Mel L. Anderson, MD

In This Edition

Literature At A Glance

A guide to this month’s studies

1. Higher loading dose of clopidogrel in STEMI
2. Early vs. late surgery following hip fracture
3. Beta-blockers in chronic kidney disease
4. Long-term azithromycin in COPD
5. CT screening for lung cancer
6. Timing of parenteral nutrition in the ICU
7. Intrapleural management of empyema with DNase and t-PA
8. Effect of weekend elective admissions on hospital flow
9. Expectations and outcomes of medical comanagement

Higher-Dose Clopidogrel Improves Outcomes at 30 Days in STEMI Patients

Clinical question: Does a 600-mg loading dose of clopidogrel given before percutaneous coronary intervention (PCI) in patients with an ST-segment elevation myocardial infarction (STEMI) provide more protection from thrombotic complications at 30 days than a 300-mg dose?

Background: Clopidogrel at 600 mg is active more quickly (two hours versus 12 hours) and inhibits platelets more completely than does a 300-mg dose, but it has never been tested prospectively in patients undergoing percutaneous intervention with a STEMI.

Study design: Prospective, multicenter, randomized controlled trial.

Setting: Five hospitals in Italy, Belgium, Serbia, and Hungary.

Synopsis: Two-hundred-one patients with STEMI were randomized to either 600 mg or 300 mg of clopidogrel, given an average of 30 minutes before initial PCI, as well as other standard treatment for STEMI. The primary outcome was “infarct size,” judged as the area under the curve (AUC) of serial creatine kinase-MB (CK-MB) and troponin measurements. At 30 days, patients who received the 600-mg dose of clopidogrel had lower AUCs of cardiac biomarkers, statistically significant (though clinically small) improvement in left ventricle ejection fraction at discharge, lower incidence of severely impaired post-PCI thrombolitis in myocardial infarction (TIMI) flow, and fewer “major cardiovascular events,” driven mainly by a reduction in revascularizations. Measurement of biomarkers to calculate infarct size can be confounded by hypertrophy, and the trial was underpowered for cardiovascular events. However, there was no increase in bleeding events.

Bottom line: In patients with STEMI, treatment with a higher loading dose of clopidogrel before PCI reduces revascularizations and might decrease infarct size without an increase in adverse events.

Citation: Patti G, Bárczi G, Orlic D, et al. Outcome comparison of 600- and 300-mg loading doses of clopidogrel in patients undergoing primary percutaneous coronary intervention for ST-segment elevation myocardial infarction: results from the ARMYDA-6 MI (Antiplatelet therapy for Reduction of MYocardial Damage during Angioplasty-Myocardial Infarction) randomized study. J Am Coll Cardiol. 2011;58:1592-1599.

Medical Comorbidities Explain Most of Excess Risk Seen in Patients with Delayed Hip Fracture Repair

Clinical question: Could the increased mortality found with delays in hip fracture surgery be confounded by the premorbid functional status and medical comorbidities of patients whose surgery is more likely to be delayed?

Background: Guidelines recommend operating on patients with hip fracture within 24 hours, but the supporting evidence has not adjusted for underlying medical comorbidities, which could delay surgery and contribute to poor outcomes, making delays look harmful.

Study design: Prospective cohort, single-center design.

Setting: University hospital in Spain.

Synopsis: The study included 2,250 consecutive elderly patients admitted to the hospital for hip fracture who had their functional status and medical comorbidities assessed at enrollment. If their surgery was delayed beyond 24 hours, the reason was sought. Medical outcomes assessed daily while in hospital were delirium, pneumonia, heart failure, urinary tract infection, and new pressure sores, while the dose of pain medication, surgical complications, and in-hospital mortality were also compiled. No post-discharge data were available.

The median time to surgery was 72 hours. Patients with more medical comorbidities and poorer preoperative functional status had longer delays to operation, most commonly due to interrupting antiplatelet treatment or need for preoperative “echocardiography or other examinations.” When these medical factors were included in logistic regression analysis, the increased mortality seen with delays of surgery in the cohort was no longer statistically significant, suggesting the underlying comorbidities of these patients, rather than the delay to surgery itself, explained the increased mortality.

Bottom line: Delaying hip fracture surgery is less important than preoperative functional status and medical comorbidity in contributing to poor outcomes.

Citation: Vidán MT, Sánchez E, Gracia Y, Marañón E, Vaquero J, Serra JA. Causes and effects of surgical delay in patients with hip fracture: a cohort study. Ann Intern Med. 2011;155:226-233.

Beta-Blockers Decrease All-Cause and Cardiovascular Mortality in Patients with Chronic Kidney Disease

Clinical question: Are beta-blockers as effective in patients on dialysis and with end-stage chronic kidney disease (CKD) as they are in patients without severe renal disease?

Background: Patients with CKD have been largely excluded from trials of beta-blocker therapy even though they have high rates of cardiovascular disease and might be most likely to benefit. However, patients on dialysis might be predisposed to adverse complications of beta-blocker therapy, including hypotension.

Study design: Meta-analysis of eight trials of beta-blockade versus placebo (six heart failure trials) or ACE-I (two non-heart-failure trials) that included post-hoc analyses of CKD patients.

Setting: Varied, usually multinational RCTs.

Synopsis: The six congestive heart failure (CHF) studies were not designed to evaluate patients with CKD, and the two non-CHF studies were intended to evaluate progression of CKD, not cardiac outcomes. Thus, this is a meta-analysis of post-hoc CKD subgroups included in these trials. Compared with placebo, beta-blockers reduced all-cause and cardiovascular mortality without significant heterogeneity between trials. The magnitude of the effect was similar in CKD and non-CKD patients. Patients with CKD treated with beta-blockers were at increased risk of bradycardia and hypotension, but this did not lead to increased discontinuation of the drug. Only 114 dialysis patients were included in one of the eight trials (7,000 patients overall) and no outcomes were assessed.

Bottom line: Beta-blockers lower all-cause and cardiovascular mortality in patients with CKD similarly to patients without kidney disease but are associated with an increased risk for hypotension and bradycardia. Their effect in dialysis patients is unknown.

Citation: Badve SV, Roberts MA, Hawley CM, et al. Effects of beta-adrenergic antagonists in patients with chronic kidney disease: a systematic review and meta-analysis. J Am Coll Cardiol. 2011;58:1152-1161.

Daily Long-Term Azithromycin in COPD Patients Decreases Frequency of Exacerbations

Clinical question: Does long-term treatment with azithromycin decrease COPD exacerbations and improve quality of life with an acceptable risk profile?

Background: Patients with acute exacerbations of COPD have increased risks of death and more rapid decline in lung function. Macrolide antibiotics might decrease exacerbations via antibacterial and anti-inflammatory effects. Small studies of long-term treatment with macrolides in COPD have had conflicting results.

Study design: Prospective, multicenter, parallel-group, placebo-controlled trial.

Setting: Twelve U.S. academic health centers.

Synopsis: Eligible patients were those older than 40 with pulmonary function test-proven obstructive disease, a significant smoking history, a use of supplemental oxygen, or an oral glucocorticoid treatment in the previous year, and those who had previously come to healthcare attention for a COPD exacerbation. They were randomized to daily azithromycin (250 mg) or placebo. The primary outcome was time to first COPD exacerbation at one year. The investigators used deep nasopharyngeal swabs to evaluate the development of microbial resistance, and all patients were regularly screened for hearing loss. Time to first exacerbation and frequency of exacerbations decreased significantly with azithromycin treatment; the number needed to treat to prevent a COPD exacerbation was 2.86. More than half of nasopharyngeal samples had evidence of macrolide resistance at enrollment, and this increased to more than 80% at one year. Audiometric testing did show a decrease in hearing in those treated with azithromycin, but even those who did not stop their medication had recovery on subsequent testing.

Bottom line: Daily azithromycin decreases COPD exacerbations in those with a history of previous exacerbation at the cost of increased macrolide resistance and possible reversible decrements in hearing. The high degree of macrolide resistance at enrollment suggests non-antibacterial mechanisms might be responsible.

Citation: Albert RK, Connett J, Bailey WC, et al. Azithromycin for prevention of exacerbations of COPD. N Engl J Med. 2011;365:689-698.

Serial Low-Dose CT Scans Decrease Lung Cancer Mortality

Clinical question: Does annual screening with low-dose CT scans reduce mortality from lung cancer in current or former heavy smokers?

Background: Lung cancer is still the top cause of cancer death in the United States, and its prevalence is increasing in the developing world. Prior trials of screening chest radiography and sputum samples have not shown a decrease in lung cancer mortality, but CT scans could help identify lung cancer at an earlier, more treatable stage.

Study design: Prospective, multicenter, randomized trial of low-dose (roughly one-fifth the radiation of traditional CT) annual CT versus annual chest radiography.

Setting: Thirty-three U.S. medical institutions.

Synopsis: The study enrolled 53,454 current or prior smokers with a history of smoking more than 30 packs a year who were randomly assigned to undergo three annual CT scans or chest X-rays. Any CT scans that showed a noncalcified nodule greater than 4 mm and chest X-rays that showed a noncalcified nodule or mass of any size were classified as “positive,” but follow-up was left to the discretion of the treating physicians. Participants were followed for 6.5 years on average.

Of those screened with CT, 40% had a positive screening test at some point, more than three times the rate of chest radiography, and 96.4% of these were false-positives, which was similar to chest radiography. Adverse events as a result of workup of eventual false positives were uncommon, occurring in around 1% of those who did not have lung cancer and in 11% of those who did. Screening reduced lung cancer mortality by 20% compared with chest radiography, with a number needed to screen to prevent one lung cancer death of 320. Cost-effectiveness and effects of radiation were not assessed.

Bottom line: Serial screening with low-dose CT reduces lung cancer mortality at the cost of a high rate of false-positives. Questions remain about cost-effectiveness and radiation exposure.

Citation: National Lung Screening Trial Research Team, Aberle DR, Adams AM, Berg CD, et al. Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med. 2011;365:395-409.

One-Week Delay in Starting Parenteral Nutrition in ICU Patients Is Associated with Better Outcomes

Clinical question: In patients admitted to the ICU who are at risk for malnutrition, does supplementing enteral feeding with parenteral feeding on the day of admission improve outcomes when compared with supplementation starting on Day 8?

Background: Patients with critical illness are at risk for malnutrition, which may lead to worsened outcomes. Many are unable to tolerate enteral feeding. However, adding parenteral nutrition has risks, including overfeeding and hyperglycemia.

Study design: Prospective, multicenter, randomized controlled trial. Neither patients/families nor ICU physicians were blinded.

Setting: Two university hospitals in Belgium.

Synopsis: The study included 4,640 patients admitted to the ICU who were “at risk” for malnutrition (assessed using a Nutritional Risk Score of >3). They were randomized to early initiation of parenteral nutrition on Day 1 or late initiation of parenteral nutrition on Day 8, in both cases only if needed to supplement enteral feeding. Both groups received intensive IV insulin protocols to keep blood glucose at 80 mg/dL to 110 mg/dL. The study populations were well-matched, with similar APACHE II scores. Of the total patients, 42% were emergency admissions to the ICU (more than half of which had sepsis), while scheduled cardiac surgery patients made up the majority of the rest of the study participants.

Patients with late initiation of total parenteral nutrition (TPN) were more likely to be discharged alive from the ICU within eight days despite having increased risk of hypoglycemia and more elevation of inflammatory markers. They had shorter ICU and hospital stays, fewer days on the ventilator, fewer infectious complications, were less likely to develop renal failure, and had lower overall costs. The unblinded management of these patients raises concern in interpreting infectious outcomes because study investigators could have been biased to look for infection more often in the early initiation group.

