duration, and Route of Administration

Three guidelines recommended using the lowest effective dose, supported by expert consensus and observational data in the outpatient setting demonstrating that overdose risk increases with opioid dose.^16-18 Three guidelines recommended using short-acting opioids and/or avoiding use of long-acting/extended-release opioids for acute pain based on expert consensus.^16-18 Two guidelines recommended using as-needed rather than scheduled dosing of opioids based on expert recommendation.^{16, 17}

Strategies to Minimize the Risk of Opioid-Related Adverse Events

Several strategies to minimize the risk of opioid-related adverse events were identified, but most were only recommended by a single guideline. Strategies recommended by more than one guideline included using a recognized opioid dose conversion guide when prescribing, reviewing, or changing opioid prescriptions (based on expert consensus);^16,19 avoiding co-administration of parenteral and oral as-needed opioids, and if as-needed opioids from different routes are necessary, providing a clear indication for use of each (based on expert consensus and other guidelines);^17,19 and avoiding/using caution when co-prescribing opioids with other central nervous system depressant medications^16,17 (supported by observational studies demonstrating increased risk in the outpatient setting).

Safe Practices on Discharge

All 4 of the guidelines recommended prescribing a limited duration of opioids for the acute pain episode; however the maximum recommended duration varied widely from one week to 30 days.^16-19 It is important to note that because these guidelines were not focused on hospitalization specifically, these maximum recommended durations of use reflect the entire acute pain episode (ie, not prescribing on discharge specifically). The guideline with the longest maximum recommended duration was from NICE, based in the United Kingdom, while the US-based guideline development groups uniformly recommended 1 to 2 weeks as the maximum duration of opioid use, including the period of hospitalization.

This systematic review identified only 4 existing guidelines that included recommendations on safe opioid prescribing practices for managing acute, noncancer pain, outside of the context of specific conditions, specific nonhospital settings, or the intensive care setting. Although 2 of the identified guidelines offered sparse recommendations specific to the hospital setting, we found no guidelines that focused exclusively on the period of hospitalization specifically outside of the perioperative period. Furthermore, the guideline recommendations were largely based on expert opinion. Although these factors limit the confidence with which the recommendations can be applied to the hospital setting, they nonetheless represent the best guidance currently available to standardize and improve the safety of prescribing opioids in the hospital setting.

This paucity of guidance specific to patients hospitalized in general, nonintensive care areas of the hospital is important because pain management in this setting differs in a number of ways from pain management in the ambulatory or intensive care unit settings (including the post-anesthesia care unit). First, there are differences in the monitoring strategies that are available in each of these settings (eg, variability in nurse-to-patient ratios, frequency of measuring vital signs, and availability of continuous pulse oximetry/capnography). Second, there are differences in available/feasible routes of medication administration depending on the setting of care. Finally, there are differences in the patients themselves, including severity of illness, baseline and expected functional status, pain severity, and ability to communicate.

Accordingly, to avoid substantial heterogeneity in recommendations obtained from this review, we chose to focus on guidelines most relevant to clinicians practicing medicine in nonintensive care areas of the hospital. This resulted in the exclusion of 2 guidelines intended for anesthesiologists that focused exclusively on perioperative management and included use of advanced management procedures beyond the scope of practice for general internists,^20,21 and one guideline that focused on management in the intensive care unit.²² Within the set of guidelines included in this review, we did include recommendations designated for the postoperative period that we felt were relevant to the care of hospitalized patients more generally. In fact, the ACOEM guideline, which includes postoperative recommendations, specifically noted that these recommendations are mostly comparable to those for treating acute pain more generally.¹⁶

In addition to the lack of guidance specific to the setting in which most hospitalists practice, most of the recommendations in the existing guidelines are based on expert consensus. Guidelines based on expert opinion typically carry a lower strength of recommendation, and, accordingly, should be applied with some caution and accompanied by diligent tracking of outcome metrics, as these recommendations are applied to local health systems. Recommendations may have unintended consequences that are not necessarily apparent at the outset, and the specific circumstances of each patient must be considered when deciding how best to apply recommendations. Additional research will be necessary to track the impact of the recommended prescribing practices on patient outcomes, particularly given that many states have already begun instituting regulations on safe opioid prescribing despite the limited nature of the evidence. Furthermore, although several studies have identified patient- and prescribing-related risk factors for opioid-related adverse events in surgical patient populations, given the differences in patient characteristics and prescribing patterns in these settings, research to understand the risk factors in hospitalized medical patients specifically is important to inform evidence-based, safe prescribing recommendations in this setting.

Despite the largely expert consensus-based nature of the recommendations, we found substantial overlap in the recommendations between the guidelines, spanning our prespecified topics of interest related to safe prescribing. Most guidelines recommended restricting opioid use to severe pain or pain that has not responded to nonopioid therapy, checking PDMPs, using the lowest effective dose, and using short-acting opioids and/or avoiding use of long-acting/extended-release opioids for acute pain. There was less consensus on risk mitigation strategies, where the majority of recommendations were endorsed by only 1 or 2 guidelines. Finally, all 4 guidelines recommended prescribing a limited duration of opioids for the acute pain episode, with US-based guidelines recommending 1 to 2 weeks as the maximum duration of opioid use, including the period of hospitalization.

There are limitations to our evaluation. As previously noted, in order to avoid substantial heterogeneity in management recommendations, we excluded 2 guidelines intended for anesthesiologists that focused exclusively on perioperative management,^20,21 and one guideline focused on management in the intensive care unit.²² Accordingly, recommendations contained in this review may or may not be applicable to those settings, and readers interested in those settings specifically are directed to those guidelines. Additionally, we decided to exclude guidelines that focused on managing acute pain in specific conditions (eg, sickle cell disease and pancreatitis) because our goal was to identify generalizable principles of safe prescribing of opioids that apply regardless of clinical condition. Despite this goal, it is important to recognize that not all of the recommendations are generalizable to all types of pain; clinicians interested in management principles specific to certain disease states are encouraged to review disease-specific informational material. Finally, although we used rigorous, pre-defined search criteria and registered our protocol on PROSPERO, it is possible that our search strategy missed relevant guidelines.

In conclusion, we identified few guidelines on safe opioid prescribing practices for managing acute, noncancer pain, outside of the context of specific conditions or nonhospital settings, and no guidelines focused on acute pain management in general, nonintensive care areas of the hospital specifically. Nevertheless, the guidelines that we identified make consistent recommendations related to our prespecified topic areas of relevance to the hospital setting, although most recommendations are based exclusively on expert opinion. Our systematic review nonetheless provides guidance in an area where guidance has thus far been limited. Future research should investigate risk factors for opioid-related adverse events in hospitalized, nonsurgical patients, and the effectiveness of interventions designed to reduce their occurrence.

Dr. Herzig had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

The authors would like to acknowledge and thank Kevin Vuernick, Jenna Goldstein, Meghan Mallouk, and Chris Frost, MD, from SHM for their facilitation of this project and dedication to this purpose.

Disclosures: Dr. Herzig received compensation from the Society of Hospital Medicine for her editorial role at the Journal of Hospital Medicine (unrelated to the present work). Dr. Jena received consulting fees from Pfizer, Inc., Hill Rom Services, Inc., Bristol Myers Squibb, Novartis Pharmaceuticals, Vertex Pharmaceuticals, and Precision Health Economics (all unrelated to the present work). None of the other authors have any conflicts of interest to disclose.

Funding: The Society of Hospital Medicine (SHM) provided administrative assistance and material support, but had no role in or influence on the scientific conduct of the study. Dr. Herzig was funded by grant number K23AG042459 from the National Institute on Aging. Dr. Mosher was supported, in part, by the Department of Veterans Affairs Office of Academic Affiliations and Office of Research and Development and Health Services Research and Development Service (HSR&D) through the Comprehensive Access and Delivery Research and Evaluation Center (CIN 13-412). None of the funding agencies had involvement in any aspect of the study, including design, conduct, or reporting of the study

Pain is prevalent among hospitalized patients, occurring in 52%-71% of patients in cross-sectional surveys.^1-3 Opioid administration is also common, with more than half of nonsurgical patients in United States (US) hospitals receiving at least one dose of opioid during hospitalization.⁴ Studies have also begun to define the degree to which hospital prescribing contributes to long-term use. Among opioid-naïve patients admitted to the hospital, 15%-25% fill an opioid prescription in the week after hospital discharge,^5,6 43% of such patients fill another opioid prescription 90 days postdischarge,⁶ and 15% meet the criteria for long-term use at one year.⁷ With about 37 million discharges from US hospitals each year,⁸ these estimates suggest that hospitalization contributes to initiation of long-term opioid use in millions of adults each year.

Additionally, studies in the emergency department and hospital settings demonstrate large variations in prescribing of opioids between providers and hospitals.^4,9 Variation unrelated to patient characteristics highlights areas of clinical uncertainty and the corresponding need for prescribing standards and guidance. To our knowledge, there are no existing guidelines on safe prescribing of opioids in hospitalized patients, aside from guidelines specifically focused on the perioperative, palliative care, or end-of-life settings.

Thus, in the context of the current opioid epidemic, the Society of Hospital Medicine (SHM) sought to develop a consensus statement to assist clinicians practicing medicine in the inpatient setting in safe prescribing of opioids for acute, noncancer pain on the medical services. We define “safe” prescribing as proposed by Aronson: “a process that recommends a medicine appropriate to the patient’s condition and minimizes the risk of undue harm from it.”¹⁰ To inform development of the consensus statement, SHM convened a working group to systematically review existing guidelines on the more general management of acute pain. This article describes the methods and results of our systematic review of existing guidelines for managing acute pain. The Consensus Statement derived from these existing guidelines, applied to the hospital setting, appears in a companion article.

Steps in the systematic review process included: 1) searching for relevant guidelines, 2) applying exclusion criteria, 3) assessing the quality of the guidelines, and 4) synthesizing guideline recommendations to identify issues potentially relevant to medical inpatients with acute pain. Details of the protocol for this systematic review were registered on PROSPERO and can be accessed at https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=71846.

Data Sources and Search Terms

Guideline Inclusion/Exclusion Criteria

We defined guidelines as statements that include recommendations intended to optimize patient care that are informed by a systematic review of evidence and an assessment of the benefits and harm of alternative care options, consistent with the National Academies’ definition.¹¹ To be eligible, guidelines had to be published in English and include recommendations on prescribing opioids for acute, noncancer pain. We excluded guidelines focused on chronic pain or palliative care, guidelines derived entirely from another guideline, and guidelines published before 2010, since such guidelines may contain outdated information.¹² Because we were interested in general principles regarding safe use of opioids for managing acute pain, we excluded guidelines that focused exclusively on specific disease processes (eg, cancer, low-back pain, and sickle cell anemia). As we were specifically interested in the management of acute pain in the hospital setting, we also excluded guidelines that focused exclusively on specific nonhospital settings of care (eg, outpatient care clinics and nursing homes). We included guidelines related to care in the emergency department (ED) given the hospital-based location of care and the high degree of similarity in scope of practice and patient population, as most hospitalized adults are admitted through the ED. Finally, we excluded guidelines focusing on management in the intensive care setting (including the post-anesthesia care unit) given the inherent differences in patient population and management options between the intensive and nonintensive care areas of the hospital.

Guideline Quality Assessment

Guideline Synthesis and Analysis

We extracted recommendations from each guideline related to the following topics: 1) deciding when to use opioids, nonopioid medications, and nonmedication-based pain management modalities, 2) best practices in screening/monitoring/education prior to prescribing an opioid and/or during treatment, 3) opioid selection considerations, including selection of dose, duration, and route of administration, 4) strategies to minimize the risk of opioid-related adverse events, and 5) safe practices on discharge.

Role of the Funding Source

The Society of Hospital Medicine provided administrative and material support for the project, but had no role in the design or execution of the scientific evaluation.

Guideline Quality Assessment

See Table 1 for the AGREE II scaled domain scores, and Appendix Table 1 for the ratings on each individual item within a domain. The range of scaled scores for each of the AGREE II domains were as follows: Scope and purpose 52%-89%, stakeholder involvement 30%-81%, rigor of development 46%-81%, clarity of presentation 59%-72%, applicability 10%-57%, and editorial independence 42%-78%. Overall guideline assessment scores ranged from 4 to 5.33 on a scale from 1 to 7. Three of the guidelines (NICE, ACOEM, and WSAMDG)^16,17,19 were recommended for use without modification by 2 out of 3 guideline appraisers, and one of the guidelines (ACEP)¹⁸ was recommended for use with modification by all 3 appraisers. The guideline by NICE¹⁹ was rated the highest both overall (5.33), and on 4 of the 6 AGREE II domains.

Although the guidelines each included a systematic review of the literature, the NICE¹⁹ and WSAMDG¹⁷ guidelines did not include the strength of recommendations or provide clear links between each recommendation and the underlying evidence base. When citations were present, we reviewed them to determine the type of data upon which the recommendations were based and included this information in Table 2. The majority of the recommendations in Table 2 are based on expert opinion alone, or other guidelines.

Guideline Synthesis and Analysis

Table 2 contains a synthesis of the recommendations related to each of our 5 prespecified content areas. Despite the generally low quality of the evidence supporting the recommendations, there were many areas of concordance across guidelines.

Deciding When to Use Opioids, Nonopioid Medications, and Nonmedication-Based Pain Management Modalities

Three out of 4 guidelines recommended restricting opioid use to severe pain or pain that has not responded to nonopioid therapy,^16-18 2 guidelines recommended treating mild to moderate pain with nonopioid medications, including acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs),^16,17 and 2 guidelines recommended co-prescribing opioids with nonopioid analgesic medications to reduce total opioid requirements and improve pain control.^16,17 Each of these recommendations was supported by at least one randomized controlled trial.

Best Practices in Screening/Monitoring/Education to Occur Prior to Prescribing an Opioid and/or During Treatment

Three guidelines recommended checking prescription drug monitoring programs (PDMPs), all based on expert consensus.^16-18 Only the WSAMDG guideline offered guidance as to the optimal timing to check the PDMP in this setting, specifically recommending to check before prescribing opioids.¹⁷ Two guidelines also recommended helping patients set reasonable expectations about their recovery and educating patients about the risks/side effects of opioid therapy, all based on expert consensus or other guidelines.^17,19

Opioid Selection Considerations, Including Selection of Dose, Duration, and Route of Administration

Three guidelines recommended using the lowest effective dose, supported by expert consensus and observational data in the outpatient setting demonstrating that overdose risk increases with opioid dose.^16-18 Three guidelines recommended using short-acting opioids and/or avoiding use of long-acting/extended-release opioids for acute pain based on expert consensus.^16-18 Two guidelines recommended using as-needed rather than scheduled dosing of opioids based on expert recommendation.^{16, 17}

Strategies to Minimize the Risk of Opioid-Related Adverse Events

Several strategies to minimize the risk of opioid-related adverse events were identified, but most were only recommended by a single guideline. Strategies recommended by more than one guideline included using a recognized opioid dose conversion guide when prescribing, reviewing, or changing opioid prescriptions (based on expert consensus);^16,19 avoiding co-administration of parenteral and oral as-needed opioids, and if as-needed opioids from different routes are necessary, providing a clear indication for use of each (based on expert consensus and other guidelines);^17,19 and avoiding/using caution when co-prescribing opioids with other central nervous system depressant medications^16,17 (supported by observational studies demonstrating increased risk in the outpatient setting).

Safe Practices on Discharge

All 4 of the guidelines recommended prescribing a limited duration of opioids for the acute pain episode; however the maximum recommended duration varied widely from one week to 30 days.^16-19 It is important to note that because these guidelines were not focused on hospitalization specifically, these maximum recommended durations of use reflect the entire acute pain episode (ie, not prescribing on discharge specifically). The guideline with the longest maximum recommended duration was from NICE, based in the United Kingdom, while the US-based guideline development groups uniformly recommended 1 to 2 weeks as the maximum duration of opioid use, including the period of hospitalization.

This systematic review identified only 4 existing guidelines that included recommendations on safe opioid prescribing practices for managing acute, noncancer pain, outside of the context of specific conditions, specific nonhospital settings, or the intensive care setting. Although 2 of the identified guidelines offered sparse recommendations specific to the hospital setting, we found no guidelines that focused exclusively on the period of hospitalization specifically outside of the perioperative period. Furthermore, the guideline recommendations were largely based on expert opinion. Although these factors limit the confidence with which the recommendations can be applied to the hospital setting, they nonetheless represent the best guidance currently available to standardize and improve the safety of prescribing opioids in the hospital setting.

This paucity of guidance specific to patients hospitalized in general, nonintensive care areas of the hospital is important because pain management in this setting differs in a number of ways from pain management in the ambulatory or intensive care unit settings (including the post-anesthesia care unit). First, there are differences in the monitoring strategies that are available in each of these settings (eg, variability in nurse-to-patient ratios, frequency of measuring vital signs, and availability of continuous pulse oximetry/capnography). Second, there are differences in available/feasible routes of medication administration depending on the setting of care. Finally, there are differences in the patients themselves, including severity of illness, baseline and expected functional status, pain severity, and ability to communicate.

Accordingly, to avoid substantial heterogeneity in recommendations obtained from this review, we chose to focus on guidelines most relevant to clinicians practicing medicine in nonintensive care areas of the hospital. This resulted in the exclusion of 2 guidelines intended for anesthesiologists that focused exclusively on perioperative management and included use of advanced management procedures beyond the scope of practice for general internists,^20,21 and one guideline that focused on management in the intensive care unit.²² Within the set of guidelines included in this review, we did include recommendations designated for the postoperative period that we felt were relevant to the care of hospitalized patients more generally. In fact, the ACOEM guideline, which includes postoperative recommendations, specifically noted that these recommendations are mostly comparable to those for treating acute pain more generally.¹⁶

In addition to the lack of guidance specific to the setting in which most hospitalists practice, most of the recommendations in the existing guidelines are based on expert consensus. Guidelines based on expert opinion typically carry a lower strength of recommendation, and, accordingly, should be applied with some caution and accompanied by diligent tracking of outcome metrics, as these recommendations are applied to local health systems. Recommendations may have unintended consequences that are not necessarily apparent at the outset, and the specific circumstances of each patient must be considered when deciding how best to apply recommendations. Additional research will be necessary to track the impact of the recommended prescribing practices on patient outcomes, particularly given that many states have already begun instituting regulations on safe opioid prescribing despite the limited nature of the evidence. Furthermore, although several studies have identified patient- and prescribing-related risk factors for opioid-related adverse events in surgical patient populations, given the differences in patient characteristics and prescribing patterns in these settings, research to understand the risk factors in hospitalized medical patients specifically is important to inform evidence-based, safe prescribing recommendations in this setting.

Despite the largely expert consensus-based nature of the recommendations, we found substantial overlap in the recommendations between the guidelines, spanning our prespecified topics of interest related to safe prescribing. Most guidelines recommended restricting opioid use to severe pain or pain that has not responded to nonopioid therapy, checking PDMPs, using the lowest effective dose, and using short-acting opioids and/or avoiding use of long-acting/extended-release opioids for acute pain. There was less consensus on risk mitigation strategies, where the majority of recommendations were endorsed by only 1 or 2 guidelines. Finally, all 4 guidelines recommended prescribing a limited duration of opioids for the acute pain episode, with US-based guidelines recommending 1 to 2 weeks as the maximum duration of opioid use, including the period of hospitalization.

There are limitations to our evaluation. As previously noted, in order to avoid substantial heterogeneity in management recommendations, we excluded 2 guidelines intended for anesthesiologists that focused exclusively on perioperative management,^20,21 and one guideline focused on management in the intensive care unit.²² Accordingly, recommendations contained in this review may or may not be applicable to those settings, and readers interested in those settings specifically are directed to those guidelines. Additionally, we decided to exclude guidelines that focused on managing acute pain in specific conditions (eg, sickle cell disease and pancreatitis) because our goal was to identify generalizable principles of safe prescribing of opioids that apply regardless of clinical condition. Despite this goal, it is important to recognize that not all of the recommendations are generalizable to all types of pain; clinicians interested in management principles specific to certain disease states are encouraged to review disease-specific informational material. Finally, although we used rigorous, pre-defined search criteria and registered our protocol on PROSPERO, it is possible that our search strategy missed relevant guidelines.

In conclusion, we identified few guidelines on safe opioid prescribing practices for managing acute, noncancer pain, outside of the context of specific conditions or nonhospital settings, and no guidelines focused on acute pain management in general, nonintensive care areas of the hospital specifically. Nevertheless, the guidelines that we identified make consistent recommendations related to our prespecified topic areas of relevance to the hospital setting, although most recommendations are based exclusively on expert opinion. Our systematic review nonetheless provides guidance in an area where guidance has thus far been limited. Future research should investigate risk factors for opioid-related adverse events in hospitalized, nonsurgical patients, and the effectiveness of interventions designed to reduce their occurrence.

Dr. Herzig had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

The authors would like to acknowledge and thank Kevin Vuernick, Jenna Goldstein, Meghan Mallouk, and Chris Frost, MD, from SHM for their facilitation of this project and dedication to this purpose.

Disclosures: Dr. Herzig received compensation from the Society of Hospital Medicine for her editorial role at the Journal of Hospital Medicine (unrelated to the present work). Dr. Jena received consulting fees from Pfizer, Inc., Hill Rom Services, Inc., Bristol Myers Squibb, Novartis Pharmaceuticals, Vertex Pharmaceuticals, and Precision Health Economics (all unrelated to the present work). None of the other authors have any conflicts of interest to disclose.

Funding: The Society of Hospital Medicine (SHM) provided administrative assistance and material support, but had no role in or influence on the scientific conduct of the study. Dr. Herzig was funded by grant number K23AG042459 from the National Institute on Aging. Dr. Mosher was supported, in part, by the Department of Veterans Affairs Office of Academic Affiliations and Office of Research and Development and Health Services Research and Development Service (HSR&D) through the Comprehensive Access and Delivery Research and Evaluation Center (CIN 13-412). None of the funding agencies had involvement in any aspect of the study, including design, conduct, or reporting of the study

Pain is prevalent among hospitalized patients, occurring in 52%-71% of patients in cross-sectional surveys.^1-3 Opioid administration is also common, with more than half of nonsurgical patients in United States (US) hospitals receiving at least one dose of opioid during hospitalization.⁴ Studies have also begun to define the degree to which hospital prescribing contributes to long-term use. Among opioid-naïve patients admitted to the hospital, 15%-25% fill an opioid prescription in the week after hospital discharge,^5,6 43% of such patients fill another opioid prescription 90 days postdischarge,⁶ and 15% meet the criteria for long-term use at one year.⁷ With about 37 million discharges from US hospitals each year,⁸ these estimates suggest that hospitalization contributes to initiation of long-term opioid use in millions of adults each year.

Additionally, studies in the emergency department and hospital settings demonstrate large variations in prescribing of opioids between providers and hospitals.^4,9 Variation unrelated to patient characteristics highlights areas of clinical uncertainty and the corresponding need for prescribing standards and guidance. To our knowledge, there are no existing guidelines on safe prescribing of opioids in hospitalized patients, aside from guidelines specifically focused on the perioperative, palliative care, or end-of-life settings.

Thus, in the context of the current opioid epidemic, the Society of Hospital Medicine (SHM) sought to develop a consensus statement to assist clinicians practicing medicine in the inpatient setting in safe prescribing of opioids for acute, noncancer pain on the medical services. We define “safe” prescribing as proposed by Aronson: “a process that recommends a medicine appropriate to the patient’s condition and minimizes the risk of undue harm from it.”¹⁰ To inform development of the consensus statement, SHM convened a working group to systematically review existing guidelines on the more general management of acute pain. This article describes the methods and results of our systematic review of existing guidelines for managing acute pain. The Consensus Statement derived from these existing guidelines, applied to the hospital setting, appears in a companion article.

Steps in the systematic review process included: 1) searching for relevant guidelines, 2) applying exclusion criteria, 3) assessing the quality of the guidelines, and 4) synthesizing guideline recommendations to identify issues potentially relevant to medical inpatients with acute pain. Details of the protocol for this systematic review were registered on PROSPERO and can be accessed at https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=71846.

Data Sources and Search Terms

Guideline Inclusion/Exclusion Criteria

We defined guidelines as statements that include recommendations intended to optimize patient care that are informed by a systematic review of evidence and an assessment of the benefits and harm of alternative care options, consistent with the National Academies’ definition.¹¹ To be eligible, guidelines had to be published in English and include recommendations on prescribing opioids for acute, noncancer pain. We excluded guidelines focused on chronic pain or palliative care, guidelines derived entirely from another guideline, and guidelines published before 2010, since such guidelines may contain outdated information.¹² Because we were interested in general principles regarding safe use of opioids for managing acute pain, we excluded guidelines that focused exclusively on specific disease processes (eg, cancer, low-back pain, and sickle cell anemia). As we were specifically interested in the management of acute pain in the hospital setting, we also excluded guidelines that focused exclusively on specific nonhospital settings of care (eg, outpatient care clinics and nursing homes). We included guidelines related to care in the emergency department (ED) given the hospital-based location of care and the high degree of similarity in scope of practice and patient population, as most hospitalized adults are admitted through the ED. Finally, we excluded guidelines focusing on management in the intensive care setting (including the post-anesthesia care unit) given the inherent differences in patient population and management options between the intensive and nonintensive care areas of the hospital.

Guideline Quality Assessment

Guideline Synthesis and Analysis

We extracted recommendations from each guideline related to the following topics: 1) deciding when to use opioids, nonopioid medications, and nonmedication-based pain management modalities, 2) best practices in screening/monitoring/education prior to prescribing an opioid and/or during treatment, 3) opioid selection considerations, including selection of dose, duration, and route of administration, 4) strategies to minimize the risk of opioid-related adverse events, and 5) safe practices on discharge.

Role of the Funding Source

The Society of Hospital Medicine provided administrative and material support for the project, but had no role in the design or execution of the scientific evaluation.

Guideline Quality Assessment

See Table 1 for the AGREE II scaled domain scores, and Appendix Table 1 for the ratings on each individual item within a domain. The range of scaled scores for each of the AGREE II domains were as follows: Scope and purpose 52%-89%, stakeholder involvement 30%-81%, rigor of development 46%-81%, clarity of presentation 59%-72%, applicability 10%-57%, and editorial independence 42%-78%. Overall guideline assessment scores ranged from 4 to 5.33 on a scale from 1 to 7. Three of the guidelines (NICE, ACOEM, and WSAMDG)^16,17,19 were recommended for use without modification by 2 out of 3 guideline appraisers, and one of the guidelines (ACEP)¹⁸ was recommended for use with modification by all 3 appraisers. The guideline by NICE¹⁹ was rated the highest both overall (5.33), and on 4 of the 6 AGREE II domains.

Although the guidelines each included a systematic review of the literature, the NICE¹⁹ and WSAMDG¹⁷ guidelines did not include the strength of recommendations or provide clear links between each recommendation and the underlying evidence base. When citations were present, we reviewed them to determine the type of data upon which the recommendations were based and included this information in Table 2. The majority of the recommendations in Table 2 are based on expert opinion alone, or other guidelines.

Guideline Synthesis and Analysis

Table 2 contains a synthesis of the recommendations related to each of our 5 prespecified content areas. Despite the generally low quality of the evidence supporting the recommendations, there were many areas of concordance across guidelines.

Deciding When to Use Opioids, Nonopioid Medications, and Nonmedication-Based Pain Management Modalities

Three out of 4 guidelines recommended restricting opioid use to severe pain or pain that has not responded to nonopioid therapy,^16-18 2 guidelines recommended treating mild to moderate pain with nonopioid medications, including acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs),^16,17 and 2 guidelines recommended co-prescribing opioids with nonopioid analgesic medications to reduce total opioid requirements and improve pain control.^16,17 Each of these recommendations was supported by at least one randomized controlled trial.

