Shirin Poonja, DO

Clinical question: Do thrombin and factor Xa inhibitors increase the risk of gastrointestinal (GI) bleeding when compared to vitamin K antagonists and heparins?

Background: New oral anticoagulants (thrombin and factor Xa inhibitors) are available and being used with increased frequency due to equal efficacy and ease of administration. Some studies indicate a higher risk of GI bleeding with these agents. Further evaluation is needed, because no reversal therapy is available.

Study design: Systematic review and meta-analysis.

Setting: Data from MEDLINE, Embase, and the Cochrane Library.

Synopsis: More than 150,000 patients from 43 randomized controlled trials were evaluated for risk of GI bleed when treated with new anticoagulants versus traditional therapy. Patients were treated for one of the following: embolism prevention from atrial fibrillation, venous thromboembolism (VTE) prophylaxis post orthopedic surgery, VTE prophylaxis of medical patients, acute VTE, and acute coronary syndrome (ACS). Use of aspirin or NSAIDs was discouraged but not documented. The odds ratio for GI bleeding with use of the new anticoagulants was 1.45, with a number needed to harm of 500. Evaluation of subgroups revealed increased GI bleed risk in patients treated for ACS and acute thrombosis versus prophylaxis. Postsurgical patients had the lowest risk. This study was limited by the heterogeneity and differing primary outcomes (mostly efficacy rather than safety) of the included trials. Studies excluded high-risk patients, which the authors estimate to be 25%–40% of actual patients. More studies need to be done that include high-risk patients and focus on GI bleed as a primary outcome.

Bottom line: The new anticoagulants tend to have a higher incidence of GI bleed than traditional therapy, but this varies based on indication of therapy and needs further evaluation to clarify risk.

Citation: Holster IL, Valkhoff VE, Kuipers EJ, Tjwa ET. New oral anticoagulants increase risk for gastrointestinal bleeding: A systematic review and meta-analysis. Gastroenterology. 2013;145(1):105–112.

Clinical question: Do thrombin and factor Xa inhibitors increase the risk of gastrointestinal (GI) bleeding when compared to vitamin K antagonists and heparins?

Background: New oral anticoagulants (thrombin and factor Xa inhibitors) are available and being used with increased frequency due to equal efficacy and ease of administration. Some studies indicate a higher risk of GI bleeding with these agents. Further evaluation is needed, because no reversal therapy is available.

Study design: Systematic review and meta-analysis.

Setting: Data from MEDLINE, Embase, and the Cochrane Library.

Synopsis: More than 150,000 patients from 43 randomized controlled trials were evaluated for risk of GI bleed when treated with new anticoagulants versus traditional therapy. Patients were treated for one of the following: embolism prevention from atrial fibrillation, venous thromboembolism (VTE) prophylaxis post orthopedic surgery, VTE prophylaxis of medical patients, acute VTE, and acute coronary syndrome (ACS). Use of aspirin or NSAIDs was discouraged but not documented. The odds ratio for GI bleeding with use of the new anticoagulants was 1.45, with a number needed to harm of 500. Evaluation of subgroups revealed increased GI bleed risk in patients treated for ACS and acute thrombosis versus prophylaxis. Postsurgical patients had the lowest risk. This study was limited by the heterogeneity and differing primary outcomes (mostly efficacy rather than safety) of the included trials. Studies excluded high-risk patients, which the authors estimate to be 25%–40% of actual patients. More studies need to be done that include high-risk patients and focus on GI bleed as a primary outcome.

Bottom line: The new anticoagulants tend to have a higher incidence of GI bleed than traditional therapy, but this varies based on indication of therapy and needs further evaluation to clarify risk.

Citation: Holster IL, Valkhoff VE, Kuipers EJ, Tjwa ET. New oral anticoagulants increase risk for gastrointestinal bleeding: A systematic review and meta-analysis. Gastroenterology. 2013;145(1):105–112.

Clinical question: Do thrombin and factor Xa inhibitors increase the risk of gastrointestinal (GI) bleeding when compared to vitamin K antagonists and heparins?

Background: New oral anticoagulants (thrombin and factor Xa inhibitors) are available and being used with increased frequency due to equal efficacy and ease of administration. Some studies indicate a higher risk of GI bleeding with these agents. Further evaluation is needed, because no reversal therapy is available.

Study design: Systematic review and meta-analysis.

Setting: Data from MEDLINE, Embase, and the Cochrane Library.

Synopsis: More than 150,000 patients from 43 randomized controlled trials were evaluated for risk of GI bleed when treated with new anticoagulants versus traditional therapy. Patients were treated for one of the following: embolism prevention from atrial fibrillation, venous thromboembolism (VTE) prophylaxis post orthopedic surgery, VTE prophylaxis of medical patients, acute VTE, and acute coronary syndrome (ACS). Use of aspirin or NSAIDs was discouraged but not documented. The odds ratio for GI bleeding with use of the new anticoagulants was 1.45, with a number needed to harm of 500. Evaluation of subgroups revealed increased GI bleed risk in patients treated for ACS and acute thrombosis versus prophylaxis. Postsurgical patients had the lowest risk. This study was limited by the heterogeneity and differing primary outcomes (mostly efficacy rather than safety) of the included trials. Studies excluded high-risk patients, which the authors estimate to be 25%–40% of actual patients. More studies need to be done that include high-risk patients and focus on GI bleed as a primary outcome.

Bottom line: The new anticoagulants tend to have a higher incidence of GI bleed than traditional therapy, but this varies based on indication of therapy and needs further evaluation to clarify risk.

Citation: Holster IL, Valkhoff VE, Kuipers EJ, Tjwa ET. New oral anticoagulants increase risk for gastrointestinal bleeding: A systematic review and meta-analysis. Gastroenterology. 2013;145(1):105–112.

Clinical question: Does ICU strain negatively affect the outcomes of patients transferred to the floor?

Background: With healthcare costs increasing and critical care staff shortages projected, ICUs will have to operate under increasing strain. This may influence decisions on discharging patients from ICUs and could affect patient outcomes.

Study design: Retrospective cohort study.

Setting: One hundred fifty-five ICUs in the United States.

Synopsis: Using the Project IMPACT database, 200,730 adult patients from 107 different hospitals were evaluated in times of ICU strain, determined by the current census, new admissions, and acuity level. Outcomes measured were initial ICU length of stay (LOS), readmission within 72 hours, in-hospital mortality rates, and post-ICU discharge LOS.

Increases of the strain variables from the fifth to the 95th percentiles resulted in a 6.3-hour reduction in ICU LOS, a 2.0-hour decrease in post-ICU discharge LOS, and a 1.0% increase in probability of ICU readmission within 72 hours. Mortality rates during the hospital stay and odds of being discharged home showed no significant change. This study was limited because the ICUs participating were not randomly chosen, outcomes of patients transferred to other hospitals were not measured, and no post-hospital data was collected, so no long-term outcomes could be measured.

Bottom line: ICU bed pressures prompt physicians to allocate ICU resources more efficiently without changing short-term patient outcomes.

Citation: Wagner J, Gabler NB, Ratcliffe SJ, Brown SE, Strom BL, Halpern SD. Outcomes among patients discharged from busy intensive care units. Ann Intern Med. 2013;159(7):447-455.

Clinical question: Does ICU strain negatively affect the outcomes of patients transferred to the floor?

Background: With healthcare costs increasing and critical care staff shortages projected, ICUs will have to operate under increasing strain. This may influence decisions on discharging patients from ICUs and could affect patient outcomes.

Study design: Retrospective cohort study.

Setting: One hundred fifty-five ICUs in the United States.

Synopsis: Using the Project IMPACT database, 200,730 adult patients from 107 different hospitals were evaluated in times of ICU strain, determined by the current census, new admissions, and acuity level. Outcomes measured were initial ICU length of stay (LOS), readmission within 72 hours, in-hospital mortality rates, and post-ICU discharge LOS.

Increases of the strain variables from the fifth to the 95th percentiles resulted in a 6.3-hour reduction in ICU LOS, a 2.0-hour decrease in post-ICU discharge LOS, and a 1.0% increase in probability of ICU readmission within 72 hours. Mortality rates during the hospital stay and odds of being discharged home showed no significant change. This study was limited because the ICUs participating were not randomly chosen, outcomes of patients transferred to other hospitals were not measured, and no post-hospital data was collected, so no long-term outcomes could be measured.

Bottom line: ICU bed pressures prompt physicians to allocate ICU resources more efficiently without changing short-term patient outcomes.

Citation: Wagner J, Gabler NB, Ratcliffe SJ, Brown SE, Strom BL, Halpern SD. Outcomes among patients discharged from busy intensive care units. Ann Intern Med. 2013;159(7):447-455.

Clinical question: Does ICU strain negatively affect the outcomes of patients transferred to the floor?

Background: With healthcare costs increasing and critical care staff shortages projected, ICUs will have to operate under increasing strain. This may influence decisions on discharging patients from ICUs and could affect patient outcomes.

Study design: Retrospective cohort study.

Setting: One hundred fifty-five ICUs in the United States.

Synopsis: Using the Project IMPACT database, 200,730 adult patients from 107 different hospitals were evaluated in times of ICU strain, determined by the current census, new admissions, and acuity level. Outcomes measured were initial ICU length of stay (LOS), readmission within 72 hours, in-hospital mortality rates, and post-ICU discharge LOS.

Increases of the strain variables from the fifth to the 95th percentiles resulted in a 6.3-hour reduction in ICU LOS, a 2.0-hour decrease in post-ICU discharge LOS, and a 1.0% increase in probability of ICU readmission within 72 hours. Mortality rates during the hospital stay and odds of being discharged home showed no significant change. This study was limited because the ICUs participating were not randomly chosen, outcomes of patients transferred to other hospitals were not measured, and no post-hospital data was collected, so no long-term outcomes could be measured.

Bottom line: ICU bed pressures prompt physicians to allocate ICU resources more efficiently without changing short-term patient outcomes.

Citation: Wagner J, Gabler NB, Ratcliffe SJ, Brown SE, Strom BL, Halpern SD. Outcomes among patients discharged from busy intensive care units. Ann Intern Med. 2013;159(7):447-455.

In This Edition

Literature At A Glance

A guide to this month’s studies

1. ICU pressures improve transfers to the floor
2. Morbidity, mortality rates high for respiratory syncytial virus infections
3. Antibiotic algorithm can guide therapy in healthcare-associated pneumonia
4. Three-month dual antiplatelet therapy for zotarolimus-eluting stents
5. De-escalating antibiotics in sepsis
6. New oral anticoagulants increase GI bleed risk
7. Single vs. dual antiplatelet therapy after stroke
8. Endoscopic vs. surgical cystogastrostomy for pancreatic pseudocyst drainage
9. Long-term cognitive impairment after critical illness
10. Holding chambers vs. nebulizers for acute asthma

ICU Pressures Improve Transfers to the Floor

Clinical question: Does ICU strain negatively affect the outcomes of patients transferred to the floor?

Background: With healthcare costs increasing and critical care staff shortages projected, ICUs will have to operate under increasing strain. This may influence decisions on discharging patients from ICUs and could affect patient outcomes.

Study design: Retrospective cohort study.

Setting: One hundred fifty-five ICUs in the United States.

Synopsis: Using the Project IMPACT database, 200,730 adult patients from 107 different hospitals were evaluated in times of ICU strain, determined by the current census, new admissions, and acuity level. Outcomes measured were initial ICU length of stay (LOS), readmission within 72 hours, in-hospital mortality rates, and post-ICU discharge LOS.

Increases of the strain variables from the fifth to the 95th percentiles resulted in a 6.3-hour reduction in ICU LOS, a 2.0-hour decrease in post-ICU discharge LOS, and a 1.0% increase in probability of ICU readmission within 72 hours. Mortality rates during the hospital stay and odds of being discharged home showed no significant change. This study was limited because the ICUs participating were not randomly chosen, outcomes of patients transferred to other hospitals were not measured, and no post-hospital data was collected, so no long-term outcomes could be measured.

Bottom line: ICU bed pressures prompt physicians to allocate ICU resources more efficiently without changing short-term patient outcomes.

Citation: Wagner J, Gabler NB, Ratcliffe SJ, Brown SE, Strom BL, Halpern SD. Outcomes among patients discharged from busy intensive care units. Ann Intern Med. 2013;159(7):447-455.

Adults Hospitalized for Respiratory Syncytial Virus Infections Have High Morbidity, Mortality Rates

Clinical question: What are the complications and outcomes of respiratory syncytial virus (RSV) infection in adults requiring hospitalization?

Background: RSV is a common cause of lower respiratory tract infection in infants and young children, leading to hospitalization and even death. RSV has been estimated to affect 3%-10% of adults annually, generally causing mild disease. However, the outcomes of adults with more severe disease are not fully known.

Study design: Retrospective cohort study.

Setting: Three acute care, public hospitals in Hong Kong.

Synopsis: All adult patients hospitalized with laboratory-confirmed RSV infection were included during the defined time period. The main outcome measure was all-cause death, with secondary outcome measures of development of acute respiratory failure requiring ventilator support and total duration of hospitalization among survivors. Additionally, the cohort of RSV patients was compared to patients admitted with seasonal influenza during this same time frame. Patients with pandemic 2009 H1N1 infection were not included.

Of patients with RSV, pneumonia was found in 42.3%, bacterial superinfection in 12.5%, and cardiovascular complications in 14.3%. Additionally, 11.1% developed respiratory failure requiring ventilator support. All-cause mortality at 30 days and 60 days was 9.1% and 11.9%, respectively, with pneumonia the most common cause of death. Use of systemic corticosteroids did not improve survival. When the RSV cohort was compared to the influenza cohort, the patients were similar in age, but the RSV patients were more likely to have underlying chronic lung disease and major systemic co-morbidities. The rate of survival and duration of hospitalization were not significantly different.

Bottom line: RSV infection is an underappreciated cause of lower tract respiratory infection in adults; severe infections that require hospitalization have rates of mortality similar to seasonal influenza. Further research on treatment or immunization is needed.

Citation: Lee N, Lui GC, Wong KT, et al. High morbidity and mortality in adults hospitalized for respiratory syncytial virus infections. Clin Infect Dis. 2013;57(8):1069-1077.

Antibiotic Algorithm Can Guide Therapy in Healthcare-Associated Pneumonia

Clinical question: Can an algorithm based on risk for multidrug-resistant (MDR) organisms and illness severity guide antibiotic selection in healthcare-associated pneumonia (HCAP)?

Background: The 2005 American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) guidelines identify patients with HCAP as those with recent contact with a healthcare environment, including nursing homes and hemodialysis; however, previous studies have shown that not all patients with healthcare contact have equal risk for MDR organisms.

Study design: Prospective cohort study.

Setting: Japan, multi-center.

Synopsis: Of the 445 enrolled patients, 124 were diagnosed with community-acquired pneumonia (CAP) and 321 with HCAP. Patients with HCAP were classified based on severity of illness or MDR pathogen risk factors (immune suppression, hospitalization within the last 90 days, poor functional status, and antibiotics within the past six months). Patients with low risk (0-1 factors) for MDR organisms were treated for CAP, and patients with high risk (≥2 factors) or moderate risk (≥1 factor) for severe illness were treated for HCAP.

