Alpesh N. Amin, MD, MBA

Long‐term central venous catheters (CVCs) facilitate care for patients with chronic illness by providing easy venous access for laboratory tests, administration of medication, and parenteral nutrition. However, several complications resulting from the use of CVCs, including sepsis, extravasation of infusions, and venous thrombosis, can increase associated morbidity and mortality. These complications can also interrupt and delay treatment for the underlying disease and thereby affect outcomes. One of the most common CVC complications is catheter occlusion.[1]

Catheter occlusion occurs in 14% to 36% of patients within 1 to 2 years of catheter placement.[2, 3, 4, 5, 6, 7, 8] A catheter occlusion can be partial or complete, and can occur secondary to a variety of mechanical problems, including an uncommon, but potentially life‐threatening, pinch‐off syndrome. Medication or parenteral nutrition can also cause occlusion, which can be acute or gradual, with increasingly sluggish flow through the catheter. Inappropriate concentrations or incompatible mixtures can cause medications to precipitate within the catheter lumen.

Occlusions are either thrombotic or nonthrombotic. One autopsy study of patients with a long‐term CVC found that a fibrin sheath encased the catheter tip in every case.[9] An occluded catheter may compromise patient care[9, 10]; it may cause cancellation or delay of procedures, it potentially interrupts administration of critical therapies including vesicants, it may result in risk of infection, and it potentially leads to catheter replacement. This can further complicate care, leading to increased length of stay (LOS) and hospital costs.

To better understand resource utilization, LOS, and cost implications of alteplase compared with catheter replacement, we conducted a preplanned, retrospective analysis of hospitalized patients captured between January 2006 and December 2011 in the database maintained by Premier. The Premier database is a large, US hospital‐based, service‐level, all‐payer, comparative database, with information collected primarily from nearly 600 geographically diverse, nonprofit, nongovernment community and teaching hospitals.

METHODS

RESULTS

This study included 34,579 patients who first had a CVC insertion and then were treated for a CVC occlusion by receiving a replacement CVC (n=1028) or by receiving alteplase (2 mg) administration (n=33,551) during the same hospitalization (Table 1). Patients who received alteplase tended to be younger (6019 vs 6220 years old). More than 50% were at least 65 years of age. Twelve percent of alteplase patients were black, whereas 18.5% of catheter‐replacement patients were black.

Alteplase patients were significantly more likely to have a diagnosis of chronic pulmonary disease, liver disease, renal disease, chronic diabetes (ie, diabetes with complications), and cancer. There was an equivalent number of urban and rural hospitals across the 2 groups of patients (Table 2); however, there were regional differences including a higher proportion of catheter‐replacement patients from the East North Central and Middle Atlantic areas and a lower proportion of catheter‐replacement patients from Mountain and Pacific states. Catheter‐replacement patients more frequently were treated in teaching hospitals and in hospitals of larger size.

After covariate adjustment for baseline measurements significantly related to each outcome, average daily post occlusion costs were estimated to be $317 lower for alteplase recipients than for patients who received catheter replacement ($317; 95% confidence interval [CI]: $238‐$392; P<0.0001) (Table 3). Average adjusted total post occlusion costs were $1419 lower for alteplase recipients than for patients who received catheter replacement ($1418; 95% CI: $307‐$2458; P=0.012).

Contributing to the lower cost were certain revenue‐center specific costs (Table 4). Total room and board costs were different between the alteplase and catheter‐replacement groups in both the pre‐ and postocclusion periods; this was related to the difference between the 2 comparison groups in postocclusion LOS of about 0.3 days (Table 5). However, the differences favored alteplase use over catheter replacement. Cardiology/electrocardiography costs were lower for catheter replacement in the preocclusion period but lower for alteplase use in the postocclusion period. Emergency department costs were higher for catheter replacement in both periods, as were respiratory costs in the same manner. Additionally, costs for laboratory tests, nursing, operating room/surgery, pharmacy, radiology, supplies, and ICU room and board were lower in the preocclusion period but higher in the postocclusion period for catheter‐replacement patients. It was unclear why the pharmacy costs after catheter replacement would have increased for catheter‐replacement patients in contrast to the decrease for alteplase‐treated patients, but because this occurred at an average daily basis as well, it appeared that catheter‐replacement patients may have received additional medications. Average adjusted postocclusion LOS was similar for alteplase and catheter‐replacement recipients (P=0.24), suggesting that decreased total costs were due to reasons other than shorter LOS.

Unadjusted 30‐ and 90‐day readmission rates were 24.6% and 35.1% for CVC replacement and slightly lower at 23.7% and 33.9% for alteplase (Table 3), respectively. Odds of readmission after adjusting for patient and hospital factors were not significantly different at 30 days (odds ratio [OR]: 1.048, 95% CI: 0.899‐1.221; P=0.55) or at 90 days (OR: 1.051, 95% CI: 0.915‐1.207; P=0.48) (Table 5). Subgroup analyses for patients with a diagnosis of heart failure, myocardial infarction, and cancer revealed similar results.

DISCUSSION

The cost of healthcare in the United States has risen at an outstanding rate compared with other countries. Our percentage of gross national product spent on healthcare is on the order of 16% to 18%, almost twice as much as the next most industrialized country in terms of healthcare expenditure.[11] In the current era, finding opportunities to reduce healthcare costs without negatively impacting quality of care is the name of the game. Professional societies have come together under the campaign of Choosing Wisely: An Initiative of the ABIM (American Board of Internal Medicine) Foundation to help educate clinicians and patients on cost‐containment strategies.[12] Research that demonstrates opportunities to reduce cost will help healthcare providers choose wisely among diagnostic and therapeutic options for patients. Our study demonstrated that the use of a drug such as alteplase in clearing CVC catheter obstruction was significantly less costly to the hospital than catheter replacement.

Cathflo Activase (alteplase: Genentech, South San Francisco, CA), the only FDA‐approved thrombolytic for the restoration of central venous catheter function, is the current standard treatment for catheter occlusions in the United States. A dose of 2 mg in 2 mL is instilled in patients weighing 30 kg or 110% of the internal lumen volume of the catheter not to exceed 2 mg in 2 mL for those patients weighing <30 kg. Haire et al. showed that a 2‐mg dose of alteplase was more effective than urokinase (5000 IU) for treating radiographically proven thrombotic occlusion of a CVC after a dwell time of 120 minutes.[13] In the Cardiovascular thrombolytic used to Open Occluded Lines (COOL) trial, one 2‐mg dose of alteplase cleared the catheter occlusion after 120 minutes in 74% of patients, compared with only 17% of patients who received a placebo. Studies have confirmed the safety and efficacy of alteplase administered at various time intervals in different long‐term catheters, including peripherally inserted central catheters, with major hemorrhage reported in 0.3% of patients.[14, 15, 16]

Adding to the knowledge of patient outcomes from clinical studies, many health outcomes studies have demonstrated benefit in cost containment through decreasing LOS, which one can argue is just shifting the cost to an earlier part of the stay. Even though this is highly beneficial, it does not address the core resource utilization within the hospital. Our study found its cost benefit not in the LOS, but in decreasing core resource utilization such as radiology, lab, nursing, and supplies. If patients are admitted for a noncardiovascular condition and have CVC occlusion, using alteplase to clear the CVC occlusion along with implementing strategies to manage the underlying disease to reduce the LOS becomes a powerful opportunity to impact cost. Among patients who may come to the hospital for just the CVC occlusion, the LOS should be short. There may be no significant opportunity to reduce the LOS in those cases, but opportunities to decrease core hospital resource utilization with alteplase make this approach beneficial if the patient can tolerate it.

Limitations of the study include the retrospective and administrative nature of the database used, which is unable to provide certain clinical measures as would be available at the patient's bedside when treatment choices are being made. Had they been available, we might have included them in our assessment of whether patients who underwent CVC replacement were significantly different from those who received alteplase. In addition, not all hospitals in the database had charge masters that facilitated identification of CVC replacements or reinsertions, requiring the use of CPT‐4 codes and evidence of new CVCs being placed or inserted. Certain patients were excluded if there was conflicting information about whether the CVC was new within the hospital stay or dwelling in the patient prior to admission. Also, dialysis patients were excluded because they were not part of any approved indication for alteplase 2 mg, and this group is particularly prone to catheter obstruction. As such, they represent more complicated cases than the norm; this exclusion may have limited the overall generalizability of the study. The study also relied on charge master (billing) data to identify the use of alteplase and other treatments, where there is the potential, albeit minimal, for inaccuracies in the data. Of greater importance, the study relied on ICD‐9 coding to identify comorbid conditions, and as in other studies using similar data sources, such methods are subject to coding errors and omissions. However, many of the listed limitations above were not thought to be different between the comparison groups or more problematic for this study than for other studies based on similar data sources.

CONCLUSION

Among patients treated for an occluded CVC, alteplase‐treated patients had lower daily postocclusion costs and lower total postocclusion costs than patients who received catheter replacement. Differences in costs did not appear to be driven by differences in postocclusion LOS. Readmissions at 30‐ and 90‐day periods were found to be similar between alteplase recipients and catheter‐replacement patients.

Long‐term central venous catheters (CVCs) facilitate care for patients with chronic illness by providing easy venous access for laboratory tests, administration of medication, and parenteral nutrition. However, several complications resulting from the use of CVCs, including sepsis, extravasation of infusions, and venous thrombosis, can increase associated morbidity and mortality. These complications can also interrupt and delay treatment for the underlying disease and thereby affect outcomes. One of the most common CVC complications is catheter occlusion.[1]

Catheter occlusion occurs in 14% to 36% of patients within 1 to 2 years of catheter placement.[2, 3, 4, 5, 6, 7, 8] A catheter occlusion can be partial or complete, and can occur secondary to a variety of mechanical problems, including an uncommon, but potentially life‐threatening, pinch‐off syndrome. Medication or parenteral nutrition can also cause occlusion, which can be acute or gradual, with increasingly sluggish flow through the catheter. Inappropriate concentrations or incompatible mixtures can cause medications to precipitate within the catheter lumen.

Occlusions are either thrombotic or nonthrombotic. One autopsy study of patients with a long‐term CVC found that a fibrin sheath encased the catheter tip in every case.[9] An occluded catheter may compromise patient care[9, 10]; it may cause cancellation or delay of procedures, it potentially interrupts administration of critical therapies including vesicants, it may result in risk of infection, and it potentially leads to catheter replacement. This can further complicate care, leading to increased length of stay (LOS) and hospital costs.

To better understand resource utilization, LOS, and cost implications of alteplase compared with catheter replacement, we conducted a preplanned, retrospective analysis of hospitalized patients captured between January 2006 and December 2011 in the database maintained by Premier. The Premier database is a large, US hospital‐based, service‐level, all‐payer, comparative database, with information collected primarily from nearly 600 geographically diverse, nonprofit, nongovernment community and teaching hospitals.

METHODS

RESULTS

This study included 34,579 patients who first had a CVC insertion and then were treated for a CVC occlusion by receiving a replacement CVC (n=1028) or by receiving alteplase (2 mg) administration (n=33,551) during the same hospitalization (Table 1). Patients who received alteplase tended to be younger (6019 vs 6220 years old). More than 50% were at least 65 years of age. Twelve percent of alteplase patients were black, whereas 18.5% of catheter‐replacement patients were black.