Best Practices in Screening/Monitoring/Education to Occur Prior to Prescribing an Opioid and/or During Treatment

Three guidelines recommended checking prescription drug monitoring programs (PDMPs), all based on expert consensus.^16-18 Only the WSAMDG guideline offered guidance as to the optimal timing to check the PDMP in this setting, specifically recommending to check before prescribing opioids.¹⁷ Two guidelines also recommended helping patients set reasonable expectations about their recovery and educating patients about the risks/side effects of opioid therapy, all based on expert consensus or other guidelines.^17,19

Opioid Selection Considerations, Including Selection of Dose, Duration, and Route of Administration

Three guidelines recommended using the lowest effective dose, supported by expert consensus and observational data in the outpatient setting demonstrating that overdose risk increases with opioid dose.^16-18 Three guidelines recommended using short-acting opioids and/or avoiding use of long-acting/extended-release opioids for acute pain based on expert consensus.^16-18 Two guidelines recommended using as-needed rather than scheduled dosing of opioids based on expert recommendation.^{16, 17}

Strategies to Minimize the Risk of Opioid-Related Adverse Events

Several strategies to minimize the risk of opioid-related adverse events were identified, but most were only recommended by a single guideline. Strategies recommended by more than one guideline included using a recognized opioid dose conversion guide when prescribing, reviewing, or changing opioid prescriptions (based on expert consensus);^16,19 avoiding co-administration of parenteral and oral as-needed opioids, and if as-needed opioids from different routes are necessary, providing a clear indication for use of each (based on expert consensus and other guidelines);^17,19 and avoiding/using caution when co-prescribing opioids with other central nervous system depressant medications^16,17 (supported by observational studies demonstrating increased risk in the outpatient setting).

Safe Practices on Discharge

All 4 of the guidelines recommended prescribing a limited duration of opioids for the acute pain episode; however the maximum recommended duration varied widely from one week to 30 days.^16-19 It is important to note that because these guidelines were not focused on hospitalization specifically, these maximum recommended durations of use reflect the entire acute pain episode (ie, not prescribing on discharge specifically). The guideline with the longest maximum recommended duration was from NICE, based in the United Kingdom, while the US-based guideline development groups uniformly recommended 1 to 2 weeks as the maximum duration of opioid use, including the period of hospitalization.

This systematic review identified only 4 existing guidelines that included recommendations on safe opioid prescribing practices for managing acute, noncancer pain, outside of the context of specific conditions, specific nonhospital settings, or the intensive care setting. Although 2 of the identified guidelines offered sparse recommendations specific to the hospital setting, we found no guidelines that focused exclusively on the period of hospitalization specifically outside of the perioperative period. Furthermore, the guideline recommendations were largely based on expert opinion. Although these factors limit the confidence with which the recommendations can be applied to the hospital setting, they nonetheless represent the best guidance currently available to standardize and improve the safety of prescribing opioids in the hospital setting.

This paucity of guidance specific to patients hospitalized in general, nonintensive care areas of the hospital is important because pain management in this setting differs in a number of ways from pain management in the ambulatory or intensive care unit settings (including the post-anesthesia care unit). First, there are differences in the monitoring strategies that are available in each of these settings (eg, variability in nurse-to-patient ratios, frequency of measuring vital signs, and availability of continuous pulse oximetry/capnography). Second, there are differences in available/feasible routes of medication administration depending on the setting of care. Finally, there are differences in the patients themselves, including severity of illness, baseline and expected functional status, pain severity, and ability to communicate.

Accordingly, to avoid substantial heterogeneity in recommendations obtained from this review, we chose to focus on guidelines most relevant to clinicians practicing medicine in nonintensive care areas of the hospital. This resulted in the exclusion of 2 guidelines intended for anesthesiologists that focused exclusively on perioperative management and included use of advanced management procedures beyond the scope of practice for general internists,^20,21 and one guideline that focused on management in the intensive care unit.²² Within the set of guidelines included in this review, we did include recommendations designated for the postoperative period that we felt were relevant to the care of hospitalized patients more generally. In fact, the ACOEM guideline, which includes postoperative recommendations, specifically noted that these recommendations are mostly comparable to those for treating acute pain more generally.¹⁶

In addition to the lack of guidance specific to the setting in which most hospitalists practice, most of the recommendations in the existing guidelines are based on expert consensus. Guidelines based on expert opinion typically carry a lower strength of recommendation, and, accordingly, should be applied with some caution and accompanied by diligent tracking of outcome metrics, as these recommendations are applied to local health systems. Recommendations may have unintended consequences that are not necessarily apparent at the outset, and the specific circumstances of each patient must be considered when deciding how best to apply recommendations. Additional research will be necessary to track the impact of the recommended prescribing practices on patient outcomes, particularly given that many states have already begun instituting regulations on safe opioid prescribing despite the limited nature of the evidence. Furthermore, although several studies have identified patient- and prescribing-related risk factors for opioid-related adverse events in surgical patient populations, given the differences in patient characteristics and prescribing patterns in these settings, research to understand the risk factors in hospitalized medical patients specifically is important to inform evidence-based, safe prescribing recommendations in this setting.

Despite the largely expert consensus-based nature of the recommendations, we found substantial overlap in the recommendations between the guidelines, spanning our prespecified topics of interest related to safe prescribing. Most guidelines recommended restricting opioid use to severe pain or pain that has not responded to nonopioid therapy, checking PDMPs, using the lowest effective dose, and using short-acting opioids and/or avoiding use of long-acting/extended-release opioids for acute pain. There was less consensus on risk mitigation strategies, where the majority of recommendations were endorsed by only 1 or 2 guidelines. Finally, all 4 guidelines recommended prescribing a limited duration of opioids for the acute pain episode, with US-based guidelines recommending 1 to 2 weeks as the maximum duration of opioid use, including the period of hospitalization.

There are limitations to our evaluation. As previously noted, in order to avoid substantial heterogeneity in management recommendations, we excluded 2 guidelines intended for anesthesiologists that focused exclusively on perioperative management,^20,21 and one guideline focused on management in the intensive care unit.²² Accordingly, recommendations contained in this review may or may not be applicable to those settings, and readers interested in those settings specifically are directed to those guidelines. Additionally, we decided to exclude guidelines that focused on managing acute pain in specific conditions (eg, sickle cell disease and pancreatitis) because our goal was to identify generalizable principles of safe prescribing of opioids that apply regardless of clinical condition. Despite this goal, it is important to recognize that not all of the recommendations are generalizable to all types of pain; clinicians interested in management principles specific to certain disease states are encouraged to review disease-specific informational material. Finally, although we used rigorous, pre-defined search criteria and registered our protocol on PROSPERO, it is possible that our search strategy missed relevant guidelines.

In conclusion, we identified few guidelines on safe opioid prescribing practices for managing acute, noncancer pain, outside of the context of specific conditions or nonhospital settings, and no guidelines focused on acute pain management in general, nonintensive care areas of the hospital specifically. Nevertheless, the guidelines that we identified make consistent recommendations related to our prespecified topic areas of relevance to the hospital setting, although most recommendations are based exclusively on expert opinion. Our systematic review nonetheless provides guidance in an area where guidance has thus far been limited. Future research should investigate risk factors for opioid-related adverse events in hospitalized, nonsurgical patients, and the effectiveness of interventions designed to reduce their occurrence.

Dr. Herzig had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

The authors would like to acknowledge and thank Kevin Vuernick, Jenna Goldstein, Meghan Mallouk, and Chris Frost, MD, from SHM for their facilitation of this project and dedication to this purpose.

Disclosures: Dr. Herzig received compensation from the Society of Hospital Medicine for her editorial role at the Journal of Hospital Medicine (unrelated to the present work). Dr. Jena received consulting fees from Pfizer, Inc., Hill Rom Services, Inc., Bristol Myers Squibb, Novartis Pharmaceuticals, Vertex Pharmaceuticals, and Precision Health Economics (all unrelated to the present work). None of the other authors have any conflicts of interest to disclose.

Funding: The Society of Hospital Medicine (SHM) provided administrative assistance and material support, but had no role in or influence on the scientific conduct of the study. Dr. Herzig was funded by grant number K23AG042459 from the National Institute on Aging. Dr. Mosher was supported, in part, by the Department of Veterans Affairs Office of Academic Affiliations and Office of Research and Development and Health Services Research and Development Service (HSR&D) through the Comprehensive Access and Delivery Research and Evaluation Center (CIN 13-412). None of the funding agencies had involvement in any aspect of the study, including design, conduct, or reporting of the study

Since the initial reports of an emerging opioid epidemic in the early 2000s, intense focus on improving opioid prescribing in outpatient settings has culminated in new guidelines for chronic pain.^1,2 Although opioid stewardship in the setting of chronic pain is of paramount importance in curbing the ongoing epidemic, long-term prescription opioid use often begins with treatment of acute pain.¹ In addition to differences in recommended management strategies for acute and chronic pain, there are unique aspects and challenges to pain management in the acute-care setting.

Opioids are commonly used for the treatment of acute pain in hospitalized patients, often at high doses.³ Recent reports highlight that hospital use of opioids impacts downstream use.^4-6 Additionally, opioid prescribing practices vary between hospital-based providers and hospitals,^3,7 highlighting the need for prescribing standards and guidance. To our knowledge, there are no existing guidelines for improving the safety of opioid use in hospitalized patients outside of the intensive care or immediate perioperative settings.

The Society of Hospital Medicine (SHM) convened a working group to systematically review existing guidelines and develop a consensus statement to assist clinicians in safe opioid use for acute, noncancer pain in hospitalized adults.

Consensus Statement Purpose and Scope

The purpose of this Consensus Statement is to present clinical recommendations on the safe use of opioids for the treatment of acute, noncancer pain in hospitalized adults. The guidance is intended for clinicians practicing medicine in the inpatient setting (eg, hospitalists, primary care physicians, family physicians, nurse practitioners, and physician assistants) and is intended to apply to hospitalized adults with acute, noncancer pain (ie, pain that typically lasts <3 months or during the period of normal tissue healing) outside of the palliative, end-of-life, and intensive care settings.

Consensus Statement Development

Our working group included experts in opioid use in the hospital setting, defined by 1) engagement in the clinical practice of hospital medicine and 2) involvement in clinical research related to usage patterns and clinical outcomes of opioid use in hospitalized patients (see Appendix Table 1). The SHM provided administrative assistance with the project and funded the in-person working group meeting, but it had no role in formulating the recommendations. The SHM Board of Directors provided approval of the Consensus Statement without modification.

An overview of the sequential steps in the Consensus Statement development process is described below; details of the methods and results can be found in the Appendix (eMethods).

Performing the Systematic Review

Drafting the Consensus Statement

After performing the systematic review, the working group drafted and iteratively revised a set of recommendations using a variation of the Delphi Method⁸ to identify consensus among group members.

External Review

Following agreement on a draft set of recommendations, we obtained feedback from external groups, including 1) individuals involved in the SHM’s Reducing Adverse Drug Events Related to Opioids (RADEO) initiative, including those involved in the development of the implementation guide and site leads for the Mentored Implementation program, 2) SHM members, SHM Patient-Family Advisory Council (PFAC) members, and leaders of other relevant professional societies, and 3) peer-reviewers at the Journal of Hospital Medicine.

Deciding Whether to Use Opioids During Hospitalization

1. SHM recommends that clinicians limit the use of opioids to patients with 1) severe pain or 2) moderate pain that has not responded to nonopioid therapy, or where nonopioid therapy is contraindicated or anticipated to be ineffective.

Opioids are associated with several well-recognized risks ranging from mild to severe, including nausea, constipation, urinary retention, falls, delirium, sedation, physical dependence, addiction, respiratory depression, and death. Given these risks, the risk-to-benefit ratio is generally not favorable at lower levels of pain severity. Furthermore, for most painful conditions, including those causing severe pain, nonopioid analgesics, including acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs), have been demonstrated to be equally or more effective with less risk of harm than opioids.^9-13 Clinicians should consider drug–drug and drug–disease associations when deciding between these different therapies and make a determination in each patient regarding whether the benefits outweigh the risks. Often, drug–disease interactions do not represent absolute contraindications, and risks can be mitigated by adhering to dosage limits and, with respect to NSAIDs, 1) monitoring renal function, 2) monitoring volume status in patients with congestive heart failure, and 3) considering a selective cyclooxygenase-2 (COX-2) inhibitor rather than a nonselective NSAID or pairing the NSAID with an acid-suppressive medication in patients with a history of peptic ulcer disease or at elevated risk for gastroduodenal disease. For these reasons, a trial of nonopioid therapy (including pharmacologic and nonpharmacologic modalities) should always be considered before using opioids for pain of any severity. This does not imply that a trial of nonopioid therapy must be performed in all patients, but rather, that the likelihood of benefit and associated risks of opioid and nonopioid therapy should be considered for all patients in determining the best initial management strategy.

2. SHM recommends that clinicians use extra caution when administering opioids to patients with risk factors for opioid-related adverse events.

Several factors have been consistently demonstrated to increase the risk of opioid-related adverse events–most importantly, respiratory depression and overdose–in varied patient populations and settings, including age 65 years and older,^1,14-17 renal insufficiency,^1,14,18 hepatic insufficiency,^1,14 chronic respiratory failure (including chronic obstructive pulmonary disease, sleep apnea, etc.), and receipt of other central nervous system (CNS) depressant medications (including, but not limited to, benzodiazepines).^1,18-20 History of any substance use disorder and psychiatric disorders have been associated with an increased risk for the development of opioid use disorder.^21-24 These factors should be weighed against the benefits when deciding on opioid appropriateness in a given patient. However, identification of these risks should not preclude opioids as part of pain management. When a decision is made to use opioids in patients with these risk factors, clinicians should 1) use a reduced starting dose (generally, at least a 50% reduction in the usual starting dose) and 2) consider closer monitoring for adverse effects (eg, more frequent nursing assessments, capnography, or more frequent outpatient visits).

3. SHM recommends that clinicians review the information contained in the prescription drug monitoring program (PDMP) database to inform decision-making around opioid therapy.

Although data on the impact of use of the state PDMP database on prescribing practices or patient outcomes are limited, PDMP use has been advocated by multiple guidelines on acute pain management.^25-27 The PDMP provides information that can be useful in several ways, including 1) confirmation of prior opioid exposure and dosage, which should be used to guide appropriate dosage selection in the hospital, 2) identification of existing controlled substance prescriptions, which should be considered in prescribing decisions in the hospital and on discharge, and 3) identification of signs of aberrant behavior. For example, the identification of controlled substance prescriptions written by multiple different clinicians can facilitate early identification of potential diversion or evolving or existing opioid use disorder and the opportunity for intervention,²⁸ which may include referral to support services, initiation of medication-assisted treatment, and/or pain specialist consultation when available. Concerns regarding evolving or existing opioid use disorder should prompt further discussion between the clinician and the patient, both to clarify their understanding of their recent prescription history and to discuss concerns for patient safety related to the increased risk of opioid-related adverse effects (including respiratory depression and overdose) among patients with controlled substance prescriptions written by multiple providers. Although such concerns should not automatically preclude the use of opioids for acute pain in the hospital setting, they should be considered in the assessment of whether the benefits of opioid therapy outweigh the risks for a given patient.

4. SHM recommends that clinicians educate patients and families or caregivers about the potential risks and side effects of opioid therapy as well as alternative pharmacologic and nonpharmacologic therapies for managing pain.

Patients are often unaware of the risks of opioid therapy (see Consensus Statement 1 for key risks),²⁹ or that there are often equally effective alternative therapies. As with any therapy associated with substantial risk, clinicians should discuss these risks with patients and/or caregivers at the outset of therapy, as well as the potential benefits of nonopioid pharmacologic and nonpharmacologic therapies for managing pain. Patients should be informed that they may request nonopioid therapy in lieu of opioids, even for severe pain.

Once a Decision Has Been Made to Use Opioids During Hospitalization

5. SHM recommends that clinicians use the lowest effective opioid dose for the shortest duration possible.

Higher opioid doses are associated with an increased incidence of opioid-related adverse events, particularly overdose, in studies of both inpatient and outpatient populations.^{1,17,19,30,31} Studies in the inpatient and outpatient settings consistently demonstrate that risk increases with dosage.^19,30,31 Clinicians should reduce the usual starting dose by at least 50% among patients with conditions that increase susceptibility to opioid-related adverse events (see Consensus Statement 2). The ongoing need for opioids should be re-assessed regularly-at least daily-during the hospitalization, with attempts at tapering as healing occurs and/or pain and function improve.

6. SHM recommends that clinicians use immediate-release opioid formulations and avoid initiation of long-acting or extended-release formulations (including transdermal fentanyl) for treatment of acute pain.

Studies in outpatient settings demonstrate that the use of long-acting opioids is associated with greater risk for overdose–especially in opioid-naïve patients–and long-term use.^32,33 Further, hospitalized patients frequently have fluctuating renal function and rapidly changing pain levels. We therefore recommend that initiation of long-acting opioids be avoided for the treatment of acute, noncancer pain in hospitalized medical patients. It is important to note that although we recommend avoiding initiation of long-acting opioids for the treatment of acute, noncancer pain, there are circumstances outside of the scope of this Consensus Statement for which initiation of long-acting opioids may be indicated, including the treatment of opioid withdrawal. We also do not recommend discontinuation of long-acting or extended-release opioids in patients who are taking these medications for chronic pain at the time of hospital admission (unless there are concerns regarding adverse effects or drug–disease interactions).

7. SHM recommends that clinicians use the oral route of administration whenever possible. Intravenous opioids should be reserved for patients who cannot take food or medications by mouth, patients suspected of gastrointestinal malabsorption, or when immediate pain control and/or rapid dose titration is necessary.

Intravenous opioid administration is associated with an increased risk of side effects, adverse events, and medication errors.^34-36 Additionally, studies demonstrate that in general, the addiction potential of medications is greater the more rapid the onset of action (the onset of action is 5–10 min for intravenous and 15–30 minutes for oral administration).^37,38 Furthermore, the duration of action is greater for oral compared to that of intravenous administration, potentially allowing for more consistent pain relief and less frequent administrations. As such, intravenous administration should be reserved for situations when oral administration is not possible or likely to be ineffective, or when immediate pain control and/or rapid titration is necessary.

8. SHM recommends that clinicians use an opioid equivalency table or calculator to understand the relative potency of different opioids 1) when initiating opioid therapy, 2) when changing from one route of administration to another, and 3) when changing from one opioid to another. When changing from one opioid to another, clinicians should generally reduce the dose of the new opioid by at least 25%–50% of the calculated equianalgesic dose to account for interindividual variability in the response to opioids as well as possible incomplete cross-tolerance.

Most errors causing preventable adverse drug events in hospitals occur at the ordering stage.^39,40 Clinicians are often unaware of the potency of different types of opioids relative to each other or to morphine (ie, morphine equivalent dose), which can lead to inadvertent overdose when initiating therapy with nonmorphine opioids and when converting from one opioid to another. To facilitate safe opioid use, we recommend that clinicians use one of several available opioid equivalency tables or calculators to better understand the relative potencies of opioids and to inform both starting dose calculations and conversions between opioids and routes of administration. When converting from one opioid to another, we caution clinicians to reduce the dose of the new opioid by at least 25%–50% of the calculated equianalgesic dose to account for interindividual variability in the response to opioids and the potential for incomplete cross-tolerance, wherein tolerance to a currently administered opioid does not extend completely to other opioids. Clinicians should use extreme caution when performing conversions to and from methadone and consider consultation with a hospital pharmacist or a pain management specialist, when available, to assist with conversion decisions and calculations.

9. SHM recommends that clinicians pair opioids with scheduled nonopioid analgesic medications, unless contraindicated, and always consider pairing with nonpharmacologic pain management strategies (ie, multimodal analgesia).

Concurrent receipt of opioids and nonopioid analgesic medications (including acetaminophen, NSAIDs, and gabapentin or pregabalin, depending on the underlying pathophysiology of the pain) has been demonstrated to reduce total opioid requirements and improve pain management.^41,42 Clinicians should be familiar with contraindications and maximum dosage recommendations for each of these adjunctive nonopioid medications. We recommend separate orders for each, rather than using drug formulations that combine opioids and nonopioid analgesics in the same pill, due to the risk of inadvertently exceeding the maximum recommended doses of the nonopioid analgesic (particularly acetaminophen) with combination products. We recommend that nonopioid analgesics be ordered at a scheduled frequency, rather than as needed, to facilitate consistent administration that is not dependent on opioid administration. Topical agents, including lidocaine and capsaicin, should also be considered. Nonpharmacologic pain management strategies can include procedure-based (eg, regional and local anesthesia) and nonprocedure-based therapies depending on the underlying condition and institutional availability. Although few studies have assessed the benefit of nonpharmacologic, nonprocedure-based therapies for the treatment of acute pain in hospitalized patients, the lack of harm associated with their use argues for their adoption. Simple nonpharmacologic therapies that can usually be provided to patients in any hospital setting include music therapy, cold or hot packs, chaplain or social work visits (possibly including mindfulness training),⁴³ and physical therapy, among others.

10. SHM recommends that, unless contraindicated, clinicians order a bowel regimen to prevent opioid-induced constipation in patients receiving opioids.

Constipation is a common adverse effect of opioid therapy and results from the activation of mu opioid receptors in the colon, resulting in decreased peristalsis. Hospitalized patients are already prone to constipation due to their often-limited physical mobility. To mitigate this complication, we recommend the administration of a bowel regimen to all hospitalized medical patients receiving opioid therapy, provided the patient is not having diarrhea. Given the mechanism of opioid-induced constipation, stimulant laxatives (eg, senna, bisacodyl) have been recommended for this purpose.⁴⁴ Osmotic laxatives (eg, polyethylene glycol, lactulose) have demonstrated efficacy for the treatment of constipation more generally (ie, not necessarily opioid-induced constipation). Stool softeners, although frequently used in the inpatient setting, are not recommended due to limited and conflicting evidence for efficacy in prevention or treatment of constipation.⁴⁵ Bowel movements should be tracked during hospitalization, and the bowel regimen modified accordingly.

11. SHM recommends that clinicians limit co-administration of opioids with other central nervous system depressant medications to the extent possible.

This combination has been demonstrated to increase the risk of opioid-related adverse events in multiple settings of care, including during hospitalization.^1,18,19 Although benzodiazepines have received the most attention in this respect, other medications with CNS depressant properties may also increase the risk, including, but not limited to, nonbenzodiazepine sedative-hypnotics (eg, zolpidem, zaleplon, zopiclone), muscle relaxants, sedating antidepressants, antipsychotics, and antihistamines.^18,19,46 For some patients, the combination will be unavoidable, and we do not suggest routine discontinuation of longstanding medications that preexisted hospitalization, given the risks of withdrawal and/or worsening of the underlying condition for which these medications are prescribed. Rather, clinicians should carefully consider the necessity of each medication class with input from the patient’s outpatient providers, taper the frequency and/or the dose of CNS depressants when appropriate and feasible, and avoid new coprescriptions to the extent possible, both during hospitalization and on hospital discharge.

12. SHM recommends that clinicians work with patients and families or caregivers to establish realistic goals and expectations of opioid therapy and the expected course of recovery.

Discussing expectations at the start of therapy is important to facilitate a clear understanding of how meaningful improvement will be defined and measured during the hospitalization and how long the patient is anticipated to require opioid therapy. Meaningful improvement should be defined to include improvement in both pain and function. Clinicians should discuss with patients 1) that the goal of opioid therapy is tolerability of pain such that meaningful improvement in function can be achieved and 2) that a decrease in pain intensity in the absence of improved function is not considered meaningful improvement in most situations and should prompt reevaluation of the appropriateness of continued opioid therapy as well as close follow-up with a clinician following hospital discharge. Discussions regarding the expected course of recovery should include that acute pain is expected to resolve as the underlying medical condition improves and that although pain may persist beyond the hospitalization, pain that is severe enough to require opioids will often be resolved or almost resolved by the time of hospital discharge.

13. SHM recommends that clinicians monitor the response to opioid therapy, including assessment for functional improvement and development of adverse effects.

Pain severity and function should be assessed at least daily, and improvement in reported pain severity without improvement in function over several days should, in most circumstances, prompt reconsideration of ongoing opioid therapy and reconsideration of the underlying etiology of pain. Although hospital-specific functional measures in the setting of acute pain have not yet been validated, we suggest that such measures and goals should be individualized based on preexisting function and may include the ability to sit up or move in bed, move to a chair, work with physical therapy, or ambulate in the hallway. Protocols for the assessment for adverse effects are not well established. Because sedation typically precedes respiratory depression, it is generally recommended that patients are evaluated (eg, by nursing staff) for sedation after each opioid administration (10–20 minutes for intravenous and 30–60 minutes for oral administration based on the time-to-peak effect). Whether certain patients may benefit from more intensive respiratory monitoring, such as pulse oximetry or capnography, is an area of active investigation and not yet established.

Prescribing at the Time of Hospital Discharge

14. SHM recommends that clinicians ask patients about any existing opioid supply at home and account for any such supply when issuing an opioid prescription on discharge.

Even in the setting of acute pain, patients may have previously received an opioid prescription from an outpatient clinician prior to hospitalization. Unused prescription opioids create the possibility of both overdose (when patients take multiple opioids concurrently, intentionally or inadvertently) and diversion (many adults with prescription opioid misuse obtained their opioids from a friend or a relative who may or may not have known that this occurred⁴⁷). The PDMP database can provide information related to the potential existence of any prior opioid supplies, which should be confirmed with the patient and considered when providing a new prescription on hospital discharge. Information on proper disposal should be provided if use of the preexisting opioid is no longer intended.

15. SHM recommends that clinicians prescribe the minimum quantity of opioids anticipated to be necessary based on the expected course and duration of pain that is severe enough to require opioid therapy after hospital discharge.

For many patients, the condition causing their acute pain will be mostly or completely resolved by the time of hospital discharge. When pain is still present at the time of discharge, most pain can be completely managed with nonopioid therapies. For those with ongoing pain that is severe enough to require opioids after hospital discharge, decisions regarding the duration of therapy should be made on a case-by-case basis; generally, however, provision of a 3- to 5-day supply will be sufficient, and provision of more than a 7-day supply of opioids should generally be avoided for several reasons. These include 1) acute pain lasting longer than 7 days after appropriate treatment of any existing underlying conditions should prompt re-evaluation of the working diagnosis and/or reconsideration of the management approach, 2) receiving higher intensity opioid therapy (including longer courses) in the setting of acute pain has been associated with an increased risk of long-term disability and long-term opioid use,^33,48,49 and 3) unused opioids create the possibility of intentional or unintentional opioid diversion (see Consensus Statement 14).⁴⁷ Accordingly, clinicians should attempt to arrange an outpatient follow-up appointment for re-evaluation within 7 days, rather than providing an extended opioid prescription on hospital discharge. In situations where this is not feasible, and pain that is severe enough to require opioids is expected to persist longer than 7 days, an extended prescription may be indicated. However, some states have begun enacting legislation to limit the duration of first-time opioid prescriptions, typically using a 5-to-7 day supply as an upper limit; clinicians should be aware of and adhere to individual state laws governing their practice.

16. SHM recommends that clinicians ensure that patients and families or caregivers receive information regarding how to minimize the risks of opioid therapy for themselves, their families, and their communities. This includes but is not limited to 1) how to take their opioids correctly (the planned medications, doses, schedule); 2) that they should take the minimum quantity necessary to achieve tolerable levels of pain and meaningful functional improvement, reducing the dose and/or frequency as pain and function improve; 3) how to safeguard their supply and dispose of any unused supply; 4) that they should avoid agents that may potentiate the sedative effect of opioids, including sleeping medication and alcohol; 5) that they should avoid driving or operating heavy machinery while taking opioids; and 6) that they should seek help if they begin to experience any potential adverse effects, with inclusion of information on early warning signs.