HCAP patients had a higher 30-day mortality rate (13.7% vs. 5.6%, P=0.017), but mortality rate was less in the patients at low risk for MDR pathogens (8.6% vs. 18.2%, P=0.012). Of the HCAP patients, only 7.1% received inappropriate therapy (pathogen resistant to initial antibiotic regimen), and treatment failure was 19.3%.

Appropriateness of initial empiric therapy was determined not to be a mortality risk; however, this trial might be limited by its location, because Japan appears to have fewer MDR pathogens than the U.S.

Bottom line: A treatment algorithm based on risk for MDR organisms and severity of illness can be used to guide empiric antibiotic therapy in patients with HCAP, and, ideally, to reduce excessive use of broad-spectrum antibiotics.

Citation: Maruyama T, Fujisawa T, Okuno M, et al. A new strategy for healthcare-associated pneumonia: a 2-year prospective multicenter cohort study using risk factors for multidrug-resistant pathogens to select initial empiric therapy. Clin Infect Dis. 2013;57(10):1373-1383.

Three-Month Dual Antiplatelet Therapy for Zotarolimus-Eluting Stents

Clinical question: Is short-term, dual antiplatelet therapy noninferior to long-term therapy in zotarolimus-eluting stents?

Background: Current guidelines recommend long-term (>12 months) dual antiplatelet therapy after the placement of drug-eluting stents. The optimal therapy duration in second-generation drug-eluting stents has not been studied; moreover, some studies with multiple drug-eluting stents have suggested no added benefit from long-term therapy.

Study design: Randomized controlled trial.

Setting: Brazil, multi-center.

Synopsis: Researchers randomized 3,211 patients with stable coronary artery disease (CAD) or low-risk acute coronary syndrome (ACS) undergoing intervention with zotarolimus-eluting stents to short-term (three months) or long-term (12 months) dual antiplatelet therapy. Exclusion criteria included ST-elevation myocardial infarction (STEMI), previous drug-eluting stent, scheduled elective surgery within 12 months, or contraindication to aspirin or clopidogrel. Primary endpoints were a composite of death from any cause, MI, stroke, or major bleeding. Secondary endpoints were stent thrombosis, target lesion revascularization, adverse cardiac event, and any bleed.

At one-year follow-up, the short-term group had similar primary (6.0% vs. 5.8%) and secondary (8.3% vs. 7.4%) outcomes compared to the long-term. The short-term group’s noninferiority also was seen in several key subgroups.

This study included patients with stable CAD or low-risk ACS and cannot be generalized to higher-risk patients. Results for zotarolimus-eluting stents cannot be generalized to other second-generation drug-eluting stents.

Bottom line: Zotarolimus-eluting stents, followed by three months of dual antiplatelet therapy, were noninferior to 12 months of therapy in patients with stable CAD or low-risk ACS.

Citation: Feres F, Costa RA, Abizaid A, et al. Three vs. twelve months of dual antiplatelet therapy after zotarolimus-eluting stents: the OPTIMIZE randomized trial. JAMA. 2013;310(23):2510-2522.

De-Escalating Antibiotics in Sepsis

Clinical question: Does tailoring antibiotics based on known pathogens impact mortality for patients with severe sepsis or shock?

Background: In patients with sepsis, the use of early empiric antibiotics reduces morbidity and mortality. De-escalation therapy refers to narrowing the broad-spectrum antibiotics once the pathogen and sensitivities are known; however, no randomized controlled studies have assessed the impact of this therapy on critically ill patients.

Study design: Prospective observational study.

Setting: Academic hospital ICU in Spain.

Synopsis: From January 2008 to May 2012, 628 adult patients were treated empirically with broad-spectrum antibiotics. De-escalation was applied to 219 patients (34.9%). Outcomes measured were ICU mortality, hospital mortality, and 90-day mortality in patients who received de-escalation therapy, patients whose antibiotics were not changed, and patients for whom antibiotics were escalated.

The in-hospital mortality rate was 27.4% in patients who were de-escalated, 32.6% in the unchanged group, and 42.9% in the escalation group. ICU and 90-day mortality were lower in the de-escalation group. De-escalation was more commonly used in medical than in surgical patients.

This study is limited because it is not a randomized controlled study and was single-centered, so it might only be applicable on the larger scale. Also, multi-drug resistant organisms were not evaluated.

Overall, it is safe to narrow empiric antibiotics in severe sepsis and shock when the pathogen and sensitivities are known.

Bottom line: De-escalation of antibiotics in severe sepsis and septic shock is associated with a lower mortality.

Citation: Garnacho-Montero J, Gutierrez-Pizarraya A, Escoresca-Ortega A, et al. De-escalation of empirical therapy is associated with lower mortality in patients with severe sepsis and septic shock. Intensive Care Med. 2014;40(1):32-40.

New Oral Anticoagulants Increase GI Bleed Risk

Clinical question: Do thrombin and factor Xa inhibitors increase the risk of gastrointestinal (GI) bleeding when compared to vitamin K antagonists and heparins?

Background: New oral anticoagulants (thrombin and factor Xa inhibitors) are available and being used with increased frequency due to equal efficacy and ease of administration. Some studies indicate a higher risk of GI bleeding with these agents. Further evaluation is needed, because no reversal therapy is available.

Study design: Systematic review and meta-analysis.

Setting: Data from MEDLINE, Embase, and the Cochrane Library.

Synopsis: More than 150,000 patients from 43 randomized controlled trials were evaluated for risk of GI bleed when treated with new anticoagulants versus traditional therapy. Patients were treated for one of the following: embolism prevention from atrial fibrillation, venous thromboembolism (VTE) prophylaxis post orthopedic surgery, VTE prophylaxis of medical patients, acute VTE, and acute coronary syndrome (ACS). Use of aspirin or NSAIDs was discouraged but not documented. The odds ratio for GI bleeding with use of the new anticoagulants was 1.45, with a number needed to harm of 500. Evaluation of subgroups revealed increased GI bleed risk in patients treated for ACS and acute thrombosis versus prophylaxis. Post-surgical patients had the lowest risk.

This study was limited by the heterogeneity and differing primary outcomes (mostly efficacy rather than safety) of the included trials. Studies excluded high-risk patients, which the authors estimate to be 25%-40% of actual patients. More studies need to be done that include high-risk patients and focus on GI bleed as a primary outcome.

Bottom line: The new anticoagulants tend to have a higher incidence of GI bleed than traditional therapy, but this varies based on indication of therapy and needs further evaluation to clarify risk.

Citation: Holster IL, Valkhoff VE, Kuipers EJ, Tjwa ET. New oral anticoagulants increase risk for gastrointestinal bleeding: a systematic review and meta-analysis. Gastroenterology. 2013;145(1):105-112.

Single vs. Dual Antiplatelet Therapy after Stroke

Clinical question: Is dual antiplatelet therapy more beneficial or harmful than monotherapy after ischemic stroke?

Background: It is recommended that patients with ischemic stroke or transient ischemic attack (TIA) receive lifelong antiplatelet therapy; however, there have been insufficient studies evaluating the long-term safety of dual antiplatelet therapy.

Study design: Meta-analysis of randomized controlled trials (RCTs)

Setting: Data from PubMed, Embase, and the Cochrane Central Register of Controlled Trials.

Synopsis: Data from seven RCTs, including 39,574 patients with recent TIA or ischemic stroke, were reviewed. Comparisons were made regarding occurrence of intracranial hemorrhage (ICH) and recurrent stroke between patients receiving dual antiplatelet therapy and those receiving aspirin or clopidogrel monotherapy. All patients were treated for at least one year.

There was no difference in recurrent stroke or ICH between patients on dual antiplatelet therapy versus aspirin monotherapy. Patients treated with dual antiplatelet therapy did have a 46% increased risk of ICH without any additional protective benefit for recurrent stroke or TIA when compared with patients on clopidogrel monotherapy.

This information should not be applied in the acute setting, given the high risk of stroke after TIA or ischemic stroke. One major limitation of this study was that the individual trials used different combinations of dual antiplatelet therapy.

Bottom line: The risk of recurrent stroke or TIA after dual antiplatelet therapy and after monotherapy with aspirin or clopidogrel is equal, but the risk of ICH compared to clopidogrel monotherapy is increased.

Citation: Lee M, Saver JL, Hong KS, Rao NM, Wu YL, Ovbiagele B. Risk-benefit profile of long-term dual- versus single-antiplatelet therapy among patients with ischemic stroke: a systematic review and meta-analysis. Ann Intern Med. 2013;159(7):463-470.

Endoscopic vs. Surgical Cystogastrostomy for Pancreatic Pseudocyst Drainage

Clinical question: How does endoscopic cystogastrostomy for pancreatic pseudocyst drainage compare to the standard surgical approach?

Background: Pancreatic pseudocysts are a common complication of pancreatitis and necessitate decompression when they are accompanied by pain, infection, or obstruction. Decompression of the pseudocyst can be accomplished using either endoscopic or surgical cystogastrostomy.

Study design: Open-label, single-center, randomized trial.

Setting: Single-center U.S. hospital.

Synopsis: A total of 40 patients were randomly equalized to both treatment arms; 20 patients underwent endoscopic and 20 patients underwent surgical cystogastrostomy. Zero patients in the endoscopic therapy had a pseudocyst recurrence, compared with one patient treated surgically. Length of stay (LOS) and cost were lower for the endoscopic group compared to the surgical group (two days vs. six days, P<0.001, $7,011 vs. $15,052, P=0.003).

This study is limited due to several factors. First, patients with pancreatic necrosis were excluded; had these patients been included, the complication rates and LOS would have been higher. Second, cost difference cannot be generalized across the U.S., because Medicare payments are based on provider types and regions.

Bottom line: Endoscopic cystogastrostomy for pancreatic pseudocyst is equal to the standard surgical therapy and results in decreased LOS and reduced costs.

Citation: Varadarajulu S, Bang JY, Sutton BS, Trevino JM, Christein JD, Wilcox CM. Equal efficacy of endoscopic and surgical cystogastrostomy for pancreatic pseudocyst drainage in a randomized trial. Gastroenterology. 2013;145(3):583-590.

Long-Term Cognitive Impairment after Critical Illness

Clinical question: Are a longer duration of delirium and higher doses of sedatives associated with cognitive impairment in the hospital?

Background: Survivors of critical illness are at risk for prolonged cognitive dysfunction. Delirium (and factors associated with delirium, namely sedative and analgesic medications) has been implicated in cognitive dysfunction.

Study design: Prospective cohort study.

Setting: Multi-center, academic, and acute care hospitals.

Synopsis: The study examined 821 adults admitted to the ICU with respiratory failure, cardiogenic shock, or septic shock. Patients excluded were those with pre-existing cognitive impairment, those with psychotic disorders, and those for whom follow-up would not be possible. Two risk factors measured were duration of delirium and use of sedative/analgesics. Delirium was assessed at three and 12 months using the CAM-ICU algorithm in the ICU by trained psychology professionals who were unaware of the patients’ in-hospital course.

At three months, 40% of patients had global cognition scores that were 1.5 standard deviations (SD) below population mean (similar to traumatic brain injury), and 26% had scores two SD below population mean (similar to mild Alzheimer’s). At 12 months, 34% had scores similar to traumatic brain injury patients, and 24% had scores similar to mild Alzheimer’s. A longer duration of delirium was associated with worse global cognition at three and 12 months. Use of sedatives/analgesics was not associated with cognitive impairment.

Bottom line: Critically ill patients in the ICU who experience a longer duration of delirium are at risk of long-term cognitive impairments lasting 12 months.

Citation: Pandharipande PP, Girard TD, Jackson JC, et al. Long-term cognitive impairment after critical illness. N Engl J Med. 2013;369(14):1306-1316.

Holding Chambers (Spacers) vs. Nebulizers for Acute Asthma

Clinical question: Are beta-2 agonists as effective when administered through a holding chamber (spacer) as they are when administered by a nebulizer?

Background: During an acute asthma attack, beta-2 agonists must be delivered to the peripheral airways. There has been considerable controversy regarding the use of a spacer compared with a nebulizer. Aside from admission rates and length of stay, factors taken into account include cost, maintenance of nebulizer machines, and infection control (potential of cross-infection via nebulizers).

Study design: Meta-analysis review of randomized controlled trials (RCTs).

Setting: Multi-centered, worldwide studies from community setting and EDs.

Synopsis: In 39 studies of patients with an acute asthma attack (selected from Cochrane Airways Group Specialized Register), the hospital admission rates did not differ on the basis of delivery method in 729 adults (risk ratio=0.94, confidence interval 0.61-1.43) or in 1,897 children (risk ratio=0.71, confidence interval 0.47-1.08). Secondary outcomes included the duration of time in the ED and the duration of hospital admission. Time spent in the ED varied for adults but was shorter for children with spacers (based on three studies). Duration of hospital admission also did not differ when modes of delivery were compared.

Bottom line: Providing beta-2 agonists using nebulizers during an acute asthma attack is not more effective than administration using a spacer.

Citation: Cates CJ, Welsh EJ, Rowe BH. Holding chambers (spacers) versus nebulisers for beta-agonist treatment of acute asthma. Cochrane Database Syst Rev. 2013;9:CD000052.

In This Edition

Literature At A Glance

A guide to this month’s studies

1. ICU pressures improve transfers to the floor
2. Morbidity, mortality rates high for respiratory syncytial virus infections
3. Antibiotic algorithm can guide therapy in healthcare-associated pneumonia
4. Three-month dual antiplatelet therapy for zotarolimus-eluting stents
5. De-escalating antibiotics in sepsis
6. New oral anticoagulants increase GI bleed risk
7. Single vs. dual antiplatelet therapy after stroke
8. Endoscopic vs. surgical cystogastrostomy for pancreatic pseudocyst drainage
9. Long-term cognitive impairment after critical illness
10. Holding chambers vs. nebulizers for acute asthma

ICU Pressures Improve Transfers to the Floor

Clinical question: Does ICU strain negatively affect the outcomes of patients transferred to the floor?

Background: With healthcare costs increasing and critical care staff shortages projected, ICUs will have to operate under increasing strain. This may influence decisions on discharging patients from ICUs and could affect patient outcomes.

Study design: Retrospective cohort study.

Setting: One hundred fifty-five ICUs in the United States.

Synopsis: Using the Project IMPACT database, 200,730 adult patients from 107 different hospitals were evaluated in times of ICU strain, determined by the current census, new admissions, and acuity level. Outcomes measured were initial ICU length of stay (LOS), readmission within 72 hours, in-hospital mortality rates, and post-ICU discharge LOS.

Increases of the strain variables from the fifth to the 95th percentiles resulted in a 6.3-hour reduction in ICU LOS, a 2.0-hour decrease in post-ICU discharge LOS, and a 1.0% increase in probability of ICU readmission within 72 hours. Mortality rates during the hospital stay and odds of being discharged home showed no significant change. This study was limited because the ICUs participating were not randomly chosen, outcomes of patients transferred to other hospitals were not measured, and no post-hospital data was collected, so no long-term outcomes could be measured.

Bottom line: ICU bed pressures prompt physicians to allocate ICU resources more efficiently without changing short-term patient outcomes.

Citation: Wagner J, Gabler NB, Ratcliffe SJ, Brown SE, Strom BL, Halpern SD. Outcomes among patients discharged from busy intensive care units. Ann Intern Med. 2013;159(7):447-455.

Adults Hospitalized for Respiratory Syncytial Virus Infections Have High Morbidity, Mortality Rates

Clinical question: What are the complications and outcomes of respiratory syncytial virus (RSV) infection in adults requiring hospitalization?

Background: RSV is a common cause of lower respiratory tract infection in infants and young children, leading to hospitalization and even death. RSV has been estimated to affect 3%-10% of adults annually, generally causing mild disease. However, the outcomes of adults with more severe disease are not fully known.

Study design: Retrospective cohort study.

Setting: Three acute care, public hospitals in Hong Kong.

Synopsis: All adult patients hospitalized with laboratory-confirmed RSV infection were included during the defined time period. The main outcome measure was all-cause death, with secondary outcome measures of development of acute respiratory failure requiring ventilator support and total duration of hospitalization among survivors. Additionally, the cohort of RSV patients was compared to patients admitted with seasonal influenza during this same time frame. Patients with pandemic 2009 H1N1 infection were not included.

Of patients with RSV, pneumonia was found in 42.3%, bacterial superinfection in 12.5%, and cardiovascular complications in 14.3%. Additionally, 11.1% developed respiratory failure requiring ventilator support. All-cause mortality at 30 days and 60 days was 9.1% and 11.9%, respectively, with pneumonia the most common cause of death. Use of systemic corticosteroids did not improve survival. When the RSV cohort was compared to the influenza cohort, the patients were similar in age, but the RSV patients were more likely to have underlying chronic lung disease and major systemic co-morbidities. The rate of survival and duration of hospitalization were not significantly different.

Bottom line: RSV infection is an underappreciated cause of lower tract respiratory infection in adults; severe infections that require hospitalization have rates of mortality similar to seasonal influenza. Further research on treatment or immunization is needed.

Citation: Lee N, Lui GC, Wong KT, et al. High morbidity and mortality in adults hospitalized for respiratory syncytial virus infections. Clin Infect Dis. 2013;57(8):1069-1077.

Antibiotic Algorithm Can Guide Therapy in Healthcare-Associated Pneumonia

Clinical question: Can an algorithm based on risk for multidrug-resistant (MDR) organisms and illness severity guide antibiotic selection in healthcare-associated pneumonia (HCAP)?

Background: The 2005 American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) guidelines identify patients with HCAP as those with recent contact with a healthcare environment, including nursing homes and hemodialysis; however, previous studies have shown that not all patients with healthcare contact have equal risk for MDR organisms.

Study design: Prospective cohort study.

Setting: Japan, multi-center.

Synopsis: Of the 445 enrolled patients, 124 were diagnosed with community-acquired pneumonia (CAP) and 321 with HCAP. Patients with HCAP were classified based on severity of illness or MDR pathogen risk factors (immune suppression, hospitalization within the last 90 days, poor functional status, and antibiotics within the past six months). Patients with low risk (0-1 factors) for MDR organisms were treated for CAP, and patients with high risk (≥2 factors) or moderate risk (≥1 factor) for severe illness were treated for HCAP.

HCAP patients had a higher 30-day mortality rate (13.7% vs. 5.6%, P=0.017), but mortality rate was less in the patients at low risk for MDR pathogens (8.6% vs. 18.2%, P=0.012). Of the HCAP patients, only 7.1% received inappropriate therapy (pathogen resistant to initial antibiotic regimen), and treatment failure was 19.3%.

Appropriateness of initial empiric therapy was determined not to be a mortality risk; however, this trial might be limited by its location, because Japan appears to have fewer MDR pathogens than the U.S.

Bottom line: A treatment algorithm based on risk for MDR organisms and severity of illness can be used to guide empiric antibiotic therapy in patients with HCAP, and, ideally, to reduce excessive use of broad-spectrum antibiotics.

Citation: Maruyama T, Fujisawa T, Okuno M, et al. A new strategy for healthcare-associated pneumonia: a 2-year prospective multicenter cohort study using risk factors for multidrug-resistant pathogens to select initial empiric therapy. Clin Infect Dis. 2013;57(10):1373-1383.

Three-Month Dual Antiplatelet Therapy for Zotarolimus-Eluting Stents

Clinical question: Is short-term, dual antiplatelet therapy noninferior to long-term therapy in zotarolimus-eluting stents?

Background: Current guidelines recommend long-term (>12 months) dual antiplatelet therapy after the placement of drug-eluting stents. The optimal therapy duration in second-generation drug-eluting stents has not been studied; moreover, some studies with multiple drug-eluting stents have suggested no added benefit from long-term therapy.

Study design: Randomized controlled trial.

Setting: Brazil, multi-center.

Synopsis: Researchers randomized 3,211 patients with stable coronary artery disease (CAD) or low-risk acute coronary syndrome (ACS) undergoing intervention with zotarolimus-eluting stents to short-term (three months) or long-term (12 months) dual antiplatelet therapy. Exclusion criteria included ST-elevation myocardial infarction (STEMI), previous drug-eluting stent, scheduled elective surgery within 12 months, or contraindication to aspirin or clopidogrel. Primary endpoints were a composite of death from any cause, MI, stroke, or major bleeding. Secondary endpoints were stent thrombosis, target lesion revascularization, adverse cardiac event, and any bleed.

At one-year follow-up, the short-term group had similar primary (6.0% vs. 5.8%) and secondary (8.3% vs. 7.4%) outcomes compared to the long-term. The short-term group’s noninferiority also was seen in several key subgroups.

This study included patients with stable CAD or low-risk ACS and cannot be generalized to higher-risk patients. Results for zotarolimus-eluting stents cannot be generalized to other second-generation drug-eluting stents.

Bottom line: Zotarolimus-eluting stents, followed by three months of dual antiplatelet therapy, were noninferior to 12 months of therapy in patients with stable CAD or low-risk ACS.

Citation: Feres F, Costa RA, Abizaid A, et al. Three vs. twelve months of dual antiplatelet therapy after zotarolimus-eluting stents: the OPTIMIZE randomized trial. JAMA. 2013;310(23):2510-2522.

De-Escalating Antibiotics in Sepsis

Clinical question: Does tailoring antibiotics based on known pathogens impact mortality for patients with severe sepsis or shock?

Background: In patients with sepsis, the use of early empiric antibiotics reduces morbidity and mortality. De-escalation therapy refers to narrowing the broad-spectrum antibiotics once the pathogen and sensitivities are known; however, no randomized controlled studies have assessed the impact of this therapy on critically ill patients.

Study design: Prospective observational study.

Setting: Academic hospital ICU in Spain.

Synopsis: From January 2008 to May 2012, 628 adult patients were treated empirically with broad-spectrum antibiotics. De-escalation was applied to 219 patients (34.9%). Outcomes measured were ICU mortality, hospital mortality, and 90-day mortality in patients who received de-escalation therapy, patients whose antibiotics were not changed, and patients for whom antibiotics were escalated.

The in-hospital mortality rate was 27.4% in patients who were de-escalated, 32.6% in the unchanged group, and 42.9% in the escalation group. ICU and 90-day mortality were lower in the de-escalation group. De-escalation was more commonly used in medical than in surgical patients.

This study is limited because it is not a randomized controlled study and was single-centered, so it might only be applicable on the larger scale. Also, multi-drug resistant organisms were not evaluated.

Overall, it is safe to narrow empiric antibiotics in severe sepsis and shock when the pathogen and sensitivities are known.

Bottom line: De-escalation of antibiotics in severe sepsis and septic shock is associated with a lower mortality.

Citation: Garnacho-Montero J, Gutierrez-Pizarraya A, Escoresca-Ortega A, et al. De-escalation of empirical therapy is associated with lower mortality in patients with severe sepsis and septic shock. Intensive Care Med. 2014;40(1):32-40.

New Oral Anticoagulants Increase GI Bleed Risk

Clinical question: Do thrombin and factor Xa inhibitors increase the risk of gastrointestinal (GI) bleeding when compared to vitamin K antagonists and heparins?

Background: New oral anticoagulants (thrombin and factor Xa inhibitors) are available and being used with increased frequency due to equal efficacy and ease of administration. Some studies indicate a higher risk of GI bleeding with these agents. Further evaluation is needed, because no reversal therapy is available.

Study design: Systematic review and meta-analysis.

Setting: Data from MEDLINE, Embase, and the Cochrane Library.

Synopsis: More than 150,000 patients from 43 randomized controlled trials were evaluated for risk of GI bleed when treated with new anticoagulants versus traditional therapy. Patients were treated for one of the following: embolism prevention from atrial fibrillation, venous thromboembolism (VTE) prophylaxis post orthopedic surgery, VTE prophylaxis of medical patients, acute VTE, and acute coronary syndrome (ACS). Use of aspirin or NSAIDs was discouraged but not documented. The odds ratio for GI bleeding with use of the new anticoagulants was 1.45, with a number needed to harm of 500. Evaluation of subgroups revealed increased GI bleed risk in patients treated for ACS and acute thrombosis versus prophylaxis. Post-surgical patients had the lowest risk.

This study was limited by the heterogeneity and differing primary outcomes (mostly efficacy rather than safety) of the included trials. Studies excluded high-risk patients, which the authors estimate to be 25%-40% of actual patients. More studies need to be done that include high-risk patients and focus on GI bleed as a primary outcome.

Bottom line: The new anticoagulants tend to have a higher incidence of GI bleed than traditional therapy, but this varies based on indication of therapy and needs further evaluation to clarify risk.

Citation: Holster IL, Valkhoff VE, Kuipers EJ, Tjwa ET. New oral anticoagulants increase risk for gastrointestinal bleeding: a systematic review and meta-analysis. Gastroenterology. 2013;145(1):105-112.

Single vs. Dual Antiplatelet Therapy after Stroke

Clinical question: Is dual antiplatelet therapy more beneficial or harmful than monotherapy after ischemic stroke?

Background: It is recommended that patients with ischemic stroke or transient ischemic attack (TIA) receive lifelong antiplatelet therapy; however, there have been insufficient studies evaluating the long-term safety of dual antiplatelet therapy.

Study design: Meta-analysis of randomized controlled trials (RCTs)

Setting: Data from PubMed, Embase, and the Cochrane Central Register of Controlled Trials.

Synopsis: Data from seven RCTs, including 39,574 patients with recent TIA or ischemic stroke, were reviewed. Comparisons were made regarding occurrence of intracranial hemorrhage (ICH) and recurrent stroke between patients receiving dual antiplatelet therapy and those receiving aspirin or clopidogrel monotherapy. All patients were treated for at least one year.

There was no difference in recurrent stroke or ICH between patients on dual antiplatelet therapy versus aspirin monotherapy. Patients treated with dual antiplatelet therapy did have a 46% increased risk of ICH without any additional protective benefit for recurrent stroke or TIA when compared with patients on clopidogrel monotherapy.

This information should not be applied in the acute setting, given the high risk of stroke after TIA or ischemic stroke. One major limitation of this study was that the individual trials used different combinations of dual antiplatelet therapy.

Bottom line: The risk of recurrent stroke or TIA after dual antiplatelet therapy and after monotherapy with aspirin or clopidogrel is equal, but the risk of ICH compared to clopidogrel monotherapy is increased.

Citation: Lee M, Saver JL, Hong KS, Rao NM, Wu YL, Ovbiagele B. Risk-benefit profile of long-term dual- versus single-antiplatelet therapy among patients with ischemic stroke: a systematic review and meta-analysis. Ann Intern Med. 2013;159(7):463-470.

Endoscopic vs. Surgical Cystogastrostomy for Pancreatic Pseudocyst Drainage

Clinical question: How does endoscopic cystogastrostomy for pancreatic pseudocyst drainage compare to the standard surgical approach?

Background: Pancreatic pseudocysts are a common complication of pancreatitis and necessitate decompression when they are accompanied by pain, infection, or obstruction. Decompression of the pseudocyst can be accomplished using either endoscopic or surgical cystogastrostomy.

Study design: Open-label, single-center, randomized trial.

Setting: Single-center U.S. hospital.

Synopsis: A total of 40 patients were randomly equalized to both treatment arms; 20 patients underwent endoscopic and 20 patients underwent surgical cystogastrostomy. Zero patients in the endoscopic therapy had a pseudocyst recurrence, compared with one patient treated surgically. Length of stay (LOS) and cost were lower for the endoscopic group compared to the surgical group (two days vs. six days, P<0.001, $7,011 vs. $15,052, P=0.003).

This study is limited due to several factors. First, patients with pancreatic necrosis were excluded; had these patients been included, the complication rates and LOS would have been higher. Second, cost difference cannot be generalized across the U.S., because Medicare payments are based on provider types and regions.

Bottom line: Endoscopic cystogastrostomy for pancreatic pseudocyst is equal to the standard surgical therapy and results in decreased LOS and reduced costs.

Citation: Varadarajulu S, Bang JY, Sutton BS, Trevino JM, Christein JD, Wilcox CM. Equal efficacy of endoscopic and surgical cystogastrostomy for pancreatic pseudocyst drainage in a randomized trial. Gastroenterology. 2013;145(3):583-590.

Long-Term Cognitive Impairment after Critical Illness

Clinical question: Are a longer duration of delirium and higher doses of sedatives associated with cognitive impairment in the hospital?

Background: Survivors of critical illness are at risk for prolonged cognitive dysfunction. Delirium (and factors associated with delirium, namely sedative and analgesic medications) has been implicated in cognitive dysfunction.

Study design: Prospective cohort study.

Setting: Multi-center, academic, and acute care hospitals.

Synopsis: The study examined 821 adults admitted to the ICU with respiratory failure, cardiogenic shock, or septic shock. Patients excluded were those with pre-existing cognitive impairment, those with psychotic disorders, and those for whom follow-up would not be possible. Two risk factors measured were duration of delirium and use of sedative/analgesics. Delirium was assessed at three and 12 months using the CAM-ICU algorithm in the ICU by trained psychology professionals who were unaware of the patients’ in-hospital course.

At three months, 40% of patients had global cognition scores that were 1.5 standard deviations (SD) below population mean (similar to traumatic brain injury), and 26% had scores two SD below population mean (similar to mild Alzheimer’s). At 12 months, 34% had scores similar to traumatic brain injury patients, and 24% had scores similar to mild Alzheimer’s. A longer duration of delirium was associated with worse global cognition at three and 12 months. Use of sedatives/analgesics was not associated with cognitive impairment.

Bottom line: Critically ill patients in the ICU who experience a longer duration of delirium are at risk of long-term cognitive impairments lasting 12 months.

Citation: Pandharipande PP, Girard TD, Jackson JC, et al. Long-term cognitive impairment after critical illness. N Engl J Med. 2013;369(14):1306-1316.

Holding Chambers (Spacers) vs. Nebulizers for Acute Asthma

Clinical question: Are beta-2 agonists as effective when administered through a holding chamber (spacer) as they are when administered by a nebulizer?

Background: During an acute asthma attack, beta-2 agonists must be delivered to the peripheral airways. There has been considerable controversy regarding the use of a spacer compared with a nebulizer. Aside from admission rates and length of stay, factors taken into account include cost, maintenance of nebulizer machines, and infection control (potential of cross-infection via nebulizers).

Study design: Meta-analysis review of randomized controlled trials (RCTs).

Setting: Multi-centered, worldwide studies from community setting and EDs.

Synopsis: In 39 studies of patients with an acute asthma attack (selected from Cochrane Airways Group Specialized Register), the hospital admission rates did not differ on the basis of delivery method in 729 adults (risk ratio=0.94, confidence interval 0.61-1.43) or in 1,897 children (risk ratio=0.71, confidence interval 0.47-1.08). Secondary outcomes included the duration of time in the ED and the duration of hospital admission. Time spent in the ED varied for adults but was shorter for children with spacers (based on three studies). Duration of hospital admission also did not differ when modes of delivery were compared.

Bottom line: Providing beta-2 agonists using nebulizers during an acute asthma attack is not more effective than administration using a spacer.

Citation: Cates CJ, Welsh EJ, Rowe BH. Holding chambers (spacers) versus nebulisers for beta-agonist treatment of acute asthma. Cochrane Database Syst Rev. 2013;9:CD000052.

In This Edition

Literature At A Glance

A guide to this month’s studies

1. ICU pressures improve transfers to the floor
2. Morbidity, mortality rates high for respiratory syncytial virus infections
3. Antibiotic algorithm can guide therapy in healthcare-associated pneumonia
4. Three-month dual antiplatelet therapy for zotarolimus-eluting stents
5. De-escalating antibiotics in sepsis
6. New oral anticoagulants increase GI bleed risk
7. Single vs. dual antiplatelet therapy after stroke
8. Endoscopic vs. surgical cystogastrostomy for pancreatic pseudocyst drainage
9. Long-term cognitive impairment after critical illness
10. Holding chambers vs. nebulizers for acute asthma

ICU Pressures Improve Transfers to the Floor

Clinical question: Does ICU strain negatively affect the outcomes of patients transferred to the floor?

Background: With healthcare costs increasing and critical care staff shortages projected, ICUs will have to operate under increasing strain. This may influence decisions on discharging patients from ICUs and could affect patient outcomes.

Study design: Retrospective cohort study.

Setting: One hundred fifty-five ICUs in the United States.

Synopsis: Using the Project IMPACT database, 200,730 adult patients from 107 different hospitals were evaluated in times of ICU strain, determined by the current census, new admissions, and acuity level. Outcomes measured were initial ICU length of stay (LOS), readmission within 72 hours, in-hospital mortality rates, and post-ICU discharge LOS.

Increases of the strain variables from the fifth to the 95th percentiles resulted in a 6.3-hour reduction in ICU LOS, a 2.0-hour decrease in post-ICU discharge LOS, and a 1.0% increase in probability of ICU readmission within 72 hours. Mortality rates during the hospital stay and odds of being discharged home showed no significant change. This study was limited because the ICUs participating were not randomly chosen, outcomes of patients transferred to other hospitals were not measured, and no post-hospital data was collected, so no long-term outcomes could be measured.

Bottom line: ICU bed pressures prompt physicians to allocate ICU resources more efficiently without changing short-term patient outcomes.

Citation: Wagner J, Gabler NB, Ratcliffe SJ, Brown SE, Strom BL, Halpern SD. Outcomes among patients discharged from busy intensive care units. Ann Intern Med. 2013;159(7):447-455.

Adults Hospitalized for Respiratory Syncytial Virus Infections Have High Morbidity, Mortality Rates

Clinical question: What are the complications and outcomes of respiratory syncytial virus (RSV) infection in adults requiring hospitalization?

Background: RSV is a common cause of lower respiratory tract infection in infants and young children, leading to hospitalization and even death. RSV has been estimated to affect 3%-10% of adults annually, generally causing mild disease. However, the outcomes of adults with more severe disease are not fully known.

Study design: Retrospective cohort study.

Setting: Three acute care, public hospitals in Hong Kong.

Synopsis: All adult patients hospitalized with laboratory-confirmed RSV infection were included during the defined time period. The main outcome measure was all-cause death, with secondary outcome measures of development of acute respiratory failure requiring ventilator support and total duration of hospitalization among survivors. Additionally, the cohort of RSV patients was compared to patients admitted with seasonal influenza during this same time frame. Patients with pandemic 2009 H1N1 infection were not included.

Of patients with RSV, pneumonia was found in 42.3%, bacterial superinfection in 12.5%, and cardiovascular complications in 14.3%. Additionally, 11.1% developed respiratory failure requiring ventilator support. All-cause mortality at 30 days and 60 days was 9.1% and 11.9%, respectively, with pneumonia the most common cause of death. Use of systemic corticosteroids did not improve survival. When the RSV cohort was compared to the influenza cohort, the patients were similar in age, but the RSV patients were more likely to have underlying chronic lung disease and major systemic co-morbidities. The rate of survival and duration of hospitalization were not significantly different.

Bottom line: RSV infection is an underappreciated cause of lower tract respiratory infection in adults; severe infections that require hospitalization have rates of mortality similar to seasonal influenza. Further research on treatment or immunization is needed.

Citation: Lee N, Lui GC, Wong KT, et al. High morbidity and mortality in adults hospitalized for respiratory syncytial virus infections. Clin Infect Dis. 2013;57(8):1069-1077.

Antibiotic Algorithm Can Guide Therapy in Healthcare-Associated Pneumonia

Clinical question: Can an algorithm based on risk for multidrug-resistant (MDR) organisms and illness severity guide antibiotic selection in healthcare-associated pneumonia (HCAP)?

Background: The 2005 American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) guidelines identify patients with HCAP as those with recent contact with a healthcare environment, including nursing homes and hemodialysis; however, previous studies have shown that not all patients with healthcare contact have equal risk for MDR organisms.

Study design: Prospective cohort study.

Setting: Japan, multi-center.

Synopsis: Of the 445 enrolled patients, 124 were diagnosed with community-acquired pneumonia (CAP) and 321 with HCAP. Patients with HCAP were classified based on severity of illness or MDR pathogen risk factors (immune suppression, hospitalization within the last 90 days, poor functional status, and antibiotics within the past six months). Patients with low risk (0-1 factors) for MDR organisms were treated for CAP, and patients with high risk (≥2 factors) or moderate risk (≥1 factor) for severe illness were treated for HCAP.

HCAP patients had a higher 30-day mortality rate (13.7% vs. 5.6%, P=0.017), but mortality rate was less in the patients at low risk for MDR pathogens (8.6% vs. 18.2%, P=0.012). Of the HCAP patients, only 7.1% received inappropriate therapy (pathogen resistant to initial antibiotic regimen), and treatment failure was 19.3%.

Appropriateness of initial empiric therapy was determined not to be a mortality risk; however, this trial might be limited by its location, because Japan appears to have fewer MDR pathogens than the U.S.

Bottom line: A treatment algorithm based on risk for MDR organisms and severity of illness can be used to guide empiric antibiotic therapy in patients with HCAP, and, ideally, to reduce excessive use of broad-spectrum antibiotics.

Citation: Maruyama T, Fujisawa T, Okuno M, et al. A new strategy for healthcare-associated pneumonia: a 2-year prospective multicenter cohort study using risk factors for multidrug-resistant pathogens to select initial empiric therapy. Clin Infect Dis. 2013;57(10):1373-1383.

Three-Month Dual Antiplatelet Therapy for Zotarolimus-Eluting Stents

Clinical question: Is short-term, dual antiplatelet therapy noninferior to long-term therapy in zotarolimus-eluting stents?

Background: Current guidelines recommend long-term (>12 months) dual antiplatelet therapy after the placement of drug-eluting stents. The optimal therapy duration in second-generation drug-eluting stents has not been studied; moreover, some studies with multiple drug-eluting stents have suggested no added benefit from long-term therapy.

Study design: Randomized controlled trial.

Setting: Brazil, multi-center.

Synopsis: Researchers randomized 3,211 patients with stable coronary artery disease (CAD) or low-risk acute coronary syndrome (ACS) undergoing intervention with zotarolimus-eluting stents to short-term (three months) or long-term (12 months) dual antiplatelet therapy. Exclusion criteria included ST-elevation myocardial infarction (STEMI), previous drug-eluting stent, scheduled elective surgery within 12 months, or contraindication to aspirin or clopidogrel. Primary endpoints were a composite of death from any cause, MI, stroke, or major bleeding. Secondary endpoints were stent thrombosis, target lesion revascularization, adverse cardiac event, and any bleed.

At one-year follow-up, the short-term group had similar primary (6.0% vs. 5.8%) and secondary (8.3% vs. 7.4%) outcomes compared to the long-term. The short-term group’s noninferiority also was seen in several key subgroups.

This study included patients with stable CAD or low-risk ACS and cannot be generalized to higher-risk patients. Results for zotarolimus-eluting stents cannot be generalized to other second-generation drug-eluting stents.

Bottom line: Zotarolimus-eluting stents, followed by three months of dual antiplatelet therapy, were noninferior to 12 months of therapy in patients with stable CAD or low-risk ACS.

Citation: Feres F, Costa RA, Abizaid A, et al. Three vs. twelve months of dual antiplatelet therapy after zotarolimus-eluting stents: the OPTIMIZE randomized trial. JAMA. 2013;310(23):2510-2522.

De-Escalating Antibiotics in Sepsis

Clinical question: Does tailoring antibiotics based on known pathogens impact mortality for patients with severe sepsis or shock?

Background: In patients with sepsis, the use of early empiric antibiotics reduces morbidity and mortality. De-escalation therapy refers to narrowing the broad-spectrum antibiotics once the pathogen and sensitivities are known; however, no randomized controlled studies have assessed the impact of this therapy on critically ill patients.

Study design: Prospective observational study.

Setting: Academic hospital ICU in Spain.

Synopsis: From January 2008 to May 2012, 628 adult patients were treated empirically with broad-spectrum antibiotics. De-escalation was applied to 219 patients (34.9%). Outcomes measured were ICU mortality, hospital mortality, and 90-day mortality in patients who received de-escalation therapy, patients whose antibiotics were not changed, and patients for whom antibiotics were escalated.

The in-hospital mortality rate was 27.4% in patients who were de-escalated, 32.6% in the unchanged group, and 42.9% in the escalation group. ICU and 90-day mortality were lower in the de-escalation group. De-escalation was more commonly used in medical than in surgical patients.

This study is limited because it is not a randomized controlled study and was single-centered, so it might only be applicable on the larger scale. Also, multi-drug resistant organisms were not evaluated.

Overall, it is safe to narrow empiric antibiotics in severe sepsis and shock when the pathogen and sensitivities are known.

Bottom line: De-escalation of antibiotics in severe sepsis and septic shock is associated with a lower mortality.

Citation: Garnacho-Montero J, Gutierrez-Pizarraya A, Escoresca-Ortega A, et al. De-escalation of empirical therapy is associated with lower mortality in patients with severe sepsis and septic shock. Intensive Care Med. 2014;40(1):32-40.

New Oral Anticoagulants Increase GI Bleed Risk

Clinical question: Do thrombin and factor Xa inhibitors increase the risk of gastrointestinal (GI) bleeding when compared to vitamin K antagonists and heparins?

Background: New oral anticoagulants (thrombin and factor Xa inhibitors) are available and being used with increased frequency due to equal efficacy and ease of administration. Some studies indicate a higher risk of GI bleeding with these agents. Further evaluation is needed, because no reversal therapy is available.

Study design: Systematic review and meta-analysis.

Setting: Data from MEDLINE, Embase, and the Cochrane Library.

Synopsis: More than 150,000 patients from 43 randomized controlled trials were evaluated for risk of GI bleed when treated with new anticoagulants versus traditional therapy. Patients were treated for one of the following: embolism prevention from atrial fibrillation, venous thromboembolism (VTE) prophylaxis post orthopedic surgery, VTE prophylaxis of medical patients, acute VTE, and acute coronary syndrome (ACS). Use of aspirin or NSAIDs was discouraged but not documented. The odds ratio for GI bleeding with use of the new anticoagulants was 1.45, with a number needed to harm of 500. Evaluation of subgroups revealed increased GI bleed risk in patients treated for ACS and acute thrombosis versus prophylaxis. Post-surgical patients had the lowest risk.

This study was limited by the heterogeneity and differing primary outcomes (mostly efficacy rather than safety) of the included trials. Studies excluded high-risk patients, which the authors estimate to be 25%-40% of actual patients. More studies need to be done that include high-risk patients and focus on GI bleed as a primary outcome.

Bottom line: The new anticoagulants tend to have a higher incidence of GI bleed than traditional therapy, but this varies based on indication of therapy and needs further evaluation to clarify risk.

Citation: Holster IL, Valkhoff VE, Kuipers EJ, Tjwa ET. New oral anticoagulants increase risk for gastrointestinal bleeding: a systematic review and meta-analysis. Gastroenterology. 2013;145(1):105-112.

Single vs. Dual Antiplatelet Therapy after Stroke

Clinical question: Is dual antiplatelet therapy more beneficial or harmful than monotherapy after ischemic stroke?

Background: It is recommended that patients with ischemic stroke or transient ischemic attack (TIA) receive lifelong antiplatelet therapy; however, there have been insufficient studies evaluating the long-term safety of dual antiplatelet therapy.

Study design: Meta-analysis of randomized controlled trials (RCTs)

Setting: Data from PubMed, Embase, and the Cochrane Central Register of Controlled Trials.

Synopsis: Data from seven RCTs, including 39,574 patients with recent TIA or ischemic stroke, were reviewed. Comparisons were made regarding occurrence of intracranial hemorrhage (ICH) and recurrent stroke between patients receiving dual antiplatelet therapy and those receiving aspirin or clopidogrel monotherapy. All patients were treated for at least one year.

There was no difference in recurrent stroke or ICH between patients on dual antiplatelet therapy versus aspirin monotherapy. Patients treated with dual antiplatelet therapy did have a 46% increased risk of ICH without any additional protective benefit for recurrent stroke or TIA when compared with patients on clopidogrel monotherapy.

This information should not be applied in the acute setting, given the high risk of stroke after TIA or ischemic stroke. One major limitation of this study was that the individual trials used different combinations of dual antiplatelet therapy.

Bottom line: The risk of recurrent stroke or TIA after dual antiplatelet therapy and after monotherapy with aspirin or clopidogrel is equal, but the risk of ICH compared to clopidogrel monotherapy is increased.

Citation: Lee M, Saver JL, Hong KS, Rao NM, Wu YL, Ovbiagele B. Risk-benefit profile of long-term dual- versus single-antiplatelet therapy among patients with ischemic stroke: a systematic review and meta-analysis. Ann Intern Med. 2013;159(7):463-470.

Endoscopic vs. Surgical Cystogastrostomy for Pancreatic Pseudocyst Drainage

Clinical question: How does endoscopic cystogastrostomy for pancreatic pseudocyst drainage compare to the standard surgical approach?

Background: Pancreatic pseudocysts are a common complication of pancreatitis and necessitate decompression when they are accompanied by pain, infection, or obstruction. Decompression of the pseudocyst can be accomplished using either endoscopic or surgical cystogastrostomy.

Study design: Open-label, single-center, randomized trial.

Setting: Single-center U.S. hospital.