Alteplase patients were significantly more likely to have a diagnosis of chronic pulmonary disease, liver disease, renal disease, chronic diabetes (ie, diabetes with complications), and cancer. There was an equivalent number of urban and rural hospitals across the 2 groups of patients (Table 2); however, there were regional differences including a higher proportion of catheter‐replacement patients from the East North Central and Middle Atlantic areas and a lower proportion of catheter‐replacement patients from Mountain and Pacific states. Catheter‐replacement patients more frequently were treated in teaching hospitals and in hospitals of larger size.

After covariate adjustment for baseline measurements significantly related to each outcome, average daily post occlusion costs were estimated to be $317 lower for alteplase recipients than for patients who received catheter replacement ($317; 95% confidence interval [CI]: $238‐$392; P<0.0001) (Table 3). Average adjusted total post occlusion costs were $1419 lower for alteplase recipients than for patients who received catheter replacement ($1418; 95% CI: $307‐$2458; P=0.012).

Contributing to the lower cost were certain revenue‐center specific costs (Table 4). Total room and board costs were different between the alteplase and catheter‐replacement groups in both the pre‐ and postocclusion periods; this was related to the difference between the 2 comparison groups in postocclusion LOS of about 0.3 days (Table 5). However, the differences favored alteplase use over catheter replacement. Cardiology/electrocardiography costs were lower for catheter replacement in the preocclusion period but lower for alteplase use in the postocclusion period. Emergency department costs were higher for catheter replacement in both periods, as were respiratory costs in the same manner. Additionally, costs for laboratory tests, nursing, operating room/surgery, pharmacy, radiology, supplies, and ICU room and board were lower in the preocclusion period but higher in the postocclusion period for catheter‐replacement patients. It was unclear why the pharmacy costs after catheter replacement would have increased for catheter‐replacement patients in contrast to the decrease for alteplase‐treated patients, but because this occurred at an average daily basis as well, it appeared that catheter‐replacement patients may have received additional medications. Average adjusted postocclusion LOS was similar for alteplase and catheter‐replacement recipients (P=0.24), suggesting that decreased total costs were due to reasons other than shorter LOS.

Unadjusted 30‐ and 90‐day readmission rates were 24.6% and 35.1% for CVC replacement and slightly lower at 23.7% and 33.9% for alteplase (Table 3), respectively. Odds of readmission after adjusting for patient and hospital factors were not significantly different at 30 days (odds ratio [OR]: 1.048, 95% CI: 0.899‐1.221; P=0.55) or at 90 days (OR: 1.051, 95% CI: 0.915‐1.207; P=0.48) (Table 5). Subgroup analyses for patients with a diagnosis of heart failure, myocardial infarction, and cancer revealed similar results.

DISCUSSION

The cost of healthcare in the United States has risen at an outstanding rate compared with other countries. Our percentage of gross national product spent on healthcare is on the order of 16% to 18%, almost twice as much as the next most industrialized country in terms of healthcare expenditure.[11] In the current era, finding opportunities to reduce healthcare costs without negatively impacting quality of care is the name of the game. Professional societies have come together under the campaign of Choosing Wisely: An Initiative of the ABIM (American Board of Internal Medicine) Foundation to help educate clinicians and patients on cost‐containment strategies.[12] Research that demonstrates opportunities to reduce cost will help healthcare providers choose wisely among diagnostic and therapeutic options for patients. Our study demonstrated that the use of a drug such as alteplase in clearing CVC catheter obstruction was significantly less costly to the hospital than catheter replacement.

Cathflo Activase (alteplase: Genentech, South San Francisco, CA), the only FDA‐approved thrombolytic for the restoration of central venous catheter function, is the current standard treatment for catheter occlusions in the United States. A dose of 2 mg in 2 mL is instilled in patients weighing 30 kg or 110% of the internal lumen volume of the catheter not to exceed 2 mg in 2 mL for those patients weighing <30 kg. Haire et al. showed that a 2‐mg dose of alteplase was more effective than urokinase (5000 IU) for treating radiographically proven thrombotic occlusion of a CVC after a dwell time of 120 minutes.[13] In the Cardiovascular thrombolytic used to Open Occluded Lines (COOL) trial, one 2‐mg dose of alteplase cleared the catheter occlusion after 120 minutes in 74% of patients, compared with only 17% of patients who received a placebo. Studies have confirmed the safety and efficacy of alteplase administered at various time intervals in different long‐term catheters, including peripherally inserted central catheters, with major hemorrhage reported in 0.3% of patients.[14, 15, 16]

Adding to the knowledge of patient outcomes from clinical studies, many health outcomes studies have demonstrated benefit in cost containment through decreasing LOS, which one can argue is just shifting the cost to an earlier part of the stay. Even though this is highly beneficial, it does not address the core resource utilization within the hospital. Our study found its cost benefit not in the LOS, but in decreasing core resource utilization such as radiology, lab, nursing, and supplies. If patients are admitted for a noncardiovascular condition and have CVC occlusion, using alteplase to clear the CVC occlusion along with implementing strategies to manage the underlying disease to reduce the LOS becomes a powerful opportunity to impact cost. Among patients who may come to the hospital for just the CVC occlusion, the LOS should be short. There may be no significant opportunity to reduce the LOS in those cases, but opportunities to decrease core hospital resource utilization with alteplase make this approach beneficial if the patient can tolerate it.

Limitations of the study include the retrospective and administrative nature of the database used, which is unable to provide certain clinical measures as would be available at the patient's bedside when treatment choices are being made. Had they been available, we might have included them in our assessment of whether patients who underwent CVC replacement were significantly different from those who received alteplase. In addition, not all hospitals in the database had charge masters that facilitated identification of CVC replacements or reinsertions, requiring the use of CPT‐4 codes and evidence of new CVCs being placed or inserted. Certain patients were excluded if there was conflicting information about whether the CVC was new within the hospital stay or dwelling in the patient prior to admission. Also, dialysis patients were excluded because they were not part of any approved indication for alteplase 2 mg, and this group is particularly prone to catheter obstruction. As such, they represent more complicated cases than the norm; this exclusion may have limited the overall generalizability of the study. The study also relied on charge master (billing) data to identify the use of alteplase and other treatments, where there is the potential, albeit minimal, for inaccuracies in the data. Of greater importance, the study relied on ICD‐9 coding to identify comorbid conditions, and as in other studies using similar data sources, such methods are subject to coding errors and omissions. However, many of the listed limitations above were not thought to be different between the comparison groups or more problematic for this study than for other studies based on similar data sources.

CONCLUSION

Among patients treated for an occluded CVC, alteplase‐treated patients had lower daily postocclusion costs and lower total postocclusion costs than patients who received catheter replacement. Differences in costs did not appear to be driven by differences in postocclusion LOS. Readmissions at 30‐ and 90‐day periods were found to be similar between alteplase recipients and catheter‐replacement patients.

Long‐term central venous catheters (CVCs) facilitate care for patients with chronic illness by providing easy venous access for laboratory tests, administration of medication, and parenteral nutrition. However, several complications resulting from the use of CVCs, including sepsis, extravasation of infusions, and venous thrombosis, can increase associated morbidity and mortality. These complications can also interrupt and delay treatment for the underlying disease and thereby affect outcomes. One of the most common CVC complications is catheter occlusion.[1]

Catheter occlusion occurs in 14% to 36% of patients within 1 to 2 years of catheter placement.[2, 3, 4, 5, 6, 7, 8] A catheter occlusion can be partial or complete, and can occur secondary to a variety of mechanical problems, including an uncommon, but potentially life‐threatening, pinch‐off syndrome. Medication or parenteral nutrition can also cause occlusion, which can be acute or gradual, with increasingly sluggish flow through the catheter. Inappropriate concentrations or incompatible mixtures can cause medications to precipitate within the catheter lumen.

Occlusions are either thrombotic or nonthrombotic. One autopsy study of patients with a long‐term CVC found that a fibrin sheath encased the catheter tip in every case.[9] An occluded catheter may compromise patient care[9, 10]; it may cause cancellation or delay of procedures, it potentially interrupts administration of critical therapies including vesicants, it may result in risk of infection, and it potentially leads to catheter replacement. This can further complicate care, leading to increased length of stay (LOS) and hospital costs.

To better understand resource utilization, LOS, and cost implications of alteplase compared with catheter replacement, we conducted a preplanned, retrospective analysis of hospitalized patients captured between January 2006 and December 2011 in the database maintained by Premier. The Premier database is a large, US hospital‐based, service‐level, all‐payer, comparative database, with information collected primarily from nearly 600 geographically diverse, nonprofit, nongovernment community and teaching hospitals.

METHODS

RESULTS

This study included 34,579 patients who first had a CVC insertion and then were treated for a CVC occlusion by receiving a replacement CVC (n=1028) or by receiving alteplase (2 mg) administration (n=33,551) during the same hospitalization (Table 1). Patients who received alteplase tended to be younger (6019 vs 6220 years old). More than 50% were at least 65 years of age. Twelve percent of alteplase patients were black, whereas 18.5% of catheter‐replacement patients were black.

Alteplase patients were significantly more likely to have a diagnosis of chronic pulmonary disease, liver disease, renal disease, chronic diabetes (ie, diabetes with complications), and cancer. There was an equivalent number of urban and rural hospitals across the 2 groups of patients (Table 2); however, there were regional differences including a higher proportion of catheter‐replacement patients from the East North Central and Middle Atlantic areas and a lower proportion of catheter‐replacement patients from Mountain and Pacific states. Catheter‐replacement patients more frequently were treated in teaching hospitals and in hospitals of larger size.

After covariate adjustment for baseline measurements significantly related to each outcome, average daily post occlusion costs were estimated to be $317 lower for alteplase recipients than for patients who received catheter replacement ($317; 95% confidence interval [CI]: $238‐$392; P<0.0001) (Table 3). Average adjusted total post occlusion costs were $1419 lower for alteplase recipients than for patients who received catheter replacement ($1418; 95% CI: $307‐$2458; P=0.012).

Contributing to the lower cost were certain revenue‐center specific costs (Table 4). Total room and board costs were different between the alteplase and catheter‐replacement groups in both the pre‐ and postocclusion periods; this was related to the difference between the 2 comparison groups in postocclusion LOS of about 0.3 days (Table 5). However, the differences favored alteplase use over catheter replacement. Cardiology/electrocardiography costs were lower for catheter replacement in the preocclusion period but lower for alteplase use in the postocclusion period. Emergency department costs were higher for catheter replacement in both periods, as were respiratory costs in the same manner. Additionally, costs for laboratory tests, nursing, operating room/surgery, pharmacy, radiology, supplies, and ICU room and board were lower in the preocclusion period but higher in the postocclusion period for catheter‐replacement patients. It was unclear why the pharmacy costs after catheter replacement would have increased for catheter‐replacement patients in contrast to the decrease for alteplase‐treated patients, but because this occurred at an average daily basis as well, it appeared that catheter‐replacement patients may have received additional medications. Average adjusted postocclusion LOS was similar for alteplase and catheter‐replacement recipients (P=0.24), suggesting that decreased total costs were due to reasons other than shorter LOS.