Clear and concise patient instructions on home opioid dosing and administration will limit opioid-related adverse events and dosing errors upon hospital discharge. Each of these recommendations derive from one or more of the existing guidelines and reflect the transfer of responsibility for safe opioid use practices that occurs as patients transition from a closely monitored inpatient setting to the more self-regulated home environment.

This Consensus Statement reflects a synthesis of the key recommendations from a systematic review of existing guidelines on acute pain management, adapted for a hospital-specific scope of practice. Despite a paucity of data on the comparative effectiveness of different management strategies for acute pain, several areas of expert consensus emerged across existing guidelines, which were felt to be relevant and applicable to the hospital setting. The objective of these recommendations is to provide information that can be used to inform and support opioid-related management decisions for acute pain by clinicians practicing medicine in the inpatient setting.

Although these recommendations are not intended to apply to the immediate perioperative setting (ie, care in the postanesthesia care unit), many of the recommendations in the existing guidelines upon which this Consensus Statement was based were intended for the postoperative setting, and, as others have noted, recommendations in this setting are mostly comparable to those for treating acute pain more generally.²⁷ Those interested in pain management in the postoperative setting specifically may wish to review the recent guidelines released by the American Pain Society,⁵⁰ the content of which is in close alignment with our Consensus Statement.

Several important issues were raised during the extensive external feedback process undertaken as part of the development of this Consensus Statement. Although many issues were incorporated into the recommendations, there were several suggestions for which we felt the evidence base was not sufficient to allow a clear or valid recommendation to be made. For example, several reviewers requested endorsement of specific patient education tools and opioid equivalency calculators. In the absence of tools specifically validated for this purpose, we felt that the evidence was insufficient to make specific recommendations. Validating such tools for use in the inpatient setting should be an area of future investigation. In the meantime, we note that there are several existing and widely available resources for both patient education (ie, opioid information sheets, including opioid risks, safe containment and disposal, and safe use practices) and opioid equivalency calculations that clinicians and hospitals can adapt for their purposes.

Several individuals suggested recommendations on communication with outpatient continuity providers around opioid management decisions during hospitalization and on discharge. Although we believe that it is of paramount importance for outpatient providers to be aware of and have input into these decisions, the optimal timing and the method for such communication are unclear and likely to be institution-specific depending on the availability and integration of electronic records across care settings. We recommend that clinicians use their judgment as to the best format and timing for assuring that outpatient physicians are aware of and have input into these important management decisions with downstream consequences.

Concerns were also raised about the time required to complete the recommended practices and the importance of emphasizing the need for a team-based approach in this realm. We agree wholeheartedly with this sentiment and believe that many of the recommended practices can and should be automated and/or shared across the care team. For example, PDMPs allow prescribers to appoint delegates to check the PDMP on their behalf. Additionally, we suggest that hospitals work to develop systems to assist care teams with performance of these tasks in a standardized and streamlined manner (eg, integrating access to the PDMP and opioid equivalency tables within the electronic health record and developing standard patient educational handouts). Provision of written materials on opioid risks, side effects, and safety practices may be helpful in facilitating consistent messaging and efficient workflow for members of the care team.

Finally, the working group carefully considered whether to include a recommendation regarding naloxone prescribing at the time of hospital discharge. The provision of naloxone kits to laypersons through Overdose Education and Naloxone Distribution Programs has been shown to reduce opioid overdose deaths^51,52 and hospitalizations^53,54 and is both safe and cost-effective.⁵⁵ The Centers for Disease Control and Preventionrecommend that clinicians “consider offering naloxone to patients with a history of overdose, a current or past substance use disorder, receipt of ≥50 mg of morphine equivalents per day or concurrent benzodiazepine use.”¹ However, these recommendations are intended for patients on chronic opioid therapy; presently, no clear evidence exists to guide decisions about the benefits and costs associated with prescribing naloxone in the setting of short-term opioid therapy for acute pain. Further research in this area is warranted.

The greatest limitation of this Consensus Statement is the lack of high-quality studies informing most of the recommendations in the guidelines upon which our Consensus Statement was based. The majority of recommendations in the existing guidelines were based on expert opinion alone. Additional research is necessary before evidence-based recommendations can be formulated.

Accordingly, the working group identified several key areas for future research, in addition to those noted above. First, ongoing efforts to develop and evaluate the effectiveness of nonopioid and nonpharmacologic management strategies for acute pain in hospitalized patients are necessary. Second, studies identifying the risk factors for opioid-related adverse events in hospitalized patients would help inform management decisions and allow deployment of resources and specialized monitoring strategies to patients at heightened risk. The working group also noted the need for research investigating the impact of PDMP use on management decisions and downstream outcomes among hospitalized patients. Finally, conversations around pain management and concerns related to aberrant behaviors are often challenging in the hospital setting owing to the brief, high-intensity nature of the care and the lack of a longstanding therapeutic alliance. There is a great need to develop strategies and language to facilitate these conversations.

In conclusion, until more high-quality evidence becomes available, clinicians can use the recommendations contained in this Consensus Statement along with their clinical judgment and consultation with pharmacists, interventional pain specialists, and other staff (eg, social work, nursing) to help facilitate consistent, high-quality care across providers and hospitals. We believe that doing so will help increase the appropriateness of opioid therapy, minimize adverse events, facilitate shared decision-making, and foster stronger therapeutic alliances at the outset of the hospitalization for patients suffering from acute pain.

The authors would like to acknowledge and thank Kevin Vuernick, Jenna Goldstein, Meghan Mallouk, and Chris Frost, MD, from the SHM for their facilitation of this project and dedication to this purpose.

The authors would also like to thank the many individuals who provided comments on the draft recommendations, including the participants in the SHM RADEO program; the SHM members; the representatives of specialty societies, including the American Academy of Family Physicians, the American College of Physicians, the American Hospital Association, the American Society of Addiction Medicine, the American Society of Anesthesiologists, the American Society of Health-System Pharmacists, the Society of Critical Care Medicine, and the Society of General Internal Medicine; and the representatives of patient advocacy groups, including SHM PFAC, Regions Hospital Patient and Family Advisory Committee, Patient and Family Centered Care Council of St. Louis Children’s Hospital, Missouri Family Partnership, and Parent and Family Care.

Disclosures: Dr. Herzig reports receiving compensation from the Society of Hospital Medicine for her editorial role at the Journal of Hospital Medicine (unrelated to the present work). Dr. Jena reports receiving consulting fees from Pfizer, Inc., Hill Rom Services, Inc., Bristol Myers Squibb, Novartis Pharmaceuticals, Vertex Pharmaceuticals, and Precision Health Economics, a consultancy to the life sciences industry (all unrelated to the present work). None of the other authors have any conflicts of interest to disclose.

Funding: The Society of Hospital Medicine (SHM) provided administrative assistance with the project and funded the in-person working group meeting but had no role in or influence on developing the content of the recommendations themselves. The SHM Board of Directors provided approval to submit the manuscript for publication without modification. Dr. Herzig was funded by grant number K23AG042459 from the National Institute on Aging. Dr. Mosher was supported in part by the Department of Veterans Affairs Office of Academic Affiliations and Office of Research and Development and Health Services Research and Development Service (HSR&D) through the Comprehensive Access and Delivery Research and Evaluation Center (CIN 13-412). None of the funding agencies had involvement in any aspect of the study, including design, conduct, and reporting of the study

Since the initial reports of an emerging opioid epidemic in the early 2000s, intense focus on improving opioid prescribing in outpatient settings has culminated in new guidelines for chronic pain.^1,2 Although opioid stewardship in the setting of chronic pain is of paramount importance in curbing the ongoing epidemic, long-term prescription opioid use often begins with treatment of acute pain.¹ In addition to differences in recommended management strategies for acute and chronic pain, there are unique aspects and challenges to pain management in the acute-care setting.

Opioids are commonly used for the treatment of acute pain in hospitalized patients, often at high doses.³ Recent reports highlight that hospital use of opioids impacts downstream use.^4-6 Additionally, opioid prescribing practices vary between hospital-based providers and hospitals,^3,7 highlighting the need for prescribing standards and guidance. To our knowledge, there are no existing guidelines for improving the safety of opioid use in hospitalized patients outside of the intensive care or immediate perioperative settings.

The Society of Hospital Medicine (SHM) convened a working group to systematically review existing guidelines and develop a consensus statement to assist clinicians in safe opioid use for acute, noncancer pain in hospitalized adults.

Consensus Statement Purpose and Scope

The purpose of this Consensus Statement is to present clinical recommendations on the safe use of opioids for the treatment of acute, noncancer pain in hospitalized adults. The guidance is intended for clinicians practicing medicine in the inpatient setting (eg, hospitalists, primary care physicians, family physicians, nurse practitioners, and physician assistants) and is intended to apply to hospitalized adults with acute, noncancer pain (ie, pain that typically lasts <3 months or during the period of normal tissue healing) outside of the palliative, end-of-life, and intensive care settings.

Consensus Statement Development

Our working group included experts in opioid use in the hospital setting, defined by 1) engagement in the clinical practice of hospital medicine and 2) involvement in clinical research related to usage patterns and clinical outcomes of opioid use in hospitalized patients (see Appendix Table 1). The SHM provided administrative assistance with the project and funded the in-person working group meeting, but it had no role in formulating the recommendations. The SHM Board of Directors provided approval of the Consensus Statement without modification.

An overview of the sequential steps in the Consensus Statement development process is described below; details of the methods and results can be found in the Appendix (eMethods).

Performing the Systematic Review

Drafting the Consensus Statement

After performing the systematic review, the working group drafted and iteratively revised a set of recommendations using a variation of the Delphi Method⁸ to identify consensus among group members.

External Review

Following agreement on a draft set of recommendations, we obtained feedback from external groups, including 1) individuals involved in the SHM’s Reducing Adverse Drug Events Related to Opioids (RADEO) initiative, including those involved in the development of the implementation guide and site leads for the Mentored Implementation program, 2) SHM members, SHM Patient-Family Advisory Council (PFAC) members, and leaders of other relevant professional societies, and 3) peer-reviewers at the Journal of Hospital Medicine.

Deciding Whether to Use Opioids During Hospitalization

1. SHM recommends that clinicians limit the use of opioids to patients with 1) severe pain or 2) moderate pain that has not responded to nonopioid therapy, or where nonopioid therapy is contraindicated or anticipated to be ineffective.

Opioids are associated with several well-recognized risks ranging from mild to severe, including nausea, constipation, urinary retention, falls, delirium, sedation, physical dependence, addiction, respiratory depression, and death. Given these risks, the risk-to-benefit ratio is generally not favorable at lower levels of pain severity. Furthermore, for most painful conditions, including those causing severe pain, nonopioid analgesics, including acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs), have been demonstrated to be equally or more effective with less risk of harm than opioids.^9-13 Clinicians should consider drug–drug and drug–disease associations when deciding between these different therapies and make a determination in each patient regarding whether the benefits outweigh the risks. Often, drug–disease interactions do not represent absolute contraindications, and risks can be mitigated by adhering to dosage limits and, with respect to NSAIDs, 1) monitoring renal function, 2) monitoring volume status in patients with congestive heart failure, and 3) considering a selective cyclooxygenase-2 (COX-2) inhibitor rather than a nonselective NSAID or pairing the NSAID with an acid-suppressive medication in patients with a history of peptic ulcer disease or at elevated risk for gastroduodenal disease. For these reasons, a trial of nonopioid therapy (including pharmacologic and nonpharmacologic modalities) should always be considered before using opioids for pain of any severity. This does not imply that a trial of nonopioid therapy must be performed in all patients, but rather, that the likelihood of benefit and associated risks of opioid and nonopioid therapy should be considered for all patients in determining the best initial management strategy.

2. SHM recommends that clinicians use extra caution when administering opioids to patients with risk factors for opioid-related adverse events.

Several factors have been consistently demonstrated to increase the risk of opioid-related adverse events–most importantly, respiratory depression and overdose–in varied patient populations and settings, including age 65 years and older,^1,14-17 renal insufficiency,^1,14,18 hepatic insufficiency,^1,14 chronic respiratory failure (including chronic obstructive pulmonary disease, sleep apnea, etc.), and receipt of other central nervous system (CNS) depressant medications (including, but not limited to, benzodiazepines).^1,18-20 History of any substance use disorder and psychiatric disorders have been associated with an increased risk for the development of opioid use disorder.^21-24 These factors should be weighed against the benefits when deciding on opioid appropriateness in a given patient. However, identification of these risks should not preclude opioids as part of pain management. When a decision is made to use opioids in patients with these risk factors, clinicians should 1) use a reduced starting dose (generally, at least a 50% reduction in the usual starting dose) and 2) consider closer monitoring for adverse effects (eg, more frequent nursing assessments, capnography, or more frequent outpatient visits).

3. SHM recommends that clinicians review the information contained in the prescription drug monitoring program (PDMP) database to inform decision-making around opioid therapy.

Although data on the impact of use of the state PDMP database on prescribing practices or patient outcomes are limited, PDMP use has been advocated by multiple guidelines on acute pain management.^25-27 The PDMP provides information that can be useful in several ways, including 1) confirmation of prior opioid exposure and dosage, which should be used to guide appropriate dosage selection in the hospital, 2) identification of existing controlled substance prescriptions, which should be considered in prescribing decisions in the hospital and on discharge, and 3) identification of signs of aberrant behavior. For example, the identification of controlled substance prescriptions written by multiple different clinicians can facilitate early identification of potential diversion or evolving or existing opioid use disorder and the opportunity for intervention,²⁸ which may include referral to support services, initiation of medication-assisted treatment, and/or pain specialist consultation when available. Concerns regarding evolving or existing opioid use disorder should prompt further discussion between the clinician and the patient, both to clarify their understanding of their recent prescription history and to discuss concerns for patient safety related to the increased risk of opioid-related adverse effects (including respiratory depression and overdose) among patients with controlled substance prescriptions written by multiple providers. Although such concerns should not automatically preclude the use of opioids for acute pain in the hospital setting, they should be considered in the assessment of whether the benefits of opioid therapy outweigh the risks for a given patient.

4. SHM recommends that clinicians educate patients and families or caregivers about the potential risks and side effects of opioid therapy as well as alternative pharmacologic and nonpharmacologic therapies for managing pain.

Patients are often unaware of the risks of opioid therapy (see Consensus Statement 1 for key risks),²⁹ or that there are often equally effective alternative therapies. As with any therapy associated with substantial risk, clinicians should discuss these risks with patients and/or caregivers at the outset of therapy, as well as the potential benefits of nonopioid pharmacologic and nonpharmacologic therapies for managing pain. Patients should be informed that they may request nonopioid therapy in lieu of opioids, even for severe pain.

Once a Decision Has Been Made to Use Opioids During Hospitalization

5. SHM recommends that clinicians use the lowest effective opioid dose for the shortest duration possible.

Higher opioid doses are associated with an increased incidence of opioid-related adverse events, particularly overdose, in studies of both inpatient and outpatient populations.^{1,17,19,30,31} Studies in the inpatient and outpatient settings consistently demonstrate that risk increases with dosage.^19,30,31 Clinicians should reduce the usual starting dose by at least 50% among patients with conditions that increase susceptibility to opioid-related adverse events (see Consensus Statement 2). The ongoing need for opioids should be re-assessed regularly-at least daily-during the hospitalization, with attempts at tapering as healing occurs and/or pain and function improve.

6. SHM recommends that clinicians use immediate-release opioid formulations and avoid initiation of long-acting or extended-release formulations (including transdermal fentanyl) for treatment of acute pain.

Studies in outpatient settings demonstrate that the use of long-acting opioids is associated with greater risk for overdose–especially in opioid-naïve patients–and long-term use.^32,33 Further, hospitalized patients frequently have fluctuating renal function and rapidly changing pain levels. We therefore recommend that initiation of long-acting opioids be avoided for the treatment of acute, noncancer pain in hospitalized medical patients. It is important to note that although we recommend avoiding initiation of long-acting opioids for the treatment of acute, noncancer pain, there are circumstances outside of the scope of this Consensus Statement for which initiation of long-acting opioids may be indicated, including the treatment of opioid withdrawal. We also do not recommend discontinuation of long-acting or extended-release opioids in patients who are taking these medications for chronic pain at the time of hospital admission (unless there are concerns regarding adverse effects or drug–disease interactions).

7. SHM recommends that clinicians use the oral route of administration whenever possible. Intravenous opioids should be reserved for patients who cannot take food or medications by mouth, patients suspected of gastrointestinal malabsorption, or when immediate pain control and/or rapid dose titration is necessary.

Intravenous opioid administration is associated with an increased risk of side effects, adverse events, and medication errors.^34-36 Additionally, studies demonstrate that in general, the addiction potential of medications is greater the more rapid the onset of action (the onset of action is 5–10 min for intravenous and 15–30 minutes for oral administration).^37,38 Furthermore, the duration of action is greater for oral compared to that of intravenous administration, potentially allowing for more consistent pain relief and less frequent administrations. As such, intravenous administration should be reserved for situations when oral administration is not possible or likely to be ineffective, or when immediate pain control and/or rapid titration is necessary.

8. SHM recommends that clinicians use an opioid equivalency table or calculator to understand the relative potency of different opioids 1) when initiating opioid therapy, 2) when changing from one route of administration to another, and 3) when changing from one opioid to another. When changing from one opioid to another, clinicians should generally reduce the dose of the new opioid by at least 25%–50% of the calculated equianalgesic dose to account for interindividual variability in the response to opioids as well as possible incomplete cross-tolerance.

Most errors causing preventable adverse drug events in hospitals occur at the ordering stage.^39,40 Clinicians are often unaware of the potency of different types of opioids relative to each other or to morphine (ie, morphine equivalent dose), which can lead to inadvertent overdose when initiating therapy with nonmorphine opioids and when converting from one opioid to another. To facilitate safe opioid use, we recommend that clinicians use one of several available opioid equivalency tables or calculators to better understand the relative potencies of opioids and to inform both starting dose calculations and conversions between opioids and routes of administration. When converting from one opioid to another, we caution clinicians to reduce the dose of the new opioid by at least 25%–50% of the calculated equianalgesic dose to account for interindividual variability in the response to opioids and the potential for incomplete cross-tolerance, wherein tolerance to a currently administered opioid does not extend completely to other opioids. Clinicians should use extreme caution when performing conversions to and from methadone and consider consultation with a hospital pharmacist or a pain management specialist, when available, to assist with conversion decisions and calculations.

9. SHM recommends that clinicians pair opioids with scheduled nonopioid analgesic medications, unless contraindicated, and always consider pairing with nonpharmacologic pain management strategies (ie, multimodal analgesia).

Concurrent receipt of opioids and nonopioid analgesic medications (including acetaminophen, NSAIDs, and gabapentin or pregabalin, depending on the underlying pathophysiology of the pain) has been demonstrated to reduce total opioid requirements and improve pain management.^41,42 Clinicians should be familiar with contraindications and maximum dosage recommendations for each of these adjunctive nonopioid medications. We recommend separate orders for each, rather than using drug formulations that combine opioids and nonopioid analgesics in the same pill, due to the risk of inadvertently exceeding the maximum recommended doses of the nonopioid analgesic (particularly acetaminophen) with combination products. We recommend that nonopioid analgesics be ordered at a scheduled frequency, rather than as needed, to facilitate consistent administration that is not dependent on opioid administration. Topical agents, including lidocaine and capsaicin, should also be considered. Nonpharmacologic pain management strategies can include procedure-based (eg, regional and local anesthesia) and nonprocedure-based therapies depending on the underlying condition and institutional availability. Although few studies have assessed the benefit of nonpharmacologic, nonprocedure-based therapies for the treatment of acute pain in hospitalized patients, the lack of harm associated with their use argues for their adoption. Simple nonpharmacologic therapies that can usually be provided to patients in any hospital setting include music therapy, cold or hot packs, chaplain or social work visits (possibly including mindfulness training),⁴³ and physical therapy, among others.

10. SHM recommends that, unless contraindicated, clinicians order a bowel regimen to prevent opioid-induced constipation in patients receiving opioids.

Constipation is a common adverse effect of opioid therapy and results from the activation of mu opioid receptors in the colon, resulting in decreased peristalsis. Hospitalized patients are already prone to constipation due to their often-limited physical mobility. To mitigate this complication, we recommend the administration of a bowel regimen to all hospitalized medical patients receiving opioid therapy, provided the patient is not having diarrhea. Given the mechanism of opioid-induced constipation, stimulant laxatives (eg, senna, bisacodyl) have been recommended for this purpose.⁴⁴ Osmotic laxatives (eg, polyethylene glycol, lactulose) have demonstrated efficacy for the treatment of constipation more generally (ie, not necessarily opioid-induced constipation). Stool softeners, although frequently used in the inpatient setting, are not recommended due to limited and conflicting evidence for efficacy in prevention or treatment of constipation.⁴⁵ Bowel movements should be tracked during hospitalization, and the bowel regimen modified accordingly.

11. SHM recommends that clinicians limit co-administration of opioids with other central nervous system depressant medications to the extent possible.

This combination has been demonstrated to increase the risk of opioid-related adverse events in multiple settings of care, including during hospitalization.^1,18,19 Although benzodiazepines have received the most attention in this respect, other medications with CNS depressant properties may also increase the risk, including, but not limited to, nonbenzodiazepine sedative-hypnotics (eg, zolpidem, zaleplon, zopiclone), muscle relaxants, sedating antidepressants, antipsychotics, and antihistamines.^18,19,46 For some patients, the combination will be unavoidable, and we do not suggest routine discontinuation of longstanding medications that preexisted hospitalization, given the risks of withdrawal and/or worsening of the underlying condition for which these medications are prescribed. Rather, clinicians should carefully consider the necessity of each medication class with input from the patient’s outpatient providers, taper the frequency and/or the dose of CNS depressants when appropriate and feasible, and avoid new coprescriptions to the extent possible, both during hospitalization and on hospital discharge.

12. SHM recommends that clinicians work with patients and families or caregivers to establish realistic goals and expectations of opioid therapy and the expected course of recovery.

Discussing expectations at the start of therapy is important to facilitate a clear understanding of how meaningful improvement will be defined and measured during the hospitalization and how long the patient is anticipated to require opioid therapy. Meaningful improvement should be defined to include improvement in both pain and function. Clinicians should discuss with patients 1) that the goal of opioid therapy is tolerability of pain such that meaningful improvement in function can be achieved and 2) that a decrease in pain intensity in the absence of improved function is not considered meaningful improvement in most situations and should prompt reevaluation of the appropriateness of continued opioid therapy as well as close follow-up with a clinician following hospital discharge. Discussions regarding the expected course of recovery should include that acute pain is expected to resolve as the underlying medical condition improves and that although pain may persist beyond the hospitalization, pain that is severe enough to require opioids will often be resolved or almost resolved by the time of hospital discharge.

13. SHM recommends that clinicians monitor the response to opioid therapy, including assessment for functional improvement and development of adverse effects.

Pain severity and function should be assessed at least daily, and improvement in reported pain severity without improvement in function over several days should, in most circumstances, prompt reconsideration of ongoing opioid therapy and reconsideration of the underlying etiology of pain. Although hospital-specific functional measures in the setting of acute pain have not yet been validated, we suggest that such measures and goals should be individualized based on preexisting function and may include the ability to sit up or move in bed, move to a chair, work with physical therapy, or ambulate in the hallway. Protocols for the assessment for adverse effects are not well established. Because sedation typically precedes respiratory depression, it is generally recommended that patients are evaluated (eg, by nursing staff) for sedation after each opioid administration (10–20 minutes for intravenous and 30–60 minutes for oral administration based on the time-to-peak effect). Whether certain patients may benefit from more intensive respiratory monitoring, such as pulse oximetry or capnography, is an area of active investigation and not yet established.

Prescribing at the Time of Hospital Discharge

14. SHM recommends that clinicians ask patients about any existing opioid supply at home and account for any such supply when issuing an opioid prescription on discharge.

Even in the setting of acute pain, patients may have previously received an opioid prescription from an outpatient clinician prior to hospitalization. Unused prescription opioids create the possibility of both overdose (when patients take multiple opioids concurrently, intentionally or inadvertently) and diversion (many adults with prescription opioid misuse obtained their opioids from a friend or a relative who may or may not have known that this occurred⁴⁷). The PDMP database can provide information related to the potential existence of any prior opioid supplies, which should be confirmed with the patient and considered when providing a new prescription on hospital discharge. Information on proper disposal should be provided if use of the preexisting opioid is no longer intended.

15. SHM recommends that clinicians prescribe the minimum quantity of opioids anticipated to be necessary based on the expected course and duration of pain that is severe enough to require opioid therapy after hospital discharge.

For many patients, the condition causing their acute pain will be mostly or completely resolved by the time of hospital discharge. When pain is still present at the time of discharge, most pain can be completely managed with nonopioid therapies. For those with ongoing pain that is severe enough to require opioids after hospital discharge, decisions regarding the duration of therapy should be made on a case-by-case basis; generally, however, provision of a 3- to 5-day supply will be sufficient, and provision of more than a 7-day supply of opioids should generally be avoided for several reasons. These include 1) acute pain lasting longer than 7 days after appropriate treatment of any existing underlying conditions should prompt re-evaluation of the working diagnosis and/or reconsideration of the management approach, 2) receiving higher intensity opioid therapy (including longer courses) in the setting of acute pain has been associated with an increased risk of long-term disability and long-term opioid use,^33,48,49 and 3) unused opioids create the possibility of intentional or unintentional opioid diversion (see Consensus Statement 14).⁴⁷ Accordingly, clinicians should attempt to arrange an outpatient follow-up appointment for re-evaluation within 7 days, rather than providing an extended opioid prescription on hospital discharge. In situations where this is not feasible, and pain that is severe enough to require opioids is expected to persist longer than 7 days, an extended prescription may be indicated. However, some states have begun enacting legislation to limit the duration of first-time opioid prescriptions, typically using a 5-to-7 day supply as an upper limit; clinicians should be aware of and adhere to individual state laws governing their practice.

16. SHM recommends that clinicians ensure that patients and families or caregivers receive information regarding how to minimize the risks of opioid therapy for themselves, their families, and their communities. This includes but is not limited to 1) how to take their opioids correctly (the planned medications, doses, schedule); 2) that they should take the minimum quantity necessary to achieve tolerable levels of pain and meaningful functional improvement, reducing the dose and/or frequency as pain and function improve; 3) how to safeguard their supply and dispose of any unused supply; 4) that they should avoid agents that may potentiate the sedative effect of opioids, including sleeping medication and alcohol; 5) that they should avoid driving or operating heavy machinery while taking opioids; and 6) that they should seek help if they begin to experience any potential adverse effects, with inclusion of information on early warning signs.

Clear and concise patient instructions on home opioid dosing and administration will limit opioid-related adverse events and dosing errors upon hospital discharge. Each of these recommendations derive from one or more of the existing guidelines and reflect the transfer of responsibility for safe opioid use practices that occurs as patients transition from a closely monitored inpatient setting to the more self-regulated home environment.

This Consensus Statement reflects a synthesis of the key recommendations from a systematic review of existing guidelines on acute pain management, adapted for a hospital-specific scope of practice. Despite a paucity of data on the comparative effectiveness of different management strategies for acute pain, several areas of expert consensus emerged across existing guidelines, which were felt to be relevant and applicable to the hospital setting. The objective of these recommendations is to provide information that can be used to inform and support opioid-related management decisions for acute pain by clinicians practicing medicine in the inpatient setting.

Although these recommendations are not intended to apply to the immediate perioperative setting (ie, care in the postanesthesia care unit), many of the recommendations in the existing guidelines upon which this Consensus Statement was based were intended for the postoperative setting, and, as others have noted, recommendations in this setting are mostly comparable to those for treating acute pain more generally.²⁷ Those interested in pain management in the postoperative setting specifically may wish to review the recent guidelines released by the American Pain Society,⁵⁰ the content of which is in close alignment with our Consensus Statement.