Synopsis: A total of 40 patients were randomly equalized to both treatment arms; 20 patients underwent endoscopic and 20 patients underwent surgical cystogastrostomy. Zero patients in the endoscopic therapy had a pseudocyst recurrence, compared with one patient treated surgically. Length of stay (LOS) and cost were lower for the endoscopic group compared to the surgical group (two days vs. six days, P<0.001, $7,011 vs. $15,052, P=0.003).

This study is limited due to several factors. First, patients with pancreatic necrosis were excluded; had these patients been included, the complication rates and LOS would have been higher. Second, cost difference cannot be generalized across the U.S., because Medicare payments are based on provider types and regions.

Bottom line: Endoscopic cystogastrostomy for pancreatic pseudocyst is equal to the standard surgical therapy and results in decreased LOS and reduced costs.

Citation: Varadarajulu S, Bang JY, Sutton BS, Trevino JM, Christein JD, Wilcox CM. Equal efficacy of endoscopic and surgical cystogastrostomy for pancreatic pseudocyst drainage in a randomized trial. Gastroenterology. 2013;145(3):583-590.

Long-Term Cognitive Impairment after Critical Illness

Clinical question: Are a longer duration of delirium and higher doses of sedatives associated with cognitive impairment in the hospital?

Background: Survivors of critical illness are at risk for prolonged cognitive dysfunction. Delirium (and factors associated with delirium, namely sedative and analgesic medications) has been implicated in cognitive dysfunction.

Study design: Prospective cohort study.

Setting: Multi-center, academic, and acute care hospitals.

Synopsis: The study examined 821 adults admitted to the ICU with respiratory failure, cardiogenic shock, or septic shock. Patients excluded were those with pre-existing cognitive impairment, those with psychotic disorders, and those for whom follow-up would not be possible. Two risk factors measured were duration of delirium and use of sedative/analgesics. Delirium was assessed at three and 12 months using the CAM-ICU algorithm in the ICU by trained psychology professionals who were unaware of the patients’ in-hospital course.

At three months, 40% of patients had global cognition scores that were 1.5 standard deviations (SD) below population mean (similar to traumatic brain injury), and 26% had scores two SD below population mean (similar to mild Alzheimer’s). At 12 months, 34% had scores similar to traumatic brain injury patients, and 24% had scores similar to mild Alzheimer’s. A longer duration of delirium was associated with worse global cognition at three and 12 months. Use of sedatives/analgesics was not associated with cognitive impairment.

Bottom line: Critically ill patients in the ICU who experience a longer duration of delirium are at risk of long-term cognitive impairments lasting 12 months.

Citation: Pandharipande PP, Girard TD, Jackson JC, et al. Long-term cognitive impairment after critical illness. N Engl J Med. 2013;369(14):1306-1316.

Holding Chambers (Spacers) vs. Nebulizers for Acute Asthma

Clinical question: Are beta-2 agonists as effective when administered through a holding chamber (spacer) as they are when administered by a nebulizer?

Background: During an acute asthma attack, beta-2 agonists must be delivered to the peripheral airways. There has been considerable controversy regarding the use of a spacer compared with a nebulizer. Aside from admission rates and length of stay, factors taken into account include cost, maintenance of nebulizer machines, and infection control (potential of cross-infection via nebulizers).

Study design: Meta-analysis review of randomized controlled trials (RCTs).

Setting: Multi-centered, worldwide studies from community setting and EDs.

Synopsis: In 39 studies of patients with an acute asthma attack (selected from Cochrane Airways Group Specialized Register), the hospital admission rates did not differ on the basis of delivery method in 729 adults (risk ratio=0.94, confidence interval 0.61-1.43) or in 1,897 children (risk ratio=0.71, confidence interval 0.47-1.08). Secondary outcomes included the duration of time in the ED and the duration of hospital admission. Time spent in the ED varied for adults but was shorter for children with spacers (based on three studies). Duration of hospital admission also did not differ when modes of delivery were compared.

Bottom line: Providing beta-2 agonists using nebulizers during an acute asthma attack is not more effective than administration using a spacer.

Citation: Cates CJ, Welsh EJ, Rowe BH. Holding chambers (spacers) versus nebulisers for beta-agonist treatment of acute asthma. Cochrane Database Syst Rev. 2013;9:CD000052.

Clinical question: Does fluid management guided by daily plasma natriuretic peptide-driven (BNP) levels in mechanically ventilated patients improve weaning outcomes compared with usual therapy dictated by clinical acumen?

Background: Ventilator weaning contributes at least 40% of the total duration of mechanical ventilation; strategies aimed at optimizing this process could provide substantial benefit. Previous studies have demonstrated that BNP levels prior to ventilator weaning independently predict weaning failure. No current objective practical guide to fluid management during ventilator weaning exists.

Study design: Randomized controlled trial.

Setting: Multiple international centers.

Synopsis: Three hundred four patients who met specific inclusion and exclusion criteria were randomized to either a BNP-driven or physician-guided strategy for fluid management during ventilator weaning. Patients with renal failure were excluded because of the influence of renal function on BNP levels.

All patients in both groups were ventilated with an automatic computer-driven weaning system to standardize the weaning process. In the BNP-driven group, diuretic use was higher, resulting in a more negative fluid balance and significantly shorter time to successful extubation (58.6 hours vs. 42.2 hours, P=0.03). The effect on weaning time was strongest in patients with left ventricular systolic dysfunction, whereas those with COPD seemed less likely to benefit. The two groups did not differ in baseline characteristics, length of stay, mortality, or development of adverse outcomes of renal failure, shock, or electrolyte disturbances.

Bottom line: Compared with physician-guided fluid management, a BNP-driven fluid management protocol decreased duration of ventilator weaning without significant differences in adverse events, mortality rate, or length of stay between the two groups.

Citation: Dessap AM, Roche-Campo F, Kouatchet A, et al. Natriuretic peptide-driven fluid management during ventilator weaning. Am J Respir Crit Care Med. 2012;186(12):1256-1263.

Visit our website for more physician reviews of recent HM-relevant literature.

Clinical question: Does fluid management guided by daily plasma natriuretic peptide-driven (BNP) levels in mechanically ventilated patients improve weaning outcomes compared with usual therapy dictated by clinical acumen?

Background: Ventilator weaning contributes at least 40% of the total duration of mechanical ventilation; strategies aimed at optimizing this process could provide substantial benefit. Previous studies have demonstrated that BNP levels prior to ventilator weaning independently predict weaning failure. No current objective practical guide to fluid management during ventilator weaning exists.

Study design: Randomized controlled trial.

Setting: Multiple international centers.

Synopsis: Three hundred four patients who met specific inclusion and exclusion criteria were randomized to either a BNP-driven or physician-guided strategy for fluid management during ventilator weaning. Patients with renal failure were excluded because of the influence of renal function on BNP levels.

All patients in both groups were ventilated with an automatic computer-driven weaning system to standardize the weaning process. In the BNP-driven group, diuretic use was higher, resulting in a more negative fluid balance and significantly shorter time to successful extubation (58.6 hours vs. 42.2 hours, P=0.03). The effect on weaning time was strongest in patients with left ventricular systolic dysfunction, whereas those with COPD seemed less likely to benefit. The two groups did not differ in baseline characteristics, length of stay, mortality, or development of adverse outcomes of renal failure, shock, or electrolyte disturbances.

Bottom line: Compared with physician-guided fluid management, a BNP-driven fluid management protocol decreased duration of ventilator weaning without significant differences in adverse events, mortality rate, or length of stay between the two groups.

Citation: Dessap AM, Roche-Campo F, Kouatchet A, et al. Natriuretic peptide-driven fluid management during ventilator weaning. Am J Respir Crit Care Med. 2012;186(12):1256-1263.

Visit our website for more physician reviews of recent HM-relevant literature.

Clinical question: Does fluid management guided by daily plasma natriuretic peptide-driven (BNP) levels in mechanically ventilated patients improve weaning outcomes compared with usual therapy dictated by clinical acumen?

Background: Ventilator weaning contributes at least 40% of the total duration of mechanical ventilation; strategies aimed at optimizing this process could provide substantial benefit. Previous studies have demonstrated that BNP levels prior to ventilator weaning independently predict weaning failure. No current objective practical guide to fluid management during ventilator weaning exists.

Study design: Randomized controlled trial.

Setting: Multiple international centers.

Synopsis: Three hundred four patients who met specific inclusion and exclusion criteria were randomized to either a BNP-driven or physician-guided strategy for fluid management during ventilator weaning. Patients with renal failure were excluded because of the influence of renal function on BNP levels.

All patients in both groups were ventilated with an automatic computer-driven weaning system to standardize the weaning process. In the BNP-driven group, diuretic use was higher, resulting in a more negative fluid balance and significantly shorter time to successful extubation (58.6 hours vs. 42.2 hours, P=0.03). The effect on weaning time was strongest in patients with left ventricular systolic dysfunction, whereas those with COPD seemed less likely to benefit. The two groups did not differ in baseline characteristics, length of stay, mortality, or development of adverse outcomes of renal failure, shock, or electrolyte disturbances.

Bottom line: Compared with physician-guided fluid management, a BNP-driven fluid management protocol decreased duration of ventilator weaning without significant differences in adverse events, mortality rate, or length of stay between the two groups.

Citation: Dessap AM, Roche-Campo F, Kouatchet A, et al. Natriuretic peptide-driven fluid management during ventilator weaning. Am J Respir Crit Care Med. 2012;186(12):1256-1263.

Visit our website for more physician reviews of recent HM-relevant literature.

In This Edition

Literature At A Glance

A guide to this month’s studies

1. BNP-driven fluid management to improve ventilator weaning
2. Examining 30-day readmission patterns to reduce repeat hospitalizations
3. Impact of hospitalists’ workload on patient safety, care
4. Permanent atrial fibrillation is best controlled by diltiazem
5. Low-dose thrombolysis effective for pulmonary embolism
6. High mortality rate seen in surgical patients requiring CPR
7. ED visits common for acute-care patients post-discharge
8. Restrictive transfusion strategies effective for upper GI bleeding
9. Need for non-ICU acid suppression may be predictable
10. Recommended changes for adult immunizations

BNP-Driven Fluid Management Improves Ventilator Weaning

Clinical question: Does fluid management guided by daily plasma natriuretic peptide-driven (BNP) levels in mechanically ventilated patients improve weaning outcomes compared with usual therapy dictated by clinical acumen?

Background: Ventilator weaning contributes at least 40% of the total duration of mechanical ventilation; strategies aimed at optimizing this process could provide substantial benefit. Previous studies have demonstrated that BNP levels prior to ventilator weaning independently predict weaning failure. No current objective practical guide to fluid management during ventilator weaning exists.

Study design: Randomized controlled trial.

Setting: Multiple international centers.

Synopsis: In a multicenter randomized controlled trial, 304 patients who met specific inclusion and exclusion criteria were randomized to either a BNP-driven or physician-guided strategy for fluid management during ventilator weaning. Patients with renal failure were excluded because of the influence of renal function on BNP levels.

All patients in both groups were ventilated with an automatic computer-driven weaning system to standardize the weaning process. In the BNP-driven group, diuretic use was higher, resulting in a more negative fluid balance and significantly shorter time to successful extubation (58.6 hours vs. 42.2 hours, P=0.03). The effect on weaning time was strongest in patients with left ventricular systolic dysfunction, whereas those with COPD seemed less likely to benefit. The two groups did not differ in baseline characteristics, length of stay, mortality, or development of adverse outcomes of renal failure, shock, or electrolyte disturbances.

Bottom line: Compared with physician-guided fluid management, a BNP-driven fluid management protocol decreased duration of ventilator weaning without significant differences in adverse events, mortality rate, or length of stay between the two groups.

Citation: Dessap AM, Roche-Campo F, Kouatchet A, et al. Natriuretic peptide-driven fluid management during ventilator weaning. Am J Respir Crit Care Med. 2012;186(12):1256-1263.

30-Day Readmission Patterns for MI, Heart Failure, Pneumonia

Clinical question: Do patterns exist among patients readmitted within 30 days of discharge for acute myocardial infarction (AMI), heart failure, or pneumonia that could provide insight for improving strategies aimed at reducing readmission rates?

Background: Examining readmission timing, diagnoses, and patient demographics might provide information to better guide post-discharge programs aimed at reducing overall readmissions.

Study design: Retrospective review of Centers for Medicare & Medicaid Services (CMS) data.

Setting: Acute-care hospitals.

Synopsis: Using CMS hospitalization data for principal diagnoses of AMI, heart failure, or pneumonia from 2007 through 2009, the authors examined the percentage of 30-day readmissions occurring on each day after discharge; the most common readmission diagnoses; the median time to readmission for common readmission diagnoses; and the relationship between patient demographic characteristics, readmission diagnoses, and timing. They found total readmission rates of 24.8% for heart failure, 19.9% for AMI, and 18.3% for pneumonia. Approximately two-thirds of 30-day readmissions occurred within the first 15 days after discharge for each cohort. Neither readmission diagnoses nor timing varied by patient age, sex, or race.

Although the majority of readmissions do occur soon after discharge, it is important to note that about one-third of all readmissions occur 16 to 30 days after discharge. There also was a diverse spectrum of readmission diagnoses that were not associated with patient demographic characteristics. These findings suggest that current post-discharge strategies aimed at specific diseases or time periods might only address a fraction of the patients at risk for readmission.

Bottom line: Among Medicare patients hospitalized for heart failure, AMI, or pneumonia, 30-day readmissions were frequent throughout the entire period, and readmission diagnoses or timing did not vary by patient age, sex, or race.

Citation: Dharmarajan K, Hsich AF, Lin Z, et al. Diagnosis and timing of 30-day readmissions after hospitalization for heart failure, acute myocardial infarction, or pneumonia. JAMA. 2013;309(4):355-363.

Workload Might Impact Patient Safety and Quality of Care

Clinical question: Do hospitalists’ workloads affect patient quality of care and safety?

Background: Preventable medical errors contribute to a large number of patient deaths each year. It is unclear if a hospitalist’s clinical workload affects rates of medical errors or patient harm.

Study design: Cross-sectional cohort study.

Setting: Hospitalists enrolled in online physician community QuantiaMD.com.

Synopsis: There has been limited research evaluating the correlation between physician workload and patient safety. An online survey compared the responses of 506 out of 890 enrolled physicians on the impact of average patient census and several outcome measures of quality of care. Some 40% reported that their patient census exceeded their personal safe workload at least once a month. They also reported that less time for patient evaluations led to fewer discussions with patients and family members, more unnecessary medical work-ups, and lower patient satisfaction.

A limitation of this study is that this electronic survey had the potential for selection bias. It also only measured perceptions of safety and quality, and only used standard daytime shifts (excluding night, cross-cover, weekend, and holiday shifts), which might have been associated with significantly different conclusions.

Bottom line: Increase in workload has a negative perceived impact on patient safety and quality of care for attending hospitalists.

Citation: Michtalik HJ, Yeh HC, Pronovost P, et. al. Impact of attending physician workload on patient care: a survey of hospitalists. JAMA Intern Med. 2013;173(5):375-377.

Permanent Atrial Fibrillation Best Controlled by Diltiazem

Clinical question: Is there a difference between beta-blockers and calcium channel blockers for ventricular rate control and arrhythmia-related symptoms in patients with permanent atrial fibrillation?

Background: Rate control with beta-blockers or calcium channel blockers is recommended for the initial therapy of atrial fibrillation. However, studies comparing those drug classes or drugs within them are lacking.

Study design: Prospective, randomized, investigator-blind crossover study.

Setting: Majority of patients from an atrial fibrillation outpatient clinic at Baerum Hospital in Norway.

Synopsis: The RATe Control in Atrial Fibrillation (RATAF) study included 60 participants with permanent atrial fibrillation. The goal of the study was to compare the efficacy of diltiazem at 360 mg/day, verapamil at 240 mg/day, metoprolol at 100 mg/day, and carvedilol at 25mg/day on ventricular heart rate and related symptoms in atrial fibrillation. Patients had a mean age of 71, atrial fibrillation for more than three months, and mean heart rate of 96 beats/minute. Exclusion criteria included the presence of congestive heart failure or ischemic heart disease with the need for other medications that could compromise the study.

From this study, diltiazem was shown to have the greatest effect in lowering heart rate, and those patients taking this medication had decreased symptoms related to atrial fibrillation. Hospitalists should not rely solely on this study for their treatment choice in all atrial fibrillation patients, but in certain populations, they should consider diltiazem as their first-line drug.

Bottom line: Diltiazem was shown to have the greatest reduction in heart rate and symptoms related to permanent atrial fibrillation.

Citation: Ulimoen SR, Enger S, Carlson J, et al. Comparison of four single-drug regimens on ventricular rate and arrhythmia-related symptoms in patients with permanent atrial fibrillation. Am J Cardiol. 2013:111(2):225-230.

Low-Dose Thrombolysis Effective in Moderate Pulmonary Embolism

Clinical question: Can low-dose tissue plasminogen activator (tPA) help reduce pulmonary artery pressure in those with moderate pulmonary embolism (PE)?

Background: Studies have shown full-dose thrombolysis can effectively decrease pulmonary artery pressure in patients with massive PE. However, there are limited data regarding low-dose or “safe dose” thrombolytic therapy and its effect on pulmonary artery pressure.

Study design: Prospective, controlled, randomized study.

Setting: Single center.

Synopsis: The Moderate Pulmonary Embolism Treated with Thrombolysis (MOPETT) study enrolled patients with moderate PE, defined as signs and symptoms of PE plus computed tomographic pulmonary angiographic involvement of > 70% involvement of thrombus in ≥2 lobar or left/right main pulmonary arteries or high probability ventilation/perfusion scan (mismatch in ≥2 lobes). Patients in the thrombolysis group (n=61) were given low-dose tPA (100 mg tPA) and anticoagulation vs. the control group (n=60), which received only anticoagulation.

The study ran for 22 months, and the primary end points were pulmonary hypertension and recurrent PE. After analysis, low-dose thrombolysis was shown to significantly decrease pulmonary artery pressure and occurrence of recurrent PE compared to the control group.

This study demonstrates that, while the decision to use thrombolytics should always be made cautiously, hospitalists can consider low-dose thrombolysis in patients with moderate PE.

Bottom line: Low-dose thrombolysis, in addition to anticoagulation, in patients with moderate PE decreases pulmonary hypertension and recurrent PE.

Citation: Sharifi M, Bay C, Skrocki L, Rahimi F, Mehdipour M. Moderate pulmonary embolism treated with thrombolysis (from the “MOPETT” trial). Am J Cardiol. 2013;111(2):273-277.

High Mortality in Surgical Patients Requiring CPR

Clinical question: What are the incidence, characteristics, and 30-day-outcomes of CPR in surgical patients?

Background: Most studies of CPR are based on the medical population, and little is known about the utilization, risk factors, and outcomes of CPR in surgical patients.

Study design: Retrospective cohort study.

Setting: Two hundred fifty U.S. hospitals in the American College of Surgeons’ National Surgical Quality Improvement Program.

Synopsis: A total of 1.3 million surgical cases were studied in the data set. The overall incidence was 1 event per 203 cases. Most patients (77.6%) experienced a complication and did so on or before the day of CPR in three-fourths of cases. The incidence of CPR was the highest for cardiac surgery patients. Patients who received CPR had a mortality rate of 71.6%. Mortality rates of CPR patients increased with more comorbidities.

Additionally, older age and an American Society of Anesthesiologists (ASA) class of 5 was associated with higher mortality.

Limitations of this study included coding flaws in data collection, lack of capture of resuscitation-related injuries, and failure to account for changes in DNR orders.

Hospitalists should be mindful of risk factors contributing to CPR in surgical patients when performing perioperative evaluations.

Bottom line: Surgical patients who experience CPR have a high mortality rate, but many of these patients have pre-arrest complications that can be preventable.

Citation: Kazaure HS, Roman SA, Rosenthal RA, Sosa, JA. Cardiac arrest among surgical patients. JAMA Surg. 2013;148(1):14-21.

Emergency Department Visits are Frequent Post-Discharge

Clinical question: What role do ED visits contribute to the overall use of acute-care services within 30 days of hospital discharge?

Background: Hospital readmissions within 30 days of discharge are a marker of the quality of care and reflect the effectiveness of the discharge process. ED visits are also a marker of hospital-based acute care following discharge, but little is known about the role of the ED during the post-discharge period.

Study design: Prospective study.

Setting: Acute-care hospitals in California, Florida, and Nebraska.

Synopsis: Using the Healthcare Cost and Utilization Project state inpatient and ED databases, all discharges between July 1, 2008, and Sept. 31, 2009, were evaluated for residents aged 18 years or older from three hospitals in three states. After exclusions, 5 million index hospitalizations among 4 million unique patients were studied.

Approximately 40% of the more than 1 million post-discharge acute-care encounters involved a visit to the ED.

Limitations of this study include that the data was derived from only three states, and only hospital-based acute-care visits were measured (i.e. visits to physician offices were not included). As hospitalists, we are responsible for discharges and care transitions. Being sensitive to the common medical conditions resulting in post-discharge ED encounters might improve care transitions.

Bottom line: Hospital readmission rates underestimate ED use following discharge.

Citation: Vashi AA, Fox JP, Carr BG, et al. Use of hospital-based acute care among patients recently discharged from the hospital. JAMA. 2013;309(4):364-371.

Restrictive Transfusion Strategy Beneficial in Upper GI Bleeding

Clinical question: What is the hemoglobin threshold for transfusion of red cells in patients with acute upper GI bleeding?

Background: Controlled trials have shown that restrictive transfusion strategies (Hgb<7) are as effective as liberal transfusion strategies (Hgb<9) in critically ill patients. These studies have excluded patients with GI bleeding. In cases for which GI is not severe, the safest transfusion strategy is controversial.

Study design: Single-center study at Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.

Synopsis: A total of 921 adult patients with acute upper GI bleeding were enrolled and assigned: 461 to a restrictive transfusion strategy (hemoglobin<7) and 460 to a liberal strategy (hemoglobin<9). Patients with massive exsanguinating bleeding, acute coronary syndrome, peripheral vasculopathy, stroke, transient ischemic attack, lower GI bleed, recent trauma or surgery, or low risk of rebleeding were excluded. The primary outcome measure was the rate of death from any cause within the first 45 days.

Secondary outcomes included the rate of further bleeding and the rate of in-hospital complications.

Statistically significant benefit in following a restrictive versus liberal strategy was demonstrated in all major outcomes: mortality (5% vs, 9%, P=0.02), rate of further bleeding (10% vs 18%, P=0.01), and rate of complications (40% vs. 48%, P=0.02).

The study is limited by its inability to be generalized to all patients with acute GI bleeding, as patients with massive exsanguinating bleeds and those with low risk of rebleeding were excluded.

Bottom line: Restrictive transfusion (Hgb<7) significantly improved outcomes for patients with acute upper GI bleeding.

Citation: Villanueva C, Colomo A, Bosch A, et al. Transfusion strategies for acute upper gastrointestinal bleeding. N Engl J Med. 2013;368(1):11-21.

Need for Non-ICU Acid Suppression Might Be Predictable

Clinical question: What are the risk factors for nosocomial bleeding in non-critically-ill patients?

Background: Acid-suppressive medication has been shown to reduce the incidence of nosocomial GI bleed in the ICU, but current guidelines recommend against its use in non-critically-ill patients. However, a subgroup of these patients might possess a high enough risk for GI bleed that prophylaxis is warranted.

Study design: Cohort study.

Setting: Academic medical center in Boston.

Synopsis: A total of 75,723 admissions of adult patients hospitalized for three or more days were included. Exclusion criteria included primary discharge diagnosis of GI bleed; principal procedure code of cardiac catheterization; and bleeding episodes occurring while in the ICU or within 48 hours of transfer out of the ICU. The primary outcome was nosocomial GI bleed (>24 hours after admission) occurring outside the ICU.

Nosocomial GI bleeding occurred in 203 patients (0.27%). Independent risk factors for bleeding included age >60, male sex, liver disease, acute renal failure, sepsis, being on a medicine service, prophylactic anticoagulation, and coagulopathy. Based on the data, a scoring system was created that identified a high-risk group in whom the number needed to treat with acid-suppressive medication to prevent one bleed was 48.

The major limitations of this study are its observational nature and the need for validation of the proposed scoring system.

Bottom line: Risk for nosocomial GI bleeding appears predictable and supports the selective use of prophylactic acid suppression in non-critically-ill patients.

Citation: Herzig SJ, Rothberg MB, Feinbloom DB, et al. Risk factors for nosocomial gastrointestinal bleeding and use of acid-suppressive medication in non-critically ill patients. J Gen Intern Med. 2013; January 5. [Epub ahead of print].

Additions, Modifications, and Clarifications Regarding Adult Immunization

Clinical question: What are the changes to the recommended Adult Immunization Schedule for 2013?

Background: Despite the known public health benefits of immunization, adult vaccination rates remain low. The positive impact of strong provider recommendations regarding vaccines underscores the importance of provider awareness of vaccine schedules, precautions, and contraindications.

Study design: Annual Advisory Committee on Immunization Practices (ACIP) review.

Setting: Data from 2011 National Health Interview Survey.

Synopsis: Highlighted changes include: 1) a single dose of pneumococcal 13-valent conjugate (PCV13) vaccine is now recommended for all individuals over the age of 19 with qualifying conditions; 2) clarification regarding pneumococcal polysaccharide (PPSV23) vaccine illustrates that high-risk individuals will receive up to three doses (one or two doses prior to age 65, plus an additional dose after the age of 65); 3) one dose of tetanus, diphtheria, and acellular pertussis (Tdap) vaccine is now recommended for all adults, including individuals age >65; 4) pregnant woman are advised to receive Tdap between 27 and 36 weeks’ gestation, with each pregnancy to provide protection to their newborn in the first months of life; 5) quadrivalent formulations of the live attenuated influenza vaccine (LAIV) and most likely the inactivated influenza vaccine (IIV) will be available in the 2013-2014 influenza season to increase cross-reactive protection against influenza B; and 6) both injection and noninjection illicit drug users are recommended to receive hepatitis A vaccine.

Bottom line: Expanded recommendations for adult immunization provide more opportunities for the practicing hospitalist to improve vaccine capture.

Citation: Advisory Committee on Immunization Practices. Recommended adult immunization schedule: United States, 2013. Ann Int Med. 2013;158(3):191-199.

In This Edition

Literature At A Glance

A guide to this month’s studies

1. BNP-driven fluid management to improve ventilator weaning
2. Examining 30-day readmission patterns to reduce repeat hospitalizations
3. Impact of hospitalists’ workload on patient safety, care
4. Permanent atrial fibrillation is best controlled by diltiazem
5. Low-dose thrombolysis effective for pulmonary embolism
6. High mortality rate seen in surgical patients requiring CPR
7. ED visits common for acute-care patients post-discharge
8. Restrictive transfusion strategies effective for upper GI bleeding
9. Need for non-ICU acid suppression may be predictable
10. Recommended changes for adult immunizations

BNP-Driven Fluid Management Improves Ventilator Weaning

Clinical question: Does fluid management guided by daily plasma natriuretic peptide-driven (BNP) levels in mechanically ventilated patients improve weaning outcomes compared with usual therapy dictated by clinical acumen?

Background: Ventilator weaning contributes at least 40% of the total duration of mechanical ventilation; strategies aimed at optimizing this process could provide substantial benefit. Previous studies have demonstrated that BNP levels prior to ventilator weaning independently predict weaning failure. No current objective practical guide to fluid management during ventilator weaning exists.

Study design: Randomized controlled trial.

Setting: Multiple international centers.

Synopsis: In a multicenter randomized controlled trial, 304 patients who met specific inclusion and exclusion criteria were randomized to either a BNP-driven or physician-guided strategy for fluid management during ventilator weaning. Patients with renal failure were excluded because of the influence of renal function on BNP levels.

All patients in both groups were ventilated with an automatic computer-driven weaning system to standardize the weaning process. In the BNP-driven group, diuretic use was higher, resulting in a more negative fluid balance and significantly shorter time to successful extubation (58.6 hours vs. 42.2 hours, P=0.03). The effect on weaning time was strongest in patients with left ventricular systolic dysfunction, whereas those with COPD seemed less likely to benefit. The two groups did not differ in baseline characteristics, length of stay, mortality, or development of adverse outcomes of renal failure, shock, or electrolyte disturbances.

Bottom line: Compared with physician-guided fluid management, a BNP-driven fluid management protocol decreased duration of ventilator weaning without significant differences in adverse events, mortality rate, or length of stay between the two groups.

Citation: Dessap AM, Roche-Campo F, Kouatchet A, et al. Natriuretic peptide-driven fluid management during ventilator weaning. Am J Respir Crit Care Med. 2012;186(12):1256-1263.

30-Day Readmission Patterns for MI, Heart Failure, Pneumonia

Clinical question: Do patterns exist among patients readmitted within 30 days of discharge for acute myocardial infarction (AMI), heart failure, or pneumonia that could provide insight for improving strategies aimed at reducing readmission rates?

Background: Examining readmission timing, diagnoses, and patient demographics might provide information to better guide post-discharge programs aimed at reducing overall readmissions.

Study design: Retrospective review of Centers for Medicare & Medicaid Services (CMS) data.

Setting: Acute-care hospitals.

Synopsis: Using CMS hospitalization data for principal diagnoses of AMI, heart failure, or pneumonia from 2007 through 2009, the authors examined the percentage of 30-day readmissions occurring on each day after discharge; the most common readmission diagnoses; the median time to readmission for common readmission diagnoses; and the relationship between patient demographic characteristics, readmission diagnoses, and timing. They found total readmission rates of 24.8% for heart failure, 19.9% for AMI, and 18.3% for pneumonia. Approximately two-thirds of 30-day readmissions occurred within the first 15 days after discharge for each cohort. Neither readmission diagnoses nor timing varied by patient age, sex, or race.

Although the majority of readmissions do occur soon after discharge, it is important to note that about one-third of all readmissions occur 16 to 30 days after discharge. There also was a diverse spectrum of readmission diagnoses that were not associated with patient demographic characteristics. These findings suggest that current post-discharge strategies aimed at specific diseases or time periods might only address a fraction of the patients at risk for readmission.

Bottom line: Among Medicare patients hospitalized for heart failure, AMI, or pneumonia, 30-day readmissions were frequent throughout the entire period, and readmission diagnoses or timing did not vary by patient age, sex, or race.

Citation: Dharmarajan K, Hsich AF, Lin Z, et al. Diagnosis and timing of 30-day readmissions after hospitalization for heart failure, acute myocardial infarction, or pneumonia. JAMA. 2013;309(4):355-363.

Workload Might Impact Patient Safety and Quality of Care

Clinical question: Do hospitalists’ workloads affect patient quality of care and safety?

Background: Preventable medical errors contribute to a large number of patient deaths each year. It is unclear if a hospitalist’s clinical workload affects rates of medical errors or patient harm.

Study design: Cross-sectional cohort study.

Setting: Hospitalists enrolled in online physician community QuantiaMD.com.

Synopsis: There has been limited research evaluating the correlation between physician workload and patient safety. An online survey compared the responses of 506 out of 890 enrolled physicians on the impact of average patient census and several outcome measures of quality of care. Some 40% reported that their patient census exceeded their personal safe workload at least once a month. They also reported that less time for patient evaluations led to fewer discussions with patients and family members, more unnecessary medical work-ups, and lower patient satisfaction.

A limitation of this study is that this electronic survey had the potential for selection bias. It also only measured perceptions of safety and quality, and only used standard daytime shifts (excluding night, cross-cover, weekend, and holiday shifts), which might have been associated with significantly different conclusions.

Bottom line: Increase in workload has a negative perceived impact on patient safety and quality of care for attending hospitalists.

Citation: Michtalik HJ, Yeh HC, Pronovost P, et. al. Impact of attending physician workload on patient care: a survey of hospitalists. JAMA Intern Med. 2013;173(5):375-377.

Permanent Atrial Fibrillation Best Controlled by Diltiazem

Clinical question: Is there a difference between beta-blockers and calcium channel blockers for ventricular rate control and arrhythmia-related symptoms in patients with permanent atrial fibrillation?

Background: Rate control with beta-blockers or calcium channel blockers is recommended for the initial therapy of atrial fibrillation. However, studies comparing those drug classes or drugs within them are lacking.

Study design: Prospective, randomized, investigator-blind crossover study.

Setting: Majority of patients from an atrial fibrillation outpatient clinic at Baerum Hospital in Norway.

Synopsis: The RATe Control in Atrial Fibrillation (RATAF) study included 60 participants with permanent atrial fibrillation. The goal of the study was to compare the efficacy of diltiazem at 360 mg/day, verapamil at 240 mg/day, metoprolol at 100 mg/day, and carvedilol at 25mg/day on ventricular heart rate and related symptoms in atrial fibrillation. Patients had a mean age of 71, atrial fibrillation for more than three months, and mean heart rate of 96 beats/minute. Exclusion criteria included the presence of congestive heart failure or ischemic heart disease with the need for other medications that could compromise the study.

From this study, diltiazem was shown to have the greatest effect in lowering heart rate, and those patients taking this medication had decreased symptoms related to atrial fibrillation. Hospitalists should not rely solely on this study for their treatment choice in all atrial fibrillation patients, but in certain populations, they should consider diltiazem as their first-line drug.

Bottom line: Diltiazem was shown to have the greatest reduction in heart rate and symptoms related to permanent atrial fibrillation.

Citation: Ulimoen SR, Enger S, Carlson J, et al. Comparison of four single-drug regimens on ventricular rate and arrhythmia-related symptoms in patients with permanent atrial fibrillation. Am J Cardiol. 2013:111(2):225-230.

Low-Dose Thrombolysis Effective in Moderate Pulmonary Embolism

Clinical question: Can low-dose tissue plasminogen activator (tPA) help reduce pulmonary artery pressure in those with moderate pulmonary embolism (PE)?

Background: Studies have shown full-dose thrombolysis can effectively decrease pulmonary artery pressure in patients with massive PE. However, there are limited data regarding low-dose or “safe dose” thrombolytic therapy and its effect on pulmonary artery pressure.

Study design: Prospective, controlled, randomized study.

Setting: Single center.

Synopsis: The Moderate Pulmonary Embolism Treated with Thrombolysis (MOPETT) study enrolled patients with moderate PE, defined as signs and symptoms of PE plus computed tomographic pulmonary angiographic involvement of > 70% involvement of thrombus in ≥2 lobar or left/right main pulmonary arteries or high probability ventilation/perfusion scan (mismatch in ≥2 lobes). Patients in the thrombolysis group (n=61) were given low-dose tPA (100 mg tPA) and anticoagulation vs. the control group (n=60), which received only anticoagulation.

The study ran for 22 months, and the primary end points were pulmonary hypertension and recurrent PE. After analysis, low-dose thrombolysis was shown to significantly decrease pulmonary artery pressure and occurrence of recurrent PE compared to the control group.

This study demonstrates that, while the decision to use thrombolytics should always be made cautiously, hospitalists can consider low-dose thrombolysis in patients with moderate PE.

Bottom line: Low-dose thrombolysis, in addition to anticoagulation, in patients with moderate PE decreases pulmonary hypertension and recurrent PE.

Citation: Sharifi M, Bay C, Skrocki L, Rahimi F, Mehdipour M. Moderate pulmonary embolism treated with thrombolysis (from the “MOPETT” trial). Am J Cardiol. 2013;111(2):273-277.

High Mortality in Surgical Patients Requiring CPR

Clinical question: What are the incidence, characteristics, and 30-day-outcomes of CPR in surgical patients?

Background: Most studies of CPR are based on the medical population, and little is known about the utilization, risk factors, and outcomes of CPR in surgical patients.

Study design: Retrospective cohort study.

Setting: Two hundred fifty U.S. hospitals in the American College of Surgeons’ National Surgical Quality Improvement Program.

Synopsis: A total of 1.3 million surgical cases were studied in the data set. The overall incidence was 1 event per 203 cases. Most patients (77.6%) experienced a complication and did so on or before the day of CPR in three-fourths of cases. The incidence of CPR was the highest for cardiac surgery patients. Patients who received CPR had a mortality rate of 71.6%. Mortality rates of CPR patients increased with more comorbidities.

Additionally, older age and an American Society of Anesthesiologists (ASA) class of 5 was associated with higher mortality.

Limitations of this study included coding flaws in data collection, lack of capture of resuscitation-related injuries, and failure to account for changes in DNR orders.

Hospitalists should be mindful of risk factors contributing to CPR in surgical patients when performing perioperative evaluations.

Bottom line: Surgical patients who experience CPR have a high mortality rate, but many of these patients have pre-arrest complications that can be preventable.

Citation: Kazaure HS, Roman SA, Rosenthal RA, Sosa, JA. Cardiac arrest among surgical patients. JAMA Surg. 2013;148(1):14-21.

Emergency Department Visits are Frequent Post-Discharge

Clinical question: What role do ED visits contribute to the overall use of acute-care services within 30 days of hospital discharge?

Background: Hospital readmissions within 30 days of discharge are a marker of the quality of care and reflect the effectiveness of the discharge process. ED visits are also a marker of hospital-based acute care following discharge, but little is known about the role of the ED during the post-discharge period.

Study design: Prospective study.

Setting: Acute-care hospitals in California, Florida, and Nebraska.

Synopsis: Using the Healthcare Cost and Utilization Project state inpatient and ED databases, all discharges between July 1, 2008, and Sept. 31, 2009, were evaluated for residents aged 18 years or older from three hospitals in three states. After exclusions, 5 million index hospitalizations among 4 million unique patients were studied.

Approximately 40% of the more than 1 million post-discharge acute-care encounters involved a visit to the ED.

Limitations of this study include that the data was derived from only three states, and only hospital-based acute-care visits were measured (i.e. visits to physician offices were not included). As hospitalists, we are responsible for discharges and care transitions. Being sensitive to the common medical conditions resulting in post-discharge ED encounters might improve care transitions.

Bottom line: Hospital readmission rates underestimate ED use following discharge.

Citation: Vashi AA, Fox JP, Carr BG, et al. Use of hospital-based acute care among patients recently discharged from the hospital. JAMA. 2013;309(4):364-371.

Restrictive Transfusion Strategy Beneficial in Upper GI Bleeding

Clinical question: What is the hemoglobin threshold for transfusion of red cells in patients with acute upper GI bleeding?

Background: Controlled trials have shown that restrictive transfusion strategies (Hgb<7) are as effective as liberal transfusion strategies (Hgb<9) in critically ill patients. These studies have excluded patients with GI bleeding. In cases for which GI is not severe, the safest transfusion strategy is controversial.

Study design: Single-center study at Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.

Synopsis: A total of 921 adult patients with acute upper GI bleeding were enrolled and assigned: 461 to a restrictive transfusion strategy (hemoglobin<7) and 460 to a liberal strategy (hemoglobin<9). Patients with massive exsanguinating bleeding, acute coronary syndrome, peripheral vasculopathy, stroke, transient ischemic attack, lower GI bleed, recent trauma or surgery, or low risk of rebleeding were excluded. The primary outcome measure was the rate of death from any cause within the first 45 days.

Secondary outcomes included the rate of further bleeding and the rate of in-hospital complications.

Statistically significant benefit in following a restrictive versus liberal strategy was demonstrated in all major outcomes: mortality (5% vs, 9%, P=0.02), rate of further bleeding (10% vs 18%, P=0.01), and rate of complications (40% vs. 48%, P=0.02).

The study is limited by its inability to be generalized to all patients with acute GI bleeding, as patients with massive exsanguinating bleeds and those with low risk of rebleeding were excluded.

Bottom line: Restrictive transfusion (Hgb<7) significantly improved outcomes for patients with acute upper GI bleeding.

Citation: Villanueva C, Colomo A, Bosch A, et al. Transfusion strategies for acute upper gastrointestinal bleeding. N Engl J Med. 2013;368(1):11-21.

Need for Non-ICU Acid Suppression Might Be Predictable

Clinical question: What are the risk factors for nosocomial bleeding in non-critically-ill patients?

Background: Acid-suppressive medication has been shown to reduce the incidence of nosocomial GI bleed in the ICU, but current guidelines recommend against its use in non-critically-ill patients. However, a subgroup of these patients might possess a high enough risk for GI bleed that prophylaxis is warranted.

Study design: Cohort study.

Setting: Academic medical center in Boston.

Synopsis: A total of 75,723 admissions of adult patients hospitalized for three or more days were included. Exclusion criteria included primary discharge diagnosis of GI bleed; principal procedure code of cardiac catheterization; and bleeding episodes occurring while in the ICU or within 48 hours of transfer out of the ICU. The primary outcome was nosocomial GI bleed (>24 hours after admission) occurring outside the ICU.

Nosocomial GI bleeding occurred in 203 patients (0.27%). Independent risk factors for bleeding included age >60, male sex, liver disease, acute renal failure, sepsis, being on a medicine service, prophylactic anticoagulation, and coagulopathy. Based on the data, a scoring system was created that identified a high-risk group in whom the number needed to treat with acid-suppressive medication to prevent one bleed was 48.

The major limitations of this study are its observational nature and the need for validation of the proposed scoring system.

Bottom line: Risk for nosocomial GI bleeding appears predictable and supports the selective use of prophylactic acid suppression in non-critically-ill patients.

Citation: Herzig SJ, Rothberg MB, Feinbloom DB, et al. Risk factors for nosocomial gastrointestinal bleeding and use of acid-suppressive medication in non-critically ill patients. J Gen Intern Med. 2013; January 5. [Epub ahead of print].

Additions, Modifications, and Clarifications Regarding Adult Immunization

Clinical question: What are the changes to the recommended Adult Immunization Schedule for 2013?

Background: Despite the known public health benefits of immunization, adult vaccination rates remain low. The positive impact of strong provider recommendations regarding vaccines underscores the importance of provider awareness of vaccine schedules, precautions, and contraindications.

Study design: Annual Advisory Committee on Immunization Practices (ACIP) review.

Setting: Data from 2011 National Health Interview Survey.

Synopsis: Highlighted changes include: 1) a single dose of pneumococcal 13-valent conjugate (PCV13) vaccine is now recommended for all individuals over the age of 19 with qualifying conditions; 2) clarification regarding pneumococcal polysaccharide (PPSV23) vaccine illustrates that high-risk individuals will receive up to three doses (one or two doses prior to age 65, plus an additional dose after the age of 65); 3) one dose of tetanus, diphtheria, and acellular pertussis (Tdap) vaccine is now recommended for all adults, including individuals age >65; 4) pregnant woman are advised to receive Tdap between 27 and 36 weeks’ gestation, with each pregnancy to provide protection to their newborn in the first months of life; 5) quadrivalent formulations of the live attenuated influenza vaccine (LAIV) and most likely the inactivated influenza vaccine (IIV) will be available in the 2013-2014 influenza season to increase cross-reactive protection against influenza B; and 6) both injection and noninjection illicit drug users are recommended to receive hepatitis A vaccine.

Bottom line: Expanded recommendations for adult immunization provide more opportunities for the practicing hospitalist to improve vaccine capture.

Citation: Advisory Committee on Immunization Practices. Recommended adult immunization schedule: United States, 2013. Ann Int Med. 2013;158(3):191-199.

In This Edition

Literature At A Glance

A guide to this month’s studies

1. BNP-driven fluid management to improve ventilator weaning
2. Examining 30-day readmission patterns to reduce repeat hospitalizations
3. Impact of hospitalists’ workload on patient safety, care
4. Permanent atrial fibrillation is best controlled by diltiazem
5. Low-dose thrombolysis effective for pulmonary embolism
6. High mortality rate seen in surgical patients requiring CPR
7. ED visits common for acute-care patients post-discharge
8. Restrictive transfusion strategies effective for upper GI bleeding
9. Need for non-ICU acid suppression may be predictable
10. Recommended changes for adult immunizations

BNP-Driven Fluid Management Improves Ventilator Weaning

Clinical question: Does fluid management guided by daily plasma natriuretic peptide-driven (BNP) levels in mechanically ventilated patients improve weaning outcomes compared with usual therapy dictated by clinical acumen?

Background: Ventilator weaning contributes at least 40% of the total duration of mechanical ventilation; strategies aimed at optimizing this process could provide substantial benefit. Previous studies have demonstrated that BNP levels prior to ventilator weaning independently predict weaning failure. No current objective practical guide to fluid management during ventilator weaning exists.

Study design: Randomized controlled trial.

Setting: Multiple international centers.

Synopsis: In a multicenter randomized controlled trial, 304 patients who met specific inclusion and exclusion criteria were randomized to either a BNP-driven or physician-guided strategy for fluid management during ventilator weaning. Patients with renal failure were excluded because of the influence of renal function on BNP levels.

All patients in both groups were ventilated with an automatic computer-driven weaning system to standardize the weaning process. In the BNP-driven group, diuretic use was higher, resulting in a more negative fluid balance and significantly shorter time to successful extubation (58.6 hours vs. 42.2 hours, P=0.03). The effect on weaning time was strongest in patients with left ventricular systolic dysfunction, whereas those with COPD seemed less likely to benefit. The two groups did not differ in baseline characteristics, length of stay, mortality, or development of adverse outcomes of renal failure, shock, or electrolyte disturbances.

Bottom line: Compared with physician-guided fluid management, a BNP-driven fluid management protocol decreased duration of ventilator weaning without significant differences in adverse events, mortality rate, or length of stay between the two groups.

Citation: Dessap AM, Roche-Campo F, Kouatchet A, et al. Natriuretic peptide-driven fluid management during ventilator weaning. Am J Respir Crit Care Med. 2012;186(12):1256-1263.

30-Day Readmission Patterns for MI, Heart Failure, Pneumonia

Clinical question: Do patterns exist among patients readmitted within 30 days of discharge for acute myocardial infarction (AMI), heart failure, or pneumonia that could provide insight for improving strategies aimed at reducing readmission rates?

Background: Examining readmission timing, diagnoses, and patient demographics might provide information to better guide post-discharge programs aimed at reducing overall readmissions.

Study design: Retrospective review of Centers for Medicare & Medicaid Services (CMS) data.

Setting: Acute-care hospitals.

Synopsis: Using CMS hospitalization data for principal diagnoses of AMI, heart failure, or pneumonia from 2007 through 2009, the authors examined the percentage of 30-day readmissions occurring on each day after discharge; the most common readmission diagnoses; the median time to readmission for common readmission diagnoses; and the relationship between patient demographic characteristics, readmission diagnoses, and timing. They found total readmission rates of 24.8% for heart failure, 19.9% for AMI, and 18.3% for pneumonia. Approximately two-thirds of 30-day readmissions occurred within the first 15 days after discharge for each cohort. Neither readmission diagnoses nor timing varied by patient age, sex, or race.

Although the majority of readmissions do occur soon after discharge, it is important to note that about one-third of all readmissions occur 16 to 30 days after discharge. There also was a diverse spectrum of readmission diagnoses that were not associated with patient demographic characteristics. These findings suggest that current post-discharge strategies aimed at specific diseases or time periods might only address a fraction of the patients at risk for readmission.

Bottom line: Among Medicare patients hospitalized for heart failure, AMI, or pneumonia, 30-day readmissions were frequent throughout the entire period, and readmission diagnoses or timing did not vary by patient age, sex, or race.

Citation: Dharmarajan K, Hsich AF, Lin Z, et al. Diagnosis and timing of 30-day readmissions after hospitalization for heart failure, acute myocardial infarction, or pneumonia. JAMA. 2013;309(4):355-363.

Workload Might Impact Patient Safety and Quality of Care

Clinical question: Do hospitalists’ workloads affect patient quality of care and safety?

Background: Preventable medical errors contribute to a large number of patient deaths each year. It is unclear if a hospitalist’s clinical workload affects rates of medical errors or patient harm.

Study design: Cross-sectional cohort study.

Setting: Hospitalists enrolled in online physician community QuantiaMD.com.

Synopsis: There has been limited research evaluating the correlation between physician workload and patient safety. An online survey compared the responses of 506 out of 890 enrolled physicians on the impact of average patient census and several outcome measures of quality of care. Some 40% reported that their patient census exceeded their personal safe workload at least once a month. They also reported that less time for patient evaluations led to fewer discussions with patients and family members, more unnecessary medical work-ups, and lower patient satisfaction.

A limitation of this study is that this electronic survey had the potential for selection bias. It also only measured perceptions of safety and quality, and only used standard daytime shifts (excluding night, cross-cover, weekend, and holiday shifts), which might have been associated with significantly different conclusions.

Bottom line: Increase in workload has a negative perceived impact on patient safety and quality of care for attending hospitalists.

Citation: Michtalik HJ, Yeh HC, Pronovost P, et. al. Impact of attending physician workload on patient care: a survey of hospitalists. JAMA Intern Med. 2013;173(5):375-377.

Permanent Atrial Fibrillation Best Controlled by Diltiazem

Clinical question: Is there a difference between beta-blockers and calcium channel blockers for ventricular rate control and arrhythmia-related symptoms in patients with permanent atrial fibrillation?

Background: Rate control with beta-blockers or calcium channel blockers is recommended for the initial therapy of atrial fibrillation. However, studies comparing those drug classes or drugs within them are lacking.

Study design: Prospective, randomized, investigator-blind crossover study.

Setting: Majority of patients from an atrial fibrillation outpatient clinic at Baerum Hospital in Norway.

Synopsis: The RATe Control in Atrial Fibrillation (RATAF) study included 60 participants with permanent atrial fibrillation. The goal of the study was to compare the efficacy of diltiazem at 360 mg/day, verapamil at 240 mg/day, metoprolol at 100 mg/day, and carvedilol at 25mg/day on ventricular heart rate and related symptoms in atrial fibrillation. Patients had a mean age of 71, atrial fibrillation for more than three months, and mean heart rate of 96 beats/minute. Exclusion criteria included the presence of congestive heart failure or ischemic heart disease with the need for other medications that could compromise the study.

From this study, diltiazem was shown to have the greatest effect in lowering heart rate, and those patients taking this medication had decreased symptoms related to atrial fibrillation. Hospitalists should not rely solely on this study for their treatment choice in all atrial fibrillation patients, but in certain populations, they should consider diltiazem as their first-line drug.

Bottom line: Diltiazem was shown to have the greatest reduction in heart rate and symptoms related to permanent atrial fibrillation.

Citation: Ulimoen SR, Enger S, Carlson J, et al. Comparison of four single-drug regimens on ventricular rate and arrhythmia-related symptoms in patients with permanent atrial fibrillation. Am J Cardiol. 2013:111(2):225-230.

Low-Dose Thrombolysis Effective in Moderate Pulmonary Embolism

Clinical question: Can low-dose tissue plasminogen activator (tPA) help reduce pulmonary artery pressure in those with moderate pulmonary embolism (PE)?

Background: Studies have shown full-dose thrombolysis can effectively decrease pulmonary artery pressure in patients with massive PE. However, there are limited data regarding low-dose or “safe dose” thrombolytic therapy and its effect on pulmonary artery pressure.

Study design: Prospective, controlled, randomized study.

Setting: Single center.

Synopsis: The Moderate Pulmonary Embolism Treated with Thrombolysis (MOPETT) study enrolled patients with moderate PE, defined as signs and symptoms of PE plus computed tomographic pulmonary angiographic involvement of > 70% involvement of thrombus in ≥2 lobar or left/right main pulmonary arteries or high probability ventilation/perfusion scan (mismatch in ≥2 lobes). Patients in the thrombolysis group (n=61) were given low-dose tPA (100 mg tPA) and anticoagulation vs. the control group (n=60), which received only anticoagulation.

The study ran for 22 months, and the primary end points were pulmonary hypertension and recurrent PE. After analysis, low-dose thrombolysis was shown to significantly decrease pulmonary artery pressure and occurrence of recurrent PE compared to the control group.

This study demonstrates that, while the decision to use thrombolytics should always be made cautiously, hospitalists can consider low-dose thrombolysis in patients with moderate PE.

Bottom line: Low-dose thrombolysis, in addition to anticoagulation, in patients with moderate PE decreases pulmonary hypertension and recurrent PE.

Citation: Sharifi M, Bay C, Skrocki L, Rahimi F, Mehdipour M. Moderate pulmonary embolism treated with thrombolysis (from the “MOPETT” trial). Am J Cardiol. 2013;111(2):273-277.

High Mortality in Surgical Patients Requiring CPR

Clinical question: What are the incidence, characteristics, and 30-day-outcomes of CPR in surgical patients?

Background: Most studies of CPR are based on the medical population, and little is known about the utilization, risk factors, and outcomes of CPR in surgical patients.

Study design: Retrospective cohort study.

Setting: Two hundred fifty U.S. hospitals in the American College of Surgeons’ National Surgical Quality Improvement Program.

Synopsis: A total of 1.3 million surgical cases were studied in the data set. The overall incidence was 1 event per 203 cases. Most patients (77.6%) experienced a complication and did so on or before the day of CPR in three-fourths of cases. The incidence of CPR was the highest for cardiac surgery patients. Patients who received CPR had a mortality rate of 71.6%. Mortality rates of CPR patients increased with more comorbidities.

Additionally, older age and an American Society of Anesthesiologists (ASA) class of 5 was associated with higher mortality.

Limitations of this study included coding flaws in data collection, lack of capture of resuscitation-related injuries, and failure to account for changes in DNR orders.

Hospitalists should be mindful of risk factors contributing to CPR in surgical patients when performing perioperative evaluations.

Bottom line: Surgical patients who experience CPR have a high mortality rate, but many of these patients have pre-arrest complications that can be preventable.

Citation: Kazaure HS, Roman SA, Rosenthal RA, Sosa, JA. Cardiac arrest among surgical patients. JAMA Surg. 2013;148(1):14-21.

Emergency Department Visits are Frequent Post-Discharge

Clinical question: What role do ED visits contribute to the overall use of acute-care services within 30 days of hospital discharge?

Background: Hospital readmissions within 30 days of discharge are a marker of the quality of care and reflect the effectiveness of the discharge process. ED visits are also a marker of hospital-based acute care following discharge, but little is known about the role of the ED during the post-discharge period.

Study design: Prospective study.

Setting: Acute-care hospitals in California, Florida, and Nebraska.

Synopsis: Using the Healthcare Cost and Utilization Project state inpatient and ED databases, all discharges between July 1, 2008, and Sept. 31, 2009, were evaluated for residents aged 18 years or older from three hospitals in three states. After exclusions, 5 million index hospitalizations among 4 million unique patients were studied.

Approximately 40% of the more than 1 million post-discharge acute-care encounters involved a visit to the ED.

Limitations of this study include that the data was derived from only three states, and only hospital-based acute-care visits were measured (i.e. visits to physician offices were not included). As hospitalists, we are responsible for discharges and care transitions. Being sensitive to the common medical conditions resulting in post-discharge ED encounters might improve care transitions.

Bottom line: Hospital readmission rates underestimate ED use following discharge.

Citation: Vashi AA, Fox JP, Carr BG, et al. Use of hospital-based acute care among patients recently discharged from the hospital. JAMA. 2013;309(4):364-371.

Restrictive Transfusion Strategy Beneficial in Upper GI Bleeding

Clinical question: What is the hemoglobin threshold for transfusion of red cells in patients with acute upper GI bleeding?

Background: Controlled trials have shown that restrictive transfusion strategies (Hgb<7) are as effective as liberal transfusion strategies (Hgb<9) in critically ill patients. These studies have excluded patients with GI bleeding. In cases for which GI is not severe, the safest transfusion strategy is controversial.

Study design: Single-center study at Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.

Synopsis: A total of 921 adult patients with acute upper GI bleeding were enrolled and assigned: 461 to a restrictive transfusion strategy (hemoglobin<7) and 460 to a liberal strategy (hemoglobin<9). Patients with massive exsanguinating bleeding, acute coronary syndrome, peripheral vasculopathy, stroke, transient ischemic attack, lower GI bleed, recent trauma or surgery, or low risk of rebleeding were excluded. The primary outcome measure was the rate of death from any cause within the first 45 days.

Secondary outcomes included the rate of further bleeding and the rate of in-hospital complications.

Statistically significant benefit in following a restrictive versus liberal strategy was demonstrated in all major outcomes: mortality (5% vs, 9%, P=0.02), rate of further bleeding (10% vs 18%, P=0.01), and rate of complications (40% vs. 48%, P=0.02).

The study is limited by its inability to be generalized to all patients with acute GI bleeding, as patients with massive exsanguinating bleeds and those with low risk of rebleeding were excluded.

Bottom line: Restrictive transfusion (Hgb<7) significantly improved outcomes for patients with acute upper GI bleeding.

Citation: Villanueva C, Colomo A, Bosch A, et al. Transfusion strategies for acute upper gastrointestinal bleeding. N Engl J Med. 2013;368(1):11-21.

Need for Non-ICU Acid Suppression Might Be Predictable

Clinical question: What are the risk factors for nosocomial bleeding in non-critically-ill patients?

Background: Acid-suppressive medication has been shown to reduce the incidence of nosocomial GI bleed in the ICU, but current guidelines recommend against its use in non-critically-ill patients. However, a subgroup of these patients might possess a high enough risk for GI bleed that prophylaxis is warranted.

Study design: Cohort study.

Setting: Academic medical center in Boston.

Synopsis: A total of 75,723 admissions of adult patients hospitalized for three or more days were included. Exclusion criteria included primary discharge diagnosis of GI bleed; principal procedure code of cardiac catheterization; and bleeding episodes occurring while in the ICU or within 48 hours of transfer out of the ICU. The primary outcome was nosocomial GI bleed (>24 hours after admission) occurring outside the ICU.

Nosocomial GI bleeding occurred in 203 patients (0.27%). Independent risk factors for bleeding included age >60, male sex, liver disease, acute renal failure, sepsis, being on a medicine service, prophylactic anticoagulation, and coagulopathy. Based on the data, a scoring system was created that identified a high-risk group in whom the number needed to treat with acid-suppressive medication to prevent one bleed was 48.

The major limitations of this study are its observational nature and the need for validation of the proposed scoring system.

Bottom line: Risk for nosocomial GI bleeding appears predictable and supports the selective use of prophylactic acid suppression in non-critically-ill patients.

Citation: Herzig SJ, Rothberg MB, Feinbloom DB, et al. Risk factors for nosocomial gastrointestinal bleeding and use of acid-suppressive medication in non-critically ill patients. J Gen Intern Med. 2013; January 5. [Epub ahead of print].

Additions, Modifications, and Clarifications Regarding Adult Immunization

Clinical question: What are the changes to the recommended Adult Immunization Schedule for 2013?

Background: Despite the known public health benefits of immunization, adult vaccination rates remain low. The positive impact of strong provider recommendations regarding vaccines underscores the importance of provider awareness of vaccine schedules, precautions, and contraindications.

Study design: Annual Advisory Committee on Immunization Practices (ACIP) review.

Setting: Data from 2011 National Health Interview Survey.

Synopsis: Highlighted changes include: 1) a single dose of pneumococcal 13-valent conjugate (PCV13) vaccine is now recommended for all individuals over the age of 19 with qualifying conditions; 2) clarification regarding pneumococcal polysaccharide (PPSV23) vaccine illustrates that high-risk individuals will receive up to three doses (one or two doses prior to age 65, plus an additional dose after the age of 65); 3) one dose of tetanus, diphtheria, and acellular pertussis (Tdap) vaccine is now recommended for all adults, including individuals age >65; 4) pregnant woman are advised to receive Tdap between 27 and 36 weeks’ gestation, with each pregnancy to provide protection to their newborn in the first months of life; 5) quadrivalent formulations of the live attenuated influenza vaccine (LAIV) and most likely the inactivated influenza vaccine (IIV) will be available in the 2013-2014 influenza season to increase cross-reactive protection against influenza B; and 6) both injection and noninjection illicit drug users are recommended to receive hepatitis A vaccine.

Bottom line: Expanded recommendations for adult immunization provide more opportunities for the practicing hospitalist to improve vaccine capture.

Citation: Advisory Committee on Immunization Practices. Recommended adult immunization schedule: United States, 2013. Ann Int Med. 2013;158(3):191-199.