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Two-Minute Screen Effective for Post-Op Delirium
Clinical Question: Is the 10-point cognitive screener (10-CS) effective in screening for delirium in older adults with hip fracture?
Background: Delirium in elderly hip fracture patients has been established as a significant comorbidity. There is, however, no agreement on the most appropriate and practical screening tool. Commonly used screening methods, which focus on the detection of cognitive impairment as a surrogate, are time-consuming, insensitive for mild impairment, and limited in their application to patients with impaired dexterity and poor education.
Study Design: Prospective cohort study.
Setting: Tertiary referral hospital in São Paulo, Brazil.
Synopsis: In the study, 147 consecutive hip fracture patients over age 60 were screened using the 10-CS. This test stratifies patients into three categories: normal, possible, and probable cognitive impairment. Development of in-hospital delirium was evaluated by daily Confusion Assessment Method testing administered by a geriatrician. Patients categorized as probable cognitive impairment were more likely to develop delirium (hazard ratio, 7.48; 95% CI, 2.2–25.4).
Hospitalists involved in perioperative care should consider using this simple screening tool. With an area under ROC curve of 0.83 (95% CI, 0.76–0.89), it effectively detects delirium in this high-risk population. Independently, patients who developed delirium had a longer length of stay (median 11.0 versus 7.0; P < 0.001). This serves as a reminder of the importance of screening and preventing delirium in this population.
Bottom Line: The 10-CS tool is practical in its application and effective in identifying elderly hip fracture patients at risk for delirium.
Citation: Fortes-Filho SQ, Apolinario D, Melo JA, Suzuki I, Sitta MD, Garcez-Leme LE. Predicting delirium after hip fracture with a 2-min cognitive screen: prospective cohort study [published online ahead of print May 17, 2016]. Age Ageing. pii:afw084.
Clinical Question: Is the 10-point cognitive screener (10-CS) effective in screening for delirium in older adults with hip fracture?
Background: Delirium in elderly hip fracture patients has been established as a significant comorbidity. There is, however, no agreement on the most appropriate and practical screening tool. Commonly used screening methods, which focus on the detection of cognitive impairment as a surrogate, are time-consuming, insensitive for mild impairment, and limited in their application to patients with impaired dexterity and poor education.
Study Design: Prospective cohort study.
Setting: Tertiary referral hospital in São Paulo, Brazil.
Synopsis: In the study, 147 consecutive hip fracture patients over age 60 were screened using the 10-CS. This test stratifies patients into three categories: normal, possible, and probable cognitive impairment. Development of in-hospital delirium was evaluated by daily Confusion Assessment Method testing administered by a geriatrician. Patients categorized as probable cognitive impairment were more likely to develop delirium (hazard ratio, 7.48; 95% CI, 2.2–25.4).
Hospitalists involved in perioperative care should consider using this simple screening tool. With an area under ROC curve of 0.83 (95% CI, 0.76–0.89), it effectively detects delirium in this high-risk population. Independently, patients who developed delirium had a longer length of stay (median 11.0 versus 7.0; P < 0.001). This serves as a reminder of the importance of screening and preventing delirium in this population.
Bottom Line: The 10-CS tool is practical in its application and effective in identifying elderly hip fracture patients at risk for delirium.
Citation: Fortes-Filho SQ, Apolinario D, Melo JA, Suzuki I, Sitta MD, Garcez-Leme LE. Predicting delirium after hip fracture with a 2-min cognitive screen: prospective cohort study [published online ahead of print May 17, 2016]. Age Ageing. pii:afw084.
Clinical Question: Is the 10-point cognitive screener (10-CS) effective in screening for delirium in older adults with hip fracture?
Background: Delirium in elderly hip fracture patients has been established as a significant comorbidity. There is, however, no agreement on the most appropriate and practical screening tool. Commonly used screening methods, which focus on the detection of cognitive impairment as a surrogate, are time-consuming, insensitive for mild impairment, and limited in their application to patients with impaired dexterity and poor education.
Study Design: Prospective cohort study.
Setting: Tertiary referral hospital in São Paulo, Brazil.
Synopsis: In the study, 147 consecutive hip fracture patients over age 60 were screened using the 10-CS. This test stratifies patients into three categories: normal, possible, and probable cognitive impairment. Development of in-hospital delirium was evaluated by daily Confusion Assessment Method testing administered by a geriatrician. Patients categorized as probable cognitive impairment were more likely to develop delirium (hazard ratio, 7.48; 95% CI, 2.2–25.4).
Hospitalists involved in perioperative care should consider using this simple screening tool. With an area under ROC curve of 0.83 (95% CI, 0.76–0.89), it effectively detects delirium in this high-risk population. Independently, patients who developed delirium had a longer length of stay (median 11.0 versus 7.0; P < 0.001). This serves as a reminder of the importance of screening and preventing delirium in this population.
Bottom Line: The 10-CS tool is practical in its application and effective in identifying elderly hip fracture patients at risk for delirium.
Citation: Fortes-Filho SQ, Apolinario D, Melo JA, Suzuki I, Sitta MD, Garcez-Leme LE. Predicting delirium after hip fracture with a 2-min cognitive screen: prospective cohort study [published online ahead of print May 17, 2016]. Age Ageing. pii:afw084.
HE for the Hospitalist
Reversible impairment of brain function in the setting of cirrhosis defines hepatic encephalopathy (HE). HE is associated with significantly decreased survival,[1] and patients with HE have poor outcomes whether HE occurs in isolation or in conjunction with acute‐on‐chronic liver failure.[2] A large multicenter study comparing cirrhotics with and without HE also found that those with a history of HE were hospitalized more frequently.[2]
The presentation of HE is variable, and diagnosis remains clinical. Subtle manifestations of HE persist between episodes, even if gross cognitive function normalizes.[3] Retrospective data suggest the effects of serial bouts of HE may be cumulative, because even with appropriate treatment, the severity of impairment correlates with the number of prior episodes.[3] Even minimal manifestations of hepatic encephalopathy correlate with reduced quality of life.[4]
The West Haven score is the most validated scoring system.[5] Higher grades of HE correlate with significantly increased mortality,[2] but due to difficulties differentiating stages 0 and 1, these criteria remain somewhat controversial. The Spectrum of Neurocognitive Impairment in Cirrhosis (SONIC) has been proposed as an alternate conceptualization of HE as a continuous spectrum rather than discrete stages.[6] Table 1 shows findings associated with various West Haven and SONIC stages. Both systems include covert and overt encephalopathy. Covert correlates with West Haven grades 0 to 1, and consists mainly of subtle findings that require specialized psychometric testing to detect. The SONIC system terms demonstrable but subclinical manifestations minimal HE.[6] Overt HE includes West Haven grades 2 through 4, and refers to objective findings that can be reliably detected on clinical evaluation.[7] Whereas specific numeric scores are used largely for research purposes, classifying HE as covert or overt is clinically useful.
| West Haven Grade | SONIC Classification | Neurologic Changes | Asterixis |
|---|---|---|---|
| |||
| 0 | Normal | None | None |
| Minimal HE | Requires specialized psychometric testing | ||
| 1 | Overt | Decreased attention span, hypersomnia/emnsomnia | Detectable |
| 2 | Lethargy, disorientation | Obvious | |
| 3 | Semistupor or stupor | None | |
| 4 | Coma | None | |
Although blood ammonia levels correlate well across populations, they are not diagnostically useful for individuals, because considerable overlap exists between patients with no HE and those with severe encephalopathy.[8] Ammonia levels also do not predict HE development.[9] Brain imaging is of limited utility, but may be prudent with abrupt decompensation, focal neurologic findings, or poor response to therapy.[10] A recent single‐center review of head computed tomography in cirrhotic patients presenting with altered level of consciousness found a low incidence of intracranial hemorrhage (ICH).[11] The number needed to scan was 293 patients to detect a single ICH. Only 1 patient out of 316 had ICH when fever, trauma, and focal neurological findings were excluded. The presence of acute ICH was not associated with platelet count, coagulopathy, creatinine, or Model for End‐Stage Liver Disease score.
PRECIPITANTS
Initial evaluation of patients with suspected HE must confirm the presence of HE and identify potentially reversible precipitants. Infection, bleeding, and metabolic derangements (including renal injury, hypovolemia, and hyponatremia) are common precipitants.[12] Searching for precipitants is heavily stressed in the 4‐pronged approach recommended by the American Association for the Study of Liver Disease,[7] as summarized in Table 2. Common precipitants are grouped into episodic and recurrent causes. Episodic causes are those that represent discrete insults with specific, short‐term treatments. Recurrent causes are those that are likely to require active management over time. These distinctions may help inform different approaches for initial or recurrent episodes of HE; in practice, much overlap exists.
| |
| 1. Initiate care for cirrhotic patients with altered consciousness | |
| 2. Seek and treat alternative causes of altered mental status if present | |
| 3. Identify and treat precipitating factors: | |
| Episodic | Recurrent |
| Infection | Electrolyte derangement |
| Gastrointestinal bleeding | Infection |
| Hypovolemia | Constipation |
| Electrolyte derangement | Hypovolemia |
| Constipation | Gastrointestinal bleeding |
| 4. Commence empiric HE treatment | |
Diuretic use has been clearly correlated with incidence of HE.[2] Although diuretic usage may be an indicator of more advanced liver disease, their use can also contribute to HE via increased risk of hypovolemia and dysnatremia.[2] Accordingly, caution is necessary when using diuretics to manage patients with HE and refractory ascites. These findings have led some to suggest serial paracentesis may be preferable to diuretics in this population.[2]
MANAGEMENT
The mainstay of HE treatment is administration of the nonabsorbable disaccharide lactulose. Lactulose is part of nearly all regimens because it is effective, easily titrated, and inexpensive.[13] It is efficacious orally or as an enema.[14] Lactulose increases both cognitive function and quality of life,[15] and is effective for prophylaxis and treatment of all stages of HE.[16, 17]
Rifaximin is often used as an adjunct to lactulose, particularly in cases of recurrent HE. Small trials have associated rifaximin with increased quality of life[18] and cognitive function.[19] The largest randomized trial of rifaximin was a double‐blind, placebo‐controlled trial in patients with multiple episodes of overt HE during the prior 6 months.[20] Lactulose was used concomitantly in approximately 91% of patients. At the end of the 6‐month study, rifaximin was associated with a 58% relative risk reduction in overt HE recurrence and roughly 50% reduction in HE‐related hospitalization. The numbers needed to treat were 4 patients to prevent 1 overt HE episode and 9 to prevent 1 HE‐related hospitalization.[20]
A meta‐analysis of 264 patients included in published, high‐quality trials found rifaximin monotherapy to be similar to nonabsorbable disaccharides in both efficacy and incidence of diarrhea, but with significantly less abdominal pain.[21] This analysis was limited by significant heterogeneity among trials. A larger, more recent systematic review and meta‐analysis of 19 studies (both published and unpublished) found rifaximin to be effective for treatment, secondary prophylaxis, and possibly decreased mortality.[22] Of note, this meta‐analysis included placebo studies as well as studies using varying doses of lactulose or other antibiotics as controls. Despite this variability, the authors concluded that the control used in the individual trials did not significantly affect the aggregate results.[22] In the largest individual study to show a mortality benefit, improvement seemed to be driven by decreased rates of sepsis when rifaximin was used as an adjunct to lactulose.[23] Cost is a barrier to use, as rifaximin has not proven to be cost‐effective as monotherapy instead of lactulose.[24] Many insurers will facilitate adjunctive rifaximin with prior authorization, and the manufacturer offers assistance programs.[25]
Other adjuncts, including laxatives,[26] antibiotics,[12] branched‐chain aminoacids,[27] and acarbose[28] have far less evidentiary support and require further study prior to incorporation into clinical practice.[26] A recent study showed polyethylene glycol to perform similar to lactulose, but the studied volume of 4 L daily may make routine use impractical.[29] Dietary protein restriction has been shown in a prospective randomized controlled trial to accelerate body muscle breakdown without affecting HE,[30] so is best avoided.
ISSUES PERTINENT TO HOSPITAL MANAGEMENT
Concurrent HE frequently complicates inpatient management of acute pain. Acetaminophen below 3 g daily for short‐term use is safe,[31] but may be insufficient. Non‐steroidal anti‐inflammatory agents are best avoided given risks for renal dysfunction and bleeding.[32] Although a direct connection between opiate use and HE remains unproven, these agents are problematic because they can cause both sedation and constipation. Nonetheless, they are often needed for pain control. Oxycodone has a more desirable side effect profile than other narcotics. We often prescribe doses every 6 hours initially to account for decreased hepatic metabolism. Morphine has active metabolites that can accumulate in cirrhotics, so morphine use is best avoided.[32] Fluctuations in cognition may help distinguish narcosis from HE; specifically, narcosis causes chronic somnolence worst shortly after an opiate dose, whereas HE causes alterations in sleep‐wake cycles including insomnia.[32] Frequent adjustment of opiate dose and frequency may be required to balance analgesia with unwanted sedation and constipation.
Decisional capacity frequently complicates care of patients with cirrhosis. Patients may decline therapy because of dissatisfaction with bowel frequency, but such lapses in adherence likely contribute to HE recurrence. Patients with overt HE are often incapable of making decisions based on informed consent. If such patients have inadequate social support to ensure medical attention if symptoms progress, then mandatory treatment is reasonable. This may include involuntary administration of medications via rectal or nasogastric tube. Once cognition improves enough that he or she can reliably articulate risks, benefits, and alternatives of declining therapy, then it is reasonable to allow them to do. Subspecialty consultation with psychiatry or ethics may be useful in such situations.
For cirrhotics admitted for management of nonhepatic issues (particularly operations or invasive procedures), vigilance is needed to monitor for HE during hospitalization. Patients with HE have increased risk of falls and impaired driving, which may lead to admission onto surgical services.[4] Changes in diet, medications, bowel function, and environment may all contribute to encephalopathy. HE occurring during admission for other diagnoses still requires prompt titration of lactulose. Routine inquiry about bowel function and sleep quality are likely to help identify trouble early.
Placement of transvenous intrahepatic portosystemic shunt (TIPS) increases the risk for HE via introduction of neurotoxins directly into the systemic circulation. These patients can typically be treated medically,[33] but are likely to require increased lactulose dosage. TIPS revision may be necessary for patients with treatment‐refractory HE, but retrospective evidence suggests this is rarely necessary.[33] In that study, only a single patient out of 81 with post‐TIPS HE required TIPS closure.
Under the International Classification of Disease, 10th Revision, a diagnosis of HE is often most consistent with metabolic encephalopathy (G93.41).[34] It may also be coded as chronic hepatic failure without coma (K7210) or chronic hepatic failure with coma (K7211).[35] Whenever possible, specifying the underlying liver disease (eg, hepatitis C virus, alcohol) is preferable.
TRANSITIONING TO OUTPATIENT CARE
HE patients are usually ready for community living once their cognition has improved enough to reliably take medications. Key aspects of HE management need to be communicated clearly to patients and caregivers. Barriers to optimal outpatient care mostly relate to lactulose adherence. Stressing the direct correlation between insufficient bowel movements and HE progression may enhance adherence. All patients need a lactulose titration plan including when doses can be skipped and when additional doses are needed. Even minimal symptoms of HE need to be addressed,[36] and specific vigilance for alterations in sleep‐wake cycles needs to be adopted. Table 3 is an example of a lactulose titration plan that can be used at discharge. These plans should be included in discharge documents and within communication to outpatient healthcare providers. Close follow‐up with a hepatology specialist is ideal to ensure appropriate lactulose use, answer questions that arise upon return home, and address other concerns related to cirrhosis.
|
| Your dose of lactulose is 30 mL (1 tbsp) 3 times daily with meals. |
| If you have fewer than 3 BMs in any day, take an additional dose of lactulose at bedtime. |
| If you begin to experience difficulty sleeping at night, excessive drowsiness during the day, or confusion, take 2 doses of lactulose with each meal to ensure 3 or more BMs daily. |
| If you have more than 4 BMs in any 24 hour period and are not having any of the symptoms mentioned above, skip a single dose of lactulose then resume your usual schedule. |
Although specific interventions to decrease readmission have not been studied in this population, best practices from other populations (such as medication self‐management, follow‐up plans, and red flags to be on watch for[37]) likely apply. Defining optimal strategies to decrease readmission is an opportunity for hospitalists to contribute to standardization of care for these patients.
CONCLUSIONS
HE is a common but very treatable complication of cirrhosis. Various metabolic insults may precipitate HE, and hospitalists should seek to reverse contributing factors whenever possible. Lactulose titrated to ensure adequate bowel output is the cornerstone of both therapy and prevention for HE. Adjunctive use of rifaximin improves many outcomes. Patient education about manifestations of HE and medication titration is crucial to achieving smooth transition to the outpatient setting.
Disclosure
Nothing to report.
- , , , et al. Prognostic significance of hepatic encephalopathy in patients with cirrhosis. J Hepatol. 1999;30(5):890–895.
- , , , et al. Characteristics, risk factors, and mortality of cirrhotic patients hospitalized for hepatic encephalopathy with and without acute‐on‐chronic liver failure (ACLF). J Hepatol. 2014;60(2):275–281.
- , , , et al. Persistence of cognitive impairment after resolution of overt hepatic encephalopathy. Gastroenterology. 2010;138(7):2332–2340.
- , , . Minimal hepatic encephalopathy impairs quality of life. J Clin Exp Hepatol. 2015;5(suppl 1):S42–S48.
- , ; Practice Parameters Committee of the American College of Gastroenterology. Hepatic encephalopathy. Am J Gastroenterol. 2001;96(7):1968–1976.
- , , . Spectrum of neurocognitive impairment in cirrhosis: Implications for the assessment of hepatic encephalopathy. Hepatology. 2009;50(6):2014–2021.
- , , , et al. Hepatic encephalopathy in chronic liver disease: 2014 Practice Guideline by the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver. Hepatology. 2014;60(2):715–735.
- , , , et al. Correlation between ammonia levels and the severity of hepatic encephalopathy. Am J Med. 2003;114(3):188–193.
- , . Serum ammonia level for the evaluation of hepatic encephalopathy. JAMA. 2014;312(6):643–644.
- , , . Hepatic encephalopathy in patients with acute decompensation of cirrhosis and acute‐on‐chronic liver failure. J Hepatol. 2015;62(2):437–447.
- , , , et al. Low Likelihood of intracranial hemorrhage in patients with cirrhosis and altered mental status. Clin Gastroenterol Hepatol. 2015;13(1):165–169.
- , . The management of hospitalized patients with cirrhosis: the Mount Sinai experience and a guide for hospitalists. Dig Dis Sci. 2011;56(5):1266–1281.
- , , . Nonabsorbable disaccharides for hepatic encephalopathy. Cochrane Database Syst Rev. 2004(2):CD003044.
- , , , et al. Acidifying enemas (lactitol and lactose) vs. nonacidifying enemas (tap water) to treat acute portal‐systemic encephalopathy: a double‐blind, randomized clinical trial. Hepatology. 1987;7(4):639–643.
- , . Disaccharides in the treatment of hepatic encephalopathy. Metab Brain Dis. 2013;28(2):313–320.
- , , , . Secondary prophylaxis of hepatic encephalopathy: an open‐label randomized controlled trial of lactulose versus placebo. Gastroenterology. 2009;137(3):885–891, 91.e1.
- , , , , , . Efficacy of lactulose in cirrhotic patients with subclinical hepatic encephalopathy. Dig Dis Sci. 2000;45(8):1549–1552.
- , , , et al. Randomised clinical trial: rifaximin improves health‐related quality of life in cirrhotic patients with hepatic encephalopathy—a double‐blind placebo‐controlled study. Aliment Pharmacol Ther. 2011;34(8):853–861.
- , , , , , . Rifaximin improves psychometric performance and health‐related quality of life in patients with minimal hepatic encephalopathy (the RIME Trial). Am J Gastroenterol. 2011;106(2):307–316.
- , , , et al. Rifaximin treatment in hepatic encephalopathy. N Engl J Med. 2010;362(12):1071–1081.
- , , , , , . Rifaximin versus nonabsorbable disaccharides in the management of hepatic encephalopathy: a meta‐analysis. Eur J Gastroenterol Hepatol. 2008;20(11):1064–1070.
- , , , , . Systematic review with meta‐analysis: the effects of rifaximin in hepatic encephalopathy. Aliment Pharmacol Ther. 2014;40(2):123–132.
- , , , , , . A randomized, double‐blind, controlled trial comparing rifaximin plus lactulose with lactulose alone in treatment of overt hepatic encephalopathy. Am J Gastroenterol. 2013;108(9):1458–1463.
- , , . The cost‐effectiveness and budget impact of competing therapies in hepatic encephalopathy—a decision analysis. Aliment Pharmacol Ther. 2007;26(8):1147–1161.
- Salix Pharmaceuticals. Patient assistance program. Available at: http://www.salix.com/about‐us/corporate‐responsibility/patient‐medication‐assistance. Accessed October 24, 2015.
- , . Management of overt hepatic encephalopathy. J Clin Exp Hepatol. 2015;5(suppl 1):S82–S87.
- , , , . Parenteral nutrition with branched‐chain amino acids in hepatic encephalopathy. A meta‐analysis. Gastroenterology. 1989;97(4):1033–1042.
- , , , et al. A randomized controlled trial of acarbose in hepatic encephalopathy. Clin Gastroenterol Hepatol. 2005;3(2):184–191.
- , , , . Lactulose vs polyethylene glycol 3350‐‐electrolyte solution for treatment of overt hepatic encephalopathy: the HELP randomized clinical trial. JAMA Intern Med. 2014;174(11):1727–1733.
- , , , et al. Normal protein diet for episodic hepatic encephalopathy: results of a randomized study. J Hepatol. 2004;41(1):38–43.
- , , . The therapeutic use of acetaminophen in patients with liver disease. Am J Ther. 2005;12(2):133–141.
- , . Pain management in the cirrhotic patient: the clinical challenge. Mayo Clin Proc. 2010;85(5):451–458.
- , , , et al. Clearing the confusion over hepatic encephalopathy after TIPS creation: incidence, prognostic factors, and clinical outcomes. Dig Dis Sci. 2015;60(4):1059–66.
- Centers for Medicare and Medicaid Services. ICD‐10 code lookup: encephalopathy. Available at: https://www.cms.gov/medicare‐coverage‐database/staticpages/icd‐10‐code‐lookup.aspx?KeyWord=encephalopathy5(suppl 1):S75–S81.
- , , , . The care transitions intervention: results of a randomized controlled trial. Arch Intern Med. 2006;166:1822–1828.
Reversible impairment of brain function in the setting of cirrhosis defines hepatic encephalopathy (HE). HE is associated with significantly decreased survival,[1] and patients with HE have poor outcomes whether HE occurs in isolation or in conjunction with acute‐on‐chronic liver failure.[2] A large multicenter study comparing cirrhotics with and without HE also found that those with a history of HE were hospitalized more frequently.[2]
The presentation of HE is variable, and diagnosis remains clinical. Subtle manifestations of HE persist between episodes, even if gross cognitive function normalizes.[3] Retrospective data suggest the effects of serial bouts of HE may be cumulative, because even with appropriate treatment, the severity of impairment correlates with the number of prior episodes.[3] Even minimal manifestations of hepatic encephalopathy correlate with reduced quality of life.[4]
The West Haven score is the most validated scoring system.[5] Higher grades of HE correlate with significantly increased mortality,[2] but due to difficulties differentiating stages 0 and 1, these criteria remain somewhat controversial. The Spectrum of Neurocognitive Impairment in Cirrhosis (SONIC) has been proposed as an alternate conceptualization of HE as a continuous spectrum rather than discrete stages.[6] Table 1 shows findings associated with various West Haven and SONIC stages. Both systems include covert and overt encephalopathy. Covert correlates with West Haven grades 0 to 1, and consists mainly of subtle findings that require specialized psychometric testing to detect. The SONIC system terms demonstrable but subclinical manifestations minimal HE.[6] Overt HE includes West Haven grades 2 through 4, and refers to objective findings that can be reliably detected on clinical evaluation.[7] Whereas specific numeric scores are used largely for research purposes, classifying HE as covert or overt is clinically useful.
| West Haven Grade | SONIC Classification | Neurologic Changes | Asterixis |
|---|---|---|---|
| |||
| 0 | Normal | None | None |
| Minimal HE | Requires specialized psychometric testing | ||
| 1 | Overt | Decreased attention span, hypersomnia/emnsomnia | Detectable |
| 2 | Lethargy, disorientation | Obvious | |
| 3 | Semistupor or stupor | None | |
| 4 | Coma | None | |
Although blood ammonia levels correlate well across populations, they are not diagnostically useful for individuals, because considerable overlap exists between patients with no HE and those with severe encephalopathy.[8] Ammonia levels also do not predict HE development.[9] Brain imaging is of limited utility, but may be prudent with abrupt decompensation, focal neurologic findings, or poor response to therapy.[10] A recent single‐center review of head computed tomography in cirrhotic patients presenting with altered level of consciousness found a low incidence of intracranial hemorrhage (ICH).[11] The number needed to scan was 293 patients to detect a single ICH. Only 1 patient out of 316 had ICH when fever, trauma, and focal neurological findings were excluded. The presence of acute ICH was not associated with platelet count, coagulopathy, creatinine, or Model for End‐Stage Liver Disease score.
PRECIPITANTS
Initial evaluation of patients with suspected HE must confirm the presence of HE and identify potentially reversible precipitants. Infection, bleeding, and metabolic derangements (including renal injury, hypovolemia, and hyponatremia) are common precipitants.[12] Searching for precipitants is heavily stressed in the 4‐pronged approach recommended by the American Association for the Study of Liver Disease,[7] as summarized in Table 2. Common precipitants are grouped into episodic and recurrent causes. Episodic causes are those that represent discrete insults with specific, short‐term treatments. Recurrent causes are those that are likely to require active management over time. These distinctions may help inform different approaches for initial or recurrent episodes of HE; in practice, much overlap exists.
| |
| 1. Initiate care for cirrhotic patients with altered consciousness | |
| 2. Seek and treat alternative causes of altered mental status if present | |
| 3. Identify and treat precipitating factors: | |
| Episodic | Recurrent |
| Infection | Electrolyte derangement |
| Gastrointestinal bleeding | Infection |
| Hypovolemia | Constipation |
| Electrolyte derangement | Hypovolemia |
| Constipation | Gastrointestinal bleeding |
| 4. Commence empiric HE treatment | |
Diuretic use has been clearly correlated with incidence of HE.[2] Although diuretic usage may be an indicator of more advanced liver disease, their use can also contribute to HE via increased risk of hypovolemia and dysnatremia.[2] Accordingly, caution is necessary when using diuretics to manage patients with HE and refractory ascites. These findings have led some to suggest serial paracentesis may be preferable to diuretics in this population.[2]
MANAGEMENT
The mainstay of HE treatment is administration of the nonabsorbable disaccharide lactulose. Lactulose is part of nearly all regimens because it is effective, easily titrated, and inexpensive.[13] It is efficacious orally or as an enema.[14] Lactulose increases both cognitive function and quality of life,[15] and is effective for prophylaxis and treatment of all stages of HE.[16, 17]
Rifaximin is often used as an adjunct to lactulose, particularly in cases of recurrent HE. Small trials have associated rifaximin with increased quality of life[18] and cognitive function.[19] The largest randomized trial of rifaximin was a double‐blind, placebo‐controlled trial in patients with multiple episodes of overt HE during the prior 6 months.[20] Lactulose was used concomitantly in approximately 91% of patients. At the end of the 6‐month study, rifaximin was associated with a 58% relative risk reduction in overt HE recurrence and roughly 50% reduction in HE‐related hospitalization. The numbers needed to treat were 4 patients to prevent 1 overt HE episode and 9 to prevent 1 HE‐related hospitalization.[20]
A meta‐analysis of 264 patients included in published, high‐quality trials found rifaximin monotherapy to be similar to nonabsorbable disaccharides in both efficacy and incidence of diarrhea, but with significantly less abdominal pain.[21] This analysis was limited by significant heterogeneity among trials. A larger, more recent systematic review and meta‐analysis of 19 studies (both published and unpublished) found rifaximin to be effective for treatment, secondary prophylaxis, and possibly decreased mortality.[22] Of note, this meta‐analysis included placebo studies as well as studies using varying doses of lactulose or other antibiotics as controls. Despite this variability, the authors concluded that the control used in the individual trials did not significantly affect the aggregate results.[22] In the largest individual study to show a mortality benefit, improvement seemed to be driven by decreased rates of sepsis when rifaximin was used as an adjunct to lactulose.[23] Cost is a barrier to use, as rifaximin has not proven to be cost‐effective as monotherapy instead of lactulose.[24] Many insurers will facilitate adjunctive rifaximin with prior authorization, and the manufacturer offers assistance programs.[25]
Other adjuncts, including laxatives,[26] antibiotics,[12] branched‐chain aminoacids,[27] and acarbose[28] have far less evidentiary support and require further study prior to incorporation into clinical practice.[26] A recent study showed polyethylene glycol to perform similar to lactulose, but the studied volume of 4 L daily may make routine use impractical.[29] Dietary protein restriction has been shown in a prospective randomized controlled trial to accelerate body muscle breakdown without affecting HE,[30] so is best avoided.
ISSUES PERTINENT TO HOSPITAL MANAGEMENT
Concurrent HE frequently complicates inpatient management of acute pain. Acetaminophen below 3 g daily for short‐term use is safe,[31] but may be insufficient. Non‐steroidal anti‐inflammatory agents are best avoided given risks for renal dysfunction and bleeding.[32] Although a direct connection between opiate use and HE remains unproven, these agents are problematic because they can cause both sedation and constipation. Nonetheless, they are often needed for pain control. Oxycodone has a more desirable side effect profile than other narcotics. We often prescribe doses every 6 hours initially to account for decreased hepatic metabolism. Morphine has active metabolites that can accumulate in cirrhotics, so morphine use is best avoided.[32] Fluctuations in cognition may help distinguish narcosis from HE; specifically, narcosis causes chronic somnolence worst shortly after an opiate dose, whereas HE causes alterations in sleep‐wake cycles including insomnia.[32] Frequent adjustment of opiate dose and frequency may be required to balance analgesia with unwanted sedation and constipation.
Decisional capacity frequently complicates care of patients with cirrhosis. Patients may decline therapy because of dissatisfaction with bowel frequency, but such lapses in adherence likely contribute to HE recurrence. Patients with overt HE are often incapable of making decisions based on informed consent. If such patients have inadequate social support to ensure medical attention if symptoms progress, then mandatory treatment is reasonable. This may include involuntary administration of medications via rectal or nasogastric tube. Once cognition improves enough that he or she can reliably articulate risks, benefits, and alternatives of declining therapy, then it is reasonable to allow them to do. Subspecialty consultation with psychiatry or ethics may be useful in such situations.
For cirrhotics admitted for management of nonhepatic issues (particularly operations or invasive procedures), vigilance is needed to monitor for HE during hospitalization. Patients with HE have increased risk of falls and impaired driving, which may lead to admission onto surgical services.[4] Changes in diet, medications, bowel function, and environment may all contribute to encephalopathy. HE occurring during admission for other diagnoses still requires prompt titration of lactulose. Routine inquiry about bowel function and sleep quality are likely to help identify trouble early.
Placement of transvenous intrahepatic portosystemic shunt (TIPS) increases the risk for HE via introduction of neurotoxins directly into the systemic circulation. These patients can typically be treated medically,[33] but are likely to require increased lactulose dosage. TIPS revision may be necessary for patients with treatment‐refractory HE, but retrospective evidence suggests this is rarely necessary.[33] In that study, only a single patient out of 81 with post‐TIPS HE required TIPS closure.
Under the International Classification of Disease, 10th Revision, a diagnosis of HE is often most consistent with metabolic encephalopathy (G93.41).[34] It may also be coded as chronic hepatic failure without coma (K7210) or chronic hepatic failure with coma (K7211).[35] Whenever possible, specifying the underlying liver disease (eg, hepatitis C virus, alcohol) is preferable.
TRANSITIONING TO OUTPATIENT CARE
HE patients are usually ready for community living once their cognition has improved enough to reliably take medications. Key aspects of HE management need to be communicated clearly to patients and caregivers. Barriers to optimal outpatient care mostly relate to lactulose adherence. Stressing the direct correlation between insufficient bowel movements and HE progression may enhance adherence. All patients need a lactulose titration plan including when doses can be skipped and when additional doses are needed. Even minimal symptoms of HE need to be addressed,[36] and specific vigilance for alterations in sleep‐wake cycles needs to be adopted. Table 3 is an example of a lactulose titration plan that can be used at discharge. These plans should be included in discharge documents and within communication to outpatient healthcare providers. Close follow‐up with a hepatology specialist is ideal to ensure appropriate lactulose use, answer questions that arise upon return home, and address other concerns related to cirrhosis.
|
| Your dose of lactulose is 30 mL (1 tbsp) 3 times daily with meals. |
| If you have fewer than 3 BMs in any day, take an additional dose of lactulose at bedtime. |
| If you begin to experience difficulty sleeping at night, excessive drowsiness during the day, or confusion, take 2 doses of lactulose with each meal to ensure 3 or more BMs daily. |
| If you have more than 4 BMs in any 24 hour period and are not having any of the symptoms mentioned above, skip a single dose of lactulose then resume your usual schedule. |
Although specific interventions to decrease readmission have not been studied in this population, best practices from other populations (such as medication self‐management, follow‐up plans, and red flags to be on watch for[37]) likely apply. Defining optimal strategies to decrease readmission is an opportunity for hospitalists to contribute to standardization of care for these patients.
CONCLUSIONS
HE is a common but very treatable complication of cirrhosis. Various metabolic insults may precipitate HE, and hospitalists should seek to reverse contributing factors whenever possible. Lactulose titrated to ensure adequate bowel output is the cornerstone of both therapy and prevention for HE. Adjunctive use of rifaximin improves many outcomes. Patient education about manifestations of HE and medication titration is crucial to achieving smooth transition to the outpatient setting.
Disclosure
Nothing to report.
Reversible impairment of brain function in the setting of cirrhosis defines hepatic encephalopathy (HE). HE is associated with significantly decreased survival,[1] and patients with HE have poor outcomes whether HE occurs in isolation or in conjunction with acute‐on‐chronic liver failure.[2] A large multicenter study comparing cirrhotics with and without HE also found that those with a history of HE were hospitalized more frequently.[2]
The presentation of HE is variable, and diagnosis remains clinical. Subtle manifestations of HE persist between episodes, even if gross cognitive function normalizes.[3] Retrospective data suggest the effects of serial bouts of HE may be cumulative, because even with appropriate treatment, the severity of impairment correlates with the number of prior episodes.[3] Even minimal manifestations of hepatic encephalopathy correlate with reduced quality of life.[4]
The West Haven score is the most validated scoring system.[5] Higher grades of HE correlate with significantly increased mortality,[2] but due to difficulties differentiating stages 0 and 1, these criteria remain somewhat controversial. The Spectrum of Neurocognitive Impairment in Cirrhosis (SONIC) has been proposed as an alternate conceptualization of HE as a continuous spectrum rather than discrete stages.[6] Table 1 shows findings associated with various West Haven and SONIC stages. Both systems include covert and overt encephalopathy. Covert correlates with West Haven grades 0 to 1, and consists mainly of subtle findings that require specialized psychometric testing to detect. The SONIC system terms demonstrable but subclinical manifestations minimal HE.[6] Overt HE includes West Haven grades 2 through 4, and refers to objective findings that can be reliably detected on clinical evaluation.[7] Whereas specific numeric scores are used largely for research purposes, classifying HE as covert or overt is clinically useful.
| West Haven Grade | SONIC Classification | Neurologic Changes | Asterixis |
|---|---|---|---|
| |||
| 0 | Normal | None | None |
| Minimal HE | Requires specialized psychometric testing | ||
| 1 | Overt | Decreased attention span, hypersomnia/emnsomnia | Detectable |
| 2 | Lethargy, disorientation | Obvious | |
| 3 | Semistupor or stupor | None | |
| 4 | Coma | None | |
Although blood ammonia levels correlate well across populations, they are not diagnostically useful for individuals, because considerable overlap exists between patients with no HE and those with severe encephalopathy.[8] Ammonia levels also do not predict HE development.[9] Brain imaging is of limited utility, but may be prudent with abrupt decompensation, focal neurologic findings, or poor response to therapy.[10] A recent single‐center review of head computed tomography in cirrhotic patients presenting with altered level of consciousness found a low incidence of intracranial hemorrhage (ICH).[11] The number needed to scan was 293 patients to detect a single ICH. Only 1 patient out of 316 had ICH when fever, trauma, and focal neurological findings were excluded. The presence of acute ICH was not associated with platelet count, coagulopathy, creatinine, or Model for End‐Stage Liver Disease score.
PRECIPITANTS
Initial evaluation of patients with suspected HE must confirm the presence of HE and identify potentially reversible precipitants. Infection, bleeding, and metabolic derangements (including renal injury, hypovolemia, and hyponatremia) are common precipitants.[12] Searching for precipitants is heavily stressed in the 4‐pronged approach recommended by the American Association for the Study of Liver Disease,[7] as summarized in Table 2. Common precipitants are grouped into episodic and recurrent causes. Episodic causes are those that represent discrete insults with specific, short‐term treatments. Recurrent causes are those that are likely to require active management over time. These distinctions may help inform different approaches for initial or recurrent episodes of HE; in practice, much overlap exists.
| |
| 1. Initiate care for cirrhotic patients with altered consciousness | |
| 2. Seek and treat alternative causes of altered mental status if present | |
| 3. Identify and treat precipitating factors: | |
| Episodic | Recurrent |
| Infection | Electrolyte derangement |
| Gastrointestinal bleeding | Infection |
| Hypovolemia | Constipation |
| Electrolyte derangement | Hypovolemia |
| Constipation | Gastrointestinal bleeding |
| 4. Commence empiric HE treatment | |
Diuretic use has been clearly correlated with incidence of HE.[2] Although diuretic usage may be an indicator of more advanced liver disease, their use can also contribute to HE via increased risk of hypovolemia and dysnatremia.[2] Accordingly, caution is necessary when using diuretics to manage patients with HE and refractory ascites. These findings have led some to suggest serial paracentesis may be preferable to diuretics in this population.[2]
MANAGEMENT
The mainstay of HE treatment is administration of the nonabsorbable disaccharide lactulose. Lactulose is part of nearly all regimens because it is effective, easily titrated, and inexpensive.[13] It is efficacious orally or as an enema.[14] Lactulose increases both cognitive function and quality of life,[15] and is effective for prophylaxis and treatment of all stages of HE.[16, 17]
Rifaximin is often used as an adjunct to lactulose, particularly in cases of recurrent HE. Small trials have associated rifaximin with increased quality of life[18] and cognitive function.[19] The largest randomized trial of rifaximin was a double‐blind, placebo‐controlled trial in patients with multiple episodes of overt HE during the prior 6 months.[20] Lactulose was used concomitantly in approximately 91% of patients. At the end of the 6‐month study, rifaximin was associated with a 58% relative risk reduction in overt HE recurrence and roughly 50% reduction in HE‐related hospitalization. The numbers needed to treat were 4 patients to prevent 1 overt HE episode and 9 to prevent 1 HE‐related hospitalization.[20]
A meta‐analysis of 264 patients included in published, high‐quality trials found rifaximin monotherapy to be similar to nonabsorbable disaccharides in both efficacy and incidence of diarrhea, but with significantly less abdominal pain.[21] This analysis was limited by significant heterogeneity among trials. A larger, more recent systematic review and meta‐analysis of 19 studies (both published and unpublished) found rifaximin to be effective for treatment, secondary prophylaxis, and possibly decreased mortality.[22] Of note, this meta‐analysis included placebo studies as well as studies using varying doses of lactulose or other antibiotics as controls. Despite this variability, the authors concluded that the control used in the individual trials did not significantly affect the aggregate results.[22] In the largest individual study to show a mortality benefit, improvement seemed to be driven by decreased rates of sepsis when rifaximin was used as an adjunct to lactulose.[23] Cost is a barrier to use, as rifaximin has not proven to be cost‐effective as monotherapy instead of lactulose.[24] Many insurers will facilitate adjunctive rifaximin with prior authorization, and the manufacturer offers assistance programs.[25]
Other adjuncts, including laxatives,[26] antibiotics,[12] branched‐chain aminoacids,[27] and acarbose[28] have far less evidentiary support and require further study prior to incorporation into clinical practice.[26] A recent study showed polyethylene glycol to perform similar to lactulose, but the studied volume of 4 L daily may make routine use impractical.[29] Dietary protein restriction has been shown in a prospective randomized controlled trial to accelerate body muscle breakdown without affecting HE,[30] so is best avoided.
ISSUES PERTINENT TO HOSPITAL MANAGEMENT
Concurrent HE frequently complicates inpatient management of acute pain. Acetaminophen below 3 g daily for short‐term use is safe,[31] but may be insufficient. Non‐steroidal anti‐inflammatory agents are best avoided given risks for renal dysfunction and bleeding.[32] Although a direct connection between opiate use and HE remains unproven, these agents are problematic because they can cause both sedation and constipation. Nonetheless, they are often needed for pain control. Oxycodone has a more desirable side effect profile than other narcotics. We often prescribe doses every 6 hours initially to account for decreased hepatic metabolism. Morphine has active metabolites that can accumulate in cirrhotics, so morphine use is best avoided.[32] Fluctuations in cognition may help distinguish narcosis from HE; specifically, narcosis causes chronic somnolence worst shortly after an opiate dose, whereas HE causes alterations in sleep‐wake cycles including insomnia.[32] Frequent adjustment of opiate dose and frequency may be required to balance analgesia with unwanted sedation and constipation.
Decisional capacity frequently complicates care of patients with cirrhosis. Patients may decline therapy because of dissatisfaction with bowel frequency, but such lapses in adherence likely contribute to HE recurrence. Patients with overt HE are often incapable of making decisions based on informed consent. If such patients have inadequate social support to ensure medical attention if symptoms progress, then mandatory treatment is reasonable. This may include involuntary administration of medications via rectal or nasogastric tube. Once cognition improves enough that he or she can reliably articulate risks, benefits, and alternatives of declining therapy, then it is reasonable to allow them to do. Subspecialty consultation with psychiatry or ethics may be useful in such situations.
For cirrhotics admitted for management of nonhepatic issues (particularly operations or invasive procedures), vigilance is needed to monitor for HE during hospitalization. Patients with HE have increased risk of falls and impaired driving, which may lead to admission onto surgical services.[4] Changes in diet, medications, bowel function, and environment may all contribute to encephalopathy. HE occurring during admission for other diagnoses still requires prompt titration of lactulose. Routine inquiry about bowel function and sleep quality are likely to help identify trouble early.
Placement of transvenous intrahepatic portosystemic shunt (TIPS) increases the risk for HE via introduction of neurotoxins directly into the systemic circulation. These patients can typically be treated medically,[33] but are likely to require increased lactulose dosage. TIPS revision may be necessary for patients with treatment‐refractory HE, but retrospective evidence suggests this is rarely necessary.[33] In that study, only a single patient out of 81 with post‐TIPS HE required TIPS closure.
Under the International Classification of Disease, 10th Revision, a diagnosis of HE is often most consistent with metabolic encephalopathy (G93.41).[34] It may also be coded as chronic hepatic failure without coma (K7210) or chronic hepatic failure with coma (K7211).[35] Whenever possible, specifying the underlying liver disease (eg, hepatitis C virus, alcohol) is preferable.
TRANSITIONING TO OUTPATIENT CARE
HE patients are usually ready for community living once their cognition has improved enough to reliably take medications. Key aspects of HE management need to be communicated clearly to patients and caregivers. Barriers to optimal outpatient care mostly relate to lactulose adherence. Stressing the direct correlation between insufficient bowel movements and HE progression may enhance adherence. All patients need a lactulose titration plan including when doses can be skipped and when additional doses are needed. Even minimal symptoms of HE need to be addressed,[36] and specific vigilance for alterations in sleep‐wake cycles needs to be adopted. Table 3 is an example of a lactulose titration plan that can be used at discharge. These plans should be included in discharge documents and within communication to outpatient healthcare providers. Close follow‐up with a hepatology specialist is ideal to ensure appropriate lactulose use, answer questions that arise upon return home, and address other concerns related to cirrhosis.
|
| Your dose of lactulose is 30 mL (1 tbsp) 3 times daily with meals. |
| If you have fewer than 3 BMs in any day, take an additional dose of lactulose at bedtime. |
| If you begin to experience difficulty sleeping at night, excessive drowsiness during the day, or confusion, take 2 doses of lactulose with each meal to ensure 3 or more BMs daily. |
| If you have more than 4 BMs in any 24 hour period and are not having any of the symptoms mentioned above, skip a single dose of lactulose then resume your usual schedule. |
Although specific interventions to decrease readmission have not been studied in this population, best practices from other populations (such as medication self‐management, follow‐up plans, and red flags to be on watch for[37]) likely apply. Defining optimal strategies to decrease readmission is an opportunity for hospitalists to contribute to standardization of care for these patients.
CONCLUSIONS
HE is a common but very treatable complication of cirrhosis. Various metabolic insults may precipitate HE, and hospitalists should seek to reverse contributing factors whenever possible. Lactulose titrated to ensure adequate bowel output is the cornerstone of both therapy and prevention for HE. Adjunctive use of rifaximin improves many outcomes. Patient education about manifestations of HE and medication titration is crucial to achieving smooth transition to the outpatient setting.
Disclosure
Nothing to report.
- , , , et al. Prognostic significance of hepatic encephalopathy in patients with cirrhosis. J Hepatol. 1999;30(5):890–895.
- , , , et al. Characteristics, risk factors, and mortality of cirrhotic patients hospitalized for hepatic encephalopathy with and without acute‐on‐chronic liver failure (ACLF). J Hepatol. 2014;60(2):275–281.
- , , , et al. Persistence of cognitive impairment after resolution of overt hepatic encephalopathy. Gastroenterology. 2010;138(7):2332–2340.
- , , . Minimal hepatic encephalopathy impairs quality of life. J Clin Exp Hepatol. 2015;5(suppl 1):S42–S48.
- , ; Practice Parameters Committee of the American College of Gastroenterology. Hepatic encephalopathy. Am J Gastroenterol. 2001;96(7):1968–1976.
- , , . Spectrum of neurocognitive impairment in cirrhosis: Implications for the assessment of hepatic encephalopathy. Hepatology. 2009;50(6):2014–2021.
- , , , et al. Hepatic encephalopathy in chronic liver disease: 2014 Practice Guideline by the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver. Hepatology. 2014;60(2):715–735.
- , , , et al. Correlation between ammonia levels and the severity of hepatic encephalopathy. Am J Med. 2003;114(3):188–193.
- , . Serum ammonia level for the evaluation of hepatic encephalopathy. JAMA. 2014;312(6):643–644.
- , , . Hepatic encephalopathy in patients with acute decompensation of cirrhosis and acute‐on‐chronic liver failure. J Hepatol. 2015;62(2):437–447.
- , , , et al. Low Likelihood of intracranial hemorrhage in patients with cirrhosis and altered mental status. Clin Gastroenterol Hepatol. 2015;13(1):165–169.
- , . The management of hospitalized patients with cirrhosis: the Mount Sinai experience and a guide for hospitalists. Dig Dis Sci. 2011;56(5):1266–1281.
- , , . Nonabsorbable disaccharides for hepatic encephalopathy. Cochrane Database Syst Rev. 2004(2):CD003044.
- , , , et al. Acidifying enemas (lactitol and lactose) vs. nonacidifying enemas (tap water) to treat acute portal‐systemic encephalopathy: a double‐blind, randomized clinical trial. Hepatology. 1987;7(4):639–643.
- , . Disaccharides in the treatment of hepatic encephalopathy. Metab Brain Dis. 2013;28(2):313–320.
- , , , . Secondary prophylaxis of hepatic encephalopathy: an open‐label randomized controlled trial of lactulose versus placebo. Gastroenterology. 2009;137(3):885–891, 91.e1.
- , , , , , . Efficacy of lactulose in cirrhotic patients with subclinical hepatic encephalopathy. Dig Dis Sci. 2000;45(8):1549–1552.
- , , , et al. Randomised clinical trial: rifaximin improves health‐related quality of life in cirrhotic patients with hepatic encephalopathy—a double‐blind placebo‐controlled study. Aliment Pharmacol Ther. 2011;34(8):853–861.
- , , , , , . Rifaximin improves psychometric performance and health‐related quality of life in patients with minimal hepatic encephalopathy (the RIME Trial). Am J Gastroenterol. 2011;106(2):307–316.
- , , , et al. Rifaximin treatment in hepatic encephalopathy. N Engl J Med. 2010;362(12):1071–1081.
- , , , , , . Rifaximin versus nonabsorbable disaccharides in the management of hepatic encephalopathy: a meta‐analysis. Eur J Gastroenterol Hepatol. 2008;20(11):1064–1070.
- , , , , . Systematic review with meta‐analysis: the effects of rifaximin in hepatic encephalopathy. Aliment Pharmacol Ther. 2014;40(2):123–132.
- , , , , , . A randomized, double‐blind, controlled trial comparing rifaximin plus lactulose with lactulose alone in treatment of overt hepatic encephalopathy. Am J Gastroenterol. 2013;108(9):1458–1463.
- , , . The cost‐effectiveness and budget impact of competing therapies in hepatic encephalopathy—a decision analysis. Aliment Pharmacol Ther. 2007;26(8):1147–1161.
- Salix Pharmaceuticals. Patient assistance program. Available at: http://www.salix.com/about‐us/corporate‐responsibility/patient‐medication‐assistance. Accessed October 24, 2015.
- , . Management of overt hepatic encephalopathy. J Clin Exp Hepatol. 2015;5(suppl 1):S82–S87.
- , , , . Parenteral nutrition with branched‐chain amino acids in hepatic encephalopathy. A meta‐analysis. Gastroenterology. 1989;97(4):1033–1042.
- , , , et al. A randomized controlled trial of acarbose in hepatic encephalopathy. Clin Gastroenterol Hepatol. 2005;3(2):184–191.
- , , , . Lactulose vs polyethylene glycol 3350‐‐electrolyte solution for treatment of overt hepatic encephalopathy: the HELP randomized clinical trial. JAMA Intern Med. 2014;174(11):1727–1733.
- , , , et al. Normal protein diet for episodic hepatic encephalopathy: results of a randomized study. J Hepatol. 2004;41(1):38–43.
- , , . The therapeutic use of acetaminophen in patients with liver disease. Am J Ther. 2005;12(2):133–141.
- , . Pain management in the cirrhotic patient: the clinical challenge. Mayo Clin Proc. 2010;85(5):451–458.
- , , , et al. Clearing the confusion over hepatic encephalopathy after TIPS creation: incidence, prognostic factors, and clinical outcomes. Dig Dis Sci. 2015;60(4):1059–66.
- Centers for Medicare and Medicaid Services. ICD‐10 code lookup: encephalopathy. Available at: https://www.cms.gov/medicare‐coverage‐database/staticpages/icd‐10‐code‐lookup.aspx?KeyWord=encephalopathy5(suppl 1):S75–S81.
- , , , . The care transitions intervention: results of a randomized controlled trial. Arch Intern Med. 2006;166:1822–1828.
- , , , et al. Prognostic significance of hepatic encephalopathy in patients with cirrhosis. J Hepatol. 1999;30(5):890–895.
- , , , et al. Characteristics, risk factors, and mortality of cirrhotic patients hospitalized for hepatic encephalopathy with and without acute‐on‐chronic liver failure (ACLF). J Hepatol. 2014;60(2):275–281.
- , , , et al. Persistence of cognitive impairment after resolution of overt hepatic encephalopathy. Gastroenterology. 2010;138(7):2332–2340.
- , , . Minimal hepatic encephalopathy impairs quality of life. J Clin Exp Hepatol. 2015;5(suppl 1):S42–S48.
- , ; Practice Parameters Committee of the American College of Gastroenterology. Hepatic encephalopathy. Am J Gastroenterol. 2001;96(7):1968–1976.
- , , . Spectrum of neurocognitive impairment in cirrhosis: Implications for the assessment of hepatic encephalopathy. Hepatology. 2009;50(6):2014–2021.
- , , , et al. Hepatic encephalopathy in chronic liver disease: 2014 Practice Guideline by the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver. Hepatology. 2014;60(2):715–735.
- , , , et al. Correlation between ammonia levels and the severity of hepatic encephalopathy. Am J Med. 2003;114(3):188–193.
- , . Serum ammonia level for the evaluation of hepatic encephalopathy. JAMA. 2014;312(6):643–644.
- , , . Hepatic encephalopathy in patients with acute decompensation of cirrhosis and acute‐on‐chronic liver failure. J Hepatol. 2015;62(2):437–447.
- , , , et al. Low Likelihood of intracranial hemorrhage in patients with cirrhosis and altered mental status. Clin Gastroenterol Hepatol. 2015;13(1):165–169.
- , . The management of hospitalized patients with cirrhosis: the Mount Sinai experience and a guide for hospitalists. Dig Dis Sci. 2011;56(5):1266–1281.
- , , . Nonabsorbable disaccharides for hepatic encephalopathy. Cochrane Database Syst Rev. 2004(2):CD003044.
- , , , et al. Acidifying enemas (lactitol and lactose) vs. nonacidifying enemas (tap water) to treat acute portal‐systemic encephalopathy: a double‐blind, randomized clinical trial. Hepatology. 1987;7(4):639–643.
- , . Disaccharides in the treatment of hepatic encephalopathy. Metab Brain Dis. 2013;28(2):313–320.
- , , , . Secondary prophylaxis of hepatic encephalopathy: an open‐label randomized controlled trial of lactulose versus placebo. Gastroenterology. 2009;137(3):885–891, 91.e1.
- , , , , , . Efficacy of lactulose in cirrhotic patients with subclinical hepatic encephalopathy. Dig Dis Sci. 2000;45(8):1549–1552.
- , , , et al. Randomised clinical trial: rifaximin improves health‐related quality of life in cirrhotic patients with hepatic encephalopathy—a double‐blind placebo‐controlled study. Aliment Pharmacol Ther. 2011;34(8):853–861.
- , , , , , . Rifaximin improves psychometric performance and health‐related quality of life in patients with minimal hepatic encephalopathy (the RIME Trial). Am J Gastroenterol. 2011;106(2):307–316.
- , , , et al. Rifaximin treatment in hepatic encephalopathy. N Engl J Med. 2010;362(12):1071–1081.
- , , , , , . Rifaximin versus nonabsorbable disaccharides in the management of hepatic encephalopathy: a meta‐analysis. Eur J Gastroenterol Hepatol. 2008;20(11):1064–1070.
- , , , , . Systematic review with meta‐analysis: the effects of rifaximin in hepatic encephalopathy. Aliment Pharmacol Ther. 2014;40(2):123–132.
- , , , , , . A randomized, double‐blind, controlled trial comparing rifaximin plus lactulose with lactulose alone in treatment of overt hepatic encephalopathy. Am J Gastroenterol. 2013;108(9):1458–1463.
- , , . The cost‐effectiveness and budget impact of competing therapies in hepatic encephalopathy—a decision analysis. Aliment Pharmacol Ther. 2007;26(8):1147–1161.
- Salix Pharmaceuticals. Patient assistance program. Available at: http://www.salix.com/about‐us/corporate‐responsibility/patient‐medication‐assistance. Accessed October 24, 2015.
- , . Management of overt hepatic encephalopathy. J Clin Exp Hepatol. 2015;5(suppl 1):S82–S87.
- , , , . Parenteral nutrition with branched‐chain amino acids in hepatic encephalopathy. A meta‐analysis. Gastroenterology. 1989;97(4):1033–1042.
- , , , et al. A randomized controlled trial of acarbose in hepatic encephalopathy. Clin Gastroenterol Hepatol. 2005;3(2):184–191.
- , , , . Lactulose vs polyethylene glycol 3350‐‐electrolyte solution for treatment of overt hepatic encephalopathy: the HELP randomized clinical trial. JAMA Intern Med. 2014;174(11):1727–1733.
- , , , et al. Normal protein diet for episodic hepatic encephalopathy: results of a randomized study. J Hepatol. 2004;41(1):38–43.
- , , . The therapeutic use of acetaminophen in patients with liver disease. Am J Ther. 2005;12(2):133–141.
- , . Pain management in the cirrhotic patient: the clinical challenge. Mayo Clin Proc. 2010;85(5):451–458.
- , , , et al. Clearing the confusion over hepatic encephalopathy after TIPS creation: incidence, prognostic factors, and clinical outcomes. Dig Dis Sci. 2015;60(4):1059–66.
- Centers for Medicare and Medicaid Services. ICD‐10 code lookup: encephalopathy. Available at: https://www.cms.gov/medicare‐coverage‐database/staticpages/icd‐10‐code‐lookup.aspx?KeyWord=encephalopathy5(suppl 1):S75–S81.
- , , , . The care transitions intervention: results of a randomized controlled trial. Arch Intern Med. 2006;166:1822–1828.
In the Literature: Research You Need to Know
Clinical question: What is the impact, and sustainability, of chlorhexidine bathing on central-venous-catheter-associated bloodstream infections?
Background: Chlorhexidine bathing has been associated with reductions in healthcare-associated bloodstream infections, including vancomycin-resistant enterococci and methicillin-resistant Staphylococcus aureus. No prospective studies have evaluated the impact and sustainability of chlorhexidine bathing.
Study design: Prospective, three-phase study.
Setting: Medical-surgical ICUs and respiratory-care units at five New York hospitals.
Synopsis: In the pre-intervention phase (six to nine months, 1,808 admissions), patients were bathed with soap and water or nonmedicated bathing cloths. In the intervention phase (eight months, 1,832 admissions), patients were bathed with 2% chlorhexidine cloths. In the post-intervention phase (12 months, 2,834 admissions), chlorhexidine bathing was continued without oversight by researchers.
During the intervention phase, there were significantly fewer central-venous-catheter-associated bloodstream infections (2.6/1,000 catheter days vs. 6.4/1,000 pre-intervention). The reductions in bloodstream infections were sustained during the post-intervention period (2.9/1,000 catheter days). Compliance with chlorhexidine bathing was 82% and 88% during the intervention and post-intervention phases, and was well tolerated by the patients.
Limitations of this study include lack of patient-specific data and severity of illness data, as well as lack of randomization and blinding. Although not evaluated in this study, the savings associated with decreased bloodstream infections likely outweigh the cost of chlorhexidine bathing.
Bottom line: Chlorhexidine bathing is a well-tolerated, sustainable intervention that significantly reduces central-venous-catheter-associated bloodstream infections.
Citation: Montecalvo MA, McKenna D, Yarrish R, et al. Chlorhexidine bathing to reduce central venous catheter-associated bloodstream infection: impact and sustainability.Am J Med. 2012;125(5):505-511.
For more physician reviews of recent HM-relevant literature, visit our website.
Clinical question: What is the impact, and sustainability, of chlorhexidine bathing on central-venous-catheter-associated bloodstream infections?
Background: Chlorhexidine bathing has been associated with reductions in healthcare-associated bloodstream infections, including vancomycin-resistant enterococci and methicillin-resistant Staphylococcus aureus. No prospective studies have evaluated the impact and sustainability of chlorhexidine bathing.
Study design: Prospective, three-phase study.
Setting: Medical-surgical ICUs and respiratory-care units at five New York hospitals.
Synopsis: In the pre-intervention phase (six to nine months, 1,808 admissions), patients were bathed with soap and water or nonmedicated bathing cloths. In the intervention phase (eight months, 1,832 admissions), patients were bathed with 2% chlorhexidine cloths. In the post-intervention phase (12 months, 2,834 admissions), chlorhexidine bathing was continued without oversight by researchers.
During the intervention phase, there were significantly fewer central-venous-catheter-associated bloodstream infections (2.6/1,000 catheter days vs. 6.4/1,000 pre-intervention). The reductions in bloodstream infections were sustained during the post-intervention period (2.9/1,000 catheter days). Compliance with chlorhexidine bathing was 82% and 88% during the intervention and post-intervention phases, and was well tolerated by the patients.
Limitations of this study include lack of patient-specific data and severity of illness data, as well as lack of randomization and blinding. Although not evaluated in this study, the savings associated with decreased bloodstream infections likely outweigh the cost of chlorhexidine bathing.
Bottom line: Chlorhexidine bathing is a well-tolerated, sustainable intervention that significantly reduces central-venous-catheter-associated bloodstream infections.
Citation: Montecalvo MA, McKenna D, Yarrish R, et al. Chlorhexidine bathing to reduce central venous catheter-associated bloodstream infection: impact and sustainability.Am J Med. 2012;125(5):505-511.
For more physician reviews of recent HM-relevant literature, visit our website.
Clinical question: What is the impact, and sustainability, of chlorhexidine bathing on central-venous-catheter-associated bloodstream infections?
Background: Chlorhexidine bathing has been associated with reductions in healthcare-associated bloodstream infections, including vancomycin-resistant enterococci and methicillin-resistant Staphylococcus aureus. No prospective studies have evaluated the impact and sustainability of chlorhexidine bathing.
Study design: Prospective, three-phase study.
Setting: Medical-surgical ICUs and respiratory-care units at five New York hospitals.
Synopsis: In the pre-intervention phase (six to nine months, 1,808 admissions), patients were bathed with soap and water or nonmedicated bathing cloths. In the intervention phase (eight months, 1,832 admissions), patients were bathed with 2% chlorhexidine cloths. In the post-intervention phase (12 months, 2,834 admissions), chlorhexidine bathing was continued without oversight by researchers.
During the intervention phase, there were significantly fewer central-venous-catheter-associated bloodstream infections (2.6/1,000 catheter days vs. 6.4/1,000 pre-intervention). The reductions in bloodstream infections were sustained during the post-intervention period (2.9/1,000 catheter days). Compliance with chlorhexidine bathing was 82% and 88% during the intervention and post-intervention phases, and was well tolerated by the patients.
Limitations of this study include lack of patient-specific data and severity of illness data, as well as lack of randomization and blinding. Although not evaluated in this study, the savings associated with decreased bloodstream infections likely outweigh the cost of chlorhexidine bathing.
Bottom line: Chlorhexidine bathing is a well-tolerated, sustainable intervention that significantly reduces central-venous-catheter-associated bloodstream infections.
Citation: Montecalvo MA, McKenna D, Yarrish R, et al. Chlorhexidine bathing to reduce central venous catheter-associated bloodstream infection: impact and sustainability.Am J Med. 2012;125(5):505-511.
For more physician reviews of recent HM-relevant literature, visit our website.
ITL: Physician Reviews of HM-Relevant Research
In This Edition
Literature At A Glance
A guide to this month’s studies
- Prediction tool for neurological outcomes after in-hospital cardiac arrest
- Radiation exposure in integrated healthcare systems, 1996-2010
- Postoperative troponin predicts 30-day mortality
- Clinical prediction model of mortality in acute heart failure
- Indwelling pleural catheter vs. talc pleurodesis via chest tube
- Early surgery for high-risk, native-valve endocarditis patients
- Risk factors after ED visit for syncope
- Acute hyperglycemia in CAP patients
- Hospital delirium associated with cognitive decline, institutionalization, and death
- Seven-day ciprofloxacin effective against acute pyelonephritis
- Advance directives in community patients with heart failure
- Chlorhexidine bathing effective against CVC-associated bloodstream infections
- Simulation training improves lumbar puncture skills
- PCP referrals to hospitals and publicly reported data
- Medication reconciliation best practices
Prediction Tool Validated for Prognosticating Favorable Neurological Outcome after In-Hospital Cardiac Arrest
Clinical question: Does the Cardiac Arrest Survival Post Resuscitation In-Hospital (CASPRI) score accurately predict favorable neurological outcomes?
Background: Previous cardiac arrest prediction models have been focused on survival to discharge without consideration of neurological status and have not been translated into valid bedside prognostication tools. Neurologic prognosis can assist patients, families, and physicians in decisions about continued goals of care post-arrest.
Study design: Retrospective cohort study.
Setting: Acute-care hospitals.
Synopsis: Using the Get with the Guidelines Resuscitation Registry, 551 hospitals identified 42,957 patients who were successfully resuscitated from an in-hospital cardiac arrest from January 2000 to October 2009. Researchers developed a simple prediction tool for favorable neurological outcomes (defined as “no” or “moderate” neurological disability) at discharge. The 11 predictors used to calculate the CASPRI score are age; time to defibrillation; pre-arrest neurological status; hospital location; duration of resuscitation; and pre-arrest comorbidities: mechanical ventilation, renal insufficiency, hepatic insufficiency, sepsis, malignancy,
and hypotension.
Rates of favorable neurological outcome were similar between derivation cohort (24.6%) and validation cohort (24.5%). The model had excellent discrimination with a C score of 0.80. Probability of favorable neurological survival ranged from 70.7% in the top decile of patients (CASPRI <10) and 2.8% in bottom decile (CASPRI ≥ 28).
This tool is not generalizable to patients with out-of-hospital arrest or undergoing therapeutic hypothermia.
Bottom line: CASPRI is a simple bedside tool validated to estimate probability of favorable neurological outcome after in-hospital cardiac arrest.
Citation: Chan PS, Spertus JA, Krumholz HA, et al. A validated prediction tool for initial survivors in in-hospital cardiac arrest. Arch Intern Med. 2012;172(12):947-953.
Increased Use of Radiologic Imaging and Associated Radiation Exposure in Integrated Healthcare Systems, 1996-2010
Clinical question: How much has imaging utilization and associated radiation exposure increased over 15 years in integrated healthcare systems independent of financial incentives in a fee-for-service system?
Background: Use of diagnostic imaging has increased significantly within fee-for-service healthcare models. The associated radiation exposure has increased the risk of radiation-induced malignancies. Little is known about the pattern of imaging use in integrated healthcare systems without the financial incentives seen in other models of care.
Study design: Retrospective cohort study.
Setting: Six integrated healthcare systems in the U.S.
Synopsis: The number of diagnostic imaging studies performed and estimated radiation exposure were determined from analysis of electronic medical records from member patients enrolled in health systems in the HMO Research Network from 1996 to 2010. Annual increases in use of advanced diagnostics were noted in CT (7.8% annual growth), MRI (10%), ultrasound (3.9%), and PET (57%) studies.
Increased CT use over the 15-year study period resulted in increased radiation exposure, doubling mean per capita effective dose (1.2 mSv to 2.3 mSv), as well as those receiving high exposure (1.2% to 2.5%) and very high exposure (0.6% to 1.4%).
The increased imaging use and radiation exposure among HMO enrollees was similar to that of fee-for-service Medicare patients in previous studies.
Bottom line: There is a significant increase in use of diagnostic imaging studies and associated radiation exposure among integrated healthcare system enrollees from 1996 to 2010, similar to patients in fee-for-service health plans.
Citation: Smith-Bindman R, Miglioretti DL, Johnson E, et al. Use of diagnostic imaging studies and associated radiation exposure for patients enrolled in large integrated health care systems, 1996-2010. JAMA. 2012;307(22):2400-2409.
Postoperative Troponin Predicts 30-Day Mortality
Clinical question: Does postoperative peak troponin level predict 30-day mortality in patients undergoing noncardiac surgery?
Background: The use of postoperative peak troponin levels in predicting 30-day mortality for patients undergoing noncardiac surgery has not been studied extensively. Identifying patients at high risk for death following noncardiac surgery could facilitate appropriate postoperative care and improve survival.
Study design: Prospective cohort study.
Setting: International university and nonuniversity hospitals.
Synopsis: The Vascular Events In Noncardiac Surgery Patients Cohort Evaluation (VISION) Study is a large, international, multicenter, prospective cohort study designed to evaluate the major complications of noncardiac surgery. More than 15,100 patients ages 45 and older requiring at least an overnight hospitalization were enrolled following noncardiac surgery.
Peak troponin measurements during the first three postoperative days of 0.01 ng/ml or less, 0.02 ng/ml, 0.03 ng/ml to 0.29 ng/ml, and 0.3 ng/ml or greater had 30-day mortality rates of 1.0%, 4.0%, 9.3%, and 16.9%, respectively.
This study demonstrates the sensitivity of troponin measurement for predicting postoperative 30-day mortality in patients undergoing noncardiac surgery. The study does not address interventions based on an increased postoperative troponin level. Future studies might investigate postoperative modifiable risk factors.
Bottom line: Postoperative peak troponin level predicts 30-day mortality in patients undergoing noncardiac surgery.
Citation: Devereaux PJ, Chan MT, Alonso-Coello P, et al. Association between postoperative troponin levels and 30-day mortality among patients undergoing noncardiac surgery. JAMA. 2012;307(21):2295-2304.
Clinical Prediction Model of Mortality in Acute Heart Failure
Clinical question: Can a clinical prediction model accurately risk-stratify patients presenting to the ED with acute heart failure?
Background: Accurately prognosticating mortality is essential when determining whether to hospitalize or discharge patients presenting to the ED with acute heart failure. Evidence-based clinical prediction models enable physicians to risk-stratify patients and optimize care.
Study design: Retrospective cohort study.
Setting: Multicenter study of 86 hospitals in Ontario, Canada.
Synopsis: Data collected from 12,591 patients who presented to EDs with acute heart failure in Ontario were analyzed. A clinical prediction model of seven-day mortality of discharged and hospitalized patients was derived and validated. The Emergency Heart Failure Mortality Risk Grade (EHMRG) found an increased mortality based on higher triage heart rate, lower triage systolic blood pressure, initial oxygen saturation, and elevated troponin levels. This model uses readily available data collected in ED visits. The high-risk EHMRG score predicted about 8% seven-day mortality versus 0.3% in the low-risk score.
This model was not applied to chronic heart failure, did not utilize left ventricular function, and does not differentiate between systolic and diastolic heart failure.
Bottom line: The Emergency Heart Failure Mortality Risk Grade predicts seven-day mortality in acute heart failure in the emergent setting.
Citation: Lee DS, Stitt A, Austin PC, et al. Prediction of heart failure mortality in emergent care: a cohort study. Ann Intern Med. 2012;156(11):767-775.
Indwelling Pleural Catheter Is as Effective as Talc Pleurodesis Via Chest Tube in Relieving Dyspnea in Patients with Malignant Pleural Effusion
Clinical question: Is indwelling pleural catheter (IPC) as effective as chest tube and talc pleurodesis (talc) in improving dyspnea from malignant pleural effusion in patients who had no previous pleurodesis?
Background: Despite guidelines recommending chest tube insertion with pleurodesis as a first-line treatment for symptom palliation from malignant pleural effusion, there has been no randomized trial comparing indwelling pleural catheter with chest tube and talc pleurodesis.
Study design: Open-label, randomized controlled trial.
Setting: Seven hospitals in the United Kingdom.
Synopsis: One hundred six patients with malignant pleural effusion were randomized to undergo either IPC or talc treatment, and their daily mean dyspnea was measured. There was a clinically significant improvement of dyspnea in both IPC and talc groups over the first 42 days of the trial, without any significant difference in dyspnea between the two groups. After six months, researchers found a clinically significant decrease in dyspnea in the IPC group compared with the talc group. Chest pain and global quality of life were improved and were similar in both groups throughout the trial period. Length of hospital stay was significantly shorter in the IPC group compared with the talc group, but more patients in the IPC group experienced adverse events.
Bottom line: Indwelling pleural catheter is as effective as talc pleurodesis in reliving dyspnea from malignant pleural effusion; however, IPC is associated with increased adverse events despite shorter length of hospital stay.
Citation: Davies HE, Mishra EK, Kahan BC, et al. Effect of an indwelling pleural catheter vs. chest tube and talc pleurodesis for relieving dyspnea in patients with malignant pleural effusion: the TIME2 randomized controlled trial. JAMA. 2012;307(22):2383-2389.
Early Surgery Better than Conventional Treatment in High-Risk Native-Valve Endocarditis
Clinical question: Is early cardiac surgery better than conventional treatment for patients with left-sided, native-valve, infective endocarditis?
Background: Although guidelines strongly recommend early surgery for patients with infective endocarditis and congestive heart failure, the timing of surgery for patients with large vegetations and high risk of embolism without heart failure symptoms remains controversial.
Study design: Prospective, randomized trial.
Setting: Two medical centers in South Korea.
Synopsis: Seventy-six patients with left-sided, native-valve, infective endocarditis with a high risk of embolism (defined as vegetation with a diameter greater than 10 mm or severe mitral or aortic valve disease) were randomized to undergo early surgery (within 48 hours of enrollment) or conventional treatment (antibiotic therapy and surgery only if complications required urgent surgery). The primary outcome of composite in-hospital death or
clinical embolic events within six weeks of the trial occurred in only one patient in the early surgery group, compared with nine patients in the conventional group (hazard ratio 0.10, 95% CI, 0.01-0.82, P=0.03).
There was no difference in all-cause mortality at six months between the two groups, but the rate of composite endpoint of death from any cause, embolic events, or recurrence of infective endocarditis at six months was significantly lower in the early surgery group compared with the conventional group.
Bottom line: Early cardiac surgery for patients with left-sided, native-valve infective endocarditis with a high risk of embolism significantly improved the composite outcome of all-cause mortality, embolic events, or recurrence of endocarditis compared with the conventional therapy.
Citation: Kang DH, Kim YJ, Kim SH, et al. Early surgery versus conventional treatment for infective endocarditis. N Engl J Med. 2012;366(26):2466-2473.
Risk Factors for Short-Term Mortality after Emergency Department Visit for Syncope
Clinical question: What are the risk factors for short-term mortality after an ED evaluation for syncope or near-syncope?
Background: Syncope accounts for 1% to 2% of all ED visits and an equal number of hospital admissions. The risk of death after an ED visit for syncope is poorly understood, resulting in frequent hospital admissions.
Study design: Retrospective cohort study.
Setting: EDs in Southern California.
Synopsis: Authors evaluated 23,951 ED visits resulting in syncope as sole primary diagnosis. Age was identified as the most significant risk factor for short-term mortality. Cumulative survival data revealed that more than 1% of patients 60 or older died by 30 days. There were 215 deaths (2.84%) in patients hospitalized from the ED and 66 deaths (0.45%) among patients not hospitalized.
Pre-existing comorbidities significantly associated with increased mortality included heart failure (HR=14.3 in ages 18-53; HR=3.09 in ages 60-79; HR=2.34 in ages 80-plus), diabetes (HR=1.49), seizure (HR=1.65), dementia (HR=1.41), and a recent prior visit for syncope (HR=1.86). The risk of death by 30 days was less than 0.2% in patients under 60 without heart failure and more than 2.5% in patients of all ages with heart failure.
Bottom line: After an ED visit for syncope, patients with a history of heart failure and patients 60 and older have a significantly increased risk of short-term mortality.
Citation: Derose SF, Gabayan GZ, Chiu VY, Sun BC. Patterns and preexisting risk factors of 30-day mortality after a primary discharge diagnosis of syncope or near syncope. Acad Emerg Med. 2012;19(5):488-496.
Acute Hyperglycemia Associated with Increased Mortality in Community-Acquired Pneumonia
Clinical question: In patients admitted to the hospital for community-acquired pneumonia, is serum glucose level on admission associated with mortality?
Background: Some retrospective studies have shown an association between alterations in serum glucose levels or pre-existing diabetes and higher mortality due to infections, while other studies have shown no clear association.
Study design: Multicenter, prospective cohort study.
Setting: Hospitals and private practices in Germany, Switzerland, and Austria.
Synopsis: Prospective data from 6,891 patients were included in the analysis. Patients without diabetes and normal serum glucose levels had the lowest mortality after 90 days. Patients without diabetes but with mild acute hyperglycemia (108 mg/dL to 198 mg/dL) had a significantly increased risk of death at 90 days (HR 1.56), and patients without diabetes but with more severe acute hyperglycemia (over 252 mg/dL) had an even higher risk of death at 90 days (HR 2.37).
The 90-day mortality rate was significantly higher in patients with pre-existing diabetes (HR 2.47), although this was not affected by serum glucose levels on admission.
Bottom line: Acute hyperglycemia, as well as pre-existing diabetes, was associated with an increased risk of 90-day mortality in patients with community acquired pneumonia.
Citation: Lepper PM, Ott S, Nüesch E, et al. Serum glucose levels for predicting death in patients admitted to hospital for community acquired pneumonia: prospective cohort study. BMJ. 2012;344:e3397.
Hospital Delirium Associated with Cognitive Decline, Institutionalization, and Death
Clinical question: What is the risk of subsequent cognitive decline, institutionalization, or death due to delirium in patients with dementia?
Background: Patients suffering delirium during hospitalization can suffer additional cognitive decline. Whether this is due to additional damage from the delirium state or reflects pre-existing cognitive vulnerability remains uncertain.
Study design: Prospective analysis of a cohort of Alzheimer’s patients.
Setting: Massachusetts community-based disease registry.
Synopsis: The analysis compared nonhospitalized individuals to patients hospitalized with, and without, delirium. In 771 individuals with dementia, at least one adverse outcome (including cognitive decline, institutionalization, or death) occurred in 32% of those not hospitalized, 55% of those hospitalized without delirium, and 79% of those hospitalized with delirium. Even after adjusting for confounders, hospitalization increased the risk for each of the adverse outcomes; the highest risk was in those with delirium.
Among hospitalized patients, the authors estimated 1 in 5 cases of cognitive decline, 1 in 7 institutionalizations, and 1 in 16 deaths were attributable to delirium. Some of the attributed risk could be the result of residual confounding from unmeasured variables, limiting conclusions of causality. Despite these limitations, this study supports the hypothesis that delirium prevention measures could improve important patient outcomes.
Bottom line: Hospitalization is associated with high rates of adverse outcomes in elderly patients with dementia, the worst of which occurs in those who experience delirium.
Citation: Fong TG, Jones RN, Marcantonio ER, et al. Adverse outcomes after hospitalization and delirium in persons with Alzheimer disease. Ann Int Med. 2012;156:848-856.
In Acute Pyelonephritis, a Seven-Day Course of Ciprofloxacin is Effective in Obtaining Clinical Cure
Clinical question: What is the efficacy of ciprofloxacin for seven days compared with 14 days in women with community-acquired acute pyelonephritis?
Background: Community-acquired acute pyelonephritis is a common and sometimes serious infection in women. In an era of increasing antibiotic resistance worldwide, it is prudent to reduce antibiotic utilization. There are limited controlled trials to assess the optimum duration of antibiotic treatment for this common infection.
Study design: Prospective, randomized, double-blind, noninferiority trial.
Setting: Twenty-one infectious-disease centers in Sweden.
Synopsis: Researchers randomly assigned 284 women 18 or older with a presumptive diagnosis of acute pyelonephritis to ciprofloxacin treatment for seven or 14 days. The primary endpoint was clinical and bacteriological cure 10 to 14 days after the completion of the treatment regimen. Short-term clinical cure occurred in 97% of the patients treated for seven days and 96% treated for 14 days. Long-term follow-up showed cumulative efficacy of 93% in each group. Both regimens were well tolerated.
Patients in this study had a low occurrence of complicated (9%) and recurrent (13%) infections. Whether short courses of antibiotics are effective in more complicated infections cannot be ascertained from this study. Also, the high cure rate obtained with a seven-day course of ciprofloxacin should not be extrapolated to other classes of antibiotics. Fluoroquinolones, such as ciprofloxacin, are recommended as first-line agents for empiric oral treatment of acute pyelonephritis if the resistance rate of the uropathogens remains lower than 10%; however, there is growing evidence that E. coli strains are becoming increasingly resistant to ciprofloxacin, limiting its usefulness.
Bottom line: Acute pyelonephritis in women can be treated successfully and safely with a seven-day course of ciprofloxacin, in areas with low ciprofloxacin resistance.
Citation: Sandberg T, Skoog G, Hermansson AB, et al. Ciprofloxacin for 7 days versus 14 days in women with acute pyelonephritis: a randomized, open-label and double-blind, placebo-controlled, non-inferiority trial. Lancet. 2012;380:484-490.
Advance Directives in Community Patients with Heart Failure
Clinical question: How prevalent are advance directives in heart-failure patients, and does a completed advance directive decrease end-of-life resource use (hospitalizations, ICU admissions, mechanical ventilation)?
Background: Heart failure is a common chronic and fatal disease. End-of-life care in heart-failure patients is associated with extremely high healthcare utilization. Heart failure guidelines recommend completing advance directives in all patients.
Study design: Population-based longitudinal cohort study.
Setting: Rochester Epidemiology Project in Olmstead County, Minn.
Synopsis: Investigators enrolled 608 patients presenting with heart failure between October 2007 and October 2011. At the time of enrollment, only 41% of the patients had existing advance directives. Independent predictors of advance directive completion included older age, history of malignancy, and renal dysfunction.
After a mean follow-up of 1.8 years, 164 patients (27%) had died. Among those patients, 106 had an advance directive (64.6%) at time of death—75 had an advance directive at the time of enrollment and another 31 completed an advance directive after enrollment.
Twenty-five patients (23.6%) specified DNR/DNI and another 39 (36.8%) denoted limitations on aggressiveness of care if death was imminent. Among the patients who died, 88 (53.7%) were hospitalized in the last month of their life and 50 (30.5%) died in the hospital. There was no difference in hospitalizations between those with an advance directive specifying limits and those who did not specify limits (OR 1.26, 95% CI 0.64-2.48). However, those with an advance directive specifying limits were less frequently mechanically ventilated (OR 0.26, 95% CI 0.06-0.88), and there was a trend toward them being less frequently admitted into the ICU (OR 0.45, 95% CI 0.16-1.29).
Bottom line: Less than half of community patients with heart failure had an advance directive, and many of these failed to address end-of-life decisions. Patients with an advance directive that specified limits in care were less likely to receive mechanical ventilation.
Citation: Dunlay SM, Swetz KM, Mueller PS, Roger VL. Advance directives in community patients with heart failure. Circ Cardiovasc Qual Outcomes. 2012;5:283-289.
Chlorhexidine Bathing Associated with Significant, Sustainable Reductions in Central-Venous-Catheter-Associated Bloodstream Infection
Clinical question: What is the impact, and sustainability, of chlorhexidine bathing on central-venous-catheter-associated bloodstream infections?
Background: Chlorhexidine bathing has been associated with reductions in healthcare-associated bloodstream infections, including vancomycin-resistant enterococci and methicillin-resistant Staphylococcus aureus. No prospective studies have evaluated the impact and sustainability of chlorhexidine bathing.
Study design: Prospective, three-phase study.
Setting: Medical-surgical ICUs and respiratory-care units at five New York hospitals.
Synopsis: In the pre-intervention phase (six to nine months, 1,808 admissions), patients were bathed with soap and water or nonmedicated bathing cloths. In the intervention phase (eight months, 1,832 admissions), patients were bathed with 2% chlorhexidine cloths. In the post-intervention phase (12 months, 2,834 admissions), chlorhexidine bathing was continued without oversight by researchers.
During the intervention phase, there were significantly fewer central-venous-catheter-associated bloodstream infections (2.6/1,000 catheter days vs. 6.4/1,000 pre-intervention). The reductions in bloodstream infections were sustained during the post-intervention period (2.9/1,000 catheter days). Compliance with chlorhexidine bathing was 82% and 88% during the intervention and post-intervention phases, and was well tolerated by the patients.
Limitations of this study include lack of patient-specific data and severity of illness data, as well as lack of randomization and blinding. Although not evaluated in this study, the savings associated with decreased bloodstream infections likely outweigh the cost of chlorhexidine bathing.
Bottom line: Chlorhexidine bathing is a well-tolerated, sustainable intervention that significantly reduces central-venous-catheter-associated bloodstream infections.
Citation: Montecalvo MA, McKenna D, Yarrish R, et al. Chlorhexidine bathing to reduce central venous catheter-associated bloodstream infection: impact and sustainability. Am J Med. 2012;125(5):505-511.
Simulation Training Improves Lumbar Puncture Skills
Clinical question: What effect does simulation have on lumbar puncture (LP) skills of PGY1 internal-medicine (IM) residents compared with PGY2-4 neurology residents who have not received simulation training?
Background: LPs are common procedures. The American College of General Medical Education does not define competency; neither do the internal-medicine (IM) or neurology board certifications. Simulation can improve skills in many areas but has not been well studied in LPs.
Study design: Pre-test-post-test.
Setting: Northwestern University’s Feinberg School of Medicine in Chicago.
Synopsis: The intervention group included 58 PGY1 IM residents, while the control group was 49 PGY2-to-PGY4 neurology residents. The pre-test consisted of a 21-point checklist. IM residents watched a three-hour video, performed LPs on simulators, and received feedback. The post-test was a clinical skills examination using the checklist. If this exam was failed, the participant practiced and was retested. Neurology residents completed the pre-test and demonstrated an LP using the simulator.
Pre-test passing was achieved by only 2% of IM residents and 6% of neurology residents. Post-test passing was achieved by 95% of the IM residents on the first trial and 100% of IM residents after an hour of additional training. IM mean scores increased to 95.7% from 46.3%, while the mean score of neurology residents was 65.4%.
This study is limited by its single-center nature, as education is variable from center to center. The study evaluated the proficiency on simulators only, and it did not evaluate the proficiency of the participants on patients.
Bottom line: Simulation training improves lumbar puncture skills.
Citation: Barsuk JH, Cohen ER, Caprio T, McGaghie WC, Simuni T, Wayne DB. Simulation-based education with mastery learning improves residents’ lumbar puncture skills. Neurology. 2012;79(2):132-137.
Primary-Care Physicians Do Not Use Publicly Reported Data When Referring Patients to Hospitals
Clinical question: When referring patients with pneumonia to the hospital, what factors do primary-care physicians (PCPs) consider?
Background: Publicly reported data are widely available. Pneumonia has publicly reported quality measures and is a common reason for hospitalization. Fewer PCPs are attending in the hospital due to the hospitalist movement; therefore, PCPs refer patients to a hospital when the need arises.
Study design: Online survey.
Setting: PCPs within 10 miles of Springfield, Mass.
Synopsis: A total of 92 PCPs responded to the survey, which included presentation of a case regarding a patient with pneumonia. PCPs were asked the importance of multiple factors leading to their decision to refer to a hospital. Familiarity with the hospital (70%), patient preference (62%), and admitting arrangements with a hospitalist group (62%) were considered to be very important to the PCPs that responded to the survey. Publicly reported data were very important to only 18% of respondents, and zero reported using publicly reported data when referring patients.
Importance of specific quality measures also was queried; antibiotics given within six hours of arrival (66%), appropriate choice of antibiotics (63%), and blood cultures prior to antibiotic administration (51%) were very important to respondents. Prestige, such as magnet status and U.S. News and World Report “Best Hospital” status, were deemed important by about 40% of PCPs.
Bottom line: Despite the availability of publicly reported data, PCPs do not use this information to refer patients to the hospital.
Citation: Morsi E, Lindenauer PK, Rothberg MB. Primary care physicians’ use of publicly reported quality data in hospital referral decisions. J Hosp Med. 2012;7(5):370-375.
What Works for Medication Reconciliation?
Clinical question: What are the most effective practices for medication reconciliation in the hospital setting?
Background: Medication discrepancies are common, occurring in as many as 70% of patients at hospital admission or discharge. Up to a third of these discrepancies have potential to cause patient harm, including prolonged hospital stays, ED visits, hospital recidivism, and use of other healthcare resources. Medication reconciliation (“med rec”) is a strategy for reducing these errors, though previous literature has not systematically reviewed best practices for hospital-based med rec.
Study design: Systematic review of literature.
Setting: Controlled studies from the U.S., Canada, Australia, New Zealand, Northern Ireland, United Kingdom, Belgium, Denmark, the Netherlands, and Sweden.
Synopsis: Investigators identified 26 controlled studies using a systematic search of English-language articles on med rec during inpatient hospitalizations published between Jan. 1, 1966, and Oct. 31, 2010. Fifteen studies reported on pharmacist-related interventions; six reported on technology-specific interventions; and five reported on other types of interventions, including staff education and use of standardized med-rec tools.