Several important issues were raised during the extensive external feedback process undertaken as part of the development of this Consensus Statement. Although many issues were incorporated into the recommendations, there were several suggestions for which we felt the evidence base was not sufficient to allow a clear or valid recommendation to be made. For example, several reviewers requested endorsement of specific patient education tools and opioid equivalency calculators. In the absence of tools specifically validated for this purpose, we felt that the evidence was insufficient to make specific recommendations. Validating such tools for use in the inpatient setting should be an area of future investigation. In the meantime, we note that there are several existing and widely available resources for both patient education (ie, opioid information sheets, including opioid risks, safe containment and disposal, and safe use practices) and opioid equivalency calculations that clinicians and hospitals can adapt for their purposes.

Several individuals suggested recommendations on communication with outpatient continuity providers around opioid management decisions during hospitalization and on discharge. Although we believe that it is of paramount importance for outpatient providers to be aware of and have input into these decisions, the optimal timing and the method for such communication are unclear and likely to be institution-specific depending on the availability and integration of electronic records across care settings. We recommend that clinicians use their judgment as to the best format and timing for assuring that outpatient physicians are aware of and have input into these important management decisions with downstream consequences.

Concerns were also raised about the time required to complete the recommended practices and the importance of emphasizing the need for a team-based approach in this realm. We agree wholeheartedly with this sentiment and believe that many of the recommended practices can and should be automated and/or shared across the care team. For example, PDMPs allow prescribers to appoint delegates to check the PDMP on their behalf. Additionally, we suggest that hospitals work to develop systems to assist care teams with performance of these tasks in a standardized and streamlined manner (eg, integrating access to the PDMP and opioid equivalency tables within the electronic health record and developing standard patient educational handouts). Provision of written materials on opioid risks, side effects, and safety practices may be helpful in facilitating consistent messaging and efficient workflow for members of the care team.

Finally, the working group carefully considered whether to include a recommendation regarding naloxone prescribing at the time of hospital discharge. The provision of naloxone kits to laypersons through Overdose Education and Naloxone Distribution Programs has been shown to reduce opioid overdose deaths^51,52 and hospitalizations^53,54 and is both safe and cost-effective.⁵⁵ The Centers for Disease Control and Preventionrecommend that clinicians “consider offering naloxone to patients with a history of overdose, a current or past substance use disorder, receipt of ≥50 mg of morphine equivalents per day or concurrent benzodiazepine use.”¹ However, these recommendations are intended for patients on chronic opioid therapy; presently, no clear evidence exists to guide decisions about the benefits and costs associated with prescribing naloxone in the setting of short-term opioid therapy for acute pain. Further research in this area is warranted.

The greatest limitation of this Consensus Statement is the lack of high-quality studies informing most of the recommendations in the guidelines upon which our Consensus Statement was based. The majority of recommendations in the existing guidelines were based on expert opinion alone. Additional research is necessary before evidence-based recommendations can be formulated.

Accordingly, the working group identified several key areas for future research, in addition to those noted above. First, ongoing efforts to develop and evaluate the effectiveness of nonopioid and nonpharmacologic management strategies for acute pain in hospitalized patients are necessary. Second, studies identifying the risk factors for opioid-related adverse events in hospitalized patients would help inform management decisions and allow deployment of resources and specialized monitoring strategies to patients at heightened risk. The working group also noted the need for research investigating the impact of PDMP use on management decisions and downstream outcomes among hospitalized patients. Finally, conversations around pain management and concerns related to aberrant behaviors are often challenging in the hospital setting owing to the brief, high-intensity nature of the care and the lack of a longstanding therapeutic alliance. There is a great need to develop strategies and language to facilitate these conversations.

In conclusion, until more high-quality evidence becomes available, clinicians can use the recommendations contained in this Consensus Statement along with their clinical judgment and consultation with pharmacists, interventional pain specialists, and other staff (eg, social work, nursing) to help facilitate consistent, high-quality care across providers and hospitals. We believe that doing so will help increase the appropriateness of opioid therapy, minimize adverse events, facilitate shared decision-making, and foster stronger therapeutic alliances at the outset of the hospitalization for patients suffering from acute pain.

The authors would like to acknowledge and thank Kevin Vuernick, Jenna Goldstein, Meghan Mallouk, and Chris Frost, MD, from the SHM for their facilitation of this project and dedication to this purpose.

The authors would also like to thank the many individuals who provided comments on the draft recommendations, including the participants in the SHM RADEO program; the SHM members; the representatives of specialty societies, including the American Academy of Family Physicians, the American College of Physicians, the American Hospital Association, the American Society of Addiction Medicine, the American Society of Anesthesiologists, the American Society of Health-System Pharmacists, the Society of Critical Care Medicine, and the Society of General Internal Medicine; and the representatives of patient advocacy groups, including SHM PFAC, Regions Hospital Patient and Family Advisory Committee, Patient and Family Centered Care Council of St. Louis Children’s Hospital, Missouri Family Partnership, and Parent and Family Care.

Disclosures: Dr. Herzig reports receiving compensation from the Society of Hospital Medicine for her editorial role at the Journal of Hospital Medicine (unrelated to the present work). Dr. Jena reports receiving consulting fees from Pfizer, Inc., Hill Rom Services, Inc., Bristol Myers Squibb, Novartis Pharmaceuticals, Vertex Pharmaceuticals, and Precision Health Economics, a consultancy to the life sciences industry (all unrelated to the present work). None of the other authors have any conflicts of interest to disclose.

Funding: The Society of Hospital Medicine (SHM) provided administrative assistance with the project and funded the in-person working group meeting but had no role in or influence on developing the content of the recommendations themselves. The SHM Board of Directors provided approval to submit the manuscript for publication without modification. Dr. Herzig was funded by grant number K23AG042459 from the National Institute on Aging. Dr. Mosher was supported in part by the Department of Veterans Affairs Office of Academic Affiliations and Office of Research and Development and Health Services Research and Development Service (HSR&D) through the Comprehensive Access and Delivery Research and Evaluation Center (CIN 13-412). None of the funding agencies had involvement in any aspect of the study, including design, conduct, and reporting of the study

Since the initial reports of an emerging opioid epidemic in the early 2000s, intense focus on improving opioid prescribing in outpatient settings has culminated in new guidelines for chronic pain.^1,2 Although opioid stewardship in the setting of chronic pain is of paramount importance in curbing the ongoing epidemic, long-term prescription opioid use often begins with treatment of acute pain.¹ In addition to differences in recommended management strategies for acute and chronic pain, there are unique aspects and challenges to pain management in the acute-care setting.

Opioids are commonly used for the treatment of acute pain in hospitalized patients, often at high doses.³ Recent reports highlight that hospital use of opioids impacts downstream use.^4-6 Additionally, opioid prescribing practices vary between hospital-based providers and hospitals,^3,7 highlighting the need for prescribing standards and guidance. To our knowledge, there are no existing guidelines for improving the safety of opioid use in hospitalized patients outside of the intensive care or immediate perioperative settings.

The Society of Hospital Medicine (SHM) convened a working group to systematically review existing guidelines and develop a consensus statement to assist clinicians in safe opioid use for acute, noncancer pain in hospitalized adults.

Consensus Statement Purpose and Scope

The purpose of this Consensus Statement is to present clinical recommendations on the safe use of opioids for the treatment of acute, noncancer pain in hospitalized adults. The guidance is intended for clinicians practicing medicine in the inpatient setting (eg, hospitalists, primary care physicians, family physicians, nurse practitioners, and physician assistants) and is intended to apply to hospitalized adults with acute, noncancer pain (ie, pain that typically lasts <3 months or during the period of normal tissue healing) outside of the palliative, end-of-life, and intensive care settings.

Consensus Statement Development

Our working group included experts in opioid use in the hospital setting, defined by 1) engagement in the clinical practice of hospital medicine and 2) involvement in clinical research related to usage patterns and clinical outcomes of opioid use in hospitalized patients (see Appendix Table 1). The SHM provided administrative assistance with the project and funded the in-person working group meeting, but it had no role in formulating the recommendations. The SHM Board of Directors provided approval of the Consensus Statement without modification.

An overview of the sequential steps in the Consensus Statement development process is described below; details of the methods and results can be found in the Appendix (eMethods).

Performing the Systematic Review

Drafting the Consensus Statement

After performing the systematic review, the working group drafted and iteratively revised a set of recommendations using a variation of the Delphi Method⁸ to identify consensus among group members.

External Review

Following agreement on a draft set of recommendations, we obtained feedback from external groups, including 1) individuals involved in the SHM’s Reducing Adverse Drug Events Related to Opioids (RADEO) initiative, including those involved in the development of the implementation guide and site leads for the Mentored Implementation program, 2) SHM members, SHM Patient-Family Advisory Council (PFAC) members, and leaders of other relevant professional societies, and 3) peer-reviewers at the Journal of Hospital Medicine.

Deciding Whether to Use Opioids During Hospitalization

1. SHM recommends that clinicians limit the use of opioids to patients with 1) severe pain or 2) moderate pain that has not responded to nonopioid therapy, or where nonopioid therapy is contraindicated or anticipated to be ineffective.

Opioids are associated with several well-recognized risks ranging from mild to severe, including nausea, constipation, urinary retention, falls, delirium, sedation, physical dependence, addiction, respiratory depression, and death. Given these risks, the risk-to-benefit ratio is generally not favorable at lower levels of pain severity. Furthermore, for most painful conditions, including those causing severe pain, nonopioid analgesics, including acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs), have been demonstrated to be equally or more effective with less risk of harm than opioids.^9-13 Clinicians should consider drug–drug and drug–disease associations when deciding between these different therapies and make a determination in each patient regarding whether the benefits outweigh the risks. Often, drug–disease interactions do not represent absolute contraindications, and risks can be mitigated by adhering to dosage limits and, with respect to NSAIDs, 1) monitoring renal function, 2) monitoring volume status in patients with congestive heart failure, and 3) considering a selective cyclooxygenase-2 (COX-2) inhibitor rather than a nonselective NSAID or pairing the NSAID with an acid-suppressive medication in patients with a history of peptic ulcer disease or at elevated risk for gastroduodenal disease. For these reasons, a trial of nonopioid therapy (including pharmacologic and nonpharmacologic modalities) should always be considered before using opioids for pain of any severity. This does not imply that a trial of nonopioid therapy must be performed in all patients, but rather, that the likelihood of benefit and associated risks of opioid and nonopioid therapy should be considered for all patients in determining the best initial management strategy.

2. SHM recommends that clinicians use extra caution when administering opioids to patients with risk factors for opioid-related adverse events.

Several factors have been consistently demonstrated to increase the risk of opioid-related adverse events–most importantly, respiratory depression and overdose–in varied patient populations and settings, including age 65 years and older,^1,14-17 renal insufficiency,^1,14,18 hepatic insufficiency,^1,14 chronic respiratory failure (including chronic obstructive pulmonary disease, sleep apnea, etc.), and receipt of other central nervous system (CNS) depressant medications (including, but not limited to, benzodiazepines).^1,18-20 History of any substance use disorder and psychiatric disorders have been associated with an increased risk for the development of opioid use disorder.^21-24 These factors should be weighed against the benefits when deciding on opioid appropriateness in a given patient. However, identification of these risks should not preclude opioids as part of pain management. When a decision is made to use opioids in patients with these risk factors, clinicians should 1) use a reduced starting dose (generally, at least a 50% reduction in the usual starting dose) and 2) consider closer monitoring for adverse effects (eg, more frequent nursing assessments, capnography, or more frequent outpatient visits).

3. SHM recommends that clinicians review the information contained in the prescription drug monitoring program (PDMP) database to inform decision-making around opioid therapy.

Although data on the impact of use of the state PDMP database on prescribing practices or patient outcomes are limited, PDMP use has been advocated by multiple guidelines on acute pain management.^25-27 The PDMP provides information that can be useful in several ways, including 1) confirmation of prior opioid exposure and dosage, which should be used to guide appropriate dosage selection in the hospital, 2) identification of existing controlled substance prescriptions, which should be considered in prescribing decisions in the hospital and on discharge, and 3) identification of signs of aberrant behavior. For example, the identification of controlled substance prescriptions written by multiple different clinicians can facilitate early identification of potential diversion or evolving or existing opioid use disorder and the opportunity for intervention,²⁸ which may include referral to support services, initiation of medication-assisted treatment, and/or pain specialist consultation when available. Concerns regarding evolving or existing opioid use disorder should prompt further discussion between the clinician and the patient, both to clarify their understanding of their recent prescription history and to discuss concerns for patient safety related to the increased risk of opioid-related adverse effects (including respiratory depression and overdose) among patients with controlled substance prescriptions written by multiple providers. Although such concerns should not automatically preclude the use of opioids for acute pain in the hospital setting, they should be considered in the assessment of whether the benefits of opioid therapy outweigh the risks for a given patient.

4. SHM recommends that clinicians educate patients and families or caregivers about the potential risks and side effects of opioid therapy as well as alternative pharmacologic and nonpharmacologic therapies for managing pain.

Patients are often unaware of the risks of opioid therapy (see Consensus Statement 1 for key risks),²⁹ or that there are often equally effective alternative therapies. As with any therapy associated with substantial risk, clinicians should discuss these risks with patients and/or caregivers at the outset of therapy, as well as the potential benefits of nonopioid pharmacologic and nonpharmacologic therapies for managing pain. Patients should be informed that they may request nonopioid therapy in lieu of opioids, even for severe pain.

Once a Decision Has Been Made to Use Opioids During Hospitalization

5. SHM recommends that clinicians use the lowest effective opioid dose for the shortest duration possible.

Higher opioid doses are associated with an increased incidence of opioid-related adverse events, particularly overdose, in studies of both inpatient and outpatient populations.^{1,17,19,30,31} Studies in the inpatient and outpatient settings consistently demonstrate that risk increases with dosage.^19,30,31 Clinicians should reduce the usual starting dose by at least 50% among patients with conditions that increase susceptibility to opioid-related adverse events (see Consensus Statement 2). The ongoing need for opioids should be re-assessed regularly-at least daily-during the hospitalization, with attempts at tapering as healing occurs and/or pain and function improve.

6. SHM recommends that clinicians use immediate-release opioid formulations and avoid initiation of long-acting or extended-release formulations (including transdermal fentanyl) for treatment of acute pain.

Studies in outpatient settings demonstrate that the use of long-acting opioids is associated with greater risk for overdose–especially in opioid-naïve patients–and long-term use.^32,33 Further, hospitalized patients frequently have fluctuating renal function and rapidly changing pain levels. We therefore recommend that initiation of long-acting opioids be avoided for the treatment of acute, noncancer pain in hospitalized medical patients. It is important to note that although we recommend avoiding initiation of long-acting opioids for the treatment of acute, noncancer pain, there are circumstances outside of the scope of this Consensus Statement for which initiation of long-acting opioids may be indicated, including the treatment of opioid withdrawal. We also do not recommend discontinuation of long-acting or extended-release opioids in patients who are taking these medications for chronic pain at the time of hospital admission (unless there are concerns regarding adverse effects or drug–disease interactions).

7. SHM recommends that clinicians use the oral route of administration whenever possible. Intravenous opioids should be reserved for patients who cannot take food or medications by mouth, patients suspected of gastrointestinal malabsorption, or when immediate pain control and/or rapid dose titration is necessary.

Intravenous opioid administration is associated with an increased risk of side effects, adverse events, and medication errors.^34-36 Additionally, studies demonstrate that in general, the addiction potential of medications is greater the more rapid the onset of action (the onset of action is 5–10 min for intravenous and 15–30 minutes for oral administration).^37,38 Furthermore, the duration of action is greater for oral compared to that of intravenous administration, potentially allowing for more consistent pain relief and less frequent administrations. As such, intravenous administration should be reserved for situations when oral administration is not possible or likely to be ineffective, or when immediate pain control and/or rapid titration is necessary.

8. SHM recommends that clinicians use an opioid equivalency table or calculator to understand the relative potency of different opioids 1) when initiating opioid therapy, 2) when changing from one route of administration to another, and 3) when changing from one opioid to another. When changing from one opioid to another, clinicians should generally reduce the dose of the new opioid by at least 25%–50% of the calculated equianalgesic dose to account for interindividual variability in the response to opioids as well as possible incomplete cross-tolerance.

Most errors causing preventable adverse drug events in hospitals occur at the ordering stage.^39,40 Clinicians are often unaware of the potency of different types of opioids relative to each other or to morphine (ie, morphine equivalent dose), which can lead to inadvertent overdose when initiating therapy with nonmorphine opioids and when converting from one opioid to another. To facilitate safe opioid use, we recommend that clinicians use one of several available opioid equivalency tables or calculators to better understand the relative potencies of opioids and to inform both starting dose calculations and conversions between opioids and routes of administration. When converting from one opioid to another, we caution clinicians to reduce the dose of the new opioid by at least 25%–50% of the calculated equianalgesic dose to account for interindividual variability in the response to opioids and the potential for incomplete cross-tolerance, wherein tolerance to a currently administered opioid does not extend completely to other opioids. Clinicians should use extreme caution when performing conversions to and from methadone and consider consultation with a hospital pharmacist or a pain management specialist, when available, to assist with conversion decisions and calculations.

9. SHM recommends that clinicians pair opioids with scheduled nonopioid analgesic medications, unless contraindicated, and always consider pairing with nonpharmacologic pain management strategies (ie, multimodal analgesia).

Concurrent receipt of opioids and nonopioid analgesic medications (including acetaminophen, NSAIDs, and gabapentin or pregabalin, depending on the underlying pathophysiology of the pain) has been demonstrated to reduce total opioid requirements and improve pain management.^41,42 Clinicians should be familiar with contraindications and maximum dosage recommendations for each of these adjunctive nonopioid medications. We recommend separate orders for each, rather than using drug formulations that combine opioids and nonopioid analgesics in the same pill, due to the risk of inadvertently exceeding the maximum recommended doses of the nonopioid analgesic (particularly acetaminophen) with combination products. We recommend that nonopioid analgesics be ordered at a scheduled frequency, rather than as needed, to facilitate consistent administration that is not dependent on opioid administration. Topical agents, including lidocaine and capsaicin, should also be considered. Nonpharmacologic pain management strategies can include procedure-based (eg, regional and local anesthesia) and nonprocedure-based therapies depending on the underlying condition and institutional availability. Although few studies have assessed the benefit of nonpharmacologic, nonprocedure-based therapies for the treatment of acute pain in hospitalized patients, the lack of harm associated with their use argues for their adoption. Simple nonpharmacologic therapies that can usually be provided to patients in any hospital setting include music therapy, cold or hot packs, chaplain or social work visits (possibly including mindfulness training),⁴³ and physical therapy, among others.

10. SHM recommends that, unless contraindicated, clinicians order a bowel regimen to prevent opioid-induced constipation in patients receiving opioids.

Constipation is a common adverse effect of opioid therapy and results from the activation of mu opioid receptors in the colon, resulting in decreased peristalsis. Hospitalized patients are already prone to constipation due to their often-limited physical mobility. To mitigate this complication, we recommend the administration of a bowel regimen to all hospitalized medical patients receiving opioid therapy, provided the patient is not having diarrhea. Given the mechanism of opioid-induced constipation, stimulant laxatives (eg, senna, bisacodyl) have been recommended for this purpose.⁴⁴ Osmotic laxatives (eg, polyethylene glycol, lactulose) have demonstrated efficacy for the treatment of constipation more generally (ie, not necessarily opioid-induced constipation). Stool softeners, although frequently used in the inpatient setting, are not recommended due to limited and conflicting evidence for efficacy in prevention or treatment of constipation.⁴⁵ Bowel movements should be tracked during hospitalization, and the bowel regimen modified accordingly.

11. SHM recommends that clinicians limit co-administration of opioids with other central nervous system depressant medications to the extent possible.

This combination has been demonstrated to increase the risk of opioid-related adverse events in multiple settings of care, including during hospitalization.^1,18,19 Although benzodiazepines have received the most attention in this respect, other medications with CNS depressant properties may also increase the risk, including, but not limited to, nonbenzodiazepine sedative-hypnotics (eg, zolpidem, zaleplon, zopiclone), muscle relaxants, sedating antidepressants, antipsychotics, and antihistamines.^18,19,46 For some patients, the combination will be unavoidable, and we do not suggest routine discontinuation of longstanding medications that preexisted hospitalization, given the risks of withdrawal and/or worsening of the underlying condition for which these medications are prescribed. Rather, clinicians should carefully consider the necessity of each medication class with input from the patient’s outpatient providers, taper the frequency and/or the dose of CNS depressants when appropriate and feasible, and avoid new coprescriptions to the extent possible, both during hospitalization and on hospital discharge.

12. SHM recommends that clinicians work with patients and families or caregivers to establish realistic goals and expectations of opioid therapy and the expected course of recovery.

Discussing expectations at the start of therapy is important to facilitate a clear understanding of how meaningful improvement will be defined and measured during the hospitalization and how long the patient is anticipated to require opioid therapy. Meaningful improvement should be defined to include improvement in both pain and function. Clinicians should discuss with patients 1) that the goal of opioid therapy is tolerability of pain such that meaningful improvement in function can be achieved and 2) that a decrease in pain intensity in the absence of improved function is not considered meaningful improvement in most situations and should prompt reevaluation of the appropriateness of continued opioid therapy as well as close follow-up with a clinician following hospital discharge. Discussions regarding the expected course of recovery should include that acute pain is expected to resolve as the underlying medical condition improves and that although pain may persist beyond the hospitalization, pain that is severe enough to require opioids will often be resolved or almost resolved by the time of hospital discharge.

13. SHM recommends that clinicians monitor the response to opioid therapy, including assessment for functional improvement and development of adverse effects.

Pain severity and function should be assessed at least daily, and improvement in reported pain severity without improvement in function over several days should, in most circumstances, prompt reconsideration of ongoing opioid therapy and reconsideration of the underlying etiology of pain. Although hospital-specific functional measures in the setting of acute pain have not yet been validated, we suggest that such measures and goals should be individualized based on preexisting function and may include the ability to sit up or move in bed, move to a chair, work with physical therapy, or ambulate in the hallway. Protocols for the assessment for adverse effects are not well established. Because sedation typically precedes respiratory depression, it is generally recommended that patients are evaluated (eg, by nursing staff) for sedation after each opioid administration (10–20 minutes for intravenous and 30–60 minutes for oral administration based on the time-to-peak effect). Whether certain patients may benefit from more intensive respiratory monitoring, such as pulse oximetry or capnography, is an area of active investigation and not yet established.

Prescribing at the Time of Hospital Discharge

14. SHM recommends that clinicians ask patients about any existing opioid supply at home and account for any such supply when issuing an opioid prescription on discharge.

Even in the setting of acute pain, patients may have previously received an opioid prescription from an outpatient clinician prior to hospitalization. Unused prescription opioids create the possibility of both overdose (when patients take multiple opioids concurrently, intentionally or inadvertently) and diversion (many adults with prescription opioid misuse obtained their opioids from a friend or a relative who may or may not have known that this occurred⁴⁷). The PDMP database can provide information related to the potential existence of any prior opioid supplies, which should be confirmed with the patient and considered when providing a new prescription on hospital discharge. Information on proper disposal should be provided if use of the preexisting opioid is no longer intended.

15. SHM recommends that clinicians prescribe the minimum quantity of opioids anticipated to be necessary based on the expected course and duration of pain that is severe enough to require opioid therapy after hospital discharge.

For many patients, the condition causing their acute pain will be mostly or completely resolved by the time of hospital discharge. When pain is still present at the time of discharge, most pain can be completely managed with nonopioid therapies. For those with ongoing pain that is severe enough to require opioids after hospital discharge, decisions regarding the duration of therapy should be made on a case-by-case basis; generally, however, provision of a 3- to 5-day supply will be sufficient, and provision of more than a 7-day supply of opioids should generally be avoided for several reasons. These include 1) acute pain lasting longer than 7 days after appropriate treatment of any existing underlying conditions should prompt re-evaluation of the working diagnosis and/or reconsideration of the management approach, 2) receiving higher intensity opioid therapy (including longer courses) in the setting of acute pain has been associated with an increased risk of long-term disability and long-term opioid use,^33,48,49 and 3) unused opioids create the possibility of intentional or unintentional opioid diversion (see Consensus Statement 14).⁴⁷ Accordingly, clinicians should attempt to arrange an outpatient follow-up appointment for re-evaluation within 7 days, rather than providing an extended opioid prescription on hospital discharge. In situations where this is not feasible, and pain that is severe enough to require opioids is expected to persist longer than 7 days, an extended prescription may be indicated. However, some states have begun enacting legislation to limit the duration of first-time opioid prescriptions, typically using a 5-to-7 day supply as an upper limit; clinicians should be aware of and adhere to individual state laws governing their practice.

16. SHM recommends that clinicians ensure that patients and families or caregivers receive information regarding how to minimize the risks of opioid therapy for themselves, their families, and their communities. This includes but is not limited to 1) how to take their opioids correctly (the planned medications, doses, schedule); 2) that they should take the minimum quantity necessary to achieve tolerable levels of pain and meaningful functional improvement, reducing the dose and/or frequency as pain and function improve; 3) how to safeguard their supply and dispose of any unused supply; 4) that they should avoid agents that may potentiate the sedative effect of opioids, including sleeping medication and alcohol; 5) that they should avoid driving or operating heavy machinery while taking opioids; and 6) that they should seek help if they begin to experience any potential adverse effects, with inclusion of information on early warning signs.

Clear and concise patient instructions on home opioid dosing and administration will limit opioid-related adverse events and dosing errors upon hospital discharge. Each of these recommendations derive from one or more of the existing guidelines and reflect the transfer of responsibility for safe opioid use practices that occurs as patients transition from a closely monitored inpatient setting to the more self-regulated home environment.

This Consensus Statement reflects a synthesis of the key recommendations from a systematic review of existing guidelines on acute pain management, adapted for a hospital-specific scope of practice. Despite a paucity of data on the comparative effectiveness of different management strategies for acute pain, several areas of expert consensus emerged across existing guidelines, which were felt to be relevant and applicable to the hospital setting. The objective of these recommendations is to provide information that can be used to inform and support opioid-related management decisions for acute pain by clinicians practicing medicine in the inpatient setting.

Although these recommendations are not intended to apply to the immediate perioperative setting (ie, care in the postanesthesia care unit), many of the recommendations in the existing guidelines upon which this Consensus Statement was based were intended for the postoperative setting, and, as others have noted, recommendations in this setting are mostly comparable to those for treating acute pain more generally.²⁷ Those interested in pain management in the postoperative setting specifically may wish to review the recent guidelines released by the American Pain Society,⁵⁰ the content of which is in close alignment with our Consensus Statement.

Several important issues were raised during the extensive external feedback process undertaken as part of the development of this Consensus Statement. Although many issues were incorporated into the recommendations, there were several suggestions for which we felt the evidence base was not sufficient to allow a clear or valid recommendation to be made. For example, several reviewers requested endorsement of specific patient education tools and opioid equivalency calculators. In the absence of tools specifically validated for this purpose, we felt that the evidence was insufficient to make specific recommendations. Validating such tools for use in the inpatient setting should be an area of future investigation. In the meantime, we note that there are several existing and widely available resources for both patient education (ie, opioid information sheets, including opioid risks, safe containment and disposal, and safe use practices) and opioid equivalency calculations that clinicians and hospitals can adapt for their purposes.

Several individuals suggested recommendations on communication with outpatient continuity providers around opioid management decisions during hospitalization and on discharge. Although we believe that it is of paramount importance for outpatient providers to be aware of and have input into these decisions, the optimal timing and the method for such communication are unclear and likely to be institution-specific depending on the availability and integration of electronic records across care settings. We recommend that clinicians use their judgment as to the best format and timing for assuring that outpatient physicians are aware of and have input into these important management decisions with downstream consequences.

Concerns were also raised about the time required to complete the recommended practices and the importance of emphasizing the need for a team-based approach in this realm. We agree wholeheartedly with this sentiment and believe that many of the recommended practices can and should be automated and/or shared across the care team. For example, PDMPs allow prescribers to appoint delegates to check the PDMP on their behalf. Additionally, we suggest that hospitals work to develop systems to assist care teams with performance of these tasks in a standardized and streamlined manner (eg, integrating access to the PDMP and opioid equivalency tables within the electronic health record and developing standard patient educational handouts). Provision of written materials on opioid risks, side effects, and safety practices may be helpful in facilitating consistent messaging and efficient workflow for members of the care team.

Finally, the working group carefully considered whether to include a recommendation regarding naloxone prescribing at the time of hospital discharge. The provision of naloxone kits to laypersons through Overdose Education and Naloxone Distribution Programs has been shown to reduce opioid overdose deaths^51,52 and hospitalizations^53,54 and is both safe and cost-effective.⁵⁵ The Centers for Disease Control and Preventionrecommend that clinicians “consider offering naloxone to patients with a history of overdose, a current or past substance use disorder, receipt of ≥50 mg of morphine equivalents per day or concurrent benzodiazepine use.”¹ However, these recommendations are intended for patients on chronic opioid therapy; presently, no clear evidence exists to guide decisions about the benefits and costs associated with prescribing naloxone in the setting of short-term opioid therapy for acute pain. Further research in this area is warranted.

The greatest limitation of this Consensus Statement is the lack of high-quality studies informing most of the recommendations in the guidelines upon which our Consensus Statement was based. The majority of recommendations in the existing guidelines were based on expert opinion alone. Additional research is necessary before evidence-based recommendations can be formulated.

Accordingly, the working group identified several key areas for future research, in addition to those noted above. First, ongoing efforts to develop and evaluate the effectiveness of nonopioid and nonpharmacologic management strategies for acute pain in hospitalized patients are necessary. Second, studies identifying the risk factors for opioid-related adverse events in hospitalized patients would help inform management decisions and allow deployment of resources and specialized monitoring strategies to patients at heightened risk. The working group also noted the need for research investigating the impact of PDMP use on management decisions and downstream outcomes among hospitalized patients. Finally, conversations around pain management and concerns related to aberrant behaviors are often challenging in the hospital setting owing to the brief, high-intensity nature of the care and the lack of a longstanding therapeutic alliance. There is a great need to develop strategies and language to facilitate these conversations.

In conclusion, until more high-quality evidence becomes available, clinicians can use the recommendations contained in this Consensus Statement along with their clinical judgment and consultation with pharmacists, interventional pain specialists, and other staff (eg, social work, nursing) to help facilitate consistent, high-quality care across providers and hospitals. We believe that doing so will help increase the appropriateness of opioid therapy, minimize adverse events, facilitate shared decision-making, and foster stronger therapeutic alliances at the outset of the hospitalization for patients suffering from acute pain.

The authors would like to acknowledge and thank Kevin Vuernick, Jenna Goldstein, Meghan Mallouk, and Chris Frost, MD, from the SHM for their facilitation of this project and dedication to this purpose.

The authors would also like to thank the many individuals who provided comments on the draft recommendations, including the participants in the SHM RADEO program; the SHM members; the representatives of specialty societies, including the American Academy of Family Physicians, the American College of Physicians, the American Hospital Association, the American Society of Addiction Medicine, the American Society of Anesthesiologists, the American Society of Health-System Pharmacists, the Society of Critical Care Medicine, and the Society of General Internal Medicine; and the representatives of patient advocacy groups, including SHM PFAC, Regions Hospital Patient and Family Advisory Committee, Patient and Family Centered Care Council of St. Louis Children’s Hospital, Missouri Family Partnership, and Parent and Family Care.

Disclosures: Dr. Herzig reports receiving compensation from the Society of Hospital Medicine for her editorial role at the Journal of Hospital Medicine (unrelated to the present work). Dr. Jena reports receiving consulting fees from Pfizer, Inc., Hill Rom Services, Inc., Bristol Myers Squibb, Novartis Pharmaceuticals, Vertex Pharmaceuticals, and Precision Health Economics, a consultancy to the life sciences industry (all unrelated to the present work). None of the other authors have any conflicts of interest to disclose.

Funding: The Society of Hospital Medicine (SHM) provided administrative assistance with the project and funded the in-person working group meeting but had no role in or influence on developing the content of the recommendations themselves. The SHM Board of Directors provided approval to submit the manuscript for publication without modification. Dr. Herzig was funded by grant number K23AG042459 from the National Institute on Aging. Dr. Mosher was supported in part by the Department of Veterans Affairs Office of Academic Affiliations and Office of Research and Development and Health Services Research and Development Service (HSR&D) through the Comprehensive Access and Delivery Research and Evaluation Center (CIN 13-412). None of the funding agencies had involvement in any aspect of the study, including design, conduct, and reporting of the study

Pneumonia is a major cause of hospitalization, mortality, and healthcare cost. ^1,2 The diagnosis involves clinical features plus radiographic evidence of infection. Hospital-acquired pneumonia (HAP) is defined by the Infectious Disease Society of America (IDSA) as a pneumonia that occurs ≥48 hours after admission and is not associated with mechanical ventilation. ³

IDSA recommendations suggest that patients with suspected HAP be treated based on results of noninvasively obtained sputum cultures rather than being treated empirically. ³ This recommendation is graded as weak with low-quality evidence based on a lack of both evidence showing that respiratory cultures improve clinical outcomes and studies examining the yield of noninvasive collection methods. ^4,5 However, resistant pathogens lead to a risk of inadequate empiric therapy, which is associated with increased mortality. ⁶ Culture data may provide an opportunity for escalation or de-escalation of antibiotic coverage. IDSA recommendations for microbiologic sampling are thus aimed at increasing appropriate coverage and minimizing unnecessary antibiotic exposure.

While the yield and clinical utility of sputum culture in community-acquired pneumonia has been studied extensively, data examining the yield of sputum culture in HAP (non–ventilator-associated pneumonia [non-VAP]) are sparse. In 1 small single-center study, researchers demonstrated positive sputum cultures in 17/35 (48.6%) patients with radiographically confirmed cases of HAP, ⁷ while in another study, researchers demonstrated positive sputum cultures in 57/63 (90.5%). ⁸ We aimed to identify the frequency with which sputum cultures positively identify an organism, identify predictors of positive sputum cultures, and characterize the microbiology of sputum cultures in a large cohort of HAP cases.

We conducted a retrospective cohort study of patients admitted to a large academic medical center in Boston, Massachusetts, from January 2007 to July 2013. All patients ≥18 years of age were eligible for inclusion. We excluded outside hospital transfers, those with a length of hospitalization <48 hours, and psychiatric admissions.

The study was approved by the institutional review board at the Beth Israel Deaconess Medical Center and granted a waiver of informed consent. Data were collected from electronic databases and supplemented by chart review.

Hospital-Acquired Pneumonia

We defined HAP as pneumonia occurring at least 48 hours after admission, consistent with American Thoracic Society and IDSA criteria.³ To identify cases, we reviewed the charts of all admissions identified as having a discharge International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code for bacterial pneumonia (481, 482, 483, 485, 486, 507), indicated as not “present-on-admission.” We validated that the treating clinician had clinically diagnosed pneumonia and initiated antibiotics for this purpose by performing chart review. We reviewed the radiologist interpretation of radiographs surrounding the date of the clinical diagnosis of pneumonia to confirm the presence of a new opacity. Uncertain cases (with respect to either the presence of pneumonia or the timing of the diagnosis) were reviewed by a second member of the study team and, in the case of disagreement, adjudicated by a third member of the study team. Only the first clinically validated HAP per hospitalization was included in the analysis. To focus on HAP rather than VAP, we excluded hospitalizations in which the date of a procedure code for mechanical ventilation preceded the date of pneumonia diagnosis.

Microbiology

In our analysis, we used sputum samples obtained from expectorated or induced samples to evaluate the yield of noninvasive sputum sampling, as recommended by the IDSA. We included sputum samples collected ≥48 hours after admission and within 7 days of the clinical diagnosis of HAP. Sputum samples with >10 epithelial cells per high-power field (hpf) were considered to be contaminated. Among noncontaminated samples, positive sputum cultures were defined as those with a microbiologic diagnosis other than “oral flora,” while those with no growth or growth of oral flora or only yeast were considered to be negative. The hospital’s microbiology laboratory does not routinely provide species identification for Gram-negative rods (GNRs) growing on culture in the presence of growth of ≥3 other colony types. We considered such GNRs (not further speciated) to represent a positive culture result in our analysis given that colonization versus pathogenicity is a clinical distinction and, as such, these results may impact antibiotic choice.

Statistical Analysis

Data were analyzed by using SAS software, version 9.3. We used a 2-sided P value of <0.05 to indicate statistical significance for all comparisons. We used the χ² test and the nonparametric median test for unadjusted comparisons.

To identify predictors of a positive (versus negative or contaminated) sputum culture among patients with HAP, we used a generalized estimating equation model with a Poisson distribution error term, log link, and first-order autoregressive correlation structure to account for multiple sputum specimens per patient. We combined culture negative and contaminated samples to highlight the clinical utility of sputum culture in a real-world setting. Potential predictors chosen based on clinical grounds included all variables listed in Table 1. We defined comorbidities specified in Table 1 via ICD-9-CM secondary diagnosis codes and diagnosis related groups (DRGs) using Healthcare Cost and Utilization Project Comorbidity Software, version 3.7, based on the work of Elixhauser et al.^9,10; dialysis use was defined by an ICD-9-CM procedure code of 39.95; inpatient steroid use was defined by a hospital pharmacy charge for a systemic steroid in the 7 days preceding the sputum sample.

There were 230,635 hospitalizations of patients ≥18 years of age from January 2007 to July 2013. After excluding outside hospital transfers (n = 14,422), hospitalizations <48 hours in duration (n = 59,774), and psychiatric hospitalizations (n = 9887), there were 146,552 hospitalizations in the cohort.

To our knowledge, our study is the first to assess the predictors of positive sputum culture among patients with HAP (non-VAP) who had sputum samples obtained noninvasively, and this study is larger than prior studies in which researchers reported on sputum culture yield in HAP. Sputum samples were obtained in 29.4% cases of clinically diagnosed HAP. Although 87% of specimens obtained were culture-negative or contaminated, 13% yielded a bacterial organism. Although we do not report the antibiotic sensitivity patterns of the isolated organisms, the organisms identified frequently demonstrate antibiotic resistance, highlighting the potential for both antibiotic escalation and de-escalation based on sputum culture. In a multivariable model, presence of chronic lung disease and steroid use in the preceding week were both significantly associated with culture positivity.

The retrospective nature of the study raises the possibility of selection bias from systematic differences between the 29.4% of patients with HAP who had sputum collected and those who did not. Patients with sputum cultures were similar to patients without cultures in most measured characteristics, but we are unable to know what the yield of noninvasive sputum culture would have been had all patients with HAP been sampled. As such, our findings reflect the yield of sputum culture among patients with HAP for whom cultures were successfully obtained. It is not clear why only 29.4% of HAP patients received IDSA guideline-concordant care, but similar rates of culture use are reported elsewhere.⁷ While physician decision-making could have contributed to this finding, it is also possible that many sick, hospitalized patients are simply unable to produce sputum for analysis. In future studies, researchers should examine barriers to guideline-concordant care.

We considered a culture result of GNRs (not further speciated) as positive in our analysis because this result indicates growth of mixed bacterial types, the pathogenicity of which is a clinical determination. Physicians may request speciation and antibiotic sensitivities and, as such, these results have the potential to impact antibiotic choice. Had we considered such cultures to be negative or contaminated, the rate of culture positivity would have been only slightly reduced from 63/478 (13.2%) to 50/478 (10.5%).

The strengths of our study include the chart-based validation of administratively identified cases of pneumonia and a large cohort. There are also limitations. The single-center nature of the study has implications for pretest probability and generalizability. Additionally, in our study, we did not examine outcomes among patients treated empirically versus those treated based on sputum culture results. Finally, our reliance on administrative codes to identify cases of HAP for subsequent validation could have resulted in incomplete capture of HAP cases.

In conclusion, in our study, we provide an estimate of the diagnostic yield of sputum culture in a large cohort with chart-validated HAP, a description of HAP microbiology, and predictors of positive sputum culture. Thirteen percent of patients who had sputum culture testing received a microbiologic diagnosis. Because of the relative ease of obtaining a sputum sample and the microbiologic distribution in our study (representing a mix of commonly drug-resistant pathogens and more typical community-acquired pathogens), we suggest that sputum culture in HAP is a useful diagnostic tool with the potential to inform antibiotic escalation or de-escalation.

Acknowledgments

Dr. Herzig was funded by grant number K23AG042459 from the National Institute on Aging. Dr. Marcantonio was funded by grant number K24AG035075 from the National Institute on Aging. The funding organizations had no involvement in any aspect of the study, including design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript.

Disclosure

No conflicts of interest apply for any of the authors.

Pneumonia is a major cause of hospitalization, mortality, and healthcare cost. ^1,2 The diagnosis involves clinical features plus radiographic evidence of infection. Hospital-acquired pneumonia (HAP) is defined by the Infectious Disease Society of America (IDSA) as a pneumonia that occurs ≥48 hours after admission and is not associated with mechanical ventilation. ³

IDSA recommendations suggest that patients with suspected HAP be treated based on results of noninvasively obtained sputum cultures rather than being treated empirically. ³ This recommendation is graded as weak with low-quality evidence based on a lack of both evidence showing that respiratory cultures improve clinical outcomes and studies examining the yield of noninvasive collection methods. ^4,5 However, resistant pathogens lead to a risk of inadequate empiric therapy, which is associated with increased mortality. ⁶ Culture data may provide an opportunity for escalation or de-escalation of antibiotic coverage. IDSA recommendations for microbiologic sampling are thus aimed at increasing appropriate coverage and minimizing unnecessary antibiotic exposure.

While the yield and clinical utility of sputum culture in community-acquired pneumonia has been studied extensively, data examining the yield of sputum culture in HAP (non–ventilator-associated pneumonia [non-VAP]) are sparse. In 1 small single-center study, researchers demonstrated positive sputum cultures in 17/35 (48.6%) patients with radiographically confirmed cases of HAP, ⁷ while in another study, researchers demonstrated positive sputum cultures in 57/63 (90.5%). ⁸ We aimed to identify the frequency with which sputum cultures positively identify an organism, identify predictors of positive sputum cultures, and characterize the microbiology of sputum cultures in a large cohort of HAP cases.

We conducted a retrospective cohort study of patients admitted to a large academic medical center in Boston, Massachusetts, from January 2007 to July 2013. All patients ≥18 years of age were eligible for inclusion. We excluded outside hospital transfers, those with a length of hospitalization <48 hours, and psychiatric admissions.

The study was approved by the institutional review board at the Beth Israel Deaconess Medical Center and granted a waiver of informed consent. Data were collected from electronic databases and supplemented by chart review.

Hospital-Acquired Pneumonia

We defined HAP as pneumonia occurring at least 48 hours after admission, consistent with American Thoracic Society and IDSA criteria.³ To identify cases, we reviewed the charts of all admissions identified as having a discharge International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code for bacterial pneumonia (481, 482, 483, 485, 486, 507), indicated as not “present-on-admission.” We validated that the treating clinician had clinically diagnosed pneumonia and initiated antibiotics for this purpose by performing chart review. We reviewed the radiologist interpretation of radiographs surrounding the date of the clinical diagnosis of pneumonia to confirm the presence of a new opacity. Uncertain cases (with respect to either the presence of pneumonia or the timing of the diagnosis) were reviewed by a second member of the study team and, in the case of disagreement, adjudicated by a third member of the study team. Only the first clinically validated HAP per hospitalization was included in the analysis. To focus on HAP rather than VAP, we excluded hospitalizations in which the date of a procedure code for mechanical ventilation preceded the date of pneumonia diagnosis.

Microbiology

In our analysis, we used sputum samples obtained from expectorated or induced samples to evaluate the yield of noninvasive sputum sampling, as recommended by the IDSA. We included sputum samples collected ≥48 hours after admission and within 7 days of the clinical diagnosis of HAP. Sputum samples with >10 epithelial cells per high-power field (hpf) were considered to be contaminated. Among noncontaminated samples, positive sputum cultures were defined as those with a microbiologic diagnosis other than “oral flora,” while those with no growth or growth of oral flora or only yeast were considered to be negative. The hospital’s microbiology laboratory does not routinely provide species identification for Gram-negative rods (GNRs) growing on culture in the presence of growth of ≥3 other colony types. We considered such GNRs (not further speciated) to represent a positive culture result in our analysis given that colonization versus pathogenicity is a clinical distinction and, as such, these results may impact antibiotic choice.

Statistical Analysis

Data were analyzed by using SAS software, version 9.3. We used a 2-sided P value of <0.05 to indicate statistical significance for all comparisons. We used the χ² test and the nonparametric median test for unadjusted comparisons.

To identify predictors of a positive (versus negative or contaminated) sputum culture among patients with HAP, we used a generalized estimating equation model with a Poisson distribution error term, log link, and first-order autoregressive correlation structure to account for multiple sputum specimens per patient. We combined culture negative and contaminated samples to highlight the clinical utility of sputum culture in a real-world setting. Potential predictors chosen based on clinical grounds included all variables listed in Table 1. We defined comorbidities specified in Table 1 via ICD-9-CM secondary diagnosis codes and diagnosis related groups (DRGs) using Healthcare Cost and Utilization Project Comorbidity Software, version 3.7, based on the work of Elixhauser et al.^9,10; dialysis use was defined by an ICD-9-CM procedure code of 39.95; inpatient steroid use was defined by a hospital pharmacy charge for a systemic steroid in the 7 days preceding the sputum sample.

There were 230,635 hospitalizations of patients ≥18 years of age from January 2007 to July 2013. After excluding outside hospital transfers (n = 14,422), hospitalizations <48 hours in duration (n = 59,774), and psychiatric hospitalizations (n = 9887), there were 146,552 hospitalizations in the cohort.

To our knowledge, our study is the first to assess the predictors of positive sputum culture among patients with HAP (non-VAP) who had sputum samples obtained noninvasively, and this study is larger than prior studies in which researchers reported on sputum culture yield in HAP. Sputum samples were obtained in 29.4% cases of clinically diagnosed HAP. Although 87% of specimens obtained were culture-negative or contaminated, 13% yielded a bacterial organism. Although we do not report the antibiotic sensitivity patterns of the isolated organisms, the organisms identified frequently demonstrate antibiotic resistance, highlighting the potential for both antibiotic escalation and de-escalation based on sputum culture. In a multivariable model, presence of chronic lung disease and steroid use in the preceding week were both significantly associated with culture positivity.

The retrospective nature of the study raises the possibility of selection bias from systematic differences between the 29.4% of patients with HAP who had sputum collected and those who did not. Patients with sputum cultures were similar to patients without cultures in most measured characteristics, but we are unable to know what the yield of noninvasive sputum culture would have been had all patients with HAP been sampled. As such, our findings reflect the yield of sputum culture among patients with HAP for whom cultures were successfully obtained. It is not clear why only 29.4% of HAP patients received IDSA guideline-concordant care, but similar rates of culture use are reported elsewhere.⁷ While physician decision-making could have contributed to this finding, it is also possible that many sick, hospitalized patients are simply unable to produce sputum for analysis. In future studies, researchers should examine barriers to guideline-concordant care.

We considered a culture result of GNRs (not further speciated) as positive in our analysis because this result indicates growth of mixed bacterial types, the pathogenicity of which is a clinical determination. Physicians may request speciation and antibiotic sensitivities and, as such, these results have the potential to impact antibiotic choice. Had we considered such cultures to be negative or contaminated, the rate of culture positivity would have been only slightly reduced from 63/478 (13.2%) to 50/478 (10.5%).

The strengths of our study include the chart-based validation of administratively identified cases of pneumonia and a large cohort. There are also limitations. The single-center nature of the study has implications for pretest probability and generalizability. Additionally, in our study, we did not examine outcomes among patients treated empirically versus those treated based on sputum culture results. Finally, our reliance on administrative codes to identify cases of HAP for subsequent validation could have resulted in incomplete capture of HAP cases.

In conclusion, in our study, we provide an estimate of the diagnostic yield of sputum culture in a large cohort with chart-validated HAP, a description of HAP microbiology, and predictors of positive sputum culture. Thirteen percent of patients who had sputum culture testing received a microbiologic diagnosis. Because of the relative ease of obtaining a sputum sample and the microbiologic distribution in our study (representing a mix of commonly drug-resistant pathogens and more typical community-acquired pathogens), we suggest that sputum culture in HAP is a useful diagnostic tool with the potential to inform antibiotic escalation or de-escalation.

Acknowledgments

Dr. Herzig was funded by grant number K23AG042459 from the National Institute on Aging. Dr. Marcantonio was funded by grant number K24AG035075 from the National Institute on Aging. The funding organizations had no involvement in any aspect of the study, including design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript.

Disclosure

No conflicts of interest apply for any of the authors.

Pneumonia is a major cause of hospitalization, mortality, and healthcare cost. ^1,2 The diagnosis involves clinical features plus radiographic evidence of infection. Hospital-acquired pneumonia (HAP) is defined by the Infectious Disease Society of America (IDSA) as a pneumonia that occurs ≥48 hours after admission and is not associated with mechanical ventilation. ³

IDSA recommendations suggest that patients with suspected HAP be treated based on results of noninvasively obtained sputum cultures rather than being treated empirically. ³ This recommendation is graded as weak with low-quality evidence based on a lack of both evidence showing that respiratory cultures improve clinical outcomes and studies examining the yield of noninvasive collection methods. ^4,5 However, resistant pathogens lead to a risk of inadequate empiric therapy, which is associated with increased mortality. ⁶ Culture data may provide an opportunity for escalation or de-escalation of antibiotic coverage. IDSA recommendations for microbiologic sampling are thus aimed at increasing appropriate coverage and minimizing unnecessary antibiotic exposure.

While the yield and clinical utility of sputum culture in community-acquired pneumonia has been studied extensively, data examining the yield of sputum culture in HAP (non–ventilator-associated pneumonia [non-VAP]) are sparse. In 1 small single-center study, researchers demonstrated positive sputum cultures in 17/35 (48.6%) patients with radiographically confirmed cases of HAP, ⁷ while in another study, researchers demonstrated positive sputum cultures in 57/63 (90.5%). ⁸ We aimed to identify the frequency with which sputum cultures positively identify an organism, identify predictors of positive sputum cultures, and characterize the microbiology of sputum cultures in a large cohort of HAP cases.

We conducted a retrospective cohort study of patients admitted to a large academic medical center in Boston, Massachusetts, from January 2007 to July 2013. All patients ≥18 years of age were eligible for inclusion. We excluded outside hospital transfers, those with a length of hospitalization <48 hours, and psychiatric admissions.

The study was approved by the institutional review board at the Beth Israel Deaconess Medical Center and granted a waiver of informed consent. Data were collected from electronic databases and supplemented by chart review.

Hospital-Acquired Pneumonia

We defined HAP as pneumonia occurring at least 48 hours after admission, consistent with American Thoracic Society and IDSA criteria.³ To identify cases, we reviewed the charts of all admissions identified as having a discharge International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code for bacterial pneumonia (481, 482, 483, 485, 486, 507), indicated as not “present-on-admission.” We validated that the treating clinician had clinically diagnosed pneumonia and initiated antibiotics for this purpose by performing chart review. We reviewed the radiologist interpretation of radiographs surrounding the date of the clinical diagnosis of pneumonia to confirm the presence of a new opacity. Uncertain cases (with respect to either the presence of pneumonia or the timing of the diagnosis) were reviewed by a second member of the study team and, in the case of disagreement, adjudicated by a third member of the study team. Only the first clinically validated HAP per hospitalization was included in the analysis. To focus on HAP rather than VAP, we excluded hospitalizations in which the date of a procedure code for mechanical ventilation preceded the date of pneumonia diagnosis.

Microbiology

In our analysis, we used sputum samples obtained from expectorated or induced samples to evaluate the yield of noninvasive sputum sampling, as recommended by the IDSA. We included sputum samples collected ≥48 hours after admission and within 7 days of the clinical diagnosis of HAP. Sputum samples with >10 epithelial cells per high-power field (hpf) were considered to be contaminated. Among noncontaminated samples, positive sputum cultures were defined as those with a microbiologic diagnosis other than “oral flora,” while those with no growth or growth of oral flora or only yeast were considered to be negative. The hospital’s microbiology laboratory does not routinely provide species identification for Gram-negative rods (GNRs) growing on culture in the presence of growth of ≥3 other colony types. We considered such GNRs (not further speciated) to represent a positive culture result in our analysis given that colonization versus pathogenicity is a clinical distinction and, as such, these results may impact antibiotic choice.

Statistical Analysis

Data were analyzed by using SAS software, version 9.3. We used a 2-sided P value of <0.05 to indicate statistical significance for all comparisons. We used the χ² test and the nonparametric median test for unadjusted comparisons.

To identify predictors of a positive (versus negative or contaminated) sputum culture among patients with HAP, we used a generalized estimating equation model with a Poisson distribution error term, log link, and first-order autoregressive correlation structure to account for multiple sputum specimens per patient. We combined culture negative and contaminated samples to highlight the clinical utility of sputum culture in a real-world setting. Potential predictors chosen based on clinical grounds included all variables listed in Table 1. We defined comorbidities specified in Table 1 via ICD-9-CM secondary diagnosis codes and diagnosis related groups (DRGs) using Healthcare Cost and Utilization Project Comorbidity Software, version 3.7, based on the work of Elixhauser et al.^9,10; dialysis use was defined by an ICD-9-CM procedure code of 39.95; inpatient steroid use was defined by a hospital pharmacy charge for a systemic steroid in the 7 days preceding the sputum sample.

There were 230,635 hospitalizations of patients ≥18 years of age from January 2007 to July 2013. After excluding outside hospital transfers (n = 14,422), hospitalizations <48 hours in duration (n = 59,774), and psychiatric hospitalizations (n = 9887), there were 146,552 hospitalizations in the cohort.

To our knowledge, our study is the first to assess the predictors of positive sputum culture among patients with HAP (non-VAP) who had sputum samples obtained noninvasively, and this study is larger than prior studies in which researchers reported on sputum culture yield in HAP. Sputum samples were obtained in 29.4% cases of clinically diagnosed HAP. Although 87% of specimens obtained were culture-negative or contaminated, 13% yielded a bacterial organism. Although we do not report the antibiotic sensitivity patterns of the isolated organisms, the organisms identified frequently demonstrate antibiotic resistance, highlighting the potential for both antibiotic escalation and de-escalation based on sputum culture. In a multivariable model, presence of chronic lung disease and steroid use in the preceding week were both significantly associated with culture positivity.

The retrospective nature of the study raises the possibility of selection bias from systematic differences between the 29.4% of patients with HAP who had sputum collected and those who did not. Patients with sputum cultures were similar to patients without cultures in most measured characteristics, but we are unable to know what the yield of noninvasive sputum culture would have been had all patients with HAP been sampled. As such, our findings reflect the yield of sputum culture among patients with HAP for whom cultures were successfully obtained. It is not clear why only 29.4% of HAP patients received IDSA guideline-concordant care, but similar rates of culture use are reported elsewhere.⁷ While physician decision-making could have contributed to this finding, it is also possible that many sick, hospitalized patients are simply unable to produce sputum for analysis. In future studies, researchers should examine barriers to guideline-concordant care.