Unadjusted 30‐ and 90‐day readmission rates were 24.6% and 35.1% for CVC replacement and slightly lower at 23.7% and 33.9% for alteplase (Table 3), respectively. Odds of readmission after adjusting for patient and hospital factors were not significantly different at 30 days (odds ratio [OR]: 1.048, 95% CI: 0.899‐1.221; P=0.55) or at 90 days (OR: 1.051, 95% CI: 0.915‐1.207; P=0.48) (Table 5). Subgroup analyses for patients with a diagnosis of heart failure, myocardial infarction, and cancer revealed similar results.

DISCUSSION

The cost of healthcare in the United States has risen at an outstanding rate compared with other countries. Our percentage of gross national product spent on healthcare is on the order of 16% to 18%, almost twice as much as the next most industrialized country in terms of healthcare expenditure.[11] In the current era, finding opportunities to reduce healthcare costs without negatively impacting quality of care is the name of the game. Professional societies have come together under the campaign of Choosing Wisely: An Initiative of the ABIM (American Board of Internal Medicine) Foundation to help educate clinicians and patients on cost‐containment strategies.[12] Research that demonstrates opportunities to reduce cost will help healthcare providers choose wisely among diagnostic and therapeutic options for patients. Our study demonstrated that the use of a drug such as alteplase in clearing CVC catheter obstruction was significantly less costly to the hospital than catheter replacement.

Cathflo Activase (alteplase: Genentech, South San Francisco, CA), the only FDA‐approved thrombolytic for the restoration of central venous catheter function, is the current standard treatment for catheter occlusions in the United States. A dose of 2 mg in 2 mL is instilled in patients weighing 30 kg or 110% of the internal lumen volume of the catheter not to exceed 2 mg in 2 mL for those patients weighing <30 kg. Haire et al. showed that a 2‐mg dose of alteplase was more effective than urokinase (5000 IU) for treating radiographically proven thrombotic occlusion of a CVC after a dwell time of 120 minutes.[13] In the Cardiovascular thrombolytic used to Open Occluded Lines (COOL) trial, one 2‐mg dose of alteplase cleared the catheter occlusion after 120 minutes in 74% of patients, compared with only 17% of patients who received a placebo. Studies have confirmed the safety and efficacy of alteplase administered at various time intervals in different long‐term catheters, including peripherally inserted central catheters, with major hemorrhage reported in 0.3% of patients.[14, 15, 16]

Adding to the knowledge of patient outcomes from clinical studies, many health outcomes studies have demonstrated benefit in cost containment through decreasing LOS, which one can argue is just shifting the cost to an earlier part of the stay. Even though this is highly beneficial, it does not address the core resource utilization within the hospital. Our study found its cost benefit not in the LOS, but in decreasing core resource utilization such as radiology, lab, nursing, and supplies. If patients are admitted for a noncardiovascular condition and have CVC occlusion, using alteplase to clear the CVC occlusion along with implementing strategies to manage the underlying disease to reduce the LOS becomes a powerful opportunity to impact cost. Among patients who may come to the hospital for just the CVC occlusion, the LOS should be short. There may be no significant opportunity to reduce the LOS in those cases, but opportunities to decrease core hospital resource utilization with alteplase make this approach beneficial if the patient can tolerate it.

Limitations of the study include the retrospective and administrative nature of the database used, which is unable to provide certain clinical measures as would be available at the patient's bedside when treatment choices are being made. Had they been available, we might have included them in our assessment of whether patients who underwent CVC replacement were significantly different from those who received alteplase. In addition, not all hospitals in the database had charge masters that facilitated identification of CVC replacements or reinsertions, requiring the use of CPT‐4 codes and evidence of new CVCs being placed or inserted. Certain patients were excluded if there was conflicting information about whether the CVC was new within the hospital stay or dwelling in the patient prior to admission. Also, dialysis patients were excluded because they were not part of any approved indication for alteplase 2 mg, and this group is particularly prone to catheter obstruction. As such, they represent more complicated cases than the norm; this exclusion may have limited the overall generalizability of the study. The study also relied on charge master (billing) data to identify the use of alteplase and other treatments, where there is the potential, albeit minimal, for inaccuracies in the data. Of greater importance, the study relied on ICD‐9 coding to identify comorbid conditions, and as in other studies using similar data sources, such methods are subject to coding errors and omissions. However, many of the listed limitations above were not thought to be different between the comparison groups or more problematic for this study than for other studies based on similar data sources.

CONCLUSION

Among patients treated for an occluded CVC, alteplase‐treated patients had lower daily postocclusion costs and lower total postocclusion costs than patients who received catheter replacement. Differences in costs did not appear to be driven by differences in postocclusion LOS. Readmissions at 30‐ and 90‐day periods were found to be similar between alteplase recipients and catheter‐replacement patients.

Venous thromboembolism (VTE) is the third most prevalent cardiovascular disease in the United States, only surpassed by myocardial infarction and stroke.1 There are an estimated 600,000 symptomatic VTE events and 300,000 VTE‐related deaths per year in the United States, with two‐thirds of VTE events being acquired in‐hospital.2

High rates of VTE remain despite evidence from clinical trials showing that VTE can be safely and effectively reduced by VTE prophylaxis in at‐risk medical and surgical patients.1, 3, 4 A cohort study in 2001 suggested that as many as 1 in 6 VTE cases could have been prevented by adequate VTE prophylaxis, amounting to approximately 100,000 preventable cases per year in the United States.5 Clinical guidelines are available to guide the practitioner in the choice of prophylaxis regimen and provide evidence‐based recommendations on the choice of prophylaxis for each risk‐category group.1, 6

Awareness of the importance of preventing VTE is growing in the United States. The improvement of VTE prevention and VTE treatment has been identified as a key goal for hospitals in the United States by The Joint Commission and the National Quality Forum.7, 8 Furthermore, a 2006 U.S. Surgeon General's workshop discussed the issues surrounding deep‐vein thrombosis (DVT) prevention, and released a summary of the priority areas for action.9 The Surgical Care Improvement Project (SCIP), a national partnership initiative for improving surgical care, has also recently released 2 VTE‐focused initiatives (SCIP VTE‐1 and SCIP VTE‐2) to help reduce preventable causes of mortality and morbidity in surgical patients.10

Such quality‐assurance initiatives are likely related to the body of data on inadequate use of VTE prophylaxis in U.S. hospitals, including a number of cohort and registry studies that demonstrated low prophylaxis use compared with evidence‐based guideline recommendations.5, 1115 Although these studies provide an insight into the low levels of use of VTE prophylaxis, recent studies have suggested that the rates of appropriate VTE prophylaxis are even lower when one defines appropriate prophylaxis to include the type or choice of VTE prophylaxis (pharmacological and/or mechanical), drug dose, and duration of prophylaxis.16, 17

In these real‐world studies of U.S. hospital prophylaxis practices from 2002 to 2005, 61.8% of medical patients and 72.9% of surgical patients received at least 1 dose of prophylaxis agent, but only 33.9% of medical patients and 32.3% of surgical patients received an appropriate VTE prophylaxis course.16, 17 These data suggest that the lack of appropriate prophylaxis is not only due to physicians not being aware of the need for VTE prophylaxis, but also due to a lack of understanding of the guideline recommendations.

The seventh update of the American College of Chest Physicians (ACCP) guidelines, released in September 2004, provides more specific recommendations than in previous guidelines. With this publication, and the recent efforts to encourage greater awareness and attention to VTE prophylaxis practices, it is important to see if the combination of increased awareness activities and more specific recommendations have led to an increase in appropriate prophylaxis use compared with previous studies that assessed appropriate prophylaxis with the sixth ACCP guidelines.16, 17 This study will therefore build on studies from 2001 to 2004 to compare appropriate inpatient prophylaxis use, in accordance with the seventh ACCP guidelines, in a wide range of U.S. medical and surgical patients from January 2005 to December 2006.

Materials and Methods

Results

Among the 2,353,287 discharges in the database during the study period, 390,024 (16.6%) discharges were included in this analysis. Of these discharges, 201,224 (51.6%) were in acute medical illness groups and 188,800 (48.4%) were in surgical procedure groups (Table 1). The medical and surgical groups containing the highest numbers of discharges were critical care (97,022 discharges) and vascular surgery (90,727 discharges), respectively (Table 1).

The total rate of any prophylaxis in this analysis was 71.6%, meaning that nearly 3 in every 4 discharges that were eligible for VTE prophylaxis received at least 1 order for pharmacological or mechanical VTE prophylaxis (Table 2). Rates of any prophylaxis were lower for medical discharges at 65.9%, compared with 77.7% in surgical discharges. Variation was observed within individual discharge diagnosis groups, with the highest rate of any prophylaxis being 93.8% in the major orthopedic surgery group and the lowest rate being 36.8% in the burns group (Table 2).

However, when the recommendations of the seventh ACCP guidelines were applied for prophylaxis type, dose, and duration, only 14.5% of all patients received appropriate prophylaxis (Table 2). Medical discharges also received lower levels of appropriate prophylaxis at 12.7% than surgical discharges (16.4%). Large variations in the rates of appropriate prophylaxis were observed between discharge groups in both the medical and surgical populations. In the medical groups, the highest rate of appropriate prophylaxis was 17.5% in trauma discharges, and the lowest rate was 4.7% in burns discharges. In the surgical groups, the highest rate of appropriate prophylaxis was 48.6% in major orthopedic surgery discharges, and the lowest rate was 5.7% in neurological surgery discharges.

Further examination of the individual discharge records reveals that the primary reason that discharges in the medical diagnosis groups did not receive appropriate prophylaxis was due to no pharmacological prophylaxis being provided, despite the lack of a contraindication to anticoagulant therapy (Table 3). A total of 34.1% of all medical discharges received no pharmacological prophylaxis when indicated. Other reasons for medical discharges not receiving appropriate prophylaxis were receiving pharmacological prophylaxis at an incorrect dose (lower than the guideline‐recommended daily total; 22.7%), receiving prophylaxis for an insufficient duration (missing at least 1 day of prophylaxis that was not the admission or discharge date; 22.1%), and receiving mechanical prophylaxis alone when pharmacological prophylaxis was recommended (8.4%). Variation in the reasons for not receiving appropriate prophylaxis was observed between medical diagnosis groups, with the primary reason being mechanical prophylaxis alone in acute spinal injury discharges, and no prophylaxis in burns, cancer, and trauma discharges (Table 3).

In the total surgical discharge population, an insufficient duration of prophylaxis was the main reason for not receiving appropriate prophylaxis, with 36.1% of all surgical discharges receiving an insufficient duration of prophylaxis (Table 3). Other reasons for surgical discharges not receiving appropriate prophylaxis were receiving no pharmacological prophylaxis (22.3%), receiving pharmacological prophylaxis at an incorrect dose (13.7%), and receiving mechanical prophylaxis alone (11.5%). Variation in the reasons for not receiving appropriate prophylaxis was also observed between surgical diagnosis groups, with the primary reason being inappropriate duration in vascular surgery discharges, mechanical prophylaxis alone in gynecological, laparoscopic, and neurological surgery discharges, inappropriate dosage in orthopedic surgery discharges, and no prophylaxis provided in general and urological surgery discharges (Table 3). In medical and surgical discharges that had a critical care unit stay during their hospitalization, only 15.7% received appropriate prophylaxis, with nearly one‐half of all critical care discharges receiving an insufficient duration of VTE prophylaxis (Table 3).

Analysis of the mean rates of appropriate prophylaxis by hospital factors suggests that trends exist toward increased use of appropriate prophylaxis in larger hospitals, in urban hospitals compared with rural hospitals, and in teaching compared with nonteaching hospitals (Table 4).

Discussion

This study suggests that appropriate prophylaxis, as defined in current practice guidelines for the prevention of VTE in specific at‐risk groups, is not widely applied in a selected cohort of hospitalized patients with known risks for VTE. Current ACCP guidelines provide specific direction on safe and effective prophylaxis regimens. These recommendations include the appropriate dosing and appropriate duration of prophylaxis, according to the specific risk in defined medical and surgical risk groups. However, in nearly 400,000 medical and surgical discharges at risk for VTE in U.S. hospitals, only 14.5% of discharges received VTE prophylaxis that met the recommendations of the seventh ACCP guidelines for prophylaxis type, dose, and duration. Although 71.6% of discharges received some form of prophylaxis during hospitalization, the majority of these discharges did not receive appropriate prophylaxis. Furthermore, nearly 30% of patients who should have received prophylaxis did not have a single order for prophylaxis during their hospitalization.

The ACCP has regularly updated its VTE prevention guidelines from the first release of the guidelines in 1986 to the most recent seventh guidelines in 2008.20, 21 These updates have been in line with emerging literature for both patient populations that are at risk for VTE, and for VTE prophylaxis regimens that are safe and effective in these patients. The main changes between the two most recent guidelines in VTE prevention (sixth and seventh) were to introduce risk assessment within patient groups, resulting in a greater number of more stringent recommendations.1, 11 The combination of the more stringent recommendations, and the recently growing national focus on the need for improved VTE prevention from groups such as The Joint Commission and the National Quality Forum would suggest that the levels of appropriate VTE prophylaxis in U.S. hospitals should be increasing.7, 8

The number of patients, including both medical and surgical discharges, in this study that were eligible for prophylaxis was approximately 16.6%. This number is substantially lower than previously reported in a recent U.S. study that found that 31% of U.S. hospital discharges in 2003 were at risk of VTE.22 It is likely that the discrepancy between the 2 studies is due to the more stringent length of stay criteria (6 days) in our study compared to 2 days in the Anderson et al.22 study. This length of stay criteria will have likely selected for complicated, higher‐risk patients and as such the results of this study may be more applicable to patients at higher risk of VTE than to the general population.

However, when the results of this study are compared to similar studies of appropriate prophylaxis with the sixth ACCP guidelines during the period of 2002 to 2005, the level of appropriate prophylaxis appears to have decreased.16, 17 Although strong conclusions can not be drawn from the comparison of the analyses, the appropriate prophylaxis in medical patients during the timeframe of the sixth ACCP guidelines occurred in 33.9% of patients, compared with only 13.7% in the present study. Two of the categories with the highest rates of appropriate VTE prophylaxis in the analysis of the sixth ACCP guidelines were not included in our study (acute myocardial infarction and ischemic strokedue to these patients being likely to receive treatment dose anticoagulants), but the categories that were included in both studies, ie, acute spinal cord injury, cancer, heart failure, and severe lung disease, have a 50% to 66% decrease in appropriate prophylaxis rates in the current study.16 Only trauma patients have similar rates between studies. Interestingly, the rates of any prophylaxis have increased in the current study, with 65.9% of medical patients receiving some form of prophylaxis in this analysis, compared with 61.8% in the prior study. Similar results are observed when comparing the surgical population in this analysis to prior data on surgical discharges, with the rate of any prophylaxis being higher with the seventh ACCP guidelines than the sixth ACCP guidelines (77.7% vs. 72.9%, respectively), but the rate of appropriate prophylaxis being lower (16.4% vs. 32.3%, respectively).17

The combination of an increase in any prophylaxis, but a decrease in appropriate prophylaxis may suggest that the overall national awareness of the need for VTE prophylaxis in at‐risk patients is increasing. However, the combination of more stringent guideline recommendations, and perhaps a lack of awareness as to the guideline recommendations themselves, has actually led to a decrease in the amount of appropriate prophylaxis being prescribed. Despite this, there still remain approximately 30% of patients who receive no prophylaxis at all. To this end, it is important that awareness initiatives and quality improvement programs address both the need for prophylaxis, and the most safe and effective way to provide appropriate prophylaxis in specific patient populations. The use of electronic or manual alerts and order forms for VTE prophylaxis is one effective way of increasing appropriate prophylaxis, and ultimately reducing the incidence of hospital‐acquired VTE.23 A pivotal study by Kucher et al.23 studied over 2500 patients who were randomly assigned to an electronic intervention group or a control group. In the intervention group, the physician received an electronic alert of the patients' VTE risk, whereas in the control group no alert was issued. The study found that, compared to control, both pharmacological prophylaxis (23.6% vs. 13.0%, P < 0.001) and mechanical prophylaxis (10.0% vs. 1.5%, P < 0.001) were prescribed more frequently in the intervention group. Furthermore, this led to a significant reduction in the incidence of clinically diagnosed, objectively confirmed deep‐vein thrombosis or pulmonary embolism at 90 days, with an incidence of 4.9% in the intervention group compared with 8.2% in the control group (P < 0.001). As this study has found that prophylaxis is inappropriately provided due to insufficient prescribing, insufficient duration, and inappropriate dosing, it would be interesting to identify the educational or procedural interventions that have the biggest impact on each factor. This would allow hospitals to create multicomponent initiatives with a greater chance of increasing the rates of appropriate prophylaxis.

A strength of this study is that this is the largest database analysis of hospital discharges and seventh ACCP guideline‐recommended VTE prophylaxis use to date, giving insights into real‐world clinical practice in the United States with the most recent guidelines. This will provide a checkpoint for improvements in advance of the 2008 guidelines being released. A limitation of this study is that we have utilized a conservative approach to selecting patients who were clearly at risk of VTE. Patients were required to have a length of stay 6 days. This may have both excluded a number of orthopedic surgery and medical patients despite their requirements for VTE prophylaxis and likely have selected a cohort of sicker patients at high‐risk for VTE. It is possible that this will have created a bias for specific patient or hospital characteristics (eg, complex patients or hospitals with less efficient systems) that we cannot adjust for, and this may have affected the results of the study. Due to the use of hospital records alone, we are also unable to examine whether discharges continued to receive appropriate prophylaxis following discharge. As some orthopedic surgery patients are recommended to receive prophylaxis for up to 28 to 35 days following surgery,1 this limitation is likely to have resulted in an overestimation of appropriate prophylaxis rates in the current study. However, it is important to note that the appropriate prophylaxis rate was extremely low, even in this selected higher‐risk population. Furthermore, the use of length of stay minus 2 days as the criteria for appropriate duration may have led to a slight underestimation of appropriate prophylaxis, especially as the reasons for any interruption of prophylaxis by the physician during the hospital stay are unknown. An additional limitation is that the study uses retrospective discharge record data that cannot fully evaluate whether the prophylaxis was appropriate in a complex individual patient. For example, contraindications to anticoagulant prophylaxis are not always documented and may not have been identified in the hospital coding exclusion criteria. In addition, we are only able to assess whether mechanical prophylaxis was ordered, and not whether it was appropriately used. Another limitation is that basing assignment of prophylaxis on the principal diagnosis increases the likelihood that clinical decisions on prophylaxis were based on the primary reason for admission, when in reality there may have been multiple factors affecting the patient's risk assessment and the physician's prophylaxis decision. In this analysis, we used the ACCP guidelines as these are currently the most long‐standing VTE prophylaxis guidelines available, as well as being the most comprehensive for multiple patient groups. However, it is important to acknowledge that specific specialties, such as oncologists and orthopedic surgeons, also have their own specialized guidelines which may have different recommendations. This may therefore have led to an underestimation of appropriate prophylaxis. In addition, the ACCP guidelines have been updated in 2008, providing physicians with a revised set of recommendations for VTE prophylaxis.21 We utilized the 2004 guidelines in our analysis as we feel that it is important to assess whether the prophylaxis provided was appropriate by the standards of care during the timeframe within which the data were collected. However, we acknowledge that applying the new guidelines may impact the results of the study. One final consideration that would make an interesting follow‐up study is an assessment of whether appropriate or inappropriate prophylaxis impacts the clinical outcomes. For example, do patients with appropriate prophylaxis have fewer VTE events and improved mortality compared with those without prophylaxis or with inappropriate prophylaxis.

In summary, this work identifies that, in the United States, there is still considerable underutilization of appropriate VTE prophylaxis across a broad range of diagnostic groups with known VTE risk. While nearly three‐quarters of patients do receive at least 1 order for VTE prophylaxis during their hospitalization, only approximately 1 in 7 patients receive appropriate prophylaxis that matches evidence‐based recommendations for type, dose, and duration. Physician awareness of both the need for VTE prophylaxis, and more specifically what constitutes appropriate prophylaxis in certain patient groups, needs to be increased. The current national performance initiatives will provide a framework for this improvement, but it is the responsibility of individual hospitals to improve their VTE prophylaxis practices. Such an improvement across hospitals will lead to a sizeable reduction in the incidence and economic burden of VTE on the U.S. healthcare system.

Venous thromboembolism (VTE) is the third most prevalent cardiovascular disease in the United States, only surpassed by myocardial infarction and stroke.1 There are an estimated 600,000 symptomatic VTE events and 300,000 VTE‐related deaths per year in the United States, with two‐thirds of VTE events being acquired in‐hospital.2

High rates of VTE remain despite evidence from clinical trials showing that VTE can be safely and effectively reduced by VTE prophylaxis in at‐risk medical and surgical patients.1, 3, 4 A cohort study in 2001 suggested that as many as 1 in 6 VTE cases could have been prevented by adequate VTE prophylaxis, amounting to approximately 100,000 preventable cases per year in the United States.5 Clinical guidelines are available to guide the practitioner in the choice of prophylaxis regimen and provide evidence‐based recommendations on the choice of prophylaxis for each risk‐category group.1, 6

Awareness of the importance of preventing VTE is growing in the United States. The improvement of VTE prevention and VTE treatment has been identified as a key goal for hospitals in the United States by The Joint Commission and the National Quality Forum.7, 8 Furthermore, a 2006 U.S. Surgeon General's workshop discussed the issues surrounding deep‐vein thrombosis (DVT) prevention, and released a summary of the priority areas for action.9 The Surgical Care Improvement Project (SCIP), a national partnership initiative for improving surgical care, has also recently released 2 VTE‐focused initiatives (SCIP VTE‐1 and SCIP VTE‐2) to help reduce preventable causes of mortality and morbidity in surgical patients.10

Such quality‐assurance initiatives are likely related to the body of data on inadequate use of VTE prophylaxis in U.S. hospitals, including a number of cohort and registry studies that demonstrated low prophylaxis use compared with evidence‐based guideline recommendations.5, 1115 Although these studies provide an insight into the low levels of use of VTE prophylaxis, recent studies have suggested that the rates of appropriate VTE prophylaxis are even lower when one defines appropriate prophylaxis to include the type or choice of VTE prophylaxis (pharmacological and/or mechanical), drug dose, and duration of prophylaxis.16, 17

In these real‐world studies of U.S. hospital prophylaxis practices from 2002 to 2005, 61.8% of medical patients and 72.9% of surgical patients received at least 1 dose of prophylaxis agent, but only 33.9% of medical patients and 32.3% of surgical patients received an appropriate VTE prophylaxis course.16, 17 These data suggest that the lack of appropriate prophylaxis is not only due to physicians not being aware of the need for VTE prophylaxis, but also due to a lack of understanding of the guideline recommendations.