Analysis of these studies revealed that all of these interventions successfully decreased medication discrepancies and potential adverse drug events, but there was inconsistent benefit with regard to adverse drug events and healthcare utilization compared with usual care. The literature was most supportive of pharmacist-related interventions, including but not limited to comprehensive medication history at admission, med rec at discharge, patient counseling, discharge communication with outpatient providers, and post-discharge communication with the patient and post-hospital providers.
Bottom line: Successful med rec requires multiple interventions at various transitions of care and involves a variety of medical professionals. Patient-targeted interventions, including pharmacists, have the potential to decrease errors and adverse events.
Citation: Mueller S, Sponsler K, Kripalani S, Schnipper J. Hospital-based medication reconciliation practices: a systematic review. Arch Intern Med. 2012;172(14):1057-1069.
In This Edition
Literature At A Glance
A guide to this month’s studies
- Prediction tool for neurological outcomes after in-hospital cardiac arrest
- Radiation exposure in integrated healthcare systems, 1996-2010
- Postoperative troponin predicts 30-day mortality
- Clinical prediction model of mortality in acute heart failure
- Indwelling pleural catheter vs. talc pleurodesis via chest tube
- Early surgery for high-risk, native-valve endocarditis patients
- Risk factors after ED visit for syncope
- Acute hyperglycemia in CAP patients
- Hospital delirium associated with cognitive decline, institutionalization, and death
- Seven-day ciprofloxacin effective against acute pyelonephritis
- Advance directives in community patients with heart failure
- Chlorhexidine bathing effective against CVC-associated bloodstream infections
- Simulation training improves lumbar puncture skills
- PCP referrals to hospitals and publicly reported data
- Medication reconciliation best practices
Prediction Tool Validated for Prognosticating Favorable Neurological Outcome after In-Hospital Cardiac Arrest
Clinical question: Does the Cardiac Arrest Survival Post Resuscitation In-Hospital (CASPRI) score accurately predict favorable neurological outcomes?
Background: Previous cardiac arrest prediction models have been focused on survival to discharge without consideration of neurological status and have not been translated into valid bedside prognostication tools. Neurologic prognosis can assist patients, families, and physicians in decisions about continued goals of care post-arrest.
Study design: Retrospective cohort study.
Setting: Acute-care hospitals.
Synopsis: Using the Get with the Guidelines Resuscitation Registry, 551 hospitals identified 42,957 patients who were successfully resuscitated from an in-hospital cardiac arrest from January 2000 to October 2009. Researchers developed a simple prediction tool for favorable neurological outcomes (defined as “no” or “moderate” neurological disability) at discharge. The 11 predictors used to calculate the CASPRI score are age; time to defibrillation; pre-arrest neurological status; hospital location; duration of resuscitation; and pre-arrest comorbidities: mechanical ventilation, renal insufficiency, hepatic insufficiency, sepsis, malignancy,
and hypotension.
Rates of favorable neurological outcome were similar between derivation cohort (24.6%) and validation cohort (24.5%). The model had excellent discrimination with a C score of 0.80. Probability of favorable neurological survival ranged from 70.7% in the top decile of patients (CASPRI <10) and 2.8% in bottom decile (CASPRI ≥ 28).
This tool is not generalizable to patients with out-of-hospital arrest or undergoing therapeutic hypothermia.
Bottom line: CASPRI is a simple bedside tool validated to estimate probability of favorable neurological outcome after in-hospital cardiac arrest.
Citation: Chan PS, Spertus JA, Krumholz HA, et al. A validated prediction tool for initial survivors in in-hospital cardiac arrest. Arch Intern Med. 2012;172(12):947-953.
Increased Use of Radiologic Imaging and Associated Radiation Exposure in Integrated Healthcare Systems, 1996-2010
Clinical question: How much has imaging utilization and associated radiation exposure increased over 15 years in integrated healthcare systems independent of financial incentives in a fee-for-service system?
Background: Use of diagnostic imaging has increased significantly within fee-for-service healthcare models. The associated radiation exposure has increased the risk of radiation-induced malignancies. Little is known about the pattern of imaging use in integrated healthcare systems without the financial incentives seen in other models of care.
Study design: Retrospective cohort study.
Setting: Six integrated healthcare systems in the U.S.
Synopsis: The number of diagnostic imaging studies performed and estimated radiation exposure were determined from analysis of electronic medical records from member patients enrolled in health systems in the HMO Research Network from 1996 to 2010. Annual increases in use of advanced diagnostics were noted in CT (7.8% annual growth), MRI (10%), ultrasound (3.9%), and PET (57%) studies.
Increased CT use over the 15-year study period resulted in increased radiation exposure, doubling mean per capita effective dose (1.2 mSv to 2.3 mSv), as well as those receiving high exposure (1.2% to 2.5%) and very high exposure (0.6% to 1.4%).
The increased imaging use and radiation exposure among HMO enrollees was similar to that of fee-for-service Medicare patients in previous studies.
Bottom line: There is a significant increase in use of diagnostic imaging studies and associated radiation exposure among integrated healthcare system enrollees from 1996 to 2010, similar to patients in fee-for-service health plans.
Citation: Smith-Bindman R, Miglioretti DL, Johnson E, et al. Use of diagnostic imaging studies and associated radiation exposure for patients enrolled in large integrated health care systems, 1996-2010. JAMA. 2012;307(22):2400-2409.
Postoperative Troponin Predicts 30-Day Mortality
Clinical question: Does postoperative peak troponin level predict 30-day mortality in patients undergoing noncardiac surgery?
Background: The use of postoperative peak troponin levels in predicting 30-day mortality for patients undergoing noncardiac surgery has not been studied extensively. Identifying patients at high risk for death following noncardiac surgery could facilitate appropriate postoperative care and improve survival.
Study design: Prospective cohort study.
Setting: International university and nonuniversity hospitals.
Synopsis: The Vascular Events In Noncardiac Surgery Patients Cohort Evaluation (VISION) Study is a large, international, multicenter, prospective cohort study designed to evaluate the major complications of noncardiac surgery. More than 15,100 patients ages 45 and older requiring at least an overnight hospitalization were enrolled following noncardiac surgery.
Peak troponin measurements during the first three postoperative days of 0.01 ng/ml or less, 0.02 ng/ml, 0.03 ng/ml to 0.29 ng/ml, and 0.3 ng/ml or greater had 30-day mortality rates of 1.0%, 4.0%, 9.3%, and 16.9%, respectively.
This study demonstrates the sensitivity of troponin measurement for predicting postoperative 30-day mortality in patients undergoing noncardiac surgery. The study does not address interventions based on an increased postoperative troponin level. Future studies might investigate postoperative modifiable risk factors.
Bottom line: Postoperative peak troponin level predicts 30-day mortality in patients undergoing noncardiac surgery.
Citation: Devereaux PJ, Chan MT, Alonso-Coello P, et al. Association between postoperative troponin levels and 30-day mortality among patients undergoing noncardiac surgery. JAMA. 2012;307(21):2295-2304.
Clinical Prediction Model of Mortality in Acute Heart Failure
Clinical question: Can a clinical prediction model accurately risk-stratify patients presenting to the ED with acute heart failure?
Background: Accurately prognosticating mortality is essential when determining whether to hospitalize or discharge patients presenting to the ED with acute heart failure. Evidence-based clinical prediction models enable physicians to risk-stratify patients and optimize care.
Study design: Retrospective cohort study.
Setting: Multicenter study of 86 hospitals in Ontario, Canada.
Synopsis: Data collected from 12,591 patients who presented to EDs with acute heart failure in Ontario were analyzed. A clinical prediction model of seven-day mortality of discharged and hospitalized patients was derived and validated. The Emergency Heart Failure Mortality Risk Grade (EHMRG) found an increased mortality based on higher triage heart rate, lower triage systolic blood pressure, initial oxygen saturation, and elevated troponin levels. This model uses readily available data collected in ED visits. The high-risk EHMRG score predicted about 8% seven-day mortality versus 0.3% in the low-risk score.
This model was not applied to chronic heart failure, did not utilize left ventricular function, and does not differentiate between systolic and diastolic heart failure.
Bottom line: The Emergency Heart Failure Mortality Risk Grade predicts seven-day mortality in acute heart failure in the emergent setting.
Citation: Lee DS, Stitt A, Austin PC, et al. Prediction of heart failure mortality in emergent care: a cohort study. Ann Intern Med. 2012;156(11):767-775.
Indwelling Pleural Catheter Is as Effective as Talc Pleurodesis Via Chest Tube in Relieving Dyspnea in Patients with Malignant Pleural Effusion
Clinical question: Is indwelling pleural catheter (IPC) as effective as chest tube and talc pleurodesis (talc) in improving dyspnea from malignant pleural effusion in patients who had no previous pleurodesis?
Background: Despite guidelines recommending chest tube insertion with pleurodesis as a first-line treatment for symptom palliation from malignant pleural effusion, there has been no randomized trial comparing indwelling pleural catheter with chest tube and talc pleurodesis.
Study design: Open-label, randomized controlled trial.
Setting: Seven hospitals in the United Kingdom.
Synopsis: One hundred six patients with malignant pleural effusion were randomized to undergo either IPC or talc treatment, and their daily mean dyspnea was measured. There was a clinically significant improvement of dyspnea in both IPC and talc groups over the first 42 days of the trial, without any significant difference in dyspnea between the two groups. After six months, researchers found a clinically significant decrease in dyspnea in the IPC group compared with the talc group. Chest pain and global quality of life were improved and were similar in both groups throughout the trial period. Length of hospital stay was significantly shorter in the IPC group compared with the talc group, but more patients in the IPC group experienced adverse events.
Bottom line: Indwelling pleural catheter is as effective as talc pleurodesis in reliving dyspnea from malignant pleural effusion; however, IPC is associated with increased adverse events despite shorter length of hospital stay.
Citation: Davies HE, Mishra EK, Kahan BC, et al. Effect of an indwelling pleural catheter vs. chest tube and talc pleurodesis for relieving dyspnea in patients with malignant pleural effusion: the TIME2 randomized controlled trial. JAMA. 2012;307(22):2383-2389.
Early Surgery Better than Conventional Treatment in High-Risk Native-Valve Endocarditis
Clinical question: Is early cardiac surgery better than conventional treatment for patients with left-sided, native-valve, infective endocarditis?
Background: Although guidelines strongly recommend early surgery for patients with infective endocarditis and congestive heart failure, the timing of surgery for patients with large vegetations and high risk of embolism without heart failure symptoms remains controversial.
Study design: Prospective, randomized trial.
Setting: Two medical centers in South Korea.
Synopsis: Seventy-six patients with left-sided, native-valve, infective endocarditis with a high risk of embolism (defined as vegetation with a diameter greater than 10 mm or severe mitral or aortic valve disease) were randomized to undergo early surgery (within 48 hours of enrollment) or conventional treatment (antibiotic therapy and surgery only if complications required urgent surgery). The primary outcome of composite in-hospital death or
clinical embolic events within six weeks of the trial occurred in only one patient in the early surgery group, compared with nine patients in the conventional group (hazard ratio 0.10, 95% CI, 0.01-0.82, P=0.03).
There was no difference in all-cause mortality at six months between the two groups, but the rate of composite endpoint of death from any cause, embolic events, or recurrence of infective endocarditis at six months was significantly lower in the early surgery group compared with the conventional group.
Bottom line: Early cardiac surgery for patients with left-sided, native-valve infective endocarditis with a high risk of embolism significantly improved the composite outcome of all-cause mortality, embolic events, or recurrence of endocarditis compared with the conventional therapy.
Citation: Kang DH, Kim YJ, Kim SH, et al. Early surgery versus conventional treatment for infective endocarditis. N Engl J Med. 2012;366(26):2466-2473.
Risk Factors for Short-Term Mortality after Emergency Department Visit for Syncope
Clinical question: What are the risk factors for short-term mortality after an ED evaluation for syncope or near-syncope?
Background: Syncope accounts for 1% to 2% of all ED visits and an equal number of hospital admissions. The risk of death after an ED visit for syncope is poorly understood, resulting in frequent hospital admissions.
Study design: Retrospective cohort study.
Setting: EDs in Southern California.
Synopsis: Authors evaluated 23,951 ED visits resulting in syncope as sole primary diagnosis. Age was identified as the most significant risk factor for short-term mortality. Cumulative survival data revealed that more than 1% of patients 60 or older died by 30 days. There were 215 deaths (2.84%) in patients hospitalized from the ED and 66 deaths (0.45%) among patients not hospitalized.
Pre-existing comorbidities significantly associated with increased mortality included heart failure (HR=14.3 in ages 18-53; HR=3.09 in ages 60-79; HR=2.34 in ages 80-plus), diabetes (HR=1.49), seizure (HR=1.65), dementia (HR=1.41), and a recent prior visit for syncope (HR=1.86). The risk of death by 30 days was less than 0.2% in patients under 60 without heart failure and more than 2.5% in patients of all ages with heart failure.
Bottom line: After an ED visit for syncope, patients with a history of heart failure and patients 60 and older have a significantly increased risk of short-term mortality.
Citation: Derose SF, Gabayan GZ, Chiu VY, Sun BC. Patterns and preexisting risk factors of 30-day mortality after a primary discharge diagnosis of syncope or near syncope. Acad Emerg Med. 2012;19(5):488-496.
Acute Hyperglycemia Associated with Increased Mortality in Community-Acquired Pneumonia
Clinical question: In patients admitted to the hospital for community-acquired pneumonia, is serum glucose level on admission associated with mortality?
Background: Some retrospective studies have shown an association between alterations in serum glucose levels or pre-existing diabetes and higher mortality due to infections, while other studies have shown no clear association.
Study design: Multicenter, prospective cohort study.
Setting: Hospitals and private practices in Germany, Switzerland, and Austria.
Synopsis: Prospective data from 6,891 patients were included in the analysis. Patients without diabetes and normal serum glucose levels had the lowest mortality after 90 days. Patients without diabetes but with mild acute hyperglycemia (108 mg/dL to 198 mg/dL) had a significantly increased risk of death at 90 days (HR 1.56), and patients without diabetes but with more severe acute hyperglycemia (over 252 mg/dL) had an even higher risk of death at 90 days (HR 2.37).
The 90-day mortality rate was significantly higher in patients with pre-existing diabetes (HR 2.47), although this was not affected by serum glucose levels on admission.
Bottom line: Acute hyperglycemia, as well as pre-existing diabetes, was associated with an increased risk of 90-day mortality in patients with community acquired pneumonia.
Citation: Lepper PM, Ott S, Nüesch E, et al. Serum glucose levels for predicting death in patients admitted to hospital for community acquired pneumonia: prospective cohort study. BMJ. 2012;344:e3397.
Hospital Delirium Associated with Cognitive Decline, Institutionalization, and Death
Clinical question: What is the risk of subsequent cognitive decline, institutionalization, or death due to delirium in patients with dementia?
Background: Patients suffering delirium during hospitalization can suffer additional cognitive decline. Whether this is due to additional damage from the delirium state or reflects pre-existing cognitive vulnerability remains uncertain.
Study design: Prospective analysis of a cohort of Alzheimer’s patients.
Setting: Massachusetts community-based disease registry.
Synopsis: The analysis compared nonhospitalized individuals to patients hospitalized with, and without, delirium. In 771 individuals with dementia, at least one adverse outcome (including cognitive decline, institutionalization, or death) occurred in 32% of those not hospitalized, 55% of those hospitalized without delirium, and 79% of those hospitalized with delirium. Even after adjusting for confounders, hospitalization increased the risk for each of the adverse outcomes; the highest risk was in those with delirium.
Among hospitalized patients, the authors estimated 1 in 5 cases of cognitive decline, 1 in 7 institutionalizations, and 1 in 16 deaths were attributable to delirium. Some of the attributed risk could be the result of residual confounding from unmeasured variables, limiting conclusions of causality. Despite these limitations, this study supports the hypothesis that delirium prevention measures could improve important patient outcomes.
Bottom line: Hospitalization is associated with high rates of adverse outcomes in elderly patients with dementia, the worst of which occurs in those who experience delirium.
Citation: Fong TG, Jones RN, Marcantonio ER, et al. Adverse outcomes after hospitalization and delirium in persons with Alzheimer disease. Ann Int Med. 2012;156:848-856.
In Acute Pyelonephritis, a Seven-Day Course of Ciprofloxacin is Effective in Obtaining Clinical Cure
Clinical question: What is the efficacy of ciprofloxacin for seven days compared with 14 days in women with community-acquired acute pyelonephritis?
Background: Community-acquired acute pyelonephritis is a common and sometimes serious infection in women. In an era of increasing antibiotic resistance worldwide, it is prudent to reduce antibiotic utilization. There are limited controlled trials to assess the optimum duration of antibiotic treatment for this common infection.
Study design: Prospective, randomized, double-blind, noninferiority trial.
Setting: Twenty-one infectious-disease centers in Sweden.
Synopsis: Researchers randomly assigned 284 women 18 or older with a presumptive diagnosis of acute pyelonephritis to ciprofloxacin treatment for seven or 14 days. The primary endpoint was clinical and bacteriological cure 10 to 14 days after the completion of the treatment regimen. Short-term clinical cure occurred in 97% of the patients treated for seven days and 96% treated for 14 days. Long-term follow-up showed cumulative efficacy of 93% in each group. Both regimens were well tolerated.
Patients in this study had a low occurrence of complicated (9%) and recurrent (13%) infections. Whether short courses of antibiotics are effective in more complicated infections cannot be ascertained from this study. Also, the high cure rate obtained with a seven-day course of ciprofloxacin should not be extrapolated to other classes of antibiotics. Fluoroquinolones, such as ciprofloxacin, are recommended as first-line agents for empiric oral treatment of acute pyelonephritis if the resistance rate of the uropathogens remains lower than 10%; however, there is growing evidence that E. coli strains are becoming increasingly resistant to ciprofloxacin, limiting its usefulness.
Bottom line: Acute pyelonephritis in women can be treated successfully and safely with a seven-day course of ciprofloxacin, in areas with low ciprofloxacin resistance.
Citation: Sandberg T, Skoog G, Hermansson AB, et al. Ciprofloxacin for 7 days versus 14 days in women with acute pyelonephritis: a randomized, open-label and double-blind, placebo-controlled, non-inferiority trial. Lancet. 2012;380:484-490.
Advance Directives in Community Patients with Heart Failure
Clinical question: How prevalent are advance directives in heart-failure patients, and does a completed advance directive decrease end-of-life resource use (hospitalizations, ICU admissions, mechanical ventilation)?
Background: Heart failure is a common chronic and fatal disease. End-of-life care in heart-failure patients is associated with extremely high healthcare utilization. Heart failure guidelines recommend completing advance directives in all patients.
Study design: Population-based longitudinal cohort study.
Setting: Rochester Epidemiology Project in Olmstead County, Minn.
Synopsis: Investigators enrolled 608 patients presenting with heart failure between October 2007 and October 2011. At the time of enrollment, only 41% of the patients had existing advance directives. Independent predictors of advance directive completion included older age, history of malignancy, and renal dysfunction.
After a mean follow-up of 1.8 years, 164 patients (27%) had died. Among those patients, 106 had an advance directive (64.6%) at time of death—75 had an advance directive at the time of enrollment and another 31 completed an advance directive after enrollment.
Twenty-five patients (23.6%) specified DNR/DNI and another 39 (36.8%) denoted limitations on aggressiveness of care if death was imminent. Among the patients who died, 88 (53.7%) were hospitalized in the last month of their life and 50 (30.5%) died in the hospital. There was no difference in hospitalizations between those with an advance directive specifying limits and those who did not specify limits (OR 1.26, 95% CI 0.64-2.48). However, those with an advance directive specifying limits were less frequently mechanically ventilated (OR 0.26, 95% CI 0.06-0.88), and there was a trend toward them being less frequently admitted into the ICU (OR 0.45, 95% CI 0.16-1.29).
Bottom line: Less than half of community patients with heart failure had an advance directive, and many of these failed to address end-of-life decisions. Patients with an advance directive that specified limits in care were less likely to receive mechanical ventilation.
Citation: Dunlay SM, Swetz KM, Mueller PS, Roger VL. Advance directives in community patients with heart failure. Circ Cardiovasc Qual Outcomes. 2012;5:283-289.
Chlorhexidine Bathing Associated with Significant, Sustainable Reductions in Central-Venous-Catheter-Associated Bloodstream Infection
Clinical question: What is the impact, and sustainability, of chlorhexidine bathing on central-venous-catheter-associated bloodstream infections?
Background: Chlorhexidine bathing has been associated with reductions in healthcare-associated bloodstream infections, including vancomycin-resistant enterococci and methicillin-resistant Staphylococcus aureus. No prospective studies have evaluated the impact and sustainability of chlorhexidine bathing.
Study design: Prospective, three-phase study.
Setting: Medical-surgical ICUs and respiratory-care units at five New York hospitals.
Synopsis: In the pre-intervention phase (six to nine months, 1,808 admissions), patients were bathed with soap and water or nonmedicated bathing cloths. In the intervention phase (eight months, 1,832 admissions), patients were bathed with 2% chlorhexidine cloths. In the post-intervention phase (12 months, 2,834 admissions), chlorhexidine bathing was continued without oversight by researchers.
During the intervention phase, there were significantly fewer central-venous-catheter-associated bloodstream infections (2.6/1,000 catheter days vs. 6.4/1,000 pre-intervention). The reductions in bloodstream infections were sustained during the post-intervention period (2.9/1,000 catheter days). Compliance with chlorhexidine bathing was 82% and 88% during the intervention and post-intervention phases, and was well tolerated by the patients.
Limitations of this study include lack of patient-specific data and severity of illness data, as well as lack of randomization and blinding. Although not evaluated in this study, the savings associated with decreased bloodstream infections likely outweigh the cost of chlorhexidine bathing.
Bottom line: Chlorhexidine bathing is a well-tolerated, sustainable intervention that significantly reduces central-venous-catheter-associated bloodstream infections.
Citation: Montecalvo MA, McKenna D, Yarrish R, et al. Chlorhexidine bathing to reduce central venous catheter-associated bloodstream infection: impact and sustainability. Am J Med. 2012;125(5):505-511.
Simulation Training Improves Lumbar Puncture Skills
Clinical question: What effect does simulation have on lumbar puncture (LP) skills of PGY1 internal-medicine (IM) residents compared with PGY2-4 neurology residents who have not received simulation training?
Background: LPs are common procedures. The American College of General Medical Education does not define competency; neither do the internal-medicine (IM) or neurology board certifications. Simulation can improve skills in many areas but has not been well studied in LPs.
Study design: Pre-test-post-test.
Setting: Northwestern University’s Feinberg School of Medicine in Chicago.
Synopsis: The intervention group included 58 PGY1 IM residents, while the control group was 49 PGY2-to-PGY4 neurology residents. The pre-test consisted of a 21-point checklist. IM residents watched a three-hour video, performed LPs on simulators, and received feedback. The post-test was a clinical skills examination using the checklist. If this exam was failed, the participant practiced and was retested. Neurology residents completed the pre-test and demonstrated an LP using the simulator.
Pre-test passing was achieved by only 2% of IM residents and 6% of neurology residents. Post-test passing was achieved by 95% of the IM residents on the first trial and 100% of IM residents after an hour of additional training. IM mean scores increased to 95.7% from 46.3%, while the mean score of neurology residents was 65.4%.
This study is limited by its single-center nature, as education is variable from center to center. The study evaluated the proficiency on simulators only, and it did not evaluate the proficiency of the participants on patients.
Bottom line: Simulation training improves lumbar puncture skills.
Citation: Barsuk JH, Cohen ER, Caprio T, McGaghie WC, Simuni T, Wayne DB. Simulation-based education with mastery learning improves residents’ lumbar puncture skills. Neurology. 2012;79(2):132-137.
Primary-Care Physicians Do Not Use Publicly Reported Data When Referring Patients to Hospitals
Clinical question: When referring patients with pneumonia to the hospital, what factors do primary-care physicians (PCPs) consider?
Background: Publicly reported data are widely available. Pneumonia has publicly reported quality measures and is a common reason for hospitalization. Fewer PCPs are attending in the hospital due to the hospitalist movement; therefore, PCPs refer patients to a hospital when the need arises.
Study design: Online survey.
Setting: PCPs within 10 miles of Springfield, Mass.
Synopsis: A total of 92 PCPs responded to the survey, which included presentation of a case regarding a patient with pneumonia. PCPs were asked the importance of multiple factors leading to their decision to refer to a hospital. Familiarity with the hospital (70%), patient preference (62%), and admitting arrangements with a hospitalist group (62%) were considered to be very important to the PCPs that responded to the survey. Publicly reported data were very important to only 18% of respondents, and zero reported using publicly reported data when referring patients.
Importance of specific quality measures also was queried; antibiotics given within six hours of arrival (66%), appropriate choice of antibiotics (63%), and blood cultures prior to antibiotic administration (51%) were very important to respondents. Prestige, such as magnet status and U.S. News and World Report “Best Hospital” status, were deemed important by about 40% of PCPs.
Bottom line: Despite the availability of publicly reported data, PCPs do not use this information to refer patients to the hospital.
Citation: Morsi E, Lindenauer PK, Rothberg MB. Primary care physicians’ use of publicly reported quality data in hospital referral decisions. J Hosp Med. 2012;7(5):370-375.
What Works for Medication Reconciliation?
Clinical question: What are the most effective practices for medication reconciliation in the hospital setting?
Background: Medication discrepancies are common, occurring in as many as 70% of patients at hospital admission or discharge. Up to a third of these discrepancies have potential to cause patient harm, including prolonged hospital stays, ED visits, hospital recidivism, and use of other healthcare resources. Medication reconciliation (“med rec”) is a strategy for reducing these errors, though previous literature has not systematically reviewed best practices for hospital-based med rec.
Study design: Systematic review of literature.
Setting: Controlled studies from the U.S., Canada, Australia, New Zealand, Northern Ireland, United Kingdom, Belgium, Denmark, the Netherlands, and Sweden.
Synopsis: Investigators identified 26 controlled studies using a systematic search of English-language articles on med rec during inpatient hospitalizations published between Jan. 1, 1966, and Oct. 31, 2010. Fifteen studies reported on pharmacist-related interventions; six reported on technology-specific interventions; and five reported on other types of interventions, including staff education and use of standardized med-rec tools.
Analysis of these studies revealed that all of these interventions successfully decreased medication discrepancies and potential adverse drug events, but there was inconsistent benefit with regard to adverse drug events and healthcare utilization compared with usual care. The literature was most supportive of pharmacist-related interventions, including but not limited to comprehensive medication history at admission, med rec at discharge, patient counseling, discharge communication with outpatient providers, and post-discharge communication with the patient and post-hospital providers.
Bottom line: Successful med rec requires multiple interventions at various transitions of care and involves a variety of medical professionals. Patient-targeted interventions, including pharmacists, have the potential to decrease errors and adverse events.
Citation: Mueller S, Sponsler K, Kripalani S, Schnipper J. Hospital-based medication reconciliation practices: a systematic review. Arch Intern Med. 2012;172(14):1057-1069.
In This Edition
Literature At A Glance
A guide to this month’s studies
- Prediction tool for neurological outcomes after in-hospital cardiac arrest
- Radiation exposure in integrated healthcare systems, 1996-2010
- Postoperative troponin predicts 30-day mortality
- Clinical prediction model of mortality in acute heart failure
- Indwelling pleural catheter vs. talc pleurodesis via chest tube
- Early surgery for high-risk, native-valve endocarditis patients
- Risk factors after ED visit for syncope
- Acute hyperglycemia in CAP patients
- Hospital delirium associated with cognitive decline, institutionalization, and death
- Seven-day ciprofloxacin effective against acute pyelonephritis
- Advance directives in community patients with heart failure
- Chlorhexidine bathing effective against CVC-associated bloodstream infections
- Simulation training improves lumbar puncture skills
- PCP referrals to hospitals and publicly reported data
- Medication reconciliation best practices
Prediction Tool Validated for Prognosticating Favorable Neurological Outcome after In-Hospital Cardiac Arrest
Clinical question: Does the Cardiac Arrest Survival Post Resuscitation In-Hospital (CASPRI) score accurately predict favorable neurological outcomes?
Background: Previous cardiac arrest prediction models have been focused on survival to discharge without consideration of neurological status and have not been translated into valid bedside prognostication tools. Neurologic prognosis can assist patients, families, and physicians in decisions about continued goals of care post-arrest.
Study design: Retrospective cohort study.
Setting: Acute-care hospitals.
Synopsis: Using the Get with the Guidelines Resuscitation Registry, 551 hospitals identified 42,957 patients who were successfully resuscitated from an in-hospital cardiac arrest from January 2000 to October 2009. Researchers developed a simple prediction tool for favorable neurological outcomes (defined as “no” or “moderate” neurological disability) at discharge. The 11 predictors used to calculate the CASPRI score are age; time to defibrillation; pre-arrest neurological status; hospital location; duration of resuscitation; and pre-arrest comorbidities: mechanical ventilation, renal insufficiency, hepatic insufficiency, sepsis, malignancy,
and hypotension.
Rates of favorable neurological outcome were similar between derivation cohort (24.6%) and validation cohort (24.5%). The model had excellent discrimination with a C score of 0.80. Probability of favorable neurological survival ranged from 70.7% in the top decile of patients (CASPRI <10) and 2.8% in bottom decile (CASPRI ≥ 28).
This tool is not generalizable to patients with out-of-hospital arrest or undergoing therapeutic hypothermia.
Bottom line: CASPRI is a simple bedside tool validated to estimate probability of favorable neurological outcome after in-hospital cardiac arrest.
Citation: Chan PS, Spertus JA, Krumholz HA, et al. A validated prediction tool for initial survivors in in-hospital cardiac arrest. Arch Intern Med. 2012;172(12):947-953.
Increased Use of Radiologic Imaging and Associated Radiation Exposure in Integrated Healthcare Systems, 1996-2010
Clinical question: How much has imaging utilization and associated radiation exposure increased over 15 years in integrated healthcare systems independent of financial incentives in a fee-for-service system?
Background: Use of diagnostic imaging has increased significantly within fee-for-service healthcare models. The associated radiation exposure has increased the risk of radiation-induced malignancies. Little is known about the pattern of imaging use in integrated healthcare systems without the financial incentives seen in other models of care.
Study design: Retrospective cohort study.
Setting: Six integrated healthcare systems in the U.S.
Synopsis: The number of diagnostic imaging studies performed and estimated radiation exposure were determined from analysis of electronic medical records from member patients enrolled in health systems in the HMO Research Network from 1996 to 2010. Annual increases in use of advanced diagnostics were noted in CT (7.8% annual growth), MRI (10%), ultrasound (3.9%), and PET (57%) studies.
Increased CT use over the 15-year study period resulted in increased radiation exposure, doubling mean per capita effective dose (1.2 mSv to 2.3 mSv), as well as those receiving high exposure (1.2% to 2.5%) and very high exposure (0.6% to 1.4%).
The increased imaging use and radiation exposure among HMO enrollees was similar to that of fee-for-service Medicare patients in previous studies.
Bottom line: There is a significant increase in use of diagnostic imaging studies and associated radiation exposure among integrated healthcare system enrollees from 1996 to 2010, similar to patients in fee-for-service health plans.
Citation: Smith-Bindman R, Miglioretti DL, Johnson E, et al. Use of diagnostic imaging studies and associated radiation exposure for patients enrolled in large integrated health care systems, 1996-2010. JAMA. 2012;307(22):2400-2409.
Postoperative Troponin Predicts 30-Day Mortality
Clinical question: Does postoperative peak troponin level predict 30-day mortality in patients undergoing noncardiac surgery?
Background: The use of postoperative peak troponin levels in predicting 30-day mortality for patients undergoing noncardiac surgery has not been studied extensively. Identifying patients at high risk for death following noncardiac surgery could facilitate appropriate postoperative care and improve survival.
Study design: Prospective cohort study.
Setting: International university and nonuniversity hospitals.
Synopsis: The Vascular Events In Noncardiac Surgery Patients Cohort Evaluation (VISION) Study is a large, international, multicenter, prospective cohort study designed to evaluate the major complications of noncardiac surgery. More than 15,100 patients ages 45 and older requiring at least an overnight hospitalization were enrolled following noncardiac surgery.
Peak troponin measurements during the first three postoperative days of 0.01 ng/ml or less, 0.02 ng/ml, 0.03 ng/ml to 0.29 ng/ml, and 0.3 ng/ml or greater had 30-day mortality rates of 1.0%, 4.0%, 9.3%, and 16.9%, respectively.
This study demonstrates the sensitivity of troponin measurement for predicting postoperative 30-day mortality in patients undergoing noncardiac surgery. The study does not address interventions based on an increased postoperative troponin level. Future studies might investigate postoperative modifiable risk factors.
Bottom line: Postoperative peak troponin level predicts 30-day mortality in patients undergoing noncardiac surgery.
Citation: Devereaux PJ, Chan MT, Alonso-Coello P, et al. Association between postoperative troponin levels and 30-day mortality among patients undergoing noncardiac surgery. JAMA. 2012;307(21):2295-2304.
Clinical Prediction Model of Mortality in Acute Heart Failure
Clinical question: Can a clinical prediction model accurately risk-stratify patients presenting to the ED with acute heart failure?
Background: Accurately prognosticating mortality is essential when determining whether to hospitalize or discharge patients presenting to the ED with acute heart failure. Evidence-based clinical prediction models enable physicians to risk-stratify patients and optimize care.
Study design: Retrospective cohort study.
Setting: Multicenter study of 86 hospitals in Ontario, Canada.
Synopsis: Data collected from 12,591 patients who presented to EDs with acute heart failure in Ontario were analyzed. A clinical prediction model of seven-day mortality of discharged and hospitalized patients was derived and validated. The Emergency Heart Failure Mortality Risk Grade (EHMRG) found an increased mortality based on higher triage heart rate, lower triage systolic blood pressure, initial oxygen saturation, and elevated troponin levels. This model uses readily available data collected in ED visits. The high-risk EHMRG score predicted about 8% seven-day mortality versus 0.3% in the low-risk score.
This model was not applied to chronic heart failure, did not utilize left ventricular function, and does not differentiate between systolic and diastolic heart failure.
Bottom line: The Emergency Heart Failure Mortality Risk Grade predicts seven-day mortality in acute heart failure in the emergent setting.
Citation: Lee DS, Stitt A, Austin PC, et al. Prediction of heart failure mortality in emergent care: a cohort study. Ann Intern Med. 2012;156(11):767-775.
Indwelling Pleural Catheter Is as Effective as Talc Pleurodesis Via Chest Tube in Relieving Dyspnea in Patients with Malignant Pleural Effusion
Clinical question: Is indwelling pleural catheter (IPC) as effective as chest tube and talc pleurodesis (talc) in improving dyspnea from malignant pleural effusion in patients who had no previous pleurodesis?
Background: Despite guidelines recommending chest tube insertion with pleurodesis as a first-line treatment for symptom palliation from malignant pleural effusion, there has been no randomized trial comparing indwelling pleural catheter with chest tube and talc pleurodesis.
Study design: Open-label, randomized controlled trial.
Setting: Seven hospitals in the United Kingdom.
Synopsis: One hundred six patients with malignant pleural effusion were randomized to undergo either IPC or talc treatment, and their daily mean dyspnea was measured. There was a clinically significant improvement of dyspnea in both IPC and talc groups over the first 42 days of the trial, without any significant difference in dyspnea between the two groups. After six months, researchers found a clinically significant decrease in dyspnea in the IPC group compared with the talc group. Chest pain and global quality of life were improved and were similar in both groups throughout the trial period. Length of hospital stay was significantly shorter in the IPC group compared with the talc group, but more patients in the IPC group experienced adverse events.
Bottom line: Indwelling pleural catheter is as effective as talc pleurodesis in reliving dyspnea from malignant pleural effusion; however, IPC is associated with increased adverse events despite shorter length of hospital stay.
Citation: Davies HE, Mishra EK, Kahan BC, et al. Effect of an indwelling pleural catheter vs. chest tube and talc pleurodesis for relieving dyspnea in patients with malignant pleural effusion: the TIME2 randomized controlled trial. JAMA. 2012;307(22):2383-2389.
Early Surgery Better than Conventional Treatment in High-Risk Native-Valve Endocarditis
Clinical question: Is early cardiac surgery better than conventional treatment for patients with left-sided, native-valve, infective endocarditis?
Background: Although guidelines strongly recommend early surgery for patients with infective endocarditis and congestive heart failure, the timing of surgery for patients with large vegetations and high risk of embolism without heart failure symptoms remains controversial.
Study design: Prospective, randomized trial.
Setting: Two medical centers in South Korea.
Synopsis: Seventy-six patients with left-sided, native-valve, infective endocarditis with a high risk of embolism (defined as vegetation with a diameter greater than 10 mm or severe mitral or aortic valve disease) were randomized to undergo early surgery (within 48 hours of enrollment) or conventional treatment (antibiotic therapy and surgery only if complications required urgent surgery). The primary outcome of composite in-hospital death or
clinical embolic events within six weeks of the trial occurred in only one patient in the early surgery group, compared with nine patients in the conventional group (hazard ratio 0.10, 95% CI, 0.01-0.82, P=0.03).
There was no difference in all-cause mortality at six months between the two groups, but the rate of composite endpoint of death from any cause, embolic events, or recurrence of infective endocarditis at six months was significantly lower in the early surgery group compared with the conventional group.
Bottom line: Early cardiac surgery for patients with left-sided, native-valve infective endocarditis with a high risk of embolism significantly improved the composite outcome of all-cause mortality, embolic events, or recurrence of endocarditis compared with the conventional therapy.
Citation: Kang DH, Kim YJ, Kim SH, et al. Early surgery versus conventional treatment for infective endocarditis. N Engl J Med. 2012;366(26):2466-2473.
Risk Factors for Short-Term Mortality after Emergency Department Visit for Syncope
Clinical question: What are the risk factors for short-term mortality after an ED evaluation for syncope or near-syncope?
Background: Syncope accounts for 1% to 2% of all ED visits and an equal number of hospital admissions. The risk of death after an ED visit for syncope is poorly understood, resulting in frequent hospital admissions.
Study design: Retrospective cohort study.
Setting: EDs in Southern California.
Synopsis: Authors evaluated 23,951 ED visits resulting in syncope as sole primary diagnosis. Age was identified as the most significant risk factor for short-term mortality. Cumulative survival data revealed that more than 1% of patients 60 or older died by 30 days. There were 215 deaths (2.84%) in patients hospitalized from the ED and 66 deaths (0.45%) among patients not hospitalized.
Pre-existing comorbidities significantly associated with increased mortality included heart failure (HR=14.3 in ages 18-53; HR=3.09 in ages 60-79; HR=2.34 in ages 80-plus), diabetes (HR=1.49), seizure (HR=1.65), dementia (HR=1.41), and a recent prior visit for syncope (HR=1.86). The risk of death by 30 days was less than 0.2% in patients under 60 without heart failure and more than 2.5% in patients of all ages with heart failure.
Bottom line: After an ED visit for syncope, patients with a history of heart failure and patients 60 and older have a significantly increased risk of short-term mortality.
Citation: Derose SF, Gabayan GZ, Chiu VY, Sun BC. Patterns and preexisting risk factors of 30-day mortality after a primary discharge diagnosis of syncope or near syncope. Acad Emerg Med. 2012;19(5):488-496.
Acute Hyperglycemia Associated with Increased Mortality in Community-Acquired Pneumonia
Clinical question: In patients admitted to the hospital for community-acquired pneumonia, is serum glucose level on admission associated with mortality?
Background: Some retrospective studies have shown an association between alterations in serum glucose levels or pre-existing diabetes and higher mortality due to infections, while other studies have shown no clear association.
Study design: Multicenter, prospective cohort study.
Setting: Hospitals and private practices in Germany, Switzerland, and Austria.
Synopsis: Prospective data from 6,891 patients were included in the analysis. Patients without diabetes and normal serum glucose levels had the lowest mortality after 90 days. Patients without diabetes but with mild acute hyperglycemia (108 mg/dL to 198 mg/dL) had a significantly increased risk of death at 90 days (HR 1.56), and patients without diabetes but with more severe acute hyperglycemia (over 252 mg/dL) had an even higher risk of death at 90 days (HR 2.37).
The 90-day mortality rate was significantly higher in patients with pre-existing diabetes (HR 2.47), although this was not affected by serum glucose levels on admission.
Bottom line: Acute hyperglycemia, as well as pre-existing diabetes, was associated with an increased risk of 90-day mortality in patients with community acquired pneumonia.
Citation: Lepper PM, Ott S, Nüesch E, et al. Serum glucose levels for predicting death in patients admitted to hospital for community acquired pneumonia: prospective cohort study. BMJ. 2012;344:e3397.
Hospital Delirium Associated with Cognitive Decline, Institutionalization, and Death
Clinical question: What is the risk of subsequent cognitive decline, institutionalization, or death due to delirium in patients with dementia?
Background: Patients suffering delirium during hospitalization can suffer additional cognitive decline. Whether this is due to additional damage from the delirium state or reflects pre-existing cognitive vulnerability remains uncertain.
Study design: Prospective analysis of a cohort of Alzheimer’s patients.
Setting: Massachusetts community-based disease registry.
Synopsis: The analysis compared nonhospitalized individuals to patients hospitalized with, and without, delirium. In 771 individuals with dementia, at least one adverse outcome (including cognitive decline, institutionalization, or death) occurred in 32% of those not hospitalized, 55% of those hospitalized without delirium, and 79% of those hospitalized with delirium. Even after adjusting for confounders, hospitalization increased the risk for each of the adverse outcomes; the highest risk was in those with delirium.
Among hospitalized patients, the authors estimated 1 in 5 cases of cognitive decline, 1 in 7 institutionalizations, and 1 in 16 deaths were attributable to delirium. Some of the attributed risk could be the result of residual confounding from unmeasured variables, limiting conclusions of causality. Despite these limitations, this study supports the hypothesis that delirium prevention measures could improve important patient outcomes.
Bottom line: Hospitalization is associated with high rates of adverse outcomes in elderly patients with dementia, the worst of which occurs in those who experience delirium.
Citation: Fong TG, Jones RN, Marcantonio ER, et al. Adverse outcomes after hospitalization and delirium in persons with Alzheimer disease. Ann Int Med. 2012;156:848-856.
In Acute Pyelonephritis, a Seven-Day Course of Ciprofloxacin is Effective in Obtaining Clinical Cure
Clinical question: What is the efficacy of ciprofloxacin for seven days compared with 14 days in women with community-acquired acute pyelonephritis?
Background: Community-acquired acute pyelonephritis is a common and sometimes serious infection in women. In an era of increasing antibiotic resistance worldwide, it is prudent to reduce antibiotic utilization. There are limited controlled trials to assess the optimum duration of antibiotic treatment for this common infection.
Study design: Prospective, randomized, double-blind, noninferiority trial.
Setting: Twenty-one infectious-disease centers in Sweden.
Synopsis: Researchers randomly assigned 284 women 18 or older with a presumptive diagnosis of acute pyelonephritis to ciprofloxacin treatment for seven or 14 days. The primary endpoint was clinical and bacteriological cure 10 to 14 days after the completion of the treatment regimen. Short-term clinical cure occurred in 97% of the patients treated for seven days and 96% treated for 14 days. Long-term follow-up showed cumulative efficacy of 93% in each group. Both regimens were well tolerated.
Patients in this study had a low occurrence of complicated (9%) and recurrent (13%) infections. Whether short courses of antibiotics are effective in more complicated infections cannot be ascertained from this study. Also, the high cure rate obtained with a seven-day course of ciprofloxacin should not be extrapolated to other classes of antibiotics. Fluoroquinolones, such as ciprofloxacin, are recommended as first-line agents for empiric oral treatment of acute pyelonephritis if the resistance rate of the uropathogens remains lower than 10%; however, there is growing evidence that E. coli strains are becoming increasingly resistant to ciprofloxacin, limiting its usefulness.
Bottom line: Acute pyelonephritis in women can be treated successfully and safely with a seven-day course of ciprofloxacin, in areas with low ciprofloxacin resistance.
Citation: Sandberg T, Skoog G, Hermansson AB, et al. Ciprofloxacin for 7 days versus 14 days in women with acute pyelonephritis: a randomized, open-label and double-blind, placebo-controlled, non-inferiority trial. Lancet. 2012;380:484-490.
Advance Directives in Community Patients with Heart Failure
Clinical question: How prevalent are advance directives in heart-failure patients, and does a completed advance directive decrease end-of-life resource use (hospitalizations, ICU admissions, mechanical ventilation)?
Background: Heart failure is a common chronic and fatal disease. End-of-life care in heart-failure patients is associated with extremely high healthcare utilization. Heart failure guidelines recommend completing advance directives in all patients.
Study design: Population-based longitudinal cohort study.
Setting: Rochester Epidemiology Project in Olmstead County, Minn.
Synopsis: Investigators enrolled 608 patients presenting with heart failure between October 2007 and October 2011. At the time of enrollment, only 41% of the patients had existing advance directives. Independent predictors of advance directive completion included older age, history of malignancy, and renal dysfunction.
After a mean follow-up of 1.8 years, 164 patients (27%) had died. Among those patients, 106 had an advance directive (64.6%) at time of death—75 had an advance directive at the time of enrollment and another 31 completed an advance directive after enrollment.
Twenty-five patients (23.6%) specified DNR/DNI and another 39 (36.8%) denoted limitations on aggressiveness of care if death was imminent. Among the patients who died, 88 (53.7%) were hospitalized in the last month of their life and 50 (30.5%) died in the hospital. There was no difference in hospitalizations between those with an advance directive specifying limits and those who did not specify limits (OR 1.26, 95% CI 0.64-2.48). However, those with an advance directive specifying limits were less frequently mechanically ventilated (OR 0.26, 95% CI 0.06-0.88), and there was a trend toward them being less frequently admitted into the ICU (OR 0.45, 95% CI 0.16-1.29).
Bottom line: Less than half of community patients with heart failure had an advance directive, and many of these failed to address end-of-life decisions. Patients with an advance directive that specified limits in care were less likely to receive mechanical ventilation.
Citation: Dunlay SM, Swetz KM, Mueller PS, Roger VL. Advance directives in community patients with heart failure. Circ Cardiovasc Qual Outcomes. 2012;5:283-289.
Chlorhexidine Bathing Associated with Significant, Sustainable Reductions in Central-Venous-Catheter-Associated Bloodstream Infection
Clinical question: What is the impact, and sustainability, of chlorhexidine bathing on central-venous-catheter-associated bloodstream infections?
Background: Chlorhexidine bathing has been associated with reductions in healthcare-associated bloodstream infections, including vancomycin-resistant enterococci and methicillin-resistant Staphylococcus aureus. No prospective studies have evaluated the impact and sustainability of chlorhexidine bathing.
Study design: Prospective, three-phase study.
Setting: Medical-surgical ICUs and respiratory-care units at five New York hospitals.
Synopsis: In the pre-intervention phase (six to nine months, 1,808 admissions), patients were bathed with soap and water or nonmedicated bathing cloths. In the intervention phase (eight months, 1,832 admissions), patients were bathed with 2% chlorhexidine cloths. In the post-intervention phase (12 months, 2,834 admissions), chlorhexidine bathing was continued without oversight by researchers.
During the intervention phase, there were significantly fewer central-venous-catheter-associated bloodstream infections (2.6/1,000 catheter days vs. 6.4/1,000 pre-intervention). The reductions in bloodstream infections were sustained during the post-intervention period (2.9/1,000 catheter days). Compliance with chlorhexidine bathing was 82% and 88% during the intervention and post-intervention phases, and was well tolerated by the patients.
Limitations of this study include lack of patient-specific data and severity of illness data, as well as lack of randomization and blinding. Although not evaluated in this study, the savings associated with decreased bloodstream infections likely outweigh the cost of chlorhexidine bathing.
Bottom line: Chlorhexidine bathing is a well-tolerated, sustainable intervention that significantly reduces central-venous-catheter-associated bloodstream infections.
Citation: Montecalvo MA, McKenna D, Yarrish R, et al. Chlorhexidine bathing to reduce central venous catheter-associated bloodstream infection: impact and sustainability. Am J Med. 2012;125(5):505-511.
Simulation Training Improves Lumbar Puncture Skills
Clinical question: What effect does simulation have on lumbar puncture (LP) skills of PGY1 internal-medicine (IM) residents compared with PGY2-4 neurology residents who have not received simulation training?
Background: LPs are common procedures. The American College of General Medical Education does not define competency; neither do the internal-medicine (IM) or neurology board certifications. Simulation can improve skills in many areas but has not been well studied in LPs.
Study design: Pre-test-post-test.
Setting: Northwestern University’s Feinberg School of Medicine in Chicago.
Synopsis: The intervention group included 58 PGY1 IM residents, while the control group was 49 PGY2-to-PGY4 neurology residents. The pre-test consisted of a 21-point checklist. IM residents watched a three-hour video, performed LPs on simulators, and received feedback. The post-test was a clinical skills examination using the checklist. If this exam was failed, the participant practiced and was retested. Neurology residents completed the pre-test and demonstrated an LP using the simulator.
Pre-test passing was achieved by only 2% of IM residents and 6% of neurology residents. Post-test passing was achieved by 95% of the IM residents on the first trial and 100% of IM residents after an hour of additional training. IM mean scores increased to 95.7% from 46.3%, while the mean score of neurology residents was 65.4%.
This study is limited by its single-center nature, as education is variable from center to center. The study evaluated the proficiency on simulators only, and it did not evaluate the proficiency of the participants on patients.
Bottom line: Simulation training improves lumbar puncture skills.
Citation: Barsuk JH, Cohen ER, Caprio T, McGaghie WC, Simuni T, Wayne DB. Simulation-based education with mastery learning improves residents’ lumbar puncture skills. Neurology. 2012;79(2):132-137.
Primary-Care Physicians Do Not Use Publicly Reported Data When Referring Patients to Hospitals
Clinical question: When referring patients with pneumonia to the hospital, what factors do primary-care physicians (PCPs) consider?
Background: Publicly reported data are widely available. Pneumonia has publicly reported quality measures and is a common reason for hospitalization. Fewer PCPs are attending in the hospital due to the hospitalist movement; therefore, PCPs refer patients to a hospital when the need arises.
Study design: Online survey.
Setting: PCPs within 10 miles of Springfield, Mass.
Synopsis: A total of 92 PCPs responded to the survey, which included presentation of a case regarding a patient with pneumonia. PCPs were asked the importance of multiple factors leading to their decision to refer to a hospital. Familiarity with the hospital (70%), patient preference (62%), and admitting arrangements with a hospitalist group (62%) were considered to be very important to the PCPs that responded to the survey. Publicly reported data were very important to only 18% of respondents, and zero reported using publicly reported data when referring patients.
Importance of specific quality measures also was queried; antibiotics given within six hours of arrival (66%), appropriate choice of antibiotics (63%), and blood cultures prior to antibiotic administration (51%) were very important to respondents. Prestige, such as magnet status and U.S. News and World Report “Best Hospital” status, were deemed important by about 40% of PCPs.
Bottom line: Despite the availability of publicly reported data, PCPs do not use this information to refer patients to the hospital.
Citation: Morsi E, Lindenauer PK, Rothberg MB. Primary care physicians’ use of publicly reported quality data in hospital referral decisions. J Hosp Med. 2012;7(5):370-375.
What Works for Medication Reconciliation?
Clinical question: What are the most effective practices for medication reconciliation in the hospital setting?
Background: Medication discrepancies are common, occurring in as many as 70% of patients at hospital admission or discharge. Up to a third of these discrepancies have potential to cause patient harm, including prolonged hospital stays, ED visits, hospital recidivism, and use of other healthcare resources. Medication reconciliation (“med rec”) is a strategy for reducing these errors, though previous literature has not systematically reviewed best practices for hospital-based med rec.
Study design: Systematic review of literature.
Setting: Controlled studies from the U.S., Canada, Australia, New Zealand, Northern Ireland, United Kingdom, Belgium, Denmark, the Netherlands, and Sweden.
Synopsis: Investigators identified 26 controlled studies using a systematic search of English-language articles on med rec during inpatient hospitalizations published between Jan. 1, 1966, and Oct. 31, 2010. Fifteen studies reported on pharmacist-related interventions; six reported on technology-specific interventions; and five reported on other types of interventions, including staff education and use of standardized med-rec tools.
Analysis of these studies revealed that all of these interventions successfully decreased medication discrepancies and potential adverse drug events, but there was inconsistent benefit with regard to adverse drug events and healthcare utilization compared with usual care. The literature was most supportive of pharmacist-related interventions, including but not limited to comprehensive medication history at admission, med rec at discharge, patient counseling, discharge communication with outpatient providers, and post-discharge communication with the patient and post-hospital providers.
Bottom line: Successful med rec requires multiple interventions at various transitions of care and involves a variety of medical professionals. Patient-targeted interventions, including pharmacists, have the potential to decrease errors and adverse events.
Citation: Mueller S, Sponsler K, Kripalani S, Schnipper J. Hospital-based medication reconciliation practices: a systematic review. Arch Intern Med. 2012;172(14):1057-1069.