We considered a culture result of GNRs (not further speciated) as positive in our analysis because this result indicates growth of mixed bacterial types, the pathogenicity of which is a clinical determination. Physicians may request speciation and antibiotic sensitivities and, as such, these results have the potential to impact antibiotic choice. Had we considered such cultures to be negative or contaminated, the rate of culture positivity would have been only slightly reduced from 63/478 (13.2%) to 50/478 (10.5%).

The strengths of our study include the chart-based validation of administratively identified cases of pneumonia and a large cohort. There are also limitations. The single-center nature of the study has implications for pretest probability and generalizability. Additionally, in our study, we did not examine outcomes among patients treated empirically versus those treated based on sputum culture results. Finally, our reliance on administrative codes to identify cases of HAP for subsequent validation could have resulted in incomplete capture of HAP cases.

In conclusion, in our study, we provide an estimate of the diagnostic yield of sputum culture in a large cohort with chart-validated HAP, a description of HAP microbiology, and predictors of positive sputum culture. Thirteen percent of patients who had sputum culture testing received a microbiologic diagnosis. Because of the relative ease of obtaining a sputum sample and the microbiologic distribution in our study (representing a mix of commonly drug-resistant pathogens and more typical community-acquired pathogens), we suggest that sputum culture in HAP is a useful diagnostic tool with the potential to inform antibiotic escalation or de-escalation.

Acknowledgments

Dr. Herzig was funded by grant number K23AG042459 from the National Institute on Aging. Dr. Marcantonio was funded by grant number K24AG035075 from the National Institute on Aging. The funding organizations had no involvement in any aspect of the study, including design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript.

Disclosure

No conflicts of interest apply for any of the authors.

Hospitalists face complex questions about how to evaluate and treat the large number of individuals who are admitted on long-term opioid therapy (LTOT, defined as lasting 3 months or longer) for chronic noncancer pain. A recent study at one Veterans Affairs hospital, found 26% of medical inpatients were on LTOT.¹ Over the last 2 decades, use of LTOT has risen substantially in the United States, including among middle-aged and older adults.² Concurrently, inpatient hospitalizations related to the overuse of prescription opioids, including overdose, dependence, abuse, and adverse drug events, have increased by 153%.³ Individuals on LTOT can also be hospitalized for exacerbations of the opioid-treated chronic pain condition or unrelated conditions. In addition to affecting rates of hospitalization, use of LTOT is associated with higher rates of in-hospital adverse events, longer hospital stays, and higher readmission rates.^1,4,5

Physicians find managing chronic pain to be stressful, are often concerned about misuse and addiction, and believe their training in opioid prescribing is inadequate.⁶ Hospitalists report confidence in assessing and prescribing opioids for acute pain but limited success and satisfaction with treating exacerbations of chronic pain.⁷ Although half of all hospitalized patients receive opioids,⁵ little information is available to guide the care of hospitalized medical patients on LTOT for chronic noncancer pain.^8,9

Our multispecialty team sought to synthesize guideline recommendations and primary literature relevant to the assessment of medical inpatients on LTOT to assist practitioners balance effective pain treatment and opioid risk reduction. This article addresses obtaining a comprehensive pain history, identifying misuse and opioid use disorders, assessing the risk of overdose and adverse drug events, gauging the risk of withdrawal, and based on such findings, appraise indications for opioid therapy. Other authors have recently published narrative reviews on the management of acute pain in hospitalized patients with opioid dependence and the inpatient management of opioid use disorder.^10,11

To identify primary literature, we searched PubMed, EMBASE, The Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, Health Economic Evaluations Database, key meeting abstracts, and hand searches. To identify guidelines, we searched PubMed, National Guidelines Clearinghouse, specialty societies’ websites, the Centers for Disease Control and Prevention (CDC), the United Kingdom National Institute for Health and Care Excellence, the Canadian Medical Association, and the Australian Government National Health and Medical Research Council. Search terms related to opioids and chronic pain, which was last updated in October 2016.¹²

We selected English-language documents on opioids and chronic pain among adults, excluding pain in the setting of procedures, labor and delivery, life-limiting illness, or specific conditions. For primary literature, we considered intervention studies of any design that addressed pain management among hospitalized medical patients. We included guidelines and specialty society position statements published after January 1, 2009, that addressed pain in the hospital setting, acute pain in any setting, or chronic pain in the outpatient setting if published by a national body. Due to the paucity of documents specific to inpatient care, we used a narrative review format to synthesize information. Dual reviewers extracted guideline recommendations potentially relevant to medical inpatients on LTOT. We also summarize relevant assessment instruments, emphasizing very brief screening instruments, which may be more likely to be used by busy hospitalists.

Obtaining a Comprehensive Pain History

Hospitalists newly evaluating patients on LTOT often face a dual challenge: deciding if the patient has an immediate indication for additional opioids and if the current long-term opioid regimen should be altered or discontinued. In general, opioids are an accepted short-term treatment for moderate to severe acute pain but their role in chronic noncancer pain is controversial. Newly released guidelines by the CDC recommend initiating LTOT as a last resort, and the Departments of Veterans Affairs and Defense guidelines recommend against initiation of LTOT.^22,23

A key first step, therefore, is distinguishing between acute and chronic pain. Among patients on LTOT, pain can represent a new acute pain condition, an exacerbation of chronic pain, opioid-induced hyperalgesia, or opioid withdrawal. Acute pain is defined as an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in relation to such damage.²⁶ In contrast, chronic pain is a complex response that may not be related to actual or ongoing tissue damage, and is influenced by physiological, contextual, and psychological factors. Two acute pain guidelines and 1 chronic pain guideline recommend distinguishing acute and chronic pain,^9,16,21 3 chronic pain guidelines reinforce the importance of obtaining a pain history (including timing, intensity, frequency, onset, etc),^20,22,23 and 6 guidelines recommend ascertaining a history of prior pain-related treatments.^{9,13,14,16,20,22} Inquiring how the current pain compares with symptoms “on a good day,” what activities the patient can usually perform, and what the patient does outside the hospital to cope with pain can serve as entry into this conversation.

Identifying Misuse and Opioid Use Disorders

Nonmedical use of prescription opioids and opioid use disorders have more than doubled over the last decade.³⁵ Five guidelines, including 3 specific guidelines for acute pain or the hospital setting, recommend screening for opioid misuse.^{13,14,16,19,23} Many states mandate practitioners assess patients for substance use disorders before prescribing controlled substances.³⁶ Instruments to identify aberrant and risky use include the Current Opioid Misuse Measure,³⁷ Prescription Drug Use Questionnaire,³⁸ Addiction Behaviors Checklist,³⁹ Screening Tool for Abuse,⁴⁰ and the Self-Administered Single-Item Screening Question (Table 3).⁴¹ However, the evidence for these and other tools is limited and absent for the inpatient setting.^21,42

In addition to obtaining a history from the patient, 4 guidelines specific to hospital settings/acute pain and 4 chronic pain guidelines recommend practitioners access prescription drug monitoring programs (PDMPs).^{13-16,19,21-24} PDMPs exist in all states except Missouri, and about half of states mandate practitioners check the PDMP database in certain circumstances.³⁶ Studies examining the effects of PDMPs on prescribing are limited, but checking these databases can uncover concerning patterns including overlapping prescriptions or multiple prescribers.⁴³ PDMPs can also confirm reported medication doses, for which patient report may be less reliable.

Two hospital/acute pain guidelines and 5 chronic pain guidelines also recommend urine drug testing, although differing on when and whom to test, with some favoring universal screening.^11,20,23 Screening hospitalized patients may reveal substances not reported by patients, but medications administered in emergency departments can confound results. Furthermore, the commonly used immunoassay does not distinguish heroin from prescription opioids, nor detect hydrocodone, oxycodone, methadone, buprenorphine, or certain benzodiazepines. Chromatography/mass spectrometry assays can but are often not available from hospital laboratories. The differential for unexpected results includes substance use, self treatment of uncontrolled pain, diversion, or laboratory error.²⁰

If concerning opioid use is identified, 3 hospital setting/acute pain specific guidelines and the CDC guideline recommend sharing concerns with patients and assessing for a substance use disorder.^9,13,16,22 Determining whether patients have an opioid use disorder that meets the criteria in the Diagnostic and Statistical Manual, 5th Edition⁴⁴ can be challenging. Patients may minimize or deny symptoms or fear that the stigma of an opioid use disorder will lead to dismissive or subpar care. Additionally, substance use disorders are subject to federal confidentiality regulations, which can hamper acquisition of information from providers.⁴⁵ Thus, hospitalists may find specialty consultation helpful to confirm the diagnosis.

Assessing the Risk of Overdose and Adverse Drug Events

Oversedation, respiratory depression, and death can result from iatrogenic or self-administered opioid overdose in the hospital.5 Patient factors that increase this risk among outpatients include a prior history of overdose, preexisting substance use disorders, cognitive impairment, mood and personality disorders, chronic kidney disease, sleep apnea, obstructive lung disease, and recent abstinence from opioids.12 Medication factors include concomitant use of benzodiazepines and other central nervous system depressants, including alcohol; recent initiation of long-acting opioids; use of fentanyl patches, immediate-release fentanyl, or methadone; rapid titration; switching opioids without adequate dose reduction; pharmacokinetic drug–drug interactions; and, importantly, higher doses.12,22 Two guidelines specific to acute pain and hospital settings and 5 chronic pain guidelines recommend screening for use of benzodiazepines among patients on LTOT.13,14,16,18-20,22,21
The CDC guideline recommends careful assessment when doses exceed 50 mg of morphine equivalents per day and avoiding doses above 90 mg per day due to the heightened risk of overdose.²² In the hospital, 23% of patients receive doses at or above 100 mg of morphine equivalents per day,⁵ and concurrent use of central nervous system depressants is common. Changes in kidney and liver function during acute illness may impact opioid metabolism and contribute to overdose.

In addition to overdose, opioids are leading causes of adverse drug events during hospitalization.⁴⁶ Most studies have focused on surgical patients reporting common opioid-related events as nausea/vomiting, pruritus, rash, mental status changes, respiratory depression, ileus, and urinary retention.⁴⁷ Hospitalized patients may also exhibit chronic adverse effects due to LTOT. At least one-third of patients on LTOT eventually stop because of adverse effects, such as endocrinopathies, sleep disordered breathing, constipation, fractures, falls, and mental status changes.⁴⁸ Patients may lack awareness that their symptoms are attributable to opioids and are willing to reduce their opioid use once informed, especially when alternatives are offered to alleviate pain.

Gauging the Risk of Withdrawal

Sudden discontinuation of LTOT by patients, practitioners, or intercurrent events can have unanticipated and undesirable consequences. Withdrawal is not only distressing for patients; it can be dangerous because patients may resort to illicit use, diversion of opioids, or masking opioid withdrawal with other substances such as alcohol. The anxiety and distress associated with withdrawal, or anticipatory fear about withdrawal, can undermine therapeutic alliance and interfere with processes of care. Reviewed guidelines did not offer recommendations regarding withdrawal risk or specific strategies for avoidance. There is no specific prior dose threshold or degree of reduction in opioids that puts patients at risk for withdrawal, in part due to patients’ beliefs, expectations, and differences in response to opioid formulations. Symptoms of opioid withdrawal have been compared to a severe case of influenza, including stomach cramps, nausea and vomiting, diarrhea, tremor and muscle twitching, sweating, restlessness, yawning, tachycardia, anxiety and irritability, bone and joint aches, runny nose, tearing, and piloerection.⁴⁹ The Clinical Opiate Withdrawal Scale (COWS)⁴⁹ and the Clinical Institute Narcotic Assessment⁵¹ are clinician-administered tools to assess opioid withdrawal similar to the Clinical Institute Withdrawal Assessment of Alcohol Scale, Revised,⁵² to monitor for withdrawal in the inpatient setting.

Synthesizing and Appraising the Indications for Opioid Therapy

For medical inpatients who report adequate pain control and functional outcomes on current doses of LTOT, without evidence of misuse, the pragmatic approach is to continue the treatment plan established by the outpatient clinician rather than escalating or tapering the dose. If opioids are prescribed at discharge, 3 hospital setting/acute pain guidelines and the CDC guideline recommend prescribing the lowest effective dose of immediate release opioids for 3 to 7 days.^13,15,16,22

When patients exhibit evidence of an opioid use disorder, have a history of serious overdose, or are experiencing intolerable opioid-related adverse events, the hospitalist may conclude the harms of LTOT outweigh the benefits. For these patients, opioid treatment in the hospital can be aimed at preventing withdrawal, avoiding the perpetuation of inappropriate opioid use, managing other acute medical conditions, and communicating with outpatient prescribers. For patients with misuse, discontinuing opioids is potentially harmful and may be perceived as punitive. Hospitalists should consider consulting addiction or mental health specialists to assist with formulating a plan of care. However, such specialists may not be available in smaller or rural hospitals and referral at discharge can be challenging.⁵³

Beginning to taper opioids during the hospitalization can be appropriate when patients are motivated and can transition to an outpatient provider who will supervise the taper. In ambulatory settings, tapers of 10% to 30% every 2 to 5 days are generally well tolerated.⁵⁴ If patients started tapering opioids under supervision of an outpatient provider prior to hospitalization; ideally, the taper can be continued during hospitalization with close coordination with the outpatient clinician.

Unfortunately, many patients on LTOT are admitted with new sources of acute pain and or exacerbations of chronic pain, and some have concomitant substance use disorders; we plan to address the management of these complex situations in future work.

Despite the frequency with which patients on LTOT are hospitalized for nonsurgical stays and the challenges inherent in evaluating pain and assessing the possibility of substance use disorders, no formal guidelines or empirical research studies pertain to this population. Guidelines in this review were developed for hospital settings and acute pain in the absence of LTOT, and for outpatient care of patients on LTOT. We also included a nonsystematic synthesis of literature that varied in relevance to medical inpatients on LTOT.

Although inpatient assessment and treatment of patients with LTOT remains an underresearched area, we were able to extract and synthesize recommendations from 14 guideline statements and apply these to the assessment of patients with LTOT in the inpatient setting. Hospitalists frequently encounter patients on LTOT for chronic nonmalignant pain and are faced with complex decisions about the effectiveness and safety of LTOT; appropriate patient assessment is fundamental to making these decisions. Key guideline recommendations relevant to inpatient assessment include assessing both pain and functional status, differentiating acute from chronic pain, ascertaining preadmission pain treatment history, obtaining a psychosocial history, screening for mental health issues such as depression and anxiety, screening for substance use disorders, checking state prescription drug monitoring databases, ordering urine drug immunoassays, detecting use of sedative-hypnotics, identifying medical conditions associated with increased risk of overdose and adverse events, and appraising the potential benefits and harms of opioid therapy. Although approaches to assessing medical inpatients on LTOT can be extrapolated from outpatient guidelines, observational studies, and small studies in surgical populations, more work is needed to address these critical topics for inpatients on LTOT.

Disclosure

Dr. Herzig was funded by grant number K23AG042459 from the National Institute on Aging. The funding organization had no involvement in any aspect of the study, including design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. All other authors have no relevant conflicts of interest with the work.

Hospitalists face complex questions about how to evaluate and treat the large number of individuals who are admitted on long-term opioid therapy (LTOT, defined as lasting 3 months or longer) for chronic noncancer pain. A recent study at one Veterans Affairs hospital, found 26% of medical inpatients were on LTOT.¹ Over the last 2 decades, use of LTOT has risen substantially in the United States, including among middle-aged and older adults.² Concurrently, inpatient hospitalizations related to the overuse of prescription opioids, including overdose, dependence, abuse, and adverse drug events, have increased by 153%.³ Individuals on LTOT can also be hospitalized for exacerbations of the opioid-treated chronic pain condition or unrelated conditions. In addition to affecting rates of hospitalization, use of LTOT is associated with higher rates of in-hospital adverse events, longer hospital stays, and higher readmission rates.^1,4,5

Physicians find managing chronic pain to be stressful, are often concerned about misuse and addiction, and believe their training in opioid prescribing is inadequate.⁶ Hospitalists report confidence in assessing and prescribing opioids for acute pain but limited success and satisfaction with treating exacerbations of chronic pain.⁷ Although half of all hospitalized patients receive opioids,⁵ little information is available to guide the care of hospitalized medical patients on LTOT for chronic noncancer pain.^8,9

Our multispecialty team sought to synthesize guideline recommendations and primary literature relevant to the assessment of medical inpatients on LTOT to assist practitioners balance effective pain treatment and opioid risk reduction. This article addresses obtaining a comprehensive pain history, identifying misuse and opioid use disorders, assessing the risk of overdose and adverse drug events, gauging the risk of withdrawal, and based on such findings, appraise indications for opioid therapy. Other authors have recently published narrative reviews on the management of acute pain in hospitalized patients with opioid dependence and the inpatient management of opioid use disorder.^10,11

To identify primary literature, we searched PubMed, EMBASE, The Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, Health Economic Evaluations Database, key meeting abstracts, and hand searches. To identify guidelines, we searched PubMed, National Guidelines Clearinghouse, specialty societies’ websites, the Centers for Disease Control and Prevention (CDC), the United Kingdom National Institute for Health and Care Excellence, the Canadian Medical Association, and the Australian Government National Health and Medical Research Council. Search terms related to opioids and chronic pain, which was last updated in October 2016.¹²

We selected English-language documents on opioids and chronic pain among adults, excluding pain in the setting of procedures, labor and delivery, life-limiting illness, or specific conditions. For primary literature, we considered intervention studies of any design that addressed pain management among hospitalized medical patients. We included guidelines and specialty society position statements published after January 1, 2009, that addressed pain in the hospital setting, acute pain in any setting, or chronic pain in the outpatient setting if published by a national body. Due to the paucity of documents specific to inpatient care, we used a narrative review format to synthesize information. Dual reviewers extracted guideline recommendations potentially relevant to medical inpatients on LTOT. We also summarize relevant assessment instruments, emphasizing very brief screening instruments, which may be more likely to be used by busy hospitalists.

Obtaining a Comprehensive Pain History

Hospitalists newly evaluating patients on LTOT often face a dual challenge: deciding if the patient has an immediate indication for additional opioids and if the current long-term opioid regimen should be altered or discontinued. In general, opioids are an accepted short-term treatment for moderate to severe acute pain but their role in chronic noncancer pain is controversial. Newly released guidelines by the CDC recommend initiating LTOT as a last resort, and the Departments of Veterans Affairs and Defense guidelines recommend against initiation of LTOT.^22,23

A key first step, therefore, is distinguishing between acute and chronic pain. Among patients on LTOT, pain can represent a new acute pain condition, an exacerbation of chronic pain, opioid-induced hyperalgesia, or opioid withdrawal. Acute pain is defined as an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in relation to such damage.²⁶ In contrast, chronic pain is a complex response that may not be related to actual or ongoing tissue damage, and is influenced by physiological, contextual, and psychological factors. Two acute pain guidelines and 1 chronic pain guideline recommend distinguishing acute and chronic pain,^9,16,21 3 chronic pain guidelines reinforce the importance of obtaining a pain history (including timing, intensity, frequency, onset, etc),^20,22,23 and 6 guidelines recommend ascertaining a history of prior pain-related treatments.^{9,13,14,16,20,22} Inquiring how the current pain compares with symptoms “on a good day,” what activities the patient can usually perform, and what the patient does outside the hospital to cope with pain can serve as entry into this conversation.

Identifying Misuse and Opioid Use Disorders

Nonmedical use of prescription opioids and opioid use disorders have more than doubled over the last decade.³⁵ Five guidelines, including 3 specific guidelines for acute pain or the hospital setting, recommend screening for opioid misuse.^{13,14,16,19,23} Many states mandate practitioners assess patients for substance use disorders before prescribing controlled substances.³⁶ Instruments to identify aberrant and risky use include the Current Opioid Misuse Measure,³⁷ Prescription Drug Use Questionnaire,³⁸ Addiction Behaviors Checklist,³⁹ Screening Tool for Abuse,⁴⁰ and the Self-Administered Single-Item Screening Question (Table 3).⁴¹ However, the evidence for these and other tools is limited and absent for the inpatient setting.^21,42

In addition to obtaining a history from the patient, 4 guidelines specific to hospital settings/acute pain and 4 chronic pain guidelines recommend practitioners access prescription drug monitoring programs (PDMPs).^{13-16,19,21-24} PDMPs exist in all states except Missouri, and about half of states mandate practitioners check the PDMP database in certain circumstances.³⁶ Studies examining the effects of PDMPs on prescribing are limited, but checking these databases can uncover concerning patterns including overlapping prescriptions or multiple prescribers.⁴³ PDMPs can also confirm reported medication doses, for which patient report may be less reliable.

Two hospital/acute pain guidelines and 5 chronic pain guidelines also recommend urine drug testing, although differing on when and whom to test, with some favoring universal screening.^11,20,23 Screening hospitalized patients may reveal substances not reported by patients, but medications administered in emergency departments can confound results. Furthermore, the commonly used immunoassay does not distinguish heroin from prescription opioids, nor detect hydrocodone, oxycodone, methadone, buprenorphine, or certain benzodiazepines. Chromatography/mass spectrometry assays can but are often not available from hospital laboratories. The differential for unexpected results includes substance use, self treatment of uncontrolled pain, diversion, or laboratory error.²⁰

If concerning opioid use is identified, 3 hospital setting/acute pain specific guidelines and the CDC guideline recommend sharing concerns with patients and assessing for a substance use disorder.^9,13,16,22 Determining whether patients have an opioid use disorder that meets the criteria in the Diagnostic and Statistical Manual, 5th Edition⁴⁴ can be challenging. Patients may minimize or deny symptoms or fear that the stigma of an opioid use disorder will lead to dismissive or subpar care. Additionally, substance use disorders are subject to federal confidentiality regulations, which can hamper acquisition of information from providers.⁴⁵ Thus, hospitalists may find specialty consultation helpful to confirm the diagnosis.

Assessing the Risk of Overdose and Adverse Drug Events

Oversedation, respiratory depression, and death can result from iatrogenic or self-administered opioid overdose in the hospital.5 Patient factors that increase this risk among outpatients include a prior history of overdose, preexisting substance use disorders, cognitive impairment, mood and personality disorders, chronic kidney disease, sleep apnea, obstructive lung disease, and recent abstinence from opioids.12 Medication factors include concomitant use of benzodiazepines and other central nervous system depressants, including alcohol; recent initiation of long-acting opioids; use of fentanyl patches, immediate-release fentanyl, or methadone; rapid titration; switching opioids without adequate dose reduction; pharmacokinetic drug–drug interactions; and, importantly, higher doses.12,22 Two guidelines specific to acute pain and hospital settings and 5 chronic pain guidelines recommend screening for use of benzodiazepines among patients on LTOT.13,14,16,18-20,22,21
The CDC guideline recommends careful assessment when doses exceed 50 mg of morphine equivalents per day and avoiding doses above 90 mg per day due to the heightened risk of overdose.²² In the hospital, 23% of patients receive doses at or above 100 mg of morphine equivalents per day,⁵ and concurrent use of central nervous system depressants is common. Changes in kidney and liver function during acute illness may impact opioid metabolism and contribute to overdose.

In addition to overdose, opioids are leading causes of adverse drug events during hospitalization.⁴⁶ Most studies have focused on surgical patients reporting common opioid-related events as nausea/vomiting, pruritus, rash, mental status changes, respiratory depression, ileus, and urinary retention.⁴⁷ Hospitalized patients may also exhibit chronic adverse effects due to LTOT. At least one-third of patients on LTOT eventually stop because of adverse effects, such as endocrinopathies, sleep disordered breathing, constipation, fractures, falls, and mental status changes.⁴⁸ Patients may lack awareness that their symptoms are attributable to opioids and are willing to reduce their opioid use once informed, especially when alternatives are offered to alleviate pain.

Gauging the Risk of Withdrawal

Sudden discontinuation of LTOT by patients, practitioners, or intercurrent events can have unanticipated and undesirable consequences. Withdrawal is not only distressing for patients; it can be dangerous because patients may resort to illicit use, diversion of opioids, or masking opioid withdrawal with other substances such as alcohol. The anxiety and distress associated with withdrawal, or anticipatory fear about withdrawal, can undermine therapeutic alliance and interfere with processes of care. Reviewed guidelines did not offer recommendations regarding withdrawal risk or specific strategies for avoidance. There is no specific prior dose threshold or degree of reduction in opioids that puts patients at risk for withdrawal, in part due to patients’ beliefs, expectations, and differences in response to opioid formulations. Symptoms of opioid withdrawal have been compared to a severe case of influenza, including stomach cramps, nausea and vomiting, diarrhea, tremor and muscle twitching, sweating, restlessness, yawning, tachycardia, anxiety and irritability, bone and joint aches, runny nose, tearing, and piloerection.⁴⁹ The Clinical Opiate Withdrawal Scale (COWS)⁴⁹ and the Clinical Institute Narcotic Assessment⁵¹ are clinician-administered tools to assess opioid withdrawal similar to the Clinical Institute Withdrawal Assessment of Alcohol Scale, Revised,⁵² to monitor for withdrawal in the inpatient setting.

Synthesizing and Appraising the Indications for Opioid Therapy

For medical inpatients who report adequate pain control and functional outcomes on current doses of LTOT, without evidence of misuse, the pragmatic approach is to continue the treatment plan established by the outpatient clinician rather than escalating or tapering the dose. If opioids are prescribed at discharge, 3 hospital setting/acute pain guidelines and the CDC guideline recommend prescribing the lowest effective dose of immediate release opioids for 3 to 7 days.^13,15,16,22

When patients exhibit evidence of an opioid use disorder, have a history of serious overdose, or are experiencing intolerable opioid-related adverse events, the hospitalist may conclude the harms of LTOT outweigh the benefits. For these patients, opioid treatment in the hospital can be aimed at preventing withdrawal, avoiding the perpetuation of inappropriate opioid use, managing other acute medical conditions, and communicating with outpatient prescribers. For patients with misuse, discontinuing opioids is potentially harmful and may be perceived as punitive. Hospitalists should consider consulting addiction or mental health specialists to assist with formulating a plan of care. However, such specialists may not be available in smaller or rural hospitals and referral at discharge can be challenging.⁵³

Beginning to taper opioids during the hospitalization can be appropriate when patients are motivated and can transition to an outpatient provider who will supervise the taper. In ambulatory settings, tapers of 10% to 30% every 2 to 5 days are generally well tolerated.⁵⁴ If patients started tapering opioids under supervision of an outpatient provider prior to hospitalization; ideally, the taper can be continued during hospitalization with close coordination with the outpatient clinician.

Unfortunately, many patients on LTOT are admitted with new sources of acute pain and or exacerbations of chronic pain, and some have concomitant substance use disorders; we plan to address the management of these complex situations in future work.

Despite the frequency with which patients on LTOT are hospitalized for nonsurgical stays and the challenges inherent in evaluating pain and assessing the possibility of substance use disorders, no formal guidelines or empirical research studies pertain to this population. Guidelines in this review were developed for hospital settings and acute pain in the absence of LTOT, and for outpatient care of patients on LTOT. We also included a nonsystematic synthesis of literature that varied in relevance to medical inpatients on LTOT.

Although inpatient assessment and treatment of patients with LTOT remains an underresearched area, we were able to extract and synthesize recommendations from 14 guideline statements and apply these to the assessment of patients with LTOT in the inpatient setting. Hospitalists frequently encounter patients on LTOT for chronic nonmalignant pain and are faced with complex decisions about the effectiveness and safety of LTOT; appropriate patient assessment is fundamental to making these decisions. Key guideline recommendations relevant to inpatient assessment include assessing both pain and functional status, differentiating acute from chronic pain, ascertaining preadmission pain treatment history, obtaining a psychosocial history, screening for mental health issues such as depression and anxiety, screening for substance use disorders, checking state prescription drug monitoring databases, ordering urine drug immunoassays, detecting use of sedative-hypnotics, identifying medical conditions associated with increased risk of overdose and adverse events, and appraising the potential benefits and harms of opioid therapy. Although approaches to assessing medical inpatients on LTOT can be extrapolated from outpatient guidelines, observational studies, and small studies in surgical populations, more work is needed to address these critical topics for inpatients on LTOT.

Disclosure

Dr. Herzig was funded by grant number K23AG042459 from the National Institute on Aging. The funding organization had no involvement in any aspect of the study, including design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. All other authors have no relevant conflicts of interest with the work.

Hospitalists face complex questions about how to evaluate and treat the large number of individuals who are admitted on long-term opioid therapy (LTOT, defined as lasting 3 months or longer) for chronic noncancer pain. A recent study at one Veterans Affairs hospital, found 26% of medical inpatients were on LTOT.¹ Over the last 2 decades, use of LTOT has risen substantially in the United States, including among middle-aged and older adults.² Concurrently, inpatient hospitalizations related to the overuse of prescription opioids, including overdose, dependence, abuse, and adverse drug events, have increased by 153%.³ Individuals on LTOT can also be hospitalized for exacerbations of the opioid-treated chronic pain condition or unrelated conditions. In addition to affecting rates of hospitalization, use of LTOT is associated with higher rates of in-hospital adverse events, longer hospital stays, and higher readmission rates.^1,4,5

Physicians find managing chronic pain to be stressful, are often concerned about misuse and addiction, and believe their training in opioid prescribing is inadequate.⁶ Hospitalists report confidence in assessing and prescribing opioids for acute pain but limited success and satisfaction with treating exacerbations of chronic pain.⁷ Although half of all hospitalized patients receive opioids,⁵ little information is available to guide the care of hospitalized medical patients on LTOT for chronic noncancer pain.^8,9

Our multispecialty team sought to synthesize guideline recommendations and primary literature relevant to the assessment of medical inpatients on LTOT to assist practitioners balance effective pain treatment and opioid risk reduction. This article addresses obtaining a comprehensive pain history, identifying misuse and opioid use disorders, assessing the risk of overdose and adverse drug events, gauging the risk of withdrawal, and based on such findings, appraise indications for opioid therapy. Other authors have recently published narrative reviews on the management of acute pain in hospitalized patients with opioid dependence and the inpatient management of opioid use disorder.^10,11

To identify primary literature, we searched PubMed, EMBASE, The Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, Health Economic Evaluations Database, key meeting abstracts, and hand searches. To identify guidelines, we searched PubMed, National Guidelines Clearinghouse, specialty societies’ websites, the Centers for Disease Control and Prevention (CDC), the United Kingdom National Institute for Health and Care Excellence, the Canadian Medical Association, and the Australian Government National Health and Medical Research Council. Search terms related to opioids and chronic pain, which was last updated in October 2016.¹²

We selected English-language documents on opioids and chronic pain among adults, excluding pain in the setting of procedures, labor and delivery, life-limiting illness, or specific conditions. For primary literature, we considered intervention studies of any design that addressed pain management among hospitalized medical patients. We included guidelines and specialty society position statements published after January 1, 2009, that addressed pain in the hospital setting, acute pain in any setting, or chronic pain in the outpatient setting if published by a national body. Due to the paucity of documents specific to inpatient care, we used a narrative review format to synthesize information. Dual reviewers extracted guideline recommendations potentially relevant to medical inpatients on LTOT. We also summarize relevant assessment instruments, emphasizing very brief screening instruments, which may be more likely to be used by busy hospitalists.

Obtaining a Comprehensive Pain History

Hospitalists newly evaluating patients on LTOT often face a dual challenge: deciding if the patient has an immediate indication for additional opioids and if the current long-term opioid regimen should be altered or discontinued. In general, opioids are an accepted short-term treatment for moderate to severe acute pain but their role in chronic noncancer pain is controversial. Newly released guidelines by the CDC recommend initiating LTOT as a last resort, and the Departments of Veterans Affairs and Defense guidelines recommend against initiation of LTOT.^22,23

A key first step, therefore, is distinguishing between acute and chronic pain. Among patients on LTOT, pain can represent a new acute pain condition, an exacerbation of chronic pain, opioid-induced hyperalgesia, or opioid withdrawal. Acute pain is defined as an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in relation to such damage.²⁶ In contrast, chronic pain is a complex response that may not be related to actual or ongoing tissue damage, and is influenced by physiological, contextual, and psychological factors. Two acute pain guidelines and 1 chronic pain guideline recommend distinguishing acute and chronic pain,^9,16,21 3 chronic pain guidelines reinforce the importance of obtaining a pain history (including timing, intensity, frequency, onset, etc),^20,22,23 and 6 guidelines recommend ascertaining a history of prior pain-related treatments.^{9,13,14,16,20,22} Inquiring how the current pain compares with symptoms “on a good day,” what activities the patient can usually perform, and what the patient does outside the hospital to cope with pain can serve as entry into this conversation.

Identifying Misuse and Opioid Use Disorders

Nonmedical use of prescription opioids and opioid use disorders have more than doubled over the last decade.³⁵ Five guidelines, including 3 specific guidelines for acute pain or the hospital setting, recommend screening for opioid misuse.^{13,14,16,19,23} Many states mandate practitioners assess patients for substance use disorders before prescribing controlled substances.³⁶ Instruments to identify aberrant and risky use include the Current Opioid Misuse Measure,³⁷ Prescription Drug Use Questionnaire,³⁸ Addiction Behaviors Checklist,³⁹ Screening Tool for Abuse,⁴⁰ and the Self-Administered Single-Item Screening Question (Table 3).⁴¹ However, the evidence for these and other tools is limited and absent for the inpatient setting.^21,42

In addition to obtaining a history from the patient, 4 guidelines specific to hospital settings/acute pain and 4 chronic pain guidelines recommend practitioners access prescription drug monitoring programs (PDMPs).^{13-16,19,21-24} PDMPs exist in all states except Missouri, and about half of states mandate practitioners check the PDMP database in certain circumstances.³⁶ Studies examining the effects of PDMPs on prescribing are limited, but checking these databases can uncover concerning patterns including overlapping prescriptions or multiple prescribers.⁴³ PDMPs can also confirm reported medication doses, for which patient report may be less reliable.

Two hospital/acute pain guidelines and 5 chronic pain guidelines also recommend urine drug testing, although differing on when and whom to test, with some favoring universal screening.^11,20,23 Screening hospitalized patients may reveal substances not reported by patients, but medications administered in emergency departments can confound results. Furthermore, the commonly used immunoassay does not distinguish heroin from prescription opioids, nor detect hydrocodone, oxycodone, methadone, buprenorphine, or certain benzodiazepines. Chromatography/mass spectrometry assays can but are often not available from hospital laboratories. The differential for unexpected results includes substance use, self treatment of uncontrolled pain, diversion, or laboratory error.²⁰

If concerning opioid use is identified, 3 hospital setting/acute pain specific guidelines and the CDC guideline recommend sharing concerns with patients and assessing for a substance use disorder.^9,13,16,22 Determining whether patients have an opioid use disorder that meets the criteria in the Diagnostic and Statistical Manual, 5th Edition⁴⁴ can be challenging. Patients may minimize or deny symptoms or fear that the stigma of an opioid use disorder will lead to dismissive or subpar care. Additionally, substance use disorders are subject to federal confidentiality regulations, which can hamper acquisition of information from providers.⁴⁵ Thus, hospitalists may find specialty consultation helpful to confirm the diagnosis.

Assessing the Risk of Overdose and Adverse Drug Events

Oversedation, respiratory depression, and death can result from iatrogenic or self-administered opioid overdose in the hospital.5 Patient factors that increase this risk among outpatients include a prior history of overdose, preexisting substance use disorders, cognitive impairment, mood and personality disorders, chronic kidney disease, sleep apnea, obstructive lung disease, and recent abstinence from opioids.12 Medication factors include concomitant use of benzodiazepines and other central nervous system depressants, including alcohol; recent initiation of long-acting opioids; use of fentanyl patches, immediate-release fentanyl, or methadone; rapid titration; switching opioids without adequate dose reduction; pharmacokinetic drug–drug interactions; and, importantly, higher doses.12,22 Two guidelines specific to acute pain and hospital settings and 5 chronic pain guidelines recommend screening for use of benzodiazepines among patients on LTOT.13,14,16,18-20,22,21
The CDC guideline recommends careful assessment when doses exceed 50 mg of morphine equivalents per day and avoiding doses above 90 mg per day due to the heightened risk of overdose.²² In the hospital, 23% of patients receive doses at or above 100 mg of morphine equivalents per day,⁵ and concurrent use of central nervous system depressants is common. Changes in kidney and liver function during acute illness may impact opioid metabolism and contribute to overdose.

In addition to overdose, opioids are leading causes of adverse drug events during hospitalization.⁴⁶ Most studies have focused on surgical patients reporting common opioid-related events as nausea/vomiting, pruritus, rash, mental status changes, respiratory depression, ileus, and urinary retention.⁴⁷ Hospitalized patients may also exhibit chronic adverse effects due to LTOT. At least one-third of patients on LTOT eventually stop because of adverse effects, such as endocrinopathies, sleep disordered breathing, constipation, fractures, falls, and mental status changes.⁴⁸ Patients may lack awareness that their symptoms are attributable to opioids and are willing to reduce their opioid use once informed, especially when alternatives are offered to alleviate pain.

Gauging the Risk of Withdrawal

Sudden discontinuation of LTOT by patients, practitioners, or intercurrent events can have unanticipated and undesirable consequences. Withdrawal is not only distressing for patients; it can be dangerous because patients may resort to illicit use, diversion of opioids, or masking opioid withdrawal with other substances such as alcohol. The anxiety and distress associated with withdrawal, or anticipatory fear about withdrawal, can undermine therapeutic alliance and interfere with processes of care. Reviewed guidelines did not offer recommendations regarding withdrawal risk or specific strategies for avoidance. There is no specific prior dose threshold or degree of reduction in opioids that puts patients at risk for withdrawal, in part due to patients’ beliefs, expectations, and differences in response to opioid formulations. Symptoms of opioid withdrawal have been compared to a severe case of influenza, including stomach cramps, nausea and vomiting, diarrhea, tremor and muscle twitching, sweating, restlessness, yawning, tachycardia, anxiety and irritability, bone and joint aches, runny nose, tearing, and piloerection.⁴⁹ The Clinical Opiate Withdrawal Scale (COWS)⁴⁹ and the Clinical Institute Narcotic Assessment⁵¹ are clinician-administered tools to assess opioid withdrawal similar to the Clinical Institute Withdrawal Assessment of Alcohol Scale, Revised,⁵² to monitor for withdrawal in the inpatient setting.

Synthesizing and Appraising the Indications for Opioid Therapy

For medical inpatients who report adequate pain control and functional outcomes on current doses of LTOT, without evidence of misuse, the pragmatic approach is to continue the treatment plan established by the outpatient clinician rather than escalating or tapering the dose. If opioids are prescribed at discharge, 3 hospital setting/acute pain guidelines and the CDC guideline recommend prescribing the lowest effective dose of immediate release opioids for 3 to 7 days.^13,15,16,22

When patients exhibit evidence of an opioid use disorder, have a history of serious overdose, or are experiencing intolerable opioid-related adverse events, the hospitalist may conclude the harms of LTOT outweigh the benefits. For these patients, opioid treatment in the hospital can be aimed at preventing withdrawal, avoiding the perpetuation of inappropriate opioid use, managing other acute medical conditions, and communicating with outpatient prescribers. For patients with misuse, discontinuing opioids is potentially harmful and may be perceived as punitive. Hospitalists should consider consulting addiction or mental health specialists to assist with formulating a plan of care. However, such specialists may not be available in smaller or rural hospitals and referral at discharge can be challenging.⁵³

Beginning to taper opioids during the hospitalization can be appropriate when patients are motivated and can transition to an outpatient provider who will supervise the taper. In ambulatory settings, tapers of 10% to 30% every 2 to 5 days are generally well tolerated.⁵⁴ If patients started tapering opioids under supervision of an outpatient provider prior to hospitalization; ideally, the taper can be continued during hospitalization with close coordination with the outpatient clinician.

Unfortunately, many patients on LTOT are admitted with new sources of acute pain and or exacerbations of chronic pain, and some have concomitant substance use disorders; we plan to address the management of these complex situations in future work.

Despite the frequency with which patients on LTOT are hospitalized for nonsurgical stays and the challenges inherent in evaluating pain and assessing the possibility of substance use disorders, no formal guidelines or empirical research studies pertain to this population. Guidelines in this review were developed for hospital settings and acute pain in the absence of LTOT, and for outpatient care of patients on LTOT. We also included a nonsystematic synthesis of literature that varied in relevance to medical inpatients on LTOT.

Although inpatient assessment and treatment of patients with LTOT remains an underresearched area, we were able to extract and synthesize recommendations from 14 guideline statements and apply these to the assessment of patients with LTOT in the inpatient setting. Hospitalists frequently encounter patients on LTOT for chronic nonmalignant pain and are faced with complex decisions about the effectiveness and safety of LTOT; appropriate patient assessment is fundamental to making these decisions. Key guideline recommendations relevant to inpatient assessment include assessing both pain and functional status, differentiating acute from chronic pain, ascertaining preadmission pain treatment history, obtaining a psychosocial history, screening for mental health issues such as depression and anxiety, screening for substance use disorders, checking state prescription drug monitoring databases, ordering urine drug immunoassays, detecting use of sedative-hypnotics, identifying medical conditions associated with increased risk of overdose and adverse events, and appraising the potential benefits and harms of opioid therapy. Although approaches to assessing medical inpatients on LTOT can be extrapolated from outpatient guidelines, observational studies, and small studies in surgical populations, more work is needed to address these critical topics for inpatients on LTOT.

Disclosure

Dr. Herzig was funded by grant number K23AG042459 from the National Institute on Aging. The funding organization had no involvement in any aspect of the study, including design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. All other authors have no relevant conflicts of interest with the work.

Recent publications in the medical literature and lay press have stirred controversy regarding the use of inpatient ‘very important person’ (VIP) services.^1-3 The term “VIP services” often refers to select conveniences offered in addition to the assumed basic level of care and services provided by a hospital. Examples include additional space, enhanced facilities, specific comforts, or personal support. In some instances, these amenities may only be provided to patients who have close financial, social, or professional relationships with the hospital.

How VIP patients interact with their health system to obtain VIP services has raised unique concerns. Some have speculated that the presence of a VIP patient may be disruptive to the care of non-VIP patients, while others have cautioned physicians about potential dangers to the VIP patients themselves.^4-6 Despite much being written on the topics of VIP patients and services in both the lay and academic press, our literature review identified only 1 study on the topic, which cataloged the preferential treatment of VIP patients in the emergency department.⁶ We are unaware of any investigations of VIP-service use in the inpatient setting. Through a multisite survey of hospital medicine physicians, we assessed physician viewpoints and behavior regarding VIP services.

The Hospital Medicine Reengineering Network (HOMERuN) is a nation-wide learning organization focused on measuring and improving the outcomes of hospitalized patients.⁷ We surveyed hospitalists from 8 HOMERuN hospitals (Appendix 1). The survey instrument contained 4 sections: nonidentifying respondent demographics, local use of VIP services, reported physician perceptions of VIP services, and case-based assessments (Appendix 2). Survey questions and individual cases were developed by study authors and based on real scenarios and concerns provided by front-line clinical providers. Content, length, and reliability of physician understanding were assessed by a 5-person focus group consisting of physicians not included in the survey population.

Subjects were identified via administrative rosters from each HOMERuN site. Surveys were administered via SurveyMonkey, and results were analyzed descriptively. Populations were compared via the Fisher exact test. “VIP services” were defined as conveniences provided in addition to the assumed basic level of care and services (eg, private or luxury-style rooms, access to a special menu, better views, dedicated personal care attendants, hospital liaisons). VIP patients were defined as those patients receiving VIP services. A hospital was identified as providing VIP services if 50% or more of respondents from that site reported the presence of VIP services.

Of 366 hospitalists contacted, 160 completed the survey (44%). Respondent characteristics and reported prevalence of VIP services are demonstrated in Table 1. In total, 78 respondents (45%) reported the presence of VIP services at their hospital. Of the 8 sites surveyed, a majority of physicians at 4 sites (50%) reported presence of VIP services.

Of respondents reporting the presence of VIP services at their hospital, a majority felt that, from a patient safety perspective, the care received by VIP patients was the same as care received by non-VIP patients (Table 2). A majority reported they had felt pressured by a VIP patient or a family member to order additional tests or treatments that the physician believed were medically unnecessary and that they would be more likely to comply with VIP patient’s requests for tests or treatments they felt were unnecessary. More than one-third (36%) felt pressured by other hospital employees or representatives to comply with VIP services patient’s requests for additional tests or treatments that the physicians believed were medically unnecessary.

In our study, a majority of physicians who reported the presence of VIP services at their hospital felt pressured by VIP patients or their family members to perform unnecessary testing or treatment. While this study was not designed to quantify the burden of unnecessary care for VIP patients, our results have implications for individual patients and public health, including potential effects on resource availability, the identification of clinically irrelevant incidental findings, and short- and long-term medical complications of procedures, testing and radiation exposure.

Prior publications have advocated that physicians and hospitals should not allow VIP status to influence management decisions.^3,5 We found that more than one-third of physicians who reported the presence of VIP services at their hospital also reported receiving pressure from hospital representatives to provide care to VIP patients that was not medically indicated. These findings highlight an example of the tension faced by physicians who are caught between patient requests and the delivery of value-based care. This potential conflict may be amplified particularly for those patients with close financial, social, or professional ties to the hospitals (and physicians) providing their care. These results suggest the need for physicians, administrators, and patients to work together to address the potential blurring of ethical boundaries created by VIP relationships. Prevention of harm and avoidance of placing physicians in morally distressing situations are common goals for all involved parties.

Efforts to reduce unnecessary care have predominantly focused on structural and knowledge-based drivers.^4,8,9 Our results highlight the presence of additional forces. A majority of physician respondents who reported the presence of VIP services at their hospital also reported that they would be more likely to comply with requests for unnecessary care for a VIP patient as compared to a non-VIP patient. Furthermore, in case-based questions about the requests of a VIP patient and their family for additional unnecessary care, a significant portion of physicians who reported they would comply with these requests listed the VIP status of the patient or family as a factor underlying this decision. Only a minority of physicians reported their decision to provide additional care was the result of their own medically-based concerns. Because these cases were hypothetical and we did not include comparator cases involving non-VIP patients, it remains uncertain whether the observed perceptions accurately reflect real-world differences in the care of VIP and non-VIP patients. Nonetheless, our findings emphasize the importance of better understanding the social drivers of overuse and physician communication strategies related to medically inappropriate tests.^10,11

Demand for unnecessary testing may be driven by the mentality that “more is better.”¹² Contrary to this belief, provision of unnecessary care can increase the risk of patient harm.¹³ Despite physician respondents reporting that VIP patients requested and/or received additional unnecessary care, a majority of respondents felt that patient safety for VIP patients was equivalent to that for non-VIP patients. As we assessed only physician perceptions of safety, which may not necessarily correlate with actual safety, further research in this area is needed.

Our study was limited by several factors. While our study population included hospitalists from 8 geographically broad hospitals, including university, safety net, and community hospitals, study responses may not be reflective of nationwide trends. Our response rate may limit our ability to generalize conclusions beyond respondents. Second, our study captured physician perceptions of behavior and safety rather than actually measuring practice and outcomes. Studies comparing physician practice patterns and outcomes between VIP and non-VIP patients would be informative. Additionally, despite our inclusive survey design process, our survey was not validated, and it is possible that our questions were not interpreted as intended. Lastly, despite the anonymous nature of our survey, physicians may have felt compelled to respond in a particular way due to conflicting professional, financial, or social factors.

Our findings provide initial insight into how care for the VIP patient may present unique challenges for physicians, hospitals, and society by systematizing care inequities, as well as potentially incentivizing low-value care practices. Whether these imbalances produce clinical harms or benefits remains worthy of future studies.

Disclosure

Nothing to report.

Recent publications in the medical literature and lay press have stirred controversy regarding the use of inpatient ‘very important person’ (VIP) services.^1-3 The term “VIP services” often refers to select conveniences offered in addition to the assumed basic level of care and services provided by a hospital. Examples include additional space, enhanced facilities, specific comforts, or personal support. In some instances, these amenities may only be provided to patients who have close financial, social, or professional relationships with the hospital.

How VIP patients interact with their health system to obtain VIP services has raised unique concerns. Some have speculated that the presence of a VIP patient may be disruptive to the care of non-VIP patients, while others have cautioned physicians about potential dangers to the VIP patients themselves.^4-6 Despite much being written on the topics of VIP patients and services in both the lay and academic press, our literature review identified only 1 study on the topic, which cataloged the preferential treatment of VIP patients in the emergency department.⁶ We are unaware of any investigations of VIP-service use in the inpatient setting. Through a multisite survey of hospital medicine physicians, we assessed physician viewpoints and behavior regarding VIP services.

The Hospital Medicine Reengineering Network (HOMERuN) is a nation-wide learning organization focused on measuring and improving the outcomes of hospitalized patients.⁷ We surveyed hospitalists from 8 HOMERuN hospitals (Appendix 1). The survey instrument contained 4 sections: nonidentifying respondent demographics, local use of VIP services, reported physician perceptions of VIP services, and case-based assessments (Appendix 2). Survey questions and individual cases were developed by study authors and based on real scenarios and concerns provided by front-line clinical providers. Content, length, and reliability of physician understanding were assessed by a 5-person focus group consisting of physicians not included in the survey population.

Subjects were identified via administrative rosters from each HOMERuN site. Surveys were administered via SurveyMonkey, and results were analyzed descriptively. Populations were compared via the Fisher exact test. “VIP services” were defined as conveniences provided in addition to the assumed basic level of care and services (eg, private or luxury-style rooms, access to a special menu, better views, dedicated personal care attendants, hospital liaisons). VIP patients were defined as those patients receiving VIP services. A hospital was identified as providing VIP services if 50% or more of respondents from that site reported the presence of VIP services.

Of 366 hospitalists contacted, 160 completed the survey (44%). Respondent characteristics and reported prevalence of VIP services are demonstrated in Table 1. In total, 78 respondents (45%) reported the presence of VIP services at their hospital. Of the 8 sites surveyed, a majority of physicians at 4 sites (50%) reported presence of VIP services.

Of respondents reporting the presence of VIP services at their hospital, a majority felt that, from a patient safety perspective, the care received by VIP patients was the same as care received by non-VIP patients (Table 2). A majority reported they had felt pressured by a VIP patient or a family member to order additional tests or treatments that the physician believed were medically unnecessary and that they would be more likely to comply with VIP patient’s requests for tests or treatments they felt were unnecessary. More than one-third (36%) felt pressured by other hospital employees or representatives to comply with VIP services patient’s requests for additional tests or treatments that the physicians believed were medically unnecessary.

In our study, a majority of physicians who reported the presence of VIP services at their hospital felt pressured by VIP patients or their family members to perform unnecessary testing or treatment. While this study was not designed to quantify the burden of unnecessary care for VIP patients, our results have implications for individual patients and public health, including potential effects on resource availability, the identification of clinically irrelevant incidental findings, and short- and long-term medical complications of procedures, testing and radiation exposure.

Prior publications have advocated that physicians and hospitals should not allow VIP status to influence management decisions.^3,5 We found that more than one-third of physicians who reported the presence of VIP services at their hospital also reported receiving pressure from hospital representatives to provide care to VIP patients that was not medically indicated. These findings highlight an example of the tension faced by physicians who are caught between patient requests and the delivery of value-based care. This potential conflict may be amplified particularly for those patients with close financial, social, or professional ties to the hospitals (and physicians) providing their care. These results suggest the need for physicians, administrators, and patients to work together to address the potential blurring of ethical boundaries created by VIP relationships. Prevention of harm and avoidance of placing physicians in morally distressing situations are common goals for all involved parties.

Efforts to reduce unnecessary care have predominantly focused on structural and knowledge-based drivers.^4,8,9 Our results highlight the presence of additional forces. A majority of physician respondents who reported the presence of VIP services at their hospital also reported that they would be more likely to comply with requests for unnecessary care for a VIP patient as compared to a non-VIP patient. Furthermore, in case-based questions about the requests of a VIP patient and their family for additional unnecessary care, a significant portion of physicians who reported they would comply with these requests listed the VIP status of the patient or family as a factor underlying this decision. Only a minority of physicians reported their decision to provide additional care was the result of their own medically-based concerns. Because these cases were hypothetical and we did not include comparator cases involving non-VIP patients, it remains uncertain whether the observed perceptions accurately reflect real-world differences in the care of VIP and non-VIP patients. Nonetheless, our findings emphasize the importance of better understanding the social drivers of overuse and physician communication strategies related to medically inappropriate tests.^10,11

Demand for unnecessary testing may be driven by the mentality that “more is better.”¹² Contrary to this belief, provision of unnecessary care can increase the risk of patient harm.¹³ Despite physician respondents reporting that VIP patients requested and/or received additional unnecessary care, a majority of respondents felt that patient safety for VIP patients was equivalent to that for non-VIP patients. As we assessed only physician perceptions of safety, which may not necessarily correlate with actual safety, further research in this area is needed.

Our study was limited by several factors. While our study population included hospitalists from 8 geographically broad hospitals, including university, safety net, and community hospitals, study responses may not be reflective of nationwide trends. Our response rate may limit our ability to generalize conclusions beyond respondents. Second, our study captured physician perceptions of behavior and safety rather than actually measuring practice and outcomes. Studies comparing physician practice patterns and outcomes between VIP and non-VIP patients would be informative. Additionally, despite our inclusive survey design process, our survey was not validated, and it is possible that our questions were not interpreted as intended. Lastly, despite the anonymous nature of our survey, physicians may have felt compelled to respond in a particular way due to conflicting professional, financial, or social factors.

Our findings provide initial insight into how care for the VIP patient may present unique challenges for physicians, hospitals, and society by systematizing care inequities, as well as potentially incentivizing low-value care practices. Whether these imbalances produce clinical harms or benefits remains worthy of future studies.

Disclosure

Nothing to report.

Recent publications in the medical literature and lay press have stirred controversy regarding the use of inpatient ‘very important person’ (VIP) services.^1-3 The term “VIP services” often refers to select conveniences offered in addition to the assumed basic level of care and services provided by a hospital. Examples include additional space, enhanced facilities, specific comforts, or personal support. In some instances, these amenities may only be provided to patients who have close financial, social, or professional relationships with the hospital.

How VIP patients interact with their health system to obtain VIP services has raised unique concerns. Some have speculated that the presence of a VIP patient may be disruptive to the care of non-VIP patients, while others have cautioned physicians about potential dangers to the VIP patients themselves.^4-6 Despite much being written on the topics of VIP patients and services in both the lay and academic press, our literature review identified only 1 study on the topic, which cataloged the preferential treatment of VIP patients in the emergency department.⁶ We are unaware of any investigations of VIP-service use in the inpatient setting. Through a multisite survey of hospital medicine physicians, we assessed physician viewpoints and behavior regarding VIP services.

The Hospital Medicine Reengineering Network (HOMERuN) is a nation-wide learning organization focused on measuring and improving the outcomes of hospitalized patients.⁷ We surveyed hospitalists from 8 HOMERuN hospitals (Appendix 1). The survey instrument contained 4 sections: nonidentifying respondent demographics, local use of VIP services, reported physician perceptions of VIP services, and case-based assessments (Appendix 2). Survey questions and individual cases were developed by study authors and based on real scenarios and concerns provided by front-line clinical providers. Content, length, and reliability of physician understanding were assessed by a 5-person focus group consisting of physicians not included in the survey population.

Subjects were identified via administrative rosters from each HOMERuN site. Surveys were administered via SurveyMonkey, and results were analyzed descriptively. Populations were compared via the Fisher exact test. “VIP services” were defined as conveniences provided in addition to the assumed basic level of care and services (eg, private or luxury-style rooms, access to a special menu, better views, dedicated personal care attendants, hospital liaisons). VIP patients were defined as those patients receiving VIP services. A hospital was identified as providing VIP services if 50% or more of respondents from that site reported the presence of VIP services.

Of 366 hospitalists contacted, 160 completed the survey (44%). Respondent characteristics and reported prevalence of VIP services are demonstrated in Table 1. In total, 78 respondents (45%) reported the presence of VIP services at their hospital. Of the 8 sites surveyed, a majority of physicians at 4 sites (50%) reported presence of VIP services.

Of respondents reporting the presence of VIP services at their hospital, a majority felt that, from a patient safety perspective, the care received by VIP patients was the same as care received by non-VIP patients (Table 2). A majority reported they had felt pressured by a VIP patient or a family member to order additional tests or treatments that the physician believed were medically unnecessary and that they would be more likely to comply with VIP patient’s requests for tests or treatments they felt were unnecessary. More than one-third (36%) felt pressured by other hospital employees or representatives to comply with VIP services patient’s requests for additional tests or treatments that the physicians believed were medically unnecessary.

In our study, a majority of physicians who reported the presence of VIP services at their hospital felt pressured by VIP patients or their family members to perform unnecessary testing or treatment. While this study was not designed to quantify the burden of unnecessary care for VIP patients, our results have implications for individual patients and public health, including potential effects on resource availability, the identification of clinically irrelevant incidental findings, and short- and long-term medical complications of procedures, testing and radiation exposure.

Prior publications have advocated that physicians and hospitals should not allow VIP status to influence management decisions.^3,5 We found that more than one-third of physicians who reported the presence of VIP services at their hospital also reported receiving pressure from hospital representatives to provide care to VIP patients that was not medically indicated. These findings highlight an example of the tension faced by physicians who are caught between patient requests and the delivery of value-based care. This potential conflict may be amplified particularly for those patients with close financial, social, or professional ties to the hospitals (and physicians) providing their care. These results suggest the need for physicians, administrators, and patients to work together to address the potential blurring of ethical boundaries created by VIP relationships. Prevention of harm and avoidance of placing physicians in morally distressing situations are common goals for all involved parties.

Efforts to reduce unnecessary care have predominantly focused on structural and knowledge-based drivers.^4,8,9 Our results highlight the presence of additional forces. A majority of physician respondents who reported the presence of VIP services at their hospital also reported that they would be more likely to comply with requests for unnecessary care for a VIP patient as compared to a non-VIP patient. Furthermore, in case-based questions about the requests of a VIP patient and their family for additional unnecessary care, a significant portion of physicians who reported they would comply with these requests listed the VIP status of the patient or family as a factor underlying this decision. Only a minority of physicians reported their decision to provide additional care was the result of their own medically-based concerns. Because these cases were hypothetical and we did not include comparator cases involving non-VIP patients, it remains uncertain whether the observed perceptions accurately reflect real-world differences in the care of VIP and non-VIP patients. Nonetheless, our findings emphasize the importance of better understanding the social drivers of overuse and physician communication strategies related to medically inappropriate tests.^10,11

Demand for unnecessary testing may be driven by the mentality that “more is better.”¹² Contrary to this belief, provision of unnecessary care can increase the risk of patient harm.¹³ Despite physician respondents reporting that VIP patients requested and/or received additional unnecessary care, a majority of respondents felt that patient safety for VIP patients was equivalent to that for non-VIP patients. As we assessed only physician perceptions of safety, which may not necessarily correlate with actual safety, further research in this area is needed.

Our study was limited by several factors. While our study population included hospitalists from 8 geographically broad hospitals, including university, safety net, and community hospitals, study responses may not be reflective of nationwide trends. Our response rate may limit our ability to generalize conclusions beyond respondents. Second, our study captured physician perceptions of behavior and safety rather than actually measuring practice and outcomes. Studies comparing physician practice patterns and outcomes between VIP and non-VIP patients would be informative. Additionally, despite our inclusive survey design process, our survey was not validated, and it is possible that our questions were not interpreted as intended. Lastly, despite the anonymous nature of our survey, physicians may have felt compelled to respond in a particular way due to conflicting professional, financial, or social factors.

Our findings provide initial insight into how care for the VIP patient may present unique challenges for physicians, hospitals, and society by systematizing care inequities, as well as potentially incentivizing low-value care practices. Whether these imbalances produce clinical harms or benefits remains worthy of future studies.

Disclosure

Nothing to report.

The “Things We Do for No Reason” series reviews practices which have become common parts of hospital care but which may provide little value to our patients. Practices reviewed in the TWDFNR series do not represent “black and white” conclusions or clinical practice standards, but are meant as a starting place for research and active discussions among hospitalists and patients. We invite you to be part of that discussion. https://www.choosingwisely.org/

CASE REPORT

A 68-year-old woman with ischemic cardiomyopathy was admitted with abdominal cramping, diarrhea, and nausea, which had left her unable to keep food and liquids down for 2 days. She had been taking diuretics and had a remote history of intravenous drug use. On admission, she was afebrile and had blood pressure of 100/60 mm Hg and a heart rate of 100 bpm. Her extremities were cool and clammy. Blood test results showed an alanine aminotransferase (ALT) level of 1510 IU/L and an aspartate aminotransferase (AST) level of 1643 IU/L. The patient’s clinician did not know her baseline ALT and AST levels and thought the best approach was to identify the cause of the transaminase elevation.

Severe acute liver injury (liver enzymes, >10 × upper limit of normal [ULN], usually 40 IU/L) is a common presentation among hospitalized patients. Between 1997 and 2015, 1.5% of patients admitted to our hospital had severe liver injury. In another large cohort of hospitalized patients,¹ 0.6% had an ALT level higher than 1000 IU/L (~20 × ULN). A precise diagnosis is often needed to direct appropriate therapy, and serologic tests are available for many conditions, both common and rare (Table). Given the relative ease of bundled blood testing, nondirected testing has emerged as a popular, if reflexive, strategy.^2-5 In this approach, clinicians evaluate each patient for the set of testable diseases all at once—in contrast to taking a directed, stepwise testing approach guided by the patient’s history.

Use of nondirected testing is common in patients with severe acute liver injury. Of the 5795 such patients treated at our hospital between 2000 and 2015, within the same day of service 53% were tested for hepatitis C virus antibody, 38% for hemochromatosis (ferritin test), 28% for autoimmune hepatitis (antinuclear antibody test), and 15% for primary biliary cholangitis (antimitochondrial antibody test) by our clinical laboratory. Of the 5023 patients who had send-out tests performed for Wilson disease (ceruloplasmin), 81% were queried for hepatitis B virus infection, 76% for hepatitis C virus infection, 75% for autoimmune hepatitis, and 73.1% for hemochromatosis.² Similar trends were found for patients with severe liver injury tested for α₁-antitrypsin (AAT) deficiency.³ In sum, these data showed that each patient with severe liver injury was tested out of concern about diseases with markedly different epidemiology and clinical presentations (Table).

WHY YOU MIGHT THINK NONDIRECTED TESTING IS HELPFUL

Use of nondirected testing may reflect perceived urgency, convenience, and thoroughness.^2-6 Alternatively, it may simply involve following a consultant’s recommendations.⁴ As severe acute liver injury is often associated with tremendous morbidity, clinicians seeking answers may perceive directed, stepwise testing as inappropriately slow given the urgency of the presentation; they may think that nondirected testing can reduce hospital length of stay.

WHY NONDIRECTED TESTING IS NOT HELPFUL

Nondirected testing is a problem for at least 4 reasons: limited benefit of reflexive testing for rare diseases, no meaningful impact on outcomes, false positives, and financial cost.

First, immediately testing for rare causes of liver disease is unlikely to benefit patients with severe liver injury. The underlying etiologies of severe liver injury are relatively well circumscribed (Table). Overall, 42% of patients with severe liver injury and 57% of those with an ALT level higher than 1000 IU/L have ischemic hepatitis.⁷ Accounting for a significant percentage of severe liver injury cases are acute biliary obstruction (24%), drug-induced injury (10%-13%), and viral hepatitis (4%-7%).^1,8 Of the small subset of patients with severe liver injury that progresses to acute liver failure (ALF; encephalopathy, coagulopathy), 0.5% have autoimmune hepatitis and 0.1% have Wilson disease.⁹ Furthermore, many patients are tested for AAT deficiency, hemochromatosis, and primary biliary cholangitis, but these are never causes of severe acute liver injury (Table).

Second, diagnosing a rarer cause of acute liver injury modestly earlier has no meaningful impact on outcome. Work-up for more common etiologies can usually be completed within 2 or 3 days. This is true even for patients with ALF. Specific therapies generally are lacking for ALF, save for use of N-acetylcysteine for acetaminophen overdose and antiviral therapy for hepatitis B virus infection.^9,10 Furthermore, although effective therapies are available for both autoimmune hepatitis and Wilson disease, the potential benefit stems from altering the longer term course of disease. Initial management, even for these rare conditions, is no different from that for other etiologies. Conversely, acute liver injury caused by ischemic hepatitis, biliary disease, or drug-induced liver injury requires swift corrective action. Even if normotensive, patients with ischemic hepatitis are often in cardiogenic shock and benefit from careful monitoring and critical care.⁷ Patients with acute biliary obstruction may need therapeutic endoscopy. Last, patients with drug-induced liver injury benefit from immediate discontinuation of the offending drug.

Third, in the testing of patients with low pretest probabilities, false positives are common. For example, at our institution and at an institution in Austria, severe liver injury patients with a low ceruloplasmin level have a 95.1% to 98.1% chance of a false-positive result (they have a low ceruloplasmin level but do not have Wilson disease).^3,4 Furthermore, 91% of positive tests are never confirmed,³ indicating either that clinicians never valued the initial test or that other diagnoses were much more likely. Even worse, as was the case in 65% of patients with low AAT levels,^2,3 genetic diagnoses were based on unconfirmed, potentially false-positive serologic tests.

Fourth, although the financial cost for each individual test is small, at the population level the cost of nondirected testing is significant. For example, although each reflects testing for conditions that do not cause acute liver injury, the costs of ferritin, AAT, and antimitochondrial antibody tests are $13, $16, and $37, respectively (Medicare/Medicaid reimbursements in 2016 $US).¹¹ About 1.5% of admitted patients are found to have severe liver injury. If this proportion holds true for the roughly 40 million discharges from US hospitals each year, then there would be an annual cost of about $40 million if all 3 tests were performed for each patient with severe liver injury. In addition, although nondirected testing may seem clinically expedient, there are no data suggesting it reduces length of stay. In fact, ceruloplasmin, AAT, and many other tests are sent to external laboratories and are unlikely to be returned before discharge. If clinicians delay discharge for results, then nondirected testing would increase rather than decrease length of stay.

WHAT YOU SHOULD DO INSTEAD

In this era of increasing cost-consciousness, nondirected testing has escaped relatively unscathed. Indeed, nondirected testing is prevalent, yet has pitfalls similar to those of serologic testing (eg, vasculitis or arthritis,⁶ acute renal injury, infectious disease¹²). The alternative is deliberate, empirical, patient-centered testing that is attentive to the patient’s presentation and the harms of false positives. The idea is to select tests for each patient with acute liver injury according to presentation and the most likely corresponding diagnoses (Table, Figure).

• For each patient with severe acute liver injury, select tests on the basis of the presentation (Figure). Testing for rare diseases should be performed only after common diseases have been excluded.
• Avoid testing for hemochromatosis (iron indices, genetic tests), AAT deficiency (AAT levels or phenotypes), and primary biliary cholangitis (antimitochondrial antibodies) in patients with severe acute liver injury.
• Consider implementing decision supports that can curb nondirected testing in areas in which it is common.

Nondirected testing is associated with false positives and increased costs in the evaluation and management of severe acute liver injury. The alternative is deliberate, epidemiologically and clinically driven directed testing. Electronic ordering system decision supports can be useful in curtailing nondirected testing.

Disclosure

Nothing to report.

Do you think this is a low-value practice? Is this truly a “Thing We Do for No Reason”? Let us know what you do in your practice and propose ideas for other “Things We Do for No Reason” topics. Please join in the conversation online at Twitter (#TWDFNR)/Facebook and don’t forget to “Like It” on Facebook or retweet it on Twitter.

The “Things We Do for No Reason” series reviews practices which have become common parts of hospital care but which may provide little value to our patients. Practices reviewed in the TWDFNR series do not represent “black and white” conclusions or clinical practice standards, but are meant as a starting place for research and active discussions among hospitalists and patients. We invite you to be part of that discussion. https://www.choosingwisely.org/

CASE REPORT

A 68-year-old woman with ischemic cardiomyopathy was admitted with abdominal cramping, diarrhea, and nausea, which had left her unable to keep food and liquids down for 2 days. She had been taking diuretics and had a remote history of intravenous drug use. On admission, she was afebrile and had blood pressure of 100/60 mm Hg and a heart rate of 100 bpm. Her extremities were cool and clammy. Blood test results showed an alanine aminotransferase (ALT) level of 1510 IU/L and an aspartate aminotransferase (AST) level of 1643 IU/L. The patient’s clinician did not know her baseline ALT and AST levels and thought the best approach was to identify the cause of the transaminase elevation.

Severe acute liver injury (liver enzymes, >10 × upper limit of normal [ULN], usually 40 IU/L) is a common presentation among hospitalized patients. Between 1997 and 2015, 1.5% of patients admitted to our hospital had severe liver injury. In another large cohort of hospitalized patients,¹ 0.6% had an ALT level higher than 1000 IU/L (~20 × ULN). A precise diagnosis is often needed to direct appropriate therapy, and serologic tests are available for many conditions, both common and rare (Table). Given the relative ease of bundled blood testing, nondirected testing has emerged as a popular, if reflexive, strategy.^2-5 In this approach, clinicians evaluate each patient for the set of testable diseases all at once—in contrast to taking a directed, stepwise testing approach guided by the patient’s history.

Use of nondirected testing is common in patients with severe acute liver injury. Of the 5795 such patients treated at our hospital between 2000 and 2015, within the same day of service 53% were tested for hepatitis C virus antibody, 38% for hemochromatosis (ferritin test), 28% for autoimmune hepatitis (antinuclear antibody test), and 15% for primary biliary cholangitis (antimitochondrial antibody test) by our clinical laboratory. Of the 5023 patients who had send-out tests performed for Wilson disease (ceruloplasmin), 81% were queried for hepatitis B virus infection, 76% for hepatitis C virus infection, 75% for autoimmune hepatitis, and 73.1% for hemochromatosis.² Similar trends were found for patients with severe liver injury tested for α₁-antitrypsin (AAT) deficiency.³ In sum, these data showed that each patient with severe liver injury was tested out of concern about diseases with markedly different epidemiology and clinical presentations (Table).

WHY YOU MIGHT THINK NONDIRECTED TESTING IS HELPFUL

Use of nondirected testing may reflect perceived urgency, convenience, and thoroughness.^2-6 Alternatively, it may simply involve following a consultant’s recommendations.⁴ As severe acute liver injury is often associated with tremendous morbidity, clinicians seeking answers may perceive directed, stepwise testing as inappropriately slow given the urgency of the presentation; they may think that nondirected testing can reduce hospital length of stay.

WHY NONDIRECTED TESTING IS NOT HELPFUL

Nondirected testing is a problem for at least 4 reasons: limited benefit of reflexive testing for rare diseases, no meaningful impact on outcomes, false positives, and financial cost.

First, immediately testing for rare causes of liver disease is unlikely to benefit patients with severe liver injury. The underlying etiologies of severe liver injury are relatively well circumscribed (Table). Overall, 42% of patients with severe liver injury and 57% of those with an ALT level higher than 1000 IU/L have ischemic hepatitis.⁷ Accounting for a significant percentage of severe liver injury cases are acute biliary obstruction (24%), drug-induced injury (10%-13%), and viral hepatitis (4%-7%).^1,8 Of the small subset of patients with severe liver injury that progresses to acute liver failure (ALF; encephalopathy, coagulopathy), 0.5% have autoimmune hepatitis and 0.1% have Wilson disease.⁹ Furthermore, many patients are tested for AAT deficiency, hemochromatosis, and primary biliary cholangitis, but these are never causes of severe acute liver injury (Table).

Second, diagnosing a rarer cause of acute liver injury modestly earlier has no meaningful impact on outcome. Work-up for more common etiologies can usually be completed within 2 or 3 days. This is true even for patients with ALF. Specific therapies generally are lacking for ALF, save for use of N-acetylcysteine for acetaminophen overdose and antiviral therapy for hepatitis B virus infection.^9,10 Furthermore, although effective therapies are available for both autoimmune hepatitis and Wilson disease, the potential benefit stems from altering the longer term course of disease. Initial management, even for these rare conditions, is no different from that for other etiologies. Conversely, acute liver injury caused by ischemic hepatitis, biliary disease, or drug-induced liver injury requires swift corrective action. Even if normotensive, patients with ischemic hepatitis are often in cardiogenic shock and benefit from careful monitoring and critical care.⁷ Patients with acute biliary obstruction may need therapeutic endoscopy. Last, patients with drug-induced liver injury benefit from immediate discontinuation of the offending drug.

Third, in the testing of patients with low pretest probabilities, false positives are common. For example, at our institution and at an institution in Austria, severe liver injury patients with a low ceruloplasmin level have a 95.1% to 98.1% chance of a false-positive result (they have a low ceruloplasmin level but do not have Wilson disease).^3,4 Furthermore, 91% of positive tests are never confirmed,³ indicating either that clinicians never valued the initial test or that other diagnoses were much more likely. Even worse, as was the case in 65% of patients with low AAT levels,^2,3 genetic diagnoses were based on unconfirmed, potentially false-positive serologic tests.

Fourth, although the financial cost for each individual test is small, at the population level the cost of nondirected testing is significant. For example, although each reflects testing for conditions that do not cause acute liver injury, the costs of ferritin, AAT, and antimitochondrial antibody tests are $13, $16, and $37, respectively (Medicare/Medicaid reimbursements in 2016 $US).¹¹ About 1.5% of admitted patients are found to have severe liver injury. If this proportion holds true for the roughly 40 million discharges from US hospitals each year, then there would be an annual cost of about $40 million if all 3 tests were performed for each patient with severe liver injury. In addition, although nondirected testing may seem clinically expedient, there are no data suggesting it reduces length of stay. In fact, ceruloplasmin, AAT, and many other tests are sent to external laboratories and are unlikely to be returned before discharge. If clinicians delay discharge for results, then nondirected testing would increase rather than decrease length of stay.

WHAT YOU SHOULD DO INSTEAD

In this era of increasing cost-consciousness, nondirected testing has escaped relatively unscathed. Indeed, nondirected testing is prevalent, yet has pitfalls similar to those of serologic testing (eg, vasculitis or arthritis,⁶ acute renal injury, infectious disease¹²). The alternative is deliberate, empirical, patient-centered testing that is attentive to the patient’s presentation and the harms of false positives. The idea is to select tests for each patient with acute liver injury according to presentation and the most likely corresponding diagnoses (Table, Figure).

• For each patient with severe acute liver injury, select tests on the basis of the presentation (Figure). Testing for rare diseases should be performed only after common diseases have been excluded.
• Avoid testing for hemochromatosis (iron indices, genetic tests), AAT deficiency (AAT levels or phenotypes), and primary biliary cholangitis (antimitochondrial antibodies) in patients with severe acute liver injury.
• Consider implementing decision supports that can curb nondirected testing in areas in which it is common.

Nondirected testing is associated with false positives and increased costs in the evaluation and management of severe acute liver injury. The alternative is deliberate, epidemiologically and clinically driven directed testing. Electronic ordering system decision supports can be useful in curtailing nondirected testing.

Disclosure

Nothing to report.

Do you think this is a low-value practice? Is this truly a “Thing We Do for No Reason”? Let us know what you do in your practice and propose ideas for other “Things We Do for No Reason” topics. Please join in the conversation online at Twitter (#TWDFNR)/Facebook and don’t forget to “Like It” on Facebook or retweet it on Twitter.

The “Things We Do for No Reason” series reviews practices which have become common parts of hospital care but which may provide little value to our patients. Practices reviewed in the TWDFNR series do not represent “black and white” conclusions or clinical practice standards, but are meant as a starting place for research and active discussions among hospitalists and patients. We invite you to be part of that discussion. https://www.choosingwisely.org/

CASE REPORT

A 68-year-old woman with ischemic cardiomyopathy was admitted with abdominal cramping, diarrhea, and nausea, which had left her unable to keep food and liquids down for 2 days. She had been taking diuretics and had a remote history of intravenous drug use. On admission, she was afebrile and had blood pressure of 100/60 mm Hg and a heart rate of 100 bpm. Her extremities were cool and clammy. Blood test results showed an alanine aminotransferase (ALT) level of 1510 IU/L and an aspartate aminotransferase (AST) level of 1643 IU/L. The patient’s clinician did not know her baseline ALT and AST levels and thought the best approach was to identify the cause of the transaminase elevation.

Severe acute liver injury (liver enzymes, >10 × upper limit of normal [ULN], usually 40 IU/L) is a common presentation among hospitalized patients. Between 1997 and 2015, 1.5% of patients admitted to our hospital had severe liver injury. In another large cohort of hospitalized patients,¹ 0.6% had an ALT level higher than 1000 IU/L (~20 × ULN). A precise diagnosis is often needed to direct appropriate therapy, and serologic tests are available for many conditions, both common and rare (Table). Given the relative ease of bundled blood testing, nondirected testing has emerged as a popular, if reflexive, strategy.^2-5 In this approach, clinicians evaluate each patient for the set of testable diseases all at once—in contrast to taking a directed, stepwise testing approach guided by the patient’s history.

Use of nondirected testing is common in patients with severe acute liver injury. Of the 5795 such patients treated at our hospital between 2000 and 2015, within the same day of service 53% were tested for hepatitis C virus antibody, 38% for hemochromatosis (ferritin test), 28% for autoimmune hepatitis (antinuclear antibody test), and 15% for primary biliary cholangitis (antimitochondrial antibody test) by our clinical laboratory. Of the 5023 patients who had send-out tests performed for Wilson disease (ceruloplasmin), 81% were queried for hepatitis B virus infection, 76% for hepatitis C virus infection, 75% for autoimmune hepatitis, and 73.1% for hemochromatosis.² Similar trends were found for patients with severe liver injury tested for α₁-antitrypsin (AAT) deficiency.³ In sum, these data showed that each patient with severe liver injury was tested out of concern about diseases with markedly different epidemiology and clinical presentations (Table).

WHY YOU MIGHT THINK NONDIRECTED TESTING IS HELPFUL

Use of nondirected testing may reflect perceived urgency, convenience, and thoroughness.^2-6 Alternatively, it may simply involve following a consultant’s recommendations.⁴ As severe acute liver injury is often associated with tremendous morbidity, clinicians seeking answers may perceive directed, stepwise testing as inappropriately slow given the urgency of the presentation; they may think that nondirected testing can reduce hospital length of stay.

WHY NONDIRECTED TESTING IS NOT HELPFUL

Nondirected testing is a problem for at least 4 reasons: limited benefit of reflexive testing for rare diseases, no meaningful impact on outcomes, false positives, and financial cost.

First, immediately testing for rare causes of liver disease is unlikely to benefit patients with severe liver injury. The underlying etiologies of severe liver injury are relatively well circumscribed (Table). Overall, 42% of patients with severe liver injury and 57% of those with an ALT level higher than 1000 IU/L have ischemic hepatitis.⁷ Accounting for a significant percentage of severe liver injury cases are acute biliary obstruction (24%), drug-induced injury (10%-13%), and viral hepatitis (4%-7%).^1,8 Of the small subset of patients with severe liver injury that progresses to acute liver failure (ALF; encephalopathy, coagulopathy), 0.5% have autoimmune hepatitis and 0.1% have Wilson disease.⁹ Furthermore, many patients are tested for AAT deficiency, hemochromatosis, and primary biliary cholangitis, but these are never causes of severe acute liver injury (Table).

Second, diagnosing a rarer cause of acute liver injury modestly earlier has no meaningful impact on outcome. Work-up for more common etiologies can usually be completed within 2 or 3 days. This is true even for patients with ALF. Specific therapies generally are lacking for ALF, save for use of N-acetylcysteine for acetaminophen overdose and antiviral therapy for hepatitis B virus infection.^9,10 Furthermore, although effective therapies are available for both autoimmune hepatitis and Wilson disease, the potential benefit stems from altering the longer term course of disease. Initial management, even for these rare conditions, is no different from that for other etiologies. Conversely, acute liver injury caused by ischemic hepatitis, biliary disease, or drug-induced liver injury requires swift corrective action. Even if normotensive, patients with ischemic hepatitis are often in cardiogenic shock and benefit from careful monitoring and critical care.⁷ Patients with acute biliary obstruction may need therapeutic endoscopy. Last, patients with drug-induced liver injury benefit from immediate discontinuation of the offending drug.

Third, in the testing of patients with low pretest probabilities, false positives are common. For example, at our institution and at an institution in Austria, severe liver injury patients with a low ceruloplasmin level have a 95.1% to 98.1% chance of a false-positive result (they have a low ceruloplasmin level but do not have Wilson disease).^3,4 Furthermore, 91% of positive tests are never confirmed,³ indicating either that clinicians never valued the initial test or that other diagnoses were much more likely. Even worse, as was the case in 65% of patients with low AAT levels,^2,3 genetic diagnoses were based on unconfirmed, potentially false-positive serologic tests.

Fourth, although the financial cost for each individual test is small, at the population level the cost of nondirected testing is significant. For example, although each reflects testing for conditions that do not cause acute liver injury, the costs of ferritin, AAT, and antimitochondrial antibody tests are $13, $16, and $37, respectively (Medicare/Medicaid reimbursements in 2016 $US).¹¹ About 1.5% of admitted patients are found to have severe liver injury. If this proportion holds true for the roughly 40 million discharges from US hospitals each year, then there would be an annual cost of about $40 million if all 3 tests were performed for each patient with severe liver injury. In addition, although nondirected testing may seem clinically expedient, there are no data suggesting it reduces length of stay. In fact, ceruloplasmin, AAT, and many other tests are sent to external laboratories and are unlikely to be returned before discharge. If clinicians delay discharge for results, then nondirected testing would increase rather than decrease length of stay.

WHAT YOU SHOULD DO INSTEAD

In this era of increasing cost-consciousness, nondirected testing has escaped relatively unscathed. Indeed, nondirected testing is prevalent, yet has pitfalls similar to those of serologic testing (eg, vasculitis or arthritis,⁶ acute renal injury, infectious disease¹²). The alternative is deliberate, empirical, patient-centered testing that is attentive to the patient’s presentation and the harms of false positives. The idea is to select tests for each patient with acute liver injury according to presentation and the most likely corresponding diagnoses (Table, Figure).

• For each patient with severe acute liver injury, select tests on the basis of the presentation (Figure). Testing for rare diseases should be performed only after common diseases have been excluded.
• Avoid testing for hemochromatosis (iron indices, genetic tests), AAT deficiency (AAT levels or phenotypes), and primary biliary cholangitis (antimitochondrial antibodies) in patients with severe acute liver injury.
• Consider implementing decision supports that can curb nondirected testing in areas in which it is common.

Nondirected testing is associated with false positives and increased costs in the evaluation and management of severe acute liver injury. The alternative is deliberate, epidemiologically and clinically driven directed testing. Electronic ordering system decision supports can be useful in curtailing nondirected testing.

Disclosure

Nothing to report.

Do you think this is a low-value practice? Is this truly a “Thing We Do for No Reason”? Let us know what you do in your practice and propose ideas for other “Things We Do for No Reason” topics. Please join in the conversation online at Twitter (#TWDFNR)/Facebook and don’t forget to “Like It” on Facebook or retweet it on Twitter.