The seventh update of the American College of Chest Physicians (ACCP) guidelines, released in September 2004, provides more specific recommendations than in previous guidelines. With this publication, and the recent efforts to encourage greater awareness and attention to VTE prophylaxis practices, it is important to see if the combination of increased awareness activities and more specific recommendations have led to an increase in appropriate prophylaxis use compared with previous studies that assessed appropriate prophylaxis with the sixth ACCP guidelines.16, 17 This study will therefore build on studies from 2001 to 2004 to compare appropriate inpatient prophylaxis use, in accordance with the seventh ACCP guidelines, in a wide range of U.S. medical and surgical patients from January 2005 to December 2006.

Materials and Methods

Results

Among the 2,353,287 discharges in the database during the study period, 390,024 (16.6%) discharges were included in this analysis. Of these discharges, 201,224 (51.6%) were in acute medical illness groups and 188,800 (48.4%) were in surgical procedure groups (Table 1). The medical and surgical groups containing the highest numbers of discharges were critical care (97,022 discharges) and vascular surgery (90,727 discharges), respectively (Table 1).

The total rate of any prophylaxis in this analysis was 71.6%, meaning that nearly 3 in every 4 discharges that were eligible for VTE prophylaxis received at least 1 order for pharmacological or mechanical VTE prophylaxis (Table 2). Rates of any prophylaxis were lower for medical discharges at 65.9%, compared with 77.7% in surgical discharges. Variation was observed within individual discharge diagnosis groups, with the highest rate of any prophylaxis being 93.8% in the major orthopedic surgery group and the lowest rate being 36.8% in the burns group (Table 2).

However, when the recommendations of the seventh ACCP guidelines were applied for prophylaxis type, dose, and duration, only 14.5% of all patients received appropriate prophylaxis (Table 2). Medical discharges also received lower levels of appropriate prophylaxis at 12.7% than surgical discharges (16.4%). Large variations in the rates of appropriate prophylaxis were observed between discharge groups in both the medical and surgical populations. In the medical groups, the highest rate of appropriate prophylaxis was 17.5% in trauma discharges, and the lowest rate was 4.7% in burns discharges. In the surgical groups, the highest rate of appropriate prophylaxis was 48.6% in major orthopedic surgery discharges, and the lowest rate was 5.7% in neurological surgery discharges.

Further examination of the individual discharge records reveals that the primary reason that discharges in the medical diagnosis groups did not receive appropriate prophylaxis was due to no pharmacological prophylaxis being provided, despite the lack of a contraindication to anticoagulant therapy (Table 3). A total of 34.1% of all medical discharges received no pharmacological prophylaxis when indicated. Other reasons for medical discharges not receiving appropriate prophylaxis were receiving pharmacological prophylaxis at an incorrect dose (lower than the guideline‐recommended daily total; 22.7%), receiving prophylaxis for an insufficient duration (missing at least 1 day of prophylaxis that was not the admission or discharge date; 22.1%), and receiving mechanical prophylaxis alone when pharmacological prophylaxis was recommended (8.4%). Variation in the reasons for not receiving appropriate prophylaxis was observed between medical diagnosis groups, with the primary reason being mechanical prophylaxis alone in acute spinal injury discharges, and no prophylaxis in burns, cancer, and trauma discharges (Table 3).

In the total surgical discharge population, an insufficient duration of prophylaxis was the main reason for not receiving appropriate prophylaxis, with 36.1% of all surgical discharges receiving an insufficient duration of prophylaxis (Table 3). Other reasons for surgical discharges not receiving appropriate prophylaxis were receiving no pharmacological prophylaxis (22.3%), receiving pharmacological prophylaxis at an incorrect dose (13.7%), and receiving mechanical prophylaxis alone (11.5%). Variation in the reasons for not receiving appropriate prophylaxis was also observed between surgical diagnosis groups, with the primary reason being inappropriate duration in vascular surgery discharges, mechanical prophylaxis alone in gynecological, laparoscopic, and neurological surgery discharges, inappropriate dosage in orthopedic surgery discharges, and no prophylaxis provided in general and urological surgery discharges (Table 3). In medical and surgical discharges that had a critical care unit stay during their hospitalization, only 15.7% received appropriate prophylaxis, with nearly one‐half of all critical care discharges receiving an insufficient duration of VTE prophylaxis (Table 3).

Analysis of the mean rates of appropriate prophylaxis by hospital factors suggests that trends exist toward increased use of appropriate prophylaxis in larger hospitals, in urban hospitals compared with rural hospitals, and in teaching compared with nonteaching hospitals (Table 4).

Discussion

This study suggests that appropriate prophylaxis, as defined in current practice guidelines for the prevention of VTE in specific at‐risk groups, is not widely applied in a selected cohort of hospitalized patients with known risks for VTE. Current ACCP guidelines provide specific direction on safe and effective prophylaxis regimens. These recommendations include the appropriate dosing and appropriate duration of prophylaxis, according to the specific risk in defined medical and surgical risk groups. However, in nearly 400,000 medical and surgical discharges at risk for VTE in U.S. hospitals, only 14.5% of discharges received VTE prophylaxis that met the recommendations of the seventh ACCP guidelines for prophylaxis type, dose, and duration. Although 71.6% of discharges received some form of prophylaxis during hospitalization, the majority of these discharges did not receive appropriate prophylaxis. Furthermore, nearly 30% of patients who should have received prophylaxis did not have a single order for prophylaxis during their hospitalization.

The ACCP has regularly updated its VTE prevention guidelines from the first release of the guidelines in 1986 to the most recent seventh guidelines in 2008.20, 21 These updates have been in line with emerging literature for both patient populations that are at risk for VTE, and for VTE prophylaxis regimens that are safe and effective in these patients. The main changes between the two most recent guidelines in VTE prevention (sixth and seventh) were to introduce risk assessment within patient groups, resulting in a greater number of more stringent recommendations.1, 11 The combination of the more stringent recommendations, and the recently growing national focus on the need for improved VTE prevention from groups such as The Joint Commission and the National Quality Forum would suggest that the levels of appropriate VTE prophylaxis in U.S. hospitals should be increasing.7, 8

The number of patients, including both medical and surgical discharges, in this study that were eligible for prophylaxis was approximately 16.6%. This number is substantially lower than previously reported in a recent U.S. study that found that 31% of U.S. hospital discharges in 2003 were at risk of VTE.22 It is likely that the discrepancy between the 2 studies is due to the more stringent length of stay criteria (6 days) in our study compared to 2 days in the Anderson et al.22 study. This length of stay criteria will have likely selected for complicated, higher‐risk patients and as such the results of this study may be more applicable to patients at higher risk of VTE than to the general population.

However, when the results of this study are compared to similar studies of appropriate prophylaxis with the sixth ACCP guidelines during the period of 2002 to 2005, the level of appropriate prophylaxis appears to have decreased.16, 17 Although strong conclusions can not be drawn from the comparison of the analyses, the appropriate prophylaxis in medical patients during the timeframe of the sixth ACCP guidelines occurred in 33.9% of patients, compared with only 13.7% in the present study. Two of the categories with the highest rates of appropriate VTE prophylaxis in the analysis of the sixth ACCP guidelines were not included in our study (acute myocardial infarction and ischemic strokedue to these patients being likely to receive treatment dose anticoagulants), but the categories that were included in both studies, ie, acute spinal cord injury, cancer, heart failure, and severe lung disease, have a 50% to 66% decrease in appropriate prophylaxis rates in the current study.16 Only trauma patients have similar rates between studies. Interestingly, the rates of any prophylaxis have increased in the current study, with 65.9% of medical patients receiving some form of prophylaxis in this analysis, compared with 61.8% in the prior study. Similar results are observed when comparing the surgical population in this analysis to prior data on surgical discharges, with the rate of any prophylaxis being higher with the seventh ACCP guidelines than the sixth ACCP guidelines (77.7% vs. 72.9%, respectively), but the rate of appropriate prophylaxis being lower (16.4% vs. 32.3%, respectively).17

The combination of an increase in any prophylaxis, but a decrease in appropriate prophylaxis may suggest that the overall national awareness of the need for VTE prophylaxis in at‐risk patients is increasing. However, the combination of more stringent guideline recommendations, and perhaps a lack of awareness as to the guideline recommendations themselves, has actually led to a decrease in the amount of appropriate prophylaxis being prescribed. Despite this, there still remain approximately 30% of patients who receive no prophylaxis at all. To this end, it is important that awareness initiatives and quality improvement programs address both the need for prophylaxis, and the most safe and effective way to provide appropriate prophylaxis in specific patient populations. The use of electronic or manual alerts and order forms for VTE prophylaxis is one effective way of increasing appropriate prophylaxis, and ultimately reducing the incidence of hospital‐acquired VTE.23 A pivotal study by Kucher et al.23 studied over 2500 patients who were randomly assigned to an electronic intervention group or a control group. In the intervention group, the physician received an electronic alert of the patients' VTE risk, whereas in the control group no alert was issued. The study found that, compared to control, both pharmacological prophylaxis (23.6% vs. 13.0%, P < 0.001) and mechanical prophylaxis (10.0% vs. 1.5%, P < 0.001) were prescribed more frequently in the intervention group. Furthermore, this led to a significant reduction in the incidence of clinically diagnosed, objectively confirmed deep‐vein thrombosis or pulmonary embolism at 90 days, with an incidence of 4.9% in the intervention group compared with 8.2% in the control group (P < 0.001). As this study has found that prophylaxis is inappropriately provided due to insufficient prescribing, insufficient duration, and inappropriate dosing, it would be interesting to identify the educational or procedural interventions that have the biggest impact on each factor. This would allow hospitals to create multicomponent initiatives with a greater chance of increasing the rates of appropriate prophylaxis.

A strength of this study is that this is the largest database analysis of hospital discharges and seventh ACCP guideline‐recommended VTE prophylaxis use to date, giving insights into real‐world clinical practice in the United States with the most recent guidelines. This will provide a checkpoint for improvements in advance of the 2008 guidelines being released. A limitation of this study is that we have utilized a conservative approach to selecting patients who were clearly at risk of VTE. Patients were required to have a length of stay 6 days. This may have both excluded a number of orthopedic surgery and medical patients despite their requirements for VTE prophylaxis and likely have selected a cohort of sicker patients at high‐risk for VTE. It is possible that this will have created a bias for specific patient or hospital characteristics (eg, complex patients or hospitals with less efficient systems) that we cannot adjust for, and this may have affected the results of the study. Due to the use of hospital records alone, we are also unable to examine whether discharges continued to receive appropriate prophylaxis following discharge. As some orthopedic surgery patients are recommended to receive prophylaxis for up to 28 to 35 days following surgery,1 this limitation is likely to have resulted in an overestimation of appropriate prophylaxis rates in the current study. However, it is important to note that the appropriate prophylaxis rate was extremely low, even in this selected higher‐risk population. Furthermore, the use of length of stay minus 2 days as the criteria for appropriate duration may have led to a slight underestimation of appropriate prophylaxis, especially as the reasons for any interruption of prophylaxis by the physician during the hospital stay are unknown. An additional limitation is that the study uses retrospective discharge record data that cannot fully evaluate whether the prophylaxis was appropriate in a complex individual patient. For example, contraindications to anticoagulant prophylaxis are not always documented and may not have been identified in the hospital coding exclusion criteria. In addition, we are only able to assess whether mechanical prophylaxis was ordered, and not whether it was appropriately used. Another limitation is that basing assignment of prophylaxis on the principal diagnosis increases the likelihood that clinical decisions on prophylaxis were based on the primary reason for admission, when in reality there may have been multiple factors affecting the patient's risk assessment and the physician's prophylaxis decision. In this analysis, we used the ACCP guidelines as these are currently the most long‐standing VTE prophylaxis guidelines available, as well as being the most comprehensive for multiple patient groups. However, it is important to acknowledge that specific specialties, such as oncologists and orthopedic surgeons, also have their own specialized guidelines which may have different recommendations. This may therefore have led to an underestimation of appropriate prophylaxis. In addition, the ACCP guidelines have been updated in 2008, providing physicians with a revised set of recommendations for VTE prophylaxis.21 We utilized the 2004 guidelines in our analysis as we feel that it is important to assess whether the prophylaxis provided was appropriate by the standards of care during the timeframe within which the data were collected. However, we acknowledge that applying the new guidelines may impact the results of the study. One final consideration that would make an interesting follow‐up study is an assessment of whether appropriate or inappropriate prophylaxis impacts the clinical outcomes. For example, do patients with appropriate prophylaxis have fewer VTE events and improved mortality compared with those without prophylaxis or with inappropriate prophylaxis.

In summary, this work identifies that, in the United States, there is still considerable underutilization of appropriate VTE prophylaxis across a broad range of diagnostic groups with known VTE risk. While nearly three‐quarters of patients do receive at least 1 order for VTE prophylaxis during their hospitalization, only approximately 1 in 7 patients receive appropriate prophylaxis that matches evidence‐based recommendations for type, dose, and duration. Physician awareness of both the need for VTE prophylaxis, and more specifically what constitutes appropriate prophylaxis in certain patient groups, needs to be increased. The current national performance initiatives will provide a framework for this improvement, but it is the responsibility of individual hospitals to improve their VTE prophylaxis practices. Such an improvement across hospitals will lead to a sizeable reduction in the incidence and economic burden of VTE on the U.S. healthcare system.

Venous thromboembolism (VTE) is the third most prevalent cardiovascular disease in the United States, only surpassed by myocardial infarction and stroke.1 There are an estimated 600,000 symptomatic VTE events and 300,000 VTE‐related deaths per year in the United States, with two‐thirds of VTE events being acquired in‐hospital.2

High rates of VTE remain despite evidence from clinical trials showing that VTE can be safely and effectively reduced by VTE prophylaxis in at‐risk medical and surgical patients.1, 3, 4 A cohort study in 2001 suggested that as many as 1 in 6 VTE cases could have been prevented by adequate VTE prophylaxis, amounting to approximately 100,000 preventable cases per year in the United States.5 Clinical guidelines are available to guide the practitioner in the choice of prophylaxis regimen and provide evidence‐based recommendations on the choice of prophylaxis for each risk‐category group.1, 6

Awareness of the importance of preventing VTE is growing in the United States. The improvement of VTE prevention and VTE treatment has been identified as a key goal for hospitals in the United States by The Joint Commission and the National Quality Forum.7, 8 Furthermore, a 2006 U.S. Surgeon General's workshop discussed the issues surrounding deep‐vein thrombosis (DVT) prevention, and released a summary of the priority areas for action.9 The Surgical Care Improvement Project (SCIP), a national partnership initiative for improving surgical care, has also recently released 2 VTE‐focused initiatives (SCIP VTE‐1 and SCIP VTE‐2) to help reduce preventable causes of mortality and morbidity in surgical patients.10

Such quality‐assurance initiatives are likely related to the body of data on inadequate use of VTE prophylaxis in U.S. hospitals, including a number of cohort and registry studies that demonstrated low prophylaxis use compared with evidence‐based guideline recommendations.5, 1115 Although these studies provide an insight into the low levels of use of VTE prophylaxis, recent studies have suggested that the rates of appropriate VTE prophylaxis are even lower when one defines appropriate prophylaxis to include the type or choice of VTE prophylaxis (pharmacological and/or mechanical), drug dose, and duration of prophylaxis.16, 17

In these real‐world studies of U.S. hospital prophylaxis practices from 2002 to 2005, 61.8% of medical patients and 72.9% of surgical patients received at least 1 dose of prophylaxis agent, but only 33.9% of medical patients and 32.3% of surgical patients received an appropriate VTE prophylaxis course.16, 17 These data suggest that the lack of appropriate prophylaxis is not only due to physicians not being aware of the need for VTE prophylaxis, but also due to a lack of understanding of the guideline recommendations.

The seventh update of the American College of Chest Physicians (ACCP) guidelines, released in September 2004, provides more specific recommendations than in previous guidelines. With this publication, and the recent efforts to encourage greater awareness and attention to VTE prophylaxis practices, it is important to see if the combination of increased awareness activities and more specific recommendations have led to an increase in appropriate prophylaxis use compared with previous studies that assessed appropriate prophylaxis with the sixth ACCP guidelines.16, 17 This study will therefore build on studies from 2001 to 2004 to compare appropriate inpatient prophylaxis use, in accordance with the seventh ACCP guidelines, in a wide range of U.S. medical and surgical patients from January 2005 to December 2006.

Materials and Methods

Results

Among the 2,353,287 discharges in the database during the study period, 390,024 (16.6%) discharges were included in this analysis. Of these discharges, 201,224 (51.6%) were in acute medical illness groups and 188,800 (48.4%) were in surgical procedure groups (Table 1). The medical and surgical groups containing the highest numbers of discharges were critical care (97,022 discharges) and vascular surgery (90,727 discharges), respectively (Table 1).

The total rate of any prophylaxis in this analysis was 71.6%, meaning that nearly 3 in every 4 discharges that were eligible for VTE prophylaxis received at least 1 order for pharmacological or mechanical VTE prophylaxis (Table 2). Rates of any prophylaxis were lower for medical discharges at 65.9%, compared with 77.7% in surgical discharges. Variation was observed within individual discharge diagnosis groups, with the highest rate of any prophylaxis being 93.8% in the major orthopedic surgery group and the lowest rate being 36.8% in the burns group (Table 2).

However, when the recommendations of the seventh ACCP guidelines were applied for prophylaxis type, dose, and duration, only 14.5% of all patients received appropriate prophylaxis (Table 2). Medical discharges also received lower levels of appropriate prophylaxis at 12.7% than surgical discharges (16.4%). Large variations in the rates of appropriate prophylaxis were observed between discharge groups in both the medical and surgical populations. In the medical groups, the highest rate of appropriate prophylaxis was 17.5% in trauma discharges, and the lowest rate was 4.7% in burns discharges. In the surgical groups, the highest rate of appropriate prophylaxis was 48.6% in major orthopedic surgery discharges, and the lowest rate was 5.7% in neurological surgery discharges.

Further examination of the individual discharge records reveals that the primary reason that discharges in the medical diagnosis groups did not receive appropriate prophylaxis was due to no pharmacological prophylaxis being provided, despite the lack of a contraindication to anticoagulant therapy (Table 3). A total of 34.1% of all medical discharges received no pharmacological prophylaxis when indicated. Other reasons for medical discharges not receiving appropriate prophylaxis were receiving pharmacological prophylaxis at an incorrect dose (lower than the guideline‐recommended daily total; 22.7%), receiving prophylaxis for an insufficient duration (missing at least 1 day of prophylaxis that was not the admission or discharge date; 22.1%), and receiving mechanical prophylaxis alone when pharmacological prophylaxis was recommended (8.4%). Variation in the reasons for not receiving appropriate prophylaxis was observed between medical diagnosis groups, with the primary reason being mechanical prophylaxis alone in acute spinal injury discharges, and no prophylaxis in burns, cancer, and trauma discharges (Table 3).

In the total surgical discharge population, an insufficient duration of prophylaxis was the main reason for not receiving appropriate prophylaxis, with 36.1% of all surgical discharges receiving an insufficient duration of prophylaxis (Table 3). Other reasons for surgical discharges not receiving appropriate prophylaxis were receiving no pharmacological prophylaxis (22.3%), receiving pharmacological prophylaxis at an incorrect dose (13.7%), and receiving mechanical prophylaxis alone (11.5%). Variation in the reasons for not receiving appropriate prophylaxis was also observed between surgical diagnosis groups, with the primary reason being inappropriate duration in vascular surgery discharges, mechanical prophylaxis alone in gynecological, laparoscopic, and neurological surgery discharges, inappropriate dosage in orthopedic surgery discharges, and no prophylaxis provided in general and urological surgery discharges (Table 3). In medical and surgical discharges that had a critical care unit stay during their hospitalization, only 15.7% received appropriate prophylaxis, with nearly one‐half of all critical care discharges receiving an insufficient duration of VTE prophylaxis (Table 3).

Analysis of the mean rates of appropriate prophylaxis by hospital factors suggests that trends exist toward increased use of appropriate prophylaxis in larger hospitals, in urban hospitals compared with rural hospitals, and in teaching compared with nonteaching hospitals (Table 4).

Discussion

This study suggests that appropriate prophylaxis, as defined in current practice guidelines for the prevention of VTE in specific at‐risk groups, is not widely applied in a selected cohort of hospitalized patients with known risks for VTE. Current ACCP guidelines provide specific direction on safe and effective prophylaxis regimens. These recommendations include the appropriate dosing and appropriate duration of prophylaxis, according to the specific risk in defined medical and surgical risk groups. However, in nearly 400,000 medical and surgical discharges at risk for VTE in U.S. hospitals, only 14.5% of discharges received VTE prophylaxis that met the recommendations of the seventh ACCP guidelines for prophylaxis type, dose, and duration. Although 71.6% of discharges received some form of prophylaxis during hospitalization, the majority of these discharges did not receive appropriate prophylaxis. Furthermore, nearly 30% of patients who should have received prophylaxis did not have a single order for prophylaxis during their hospitalization.

The ACCP has regularly updated its VTE prevention guidelines from the first release of the guidelines in 1986 to the most recent seventh guidelines in 2008.20, 21 These updates have been in line with emerging literature for both patient populations that are at risk for VTE, and for VTE prophylaxis regimens that are safe and effective in these patients. The main changes between the two most recent guidelines in VTE prevention (sixth and seventh) were to introduce risk assessment within patient groups, resulting in a greater number of more stringent recommendations.1, 11 The combination of the more stringent recommendations, and the recently growing national focus on the need for improved VTE prevention from groups such as The Joint Commission and the National Quality Forum would suggest that the levels of appropriate VTE prophylaxis in U.S. hospitals should be increasing.7, 8

The number of patients, including both medical and surgical discharges, in this study that were eligible for prophylaxis was approximately 16.6%. This number is substantially lower than previously reported in a recent U.S. study that found that 31% of U.S. hospital discharges in 2003 were at risk of VTE.22 It is likely that the discrepancy between the 2 studies is due to the more stringent length of stay criteria (6 days) in our study compared to 2 days in the Anderson et al.22 study. This length of stay criteria will have likely selected for complicated, higher‐risk patients and as such the results of this study may be more applicable to patients at higher risk of VTE than to the general population.

However, when the results of this study are compared to similar studies of appropriate prophylaxis with the sixth ACCP guidelines during the period of 2002 to 2005, the level of appropriate prophylaxis appears to have decreased.16, 17 Although strong conclusions can not be drawn from the comparison of the analyses, the appropriate prophylaxis in medical patients during the timeframe of the sixth ACCP guidelines occurred in 33.9% of patients, compared with only 13.7% in the present study. Two of the categories with the highest rates of appropriate VTE prophylaxis in the analysis of the sixth ACCP guidelines were not included in our study (acute myocardial infarction and ischemic strokedue to these patients being likely to receive treatment dose anticoagulants), but the categories that were included in both studies, ie, acute spinal cord injury, cancer, heart failure, and severe lung disease, have a 50% to 66% decrease in appropriate prophylaxis rates in the current study.16 Only trauma patients have similar rates between studies. Interestingly, the rates of any prophylaxis have increased in the current study, with 65.9% of medical patients receiving some form of prophylaxis in this analysis, compared with 61.8% in the prior study. Similar results are observed when comparing the surgical population in this analysis to prior data on surgical discharges, with the rate of any prophylaxis being higher with the seventh ACCP guidelines than the sixth ACCP guidelines (77.7% vs. 72.9%, respectively), but the rate of appropriate prophylaxis being lower (16.4% vs. 32.3%, respectively).17

The combination of an increase in any prophylaxis, but a decrease in appropriate prophylaxis may suggest that the overall national awareness of the need for VTE prophylaxis in at‐risk patients is increasing. However, the combination of more stringent guideline recommendations, and perhaps a lack of awareness as to the guideline recommendations themselves, has actually led to a decrease in the amount of appropriate prophylaxis being prescribed. Despite this, there still remain approximately 30% of patients who receive no prophylaxis at all. To this end, it is important that awareness initiatives and quality improvement programs address both the need for prophylaxis, and the most safe and effective way to provide appropriate prophylaxis in specific patient populations. The use of electronic or manual alerts and order forms for VTE prophylaxis is one effective way of increasing appropriate prophylaxis, and ultimately reducing the incidence of hospital‐acquired VTE.23 A pivotal study by Kucher et al.23 studied over 2500 patients who were randomly assigned to an electronic intervention group or a control group. In the intervention group, the physician received an electronic alert of the patients' VTE risk, whereas in the control group no alert was issued. The study found that, compared to control, both pharmacological prophylaxis (23.6% vs. 13.0%, P < 0.001) and mechanical prophylaxis (10.0% vs. 1.5%, P < 0.001) were prescribed more frequently in the intervention group. Furthermore, this led to a significant reduction in the incidence of clinically diagnosed, objectively confirmed deep‐vein thrombosis or pulmonary embolism at 90 days, with an incidence of 4.9% in the intervention group compared with 8.2% in the control group (P < 0.001). As this study has found that prophylaxis is inappropriately provided due to insufficient prescribing, insufficient duration, and inappropriate dosing, it would be interesting to identify the educational or procedural interventions that have the biggest impact on each factor. This would allow hospitals to create multicomponent initiatives with a greater chance of increasing the rates of appropriate prophylaxis.

A strength of this study is that this is the largest database analysis of hospital discharges and seventh ACCP guideline‐recommended VTE prophylaxis use to date, giving insights into real‐world clinical practice in the United States with the most recent guidelines. This will provide a checkpoint for improvements in advance of the 2008 guidelines being released. A limitation of this study is that we have utilized a conservative approach to selecting patients who were clearly at risk of VTE. Patients were required to have a length of stay 6 days. This may have both excluded a number of orthopedic surgery and medical patients despite their requirements for VTE prophylaxis and likely have selected a cohort of sicker patients at high‐risk for VTE. It is possible that this will have created a bias for specific patient or hospital characteristics (eg, complex patients or hospitals with less efficient systems) that we cannot adjust for, and this may have affected the results of the study. Due to the use of hospital records alone, we are also unable to examine whether discharges continued to receive appropriate prophylaxis following discharge. As some orthopedic surgery patients are recommended to receive prophylaxis for up to 28 to 35 days following surgery,1 this limitation is likely to have resulted in an overestimation of appropriate prophylaxis rates in the current study. However, it is important to note that the appropriate prophylaxis rate was extremely low, even in this selected higher‐risk population. Furthermore, the use of length of stay minus 2 days as the criteria for appropriate duration may have led to a slight underestimation of appropriate prophylaxis, especially as the reasons for any interruption of prophylaxis by the physician during the hospital stay are unknown. An additional limitation is that the study uses retrospective discharge record data that cannot fully evaluate whether the prophylaxis was appropriate in a complex individual patient. For example, contraindications to anticoagulant prophylaxis are not always documented and may not have been identified in the hospital coding exclusion criteria. In addition, we are only able to assess whether mechanical prophylaxis was ordered, and not whether it was appropriately used. Another limitation is that basing assignment of prophylaxis on the principal diagnosis increases the likelihood that clinical decisions on prophylaxis were based on the primary reason for admission, when in reality there may have been multiple factors affecting the patient's risk assessment and the physician's prophylaxis decision. In this analysis, we used the ACCP guidelines as these are currently the most long‐standing VTE prophylaxis guidelines available, as well as being the most comprehensive for multiple patient groups. However, it is important to acknowledge that specific specialties, such as oncologists and orthopedic surgeons, also have their own specialized guidelines which may have different recommendations. This may therefore have led to an underestimation of appropriate prophylaxis. In addition, the ACCP guidelines have been updated in 2008, providing physicians with a revised set of recommendations for VTE prophylaxis.21 We utilized the 2004 guidelines in our analysis as we feel that it is important to assess whether the prophylaxis provided was appropriate by the standards of care during the timeframe within which the data were collected. However, we acknowledge that applying the new guidelines may impact the results of the study. One final consideration that would make an interesting follow‐up study is an assessment of whether appropriate or inappropriate prophylaxis impacts the clinical outcomes. For example, do patients with appropriate prophylaxis have fewer VTE events and improved mortality compared with those without prophylaxis or with inappropriate prophylaxis.

In summary, this work identifies that, in the United States, there is still considerable underutilization of appropriate VTE prophylaxis across a broad range of diagnostic groups with known VTE risk. While nearly three‐quarters of patients do receive at least 1 order for VTE prophylaxis during their hospitalization, only approximately 1 in 7 patients receive appropriate prophylaxis that matches evidence‐based recommendations for type, dose, and duration. Physician awareness of both the need for VTE prophylaxis, and more specifically what constitutes appropriate prophylaxis in certain patient groups, needs to be increased. The current national performance initiatives will provide a framework for this improvement, but it is the responsibility of individual hospitals to improve their VTE prophylaxis practices. Such an improvement across hospitals will lead to a sizeable reduction in the incidence and economic burden of VTE on the U.S. healthcare system.

Professional and patient safety organizations have recognized the importance of safe transitions as patients move through the health care system, and such attention is even more critical when attempting to achieve glycemic control.14 Since the publication of the Diabetes Control and Complications Trial (DCCT)5 and the United Kingdom Prospective Diabetes Study (UKPDS),6 we have known that intensive glycemic control in the ambulatory setting prevents complications in both type 1 and type 2 diabetes mellitus (DM). Despite the increased risk of hypoglycemia, these trials changed practice patterns in the outpatient settings in favor of intensification of diabetes therapy. In the same way, randomized, prospective trials using intravenous (IV) insulin therapy have revolutionized our thinking about inpatient care by showing that tight glycemic control in the critically ill7 and patients with acute myocardial infarction8 reduces mortality and morbidity. These, as well as additional observational studies associating hyperglycemia with poor outcomes in a variety of medical and surgical patients,915 have led to increased attention on glycemic control in all venues of care.16, 17 Concerns over excessive hypoglycemia and a nonsignificant increase in mortality in certain populations of medical intensive care unit (ICU) patients have raised questions over whether the initial studies can be reproduced or generalized to other groups of inpatients.18, 19 Additional studies are underway to clarify these questions but consensus exists that blood glucose values should at least be less than 180 mg/dL and that the traditional practice of ignoring hyperglycemia is no longer acceptable.

While a uniform focus on glycemic control will allow our patients to receive a consistent message about diabetes, the unique limitations inherent to each practice setting requires different therapeutic regimens and intentional focus on the risks as patients transition from one care area to another. This work addresses several areas of care transition that are particularly important in safely achieving glycemic control including: transition into the hospital for patients on a variety of home regimens, transitions within the hospital (related to changes in dietary intake, change from IV to subcutaneous [SC] therapy, and the perioperative setting), and the transition from the hospital to home or another healthcare facility.

TRANSITION INTO THE HOSPITAL

Until recently, most patients with diabetes admitted to the hospital were managed with sliding‐scale‐only regimens.20, 21 Unfortunately, this led to a variety of complications, including hyperglycemia, hypoglycemia, iatrogenic ketoacidosis, and an inconsistent message to patients on the importance of glycemic control.22 Some outpatient clinicians and patients combated this tradition by creating in‐hospital glucose control plans with orders, which patients would bring with them to the hospital.23 This practice continues to be a helpful way to guide inpatient therapy and is encouraged when available. Glycemic‐controlrelated documents from outpatient clinicians should include the most recent glycosylated hemoglobin (HbA1c) value, diagnosis and known complications, current names and doses of medications, and other patient‐specific preferences or needs (eg, compliance, financial, fear of needles). If the last HbA1c was performed more than 30 days before admission or is not available, one should be obtained upon hospital admission to help guide discharge therapy.24 By knowing the HbA1c, one can determine the level of diabetic control achieved with the current regimen and can help the inpatient team (clinician and patient) determine if a more aggressive glycemic control regimen is necessary at the time of discharge. It is important to note that if the patient has received a transfusion of red blood cells prior to HbA1c measurement or has a hemoglobinopathy, the HbA1c value may not be accurate.25, 26

In general, the outpatient regimen will need to be modified at admission to achieve the appropriate flexibility needed for the changing nutritional intake and insulin requirements that invariably accompany hospitalization. Sulfonylureas and dipeptidyl peptidase 4 inhibitors (DPP4), such as sitagliptin, have most of their effect immediately, but the other oral antihyperglycemic agents have a relatively long delay between treatment and effect, thus they are not a flexible enough method to achieve glycemic control in the hospital. Additionally, inpatients may have transient contraindications to their prior oral antihyperglycemic medications. Metformin is almost always on hold in the hospital setting, at least initially, due to concerns about lactic acidosis. Sulfonylureas can cause hypoglycemia in the setting of worsening renal function or reduced oral intake. Thiazoladinediones (TZDs) are often withheld due to concerns about fluid retention and should be avoided in patients admitted with heart failure. There is little experience in the hospital with the use of newer agents like exenatide, pramlintide, glinides, and DPP4 inhibitors.

Overall, it is generally recommended that oral antihyperglycemic agents be discontinued upon hospital admission and replaced with insulin infusions or scheduled SC insulin. An estimate of 0.4 to 0.5 units/kg of body weight provides a conservative starting point for the total daily dose of insulin (TDD) for most patients. This TDD should then be divided into basal and nutritional components to match the patients' caloric intake. Additional correction doses of insulin should be prescribed to cover episodes of hyperglycemia that develop despite the provision of anticipatory‐physiologic insulin. Further discussion of insulin dosing and SC regimens is available in detail elsewhere.27, 28 The recommendation for these insulin‐only regimens is made regardless of the glycemic control in the outpatient setting and is not meant to imply that they should be continued at discharge. In fact, most patients will return to their home regimen or to one that is intensified but less labor intensive than the basal‐nutritional‐correction insulin used in the hospital. The antihyperglycemic regimen planned for discharge should be anticipated as early as possible and clearly communicated to the patient and/or caregivers to allow for optimal education.

Outpatient insulin regimens that have a high percentage of basal insulin need to be modified during hospital admission to avoid hypoglycemia that may occur from variable nutritional intake. While hospitalized, the basal portion of the estimated TDD generally should not be more than 50% to 60%. The total number of units of all types of insulin used daily as an outpatient can be used as a starting point for determining the inpatient TDD by a 1:1 conversion. Adjustments up or down based on glycemic control, nutritional intake, and other factors are then necessary. If patients are on regimens with insulin plus oral agents at home, the inpatient TDD should either be the home insulin dose or the dose calculated based on their weight, whichever is greater. Patients who use carbohydrate counting to determine nutritional insulin doses as an outpatient might be continued on this regimen if they have a strong understanding of the methods, they are coherent enough to determine their doses, nursing staff are well educated, and dietary services provides the carbohydrate content for the hospital menu. If patients are on insulin pumps at home, these should be managed according to a uniform hospital policy to assure safety. If conversion to multiple daily injections is needed, the same 1:1 conversion is safe.29

TRANSITIONING FROM THE HOSPITAL

The final but perhaps most important transition is the one from the hospital. With much attention on glycemic control in the hospital, it will become clear to many clinicians that the outpatient regimen needs to be modified. However, any changes in medications increase the chances of hypoglycemia and the possibility of error. The postdischarge time frame has been poorly studied and was specifically identified by the Association for Clinical Endocrinologists (ACE) and American Diabetes Association (ADA) as an area in need of future research.36

Patients may be discharged to a nursing home, hospice, or home, and numerous factors need to be considered to determine the optimal discharge regimen. Important considerations are the HbA1c at admission, home medications, medication interactions, current medical problems, nutritional status, physical disabilities, frequency of self‐monitoring, hypoglycemic risk factors, contraindications to oral medications, goals of care/life expectancy, and financial and other resources. If there are temporary physical or self‐care limitations, then a visiting nurse may need to be arranged to assure a safe transition home with the optimal therapy. If patients are going to a skilled nursing facility or other acute care hospital, the formulary, processes, and staffing issues of that facility will be additional important considerations in determining whether therapy is the same as in the hospital or more like what it will be at home.

An algorithm for outpatient therapy for type 2 DM was recommended in a consensus statement from the ADA and European Association for the Study of Diabetes.42, 43 This has been modified using additional recommendations from the AACE44 and is depicted in Figure 1. While the delineation of these steps is helpful, it must be emphasized that both the choice of regimen and dose will need to be individualized. Prescribing the ideal frequently falls short if there is no way for the patient to implement the recommendations. Intensive insulin therapy requires training in food intake/emnsulin matching, motivation of the patient and outpatient clinician, 4 times daily self‐monitoring of blood glucose, and considerable expense. Some patients may be temporarily continued on basal‐nutritional‐correction regimens as their insulin requirements are rapidly changing and later converted to regimens that involve less frequent insulin doses, (ie, twice daily premixed insulin or basal insulin with oral agents or oral agents alone).45, 46 Other patients who may be medically appropriate for intensive insulin therapy may first need to gain confidence with more simple insulin regimens. There are numerous additional resources on initiating insulin that the reader is referred to for more detail.4448

Figure 1

Oral antihyperglycemic drugs are usually held while a patient is admitted to the hospital but once medical conditions are improved, oral intake is established, and renal function stabilized, these drugs can be restarted. If a patient has a new contraindication to metformin or sulfonylureas but does not need insulin, a TZD or DPP4 inhibitor should be considered. Elderly patients and those with renal or liver disease are at increased risk for developing hypoglycemia.49, 50 Glyburide should be avoided, and doses of other sulfonylureas may need to be adjusted. Other options that may be considered in this situation include sitagliptin and exenatide.51 When patients will be discharged on oral diabetic medications alone, discontinue the basal insulin 12 to 24 hours before and the scheduled nutritional insulin at the same time oral agents are restarted. Sulfonylureas, metformin, DPP4 inhibitors, and exenatide will have most of their effect in the first day, but TZDs have a delayed onset and may not be a good bridge for immediate control at discharge.

If patients are going to be discharged on basal insulin in addition to oral agents, several options exist for determining the dose. Because of the risk of hypoglycemia after discharge, it is advised to either reduce the doses of oral agents or choose more conservative insulin starting doses.52 One possibility is to discontinue the nutritional and correction doses, continue the hospital dose of basal insulin, and restart the oral antidiabetes medications. If the dose of basal insulin was more than 50% of the TDD of insulin, it may need to be reduced. A more conservative option for patients at a higher risk of hypoglycemia is to start 0.2 units/kg or 10 units of NPH, glargine, or detemir at bedtime (Figure 2). Once discharged, blood glucose should be measured 1 to 4 times a day and the basal dose titrated by several different validated methods.53, 54 Appropriate orders for necessary supplies for insulin therapy include a meter with test strips, lancets, syringes, needles, and glucagon kit.55

Figure 2

With a large number of patients with diabetes remaining undiagnosed, it is important to use the information available during hospitalization to identify previously unrecognized diabetes or prediabetes.24 Because there are no unique criteria for the diagnosis of DM in the stressed state, patients may have a presumptive diagnosis made in the hospital and/or follow‐up testing with fasting glucose or an oral glucose tolerance test. No ADA diagnostic thresholds for the HbA1c currently exist, but it can be a useful marker in making this distinction.56 Among patients with new hyperglycemia, an HbA1c of 6% or greater was 100% specific for predicting a future diagnosis of diabetes in the small prospective cohort study by Greci et al.,57 but many endocrinologists use a cutoff of 7%. For all hyperglycemic patients, lifestyle interventions that promote weight loss and increased activity levels should be encouraged. New hyperglycemia should be clearly identified as a diagnosis in discharge communication.

There are many barriers to diabetes self‐management education in the inpatient setting but there are also numerous resources and opportunities. New information will be available regarding patients' understanding of their disease and glycemic control and there may be plans for changes in the home medication regimen. Most of the focus of inpatient education sessions is on survival skills such as taking medications, performing blood glucose monitoring, basic meal planning, identification and treatment of hypoglycemia, sick‐day management, how to access further diabetes education as an outpatient, and when to call the healthcare team.58 The most effective way to accomplish all of this is to identify the discharge regimen early and include nurses and staff in a plan to educate all patients. An inpatient diabetes educator can provide additional help with newly‐diagnosed or uncontrolled patients. Dividing the material over the hospitalization makes it less overwhelming for patients, reinforces previously taught concepts, spreads the responsibility to more providers, and offers it in conjunction with the correlating clinical care. Throughout their hospital stay, patients can begin to practice new skills, including blood glucose monitoring and logbook use, drawing up and administering insulin, sharps disposal, basic diabetic diet information, and sick‐day management. The specific topics addressed in each session can be tracked as part of an interdisciplinary education record that allows coordination among the individuals involved in teaching.59 It is important to give patients the basics, support them with minimal written information, and provide them appropriate follow‐up diabetes education.60 Furthermore, the inpatient team should view the patient's glycemic control education as something that needs to continue across the continuum of care and develop communication strategies that connect with the follow‐up clinical team.

At the time of discharge, it is essential that written documentation and communication with outpatient care providers be completed.61, 62 The more standardized the inpatient insulin regimens are, the more likely the patient is to be on a much different glycemic control regimen than the one on admission; therefore, it is even more important to assure that the admission medication list is accurate and reconciled completely with the modified list at discharge. Discharge check lists and tools for assessing patient acceptance of the discharge plan help with this process.63 Follow‐up with the primary care physician should occur within 7 to 14 days if patients are new to insulin, had medication changes, or are elderly. An increased likelihood of keeping posthospitalization appointments with a diabetes specialty clinic has been associated with being discharged on insulin, a new diagnosis of diabetes, and direct referral.64 Additional attention should be paid to barriers to follow‐up, including lack of health insurance, prior difficulty with follow‐up, and transportation problems.65

SUMMARY

A variety of factors have contributed to difficulty in achieving inpatient and outpatient glucose control. These include care complexity, the lack of standardized protocols, limited knowledge about glucose control, and clinical inertia. Inpatient clinicians have a tendency toward keeping patients on their home regimen in hopes that they might test its effectiveness. Furthermore, there has been the notion of why optimize the glycemic regimen of inpatients because their diabetic needs will change in the outpatient setting. However, because the insulin requirements during acute illness are different and nutritional intake is variable, nearly all inpatients should be placed on multiple daily doses of scheduled insulin or IV insulin to allow the necessary flexibility for rapid titration and abrupt changes in nutrition. This intensive regimen is only appropriate for a minority of outpatients. This difference illustrates that a regimen that works perfectly in one clinical setting will not necessarily be optimal in the next. The patient's outpatient treatment regimen should be reassessed based on HbA1c, self‐monitoring prior to admission, and new contraindications based on medical issues. If a change is indicated and the inpatient physician is motivated, there are numerous helpful resources to aid in addressing all the necessary factors surrounding intensification of therapy.

Despite requiring different glycemic control regimens, the information gained from the needs in each setting guide the next, making communication and planning paramount. Important transitions that must be given attention are: (1) admission to the hospital; (2) in‐hospital transitions, including the perioperative period and IV‐to‐SC insulin; and (3) the hospital to outpatient transition. The complexity of such frequent transitions requires planning, education, and clear communication that are best handled with a systems approach and the development of standardized protocols and order sets. Hospitalists, endocrinologists, and other members of the healthcare team should take an aggressive role in developing systems and facilitating optimal transitions to maximize glycemic control. Further studies are needed to determine the best practices among the variety of options discussed in this article.