Bottom line: In ICU patients at risk for malnutrition, delaying initiation of TPN to supplement enteral feeding shortens ICU stay and reduces infectious complications when compared with early initiation of TPN.

Citation: Casaer MP, Mesotten D, Hermans G, et al. Early versus late parenteral nutrition in critically ill adults. N Engl J Med. 2011;365:506-17.

Intrapleural Instillation of Combined DNase and t-PA Improve Outcomes in Patients with Empyema

Clinical question: Does the intrapleural administration of a fibrinolytic, a recombinant DNase, or a combination of the two improve outcomes in patients with pleural infections compared with placebo?

Background: Pleural-based infections confer high morbidity and mortality, especially in the one-third of cases in which chest tube drainage fails. Observational data suggest intrapleural administration of fibrinolytics can improve drainage; however, a large randomized trial (MIST1) failed to show improvement with streptokinase.

Study design: Randomized, double-blind, double-dummy, factorial, multicenter trial.

Setting: University hospitals in the U.K.

Synopsis: A total of 193 patients with clinical evidence of an infection as well as laboratory evidence of pleural infection were randomized in factorial design to placebo, DNase alone, t-PA alone, and DNase plus t-PA as a twice-daily, hourlong instillation into the pleural space on hospital days 1 through 3. The combination group had improvements in the size of the pleural effusion compared with placebo, the primary endpoint. This group also was less likely to be referred for surgery, had shorter hospital stays, had less fever, and had lower inflammatory markers by hospital Day 7. Neither of the single-agent groups were better than placebo. The confidence intervals for all outcomes besides radiographic size of the effusion were large, as the trial had limited power for secondary endpoints.

Bottom line: In patients with empyema, the addition of twice-daily instillations of DNase and tPA can improve drainage and decrease risk of treatment failure when combined with chest tube drainage and antibiotics.

Citation: Rahman NM, Maskell NA, West A, et al. Intrapleural use of tissue plasminogen activator and DNase in pleural infection. N Engl J Med. 2011;365:518-526.

Smoothing Admissions over the Week Improves Patient Flow

Clinical question: What is the difference between weekday and weekend hospital occupancy, and what might the effect be of redistributing, or “smoothing,” elective admissions across the week?

Background: Efforts to improve patient flow have largely focused on reducing the average length of stay (ALOS). As the ALOS decreases, though, further reductions have limited yield in improving patient flow and could occur at the expense of patient safety. Smoothing admissions is a recognized but underutilized tool to address patient flow and hospital overcrowding.

Study design: Retrospective cohort.

Setting: Thirty-nine freestanding, tertiary-care children’s hospitals in the U.S.

Synopsis: Hospital occupancy ranged from 70.9% to 108.1% for weekdays, and from 65.7% to 94.4% on weekends. The mean difference between weekday and weekend occupancy was 8.2%. Using a mathematical model to redistribute admissions from peak days to nonpeak days (within a one-week time frame), the investigators found that percent occupancy on average dropped by 6.6%—the same number of patients over the same time interval, but with lower average occupancy. And, while not projected by these authors, the correlate of lower average occupancy would be reduced waits and delays for admission and within-hospital services. Only 2.6%, or about 7.5 admissions per week per hospital, would need to be rescheduled in order to realize this gain.

Bottom line: Where feasible, reshuffling elective admissions to “smooth” demand across the week is associated with improved hospital flow.

Citation: Fieldston ES, Hall M, Shah SS, et al. Addressing inpatient crowding by smoothing occupancy at children’s hospitals. J Hosp Med. 2011;6:466-473.

Variability in Preferences, Experiences, and Expectations for Hospitalist Roles in Comanagement

Clinical question: Do provider expectations and experiences in comanagement differ from the traditional medical consultation model?

Background: Hospitalists participate in traditional medical consultation and, increasingly, a variety of comanagement with surgical and various medical specialists. It is uncertain what preferences and expectations on either side of the comanagement relationship might be. Learning more might lead to a better conceptual understanding and working definition of inpatient comanagement.

Study design: Baseline and follow-up surveys.

Setting: Large single-site academic medical center, hospitalist-hepatologist comanagement service.

Synopsis: All 41 respondents completed the baseline survey, with 32 respondents completing a total of 177 follow-up surveys. Respondents included hospitalists, hepatologists, nonphysician providers (NPPs), and GI fellows. Hospitalists were more likely than hepatologists to want to be informed about every patient care decision (83% versus 17%). The majority of respondents reported understanding their roles. At baseline, nearly all agreed that “comanagement tends to improve patient care.” However, at follow-up, fewer NPP and fewer GI fellows reported that patients on their service had received “better care than they would without comanagement.” At follow-up, fewer hospitalists than at baseline reported that there was one “physician leader to direct the overall management of the patient’s hospital course.”

Bottom line: Hospitalists were more likely than hepatologists, within a comanagement relationship, to want to be informed about every decision. Most expected—but fewer actually later reported—that the comanagement model improved patient care.

Citation: Hinami K, Whelan CT, Konetzka RT, and Meltzer DO. Provider expectations and experiences of comanagement. J Hosp Med. 2011;6:401-404.

In This Edition

Literature At A Glance

A guide to this month’s studies

1. Higher loading dose of clopidogrel in STEMI
2. Early vs. late surgery following hip fracture
3. Beta-blockers in chronic kidney disease
4. Long-term azithromycin in COPD
5. CT screening for lung cancer
6. Timing of parenteral nutrition in the ICU
7. Intrapleural management of empyema with DNase and t-PA
8. Effect of weekend elective admissions on hospital flow
9. Expectations and outcomes of medical comanagement

Higher-Dose Clopidogrel Improves Outcomes at 30 Days in STEMI Patients

Clinical question: Does a 600-mg loading dose of clopidogrel given before percutaneous coronary intervention (PCI) in patients with an ST-segment elevation myocardial infarction (STEMI) provide more protection from thrombotic complications at 30 days than a 300-mg dose?

Background: Clopidogrel at 600 mg is active more quickly (two hours versus 12 hours) and inhibits platelets more completely than does a 300-mg dose, but it has never been tested prospectively in patients undergoing percutaneous intervention with a STEMI.

Study design: Prospective, multicenter, randomized controlled trial.

Setting: Five hospitals in Italy, Belgium, Serbia, and Hungary.

Synopsis: Two-hundred-one patients with STEMI were randomized to either 600 mg or 300 mg of clopidogrel, given an average of 30 minutes before initial PCI, as well as other standard treatment for STEMI. The primary outcome was “infarct size,” judged as the area under the curve (AUC) of serial creatine kinase-MB (CK-MB) and troponin measurements. At 30 days, patients who received the 600-mg dose of clopidogrel had lower AUCs of cardiac biomarkers, statistically significant (though clinically small) improvement in left ventricle ejection fraction at discharge, lower incidence of severely impaired post-PCI thrombolitis in myocardial infarction (TIMI) flow, and fewer “major cardiovascular events,” driven mainly by a reduction in revascularizations. Measurement of biomarkers to calculate infarct size can be confounded by hypertrophy, and the trial was underpowered for cardiovascular events. However, there was no increase in bleeding events.

Bottom line: In patients with STEMI, treatment with a higher loading dose of clopidogrel before PCI reduces revascularizations and might decrease infarct size without an increase in adverse events.

Citation: Patti G, Bárczi G, Orlic D, et al. Outcome comparison of 600- and 300-mg loading doses of clopidogrel in patients undergoing primary percutaneous coronary intervention for ST-segment elevation myocardial infarction: results from the ARMYDA-6 MI (Antiplatelet therapy for Reduction of MYocardial Damage during Angioplasty-Myocardial Infarction) randomized study. J Am Coll Cardiol. 2011;58:1592-1599.

Medical Comorbidities Explain Most of Excess Risk Seen in Patients with Delayed Hip Fracture Repair

Clinical question: Could the increased mortality found with delays in hip fracture surgery be confounded by the premorbid functional status and medical comorbidities of patients whose surgery is more likely to be delayed?

Background: Guidelines recommend operating on patients with hip fracture within 24 hours, but the supporting evidence has not adjusted for underlying medical comorbidities, which could delay surgery and contribute to poor outcomes, making delays look harmful.

Study design: Prospective cohort, single-center design.

Setting: University hospital in Spain.

Synopsis: The study included 2,250 consecutive elderly patients admitted to the hospital for hip fracture who had their functional status and medical comorbidities assessed at enrollment. If their surgery was delayed beyond 24 hours, the reason was sought. Medical outcomes assessed daily while in hospital were delirium, pneumonia, heart failure, urinary tract infection, and new pressure sores, while the dose of pain medication, surgical complications, and in-hospital mortality were also compiled. No post-discharge data were available.

The median time to surgery was 72 hours. Patients with more medical comorbidities and poorer preoperative functional status had longer delays to operation, most commonly due to interrupting antiplatelet treatment or need for preoperative “echocardiography or other examinations.” When these medical factors were included in logistic regression analysis, the increased mortality seen with delays of surgery in the cohort was no longer statistically significant, suggesting the underlying comorbidities of these patients, rather than the delay to surgery itself, explained the increased mortality.

Bottom line: Delaying hip fracture surgery is less important than preoperative functional status and medical comorbidity in contributing to poor outcomes.

Citation: Vidán MT, Sánchez E, Gracia Y, Marañón E, Vaquero J, Serra JA. Causes and effects of surgical delay in patients with hip fracture: a cohort study. Ann Intern Med. 2011;155:226-233.

Beta-Blockers Decrease All-Cause and Cardiovascular Mortality in Patients with Chronic Kidney Disease

Clinical question: Are beta-blockers as effective in patients on dialysis and with end-stage chronic kidney disease (CKD) as they are in patients without severe renal disease?

Background: Patients with CKD have been largely excluded from trials of beta-blocker therapy even though they have high rates of cardiovascular disease and might be most likely to benefit. However, patients on dialysis might be predisposed to adverse complications of beta-blocker therapy, including hypotension.

Study design: Meta-analysis of eight trials of beta-blockade versus placebo (six heart failure trials) or ACE-I (two non-heart-failure trials) that included post-hoc analyses of CKD patients.

Setting: Varied, usually multinational RCTs.

Synopsis: The six congestive heart failure (CHF) studies were not designed to evaluate patients with CKD, and the two non-CHF studies were intended to evaluate progression of CKD, not cardiac outcomes. Thus, this is a meta-analysis of post-hoc CKD subgroups included in these trials. Compared with placebo, beta-blockers reduced all-cause and cardiovascular mortality without significant heterogeneity between trials. The magnitude of the effect was similar in CKD and non-CKD patients. Patients with CKD treated with beta-blockers were at increased risk of bradycardia and hypotension, but this did not lead to increased discontinuation of the drug. Only 114 dialysis patients were included in one of the eight trials (7,000 patients overall) and no outcomes were assessed.

Bottom line: Beta-blockers lower all-cause and cardiovascular mortality in patients with CKD similarly to patients without kidney disease but are associated with an increased risk for hypotension and bradycardia. Their effect in dialysis patients is unknown.

Citation: Badve SV, Roberts MA, Hawley CM, et al. Effects of beta-adrenergic antagonists in patients with chronic kidney disease: a systematic review and meta-analysis. J Am Coll Cardiol. 2011;58:1152-1161.

Daily Long-Term Azithromycin in COPD Patients Decreases Frequency of Exacerbations

Clinical question: Does long-term treatment with azithromycin decrease COPD exacerbations and improve quality of life with an acceptable risk profile?

Background: Patients with acute exacerbations of COPD have increased risks of death and more rapid decline in lung function. Macrolide antibiotics might decrease exacerbations via antibacterial and anti-inflammatory effects. Small studies of long-term treatment with macrolides in COPD have had conflicting results.

Study design: Prospective, multicenter, parallel-group, placebo-controlled trial.

Setting: Twelve U.S. academic health centers.

Synopsis: Eligible patients were those older than 40 with pulmonary function test-proven obstructive disease, a significant smoking history, a use of supplemental oxygen, or an oral glucocorticoid treatment in the previous year, and those who had previously come to healthcare attention for a COPD exacerbation. They were randomized to daily azithromycin (250 mg) or placebo. The primary outcome was time to first COPD exacerbation at one year. The investigators used deep nasopharyngeal swabs to evaluate the development of microbial resistance, and all patients were regularly screened for hearing loss. Time to first exacerbation and frequency of exacerbations decreased significantly with azithromycin treatment; the number needed to treat to prevent a COPD exacerbation was 2.86. More than half of nasopharyngeal samples had evidence of macrolide resistance at enrollment, and this increased to more than 80% at one year. Audiometric testing did show a decrease in hearing in those treated with azithromycin, but even those who did not stop their medication had recovery on subsequent testing.

Bottom line: Daily azithromycin decreases COPD exacerbations in those with a history of previous exacerbation at the cost of increased macrolide resistance and possible reversible decrements in hearing. The high degree of macrolide resistance at enrollment suggests non-antibacterial mechanisms might be responsible.

Citation: Albert RK, Connett J, Bailey WC, et al. Azithromycin for prevention of exacerbations of COPD. N Engl J Med. 2011;365:689-698.

Serial Low-Dose CT Scans Decrease Lung Cancer Mortality

Clinical question: Does annual screening with low-dose CT scans reduce mortality from lung cancer in current or former heavy smokers?

Background: Lung cancer is still the top cause of cancer death in the United States, and its prevalence is increasing in the developing world. Prior trials of screening chest radiography and sputum samples have not shown a decrease in lung cancer mortality, but CT scans could help identify lung cancer at an earlier, more treatable stage.

Study design: Prospective, multicenter, randomized trial of low-dose (roughly one-fifth the radiation of traditional CT) annual CT versus annual chest radiography.

Setting: Thirty-three U.S. medical institutions.

Synopsis: The study enrolled 53,454 current or prior smokers with a history of smoking more than 30 packs a year who were randomly assigned to undergo three annual CT scans or chest X-rays. Any CT scans that showed a noncalcified nodule greater than 4 mm and chest X-rays that showed a noncalcified nodule or mass of any size were classified as “positive,” but follow-up was left to the discretion of the treating physicians. Participants were followed for 6.5 years on average.

Of those screened with CT, 40% had a positive screening test at some point, more than three times the rate of chest radiography, and 96.4% of these were false-positives, which was similar to chest radiography. Adverse events as a result of workup of eventual false positives were uncommon, occurring in around 1% of those who did not have lung cancer and in 11% of those who did. Screening reduced lung cancer mortality by 20% compared with chest radiography, with a number needed to screen to prevent one lung cancer death of 320. Cost-effectiveness and effects of radiation were not assessed.

Bottom line: Serial screening with low-dose CT reduces lung cancer mortality at the cost of a high rate of false-positives. Questions remain about cost-effectiveness and radiation exposure.

Citation: National Lung Screening Trial Research Team, Aberle DR, Adams AM, Berg CD, et al. Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med. 2011;365:395-409.

One-Week Delay in Starting Parenteral Nutrition in ICU Patients Is Associated with Better Outcomes

Clinical question: In patients admitted to the ICU who are at risk for malnutrition, does supplementing enteral feeding with parenteral feeding on the day of admission improve outcomes when compared with supplementation starting on Day 8?

Background: Patients with critical illness are at risk for malnutrition, which may lead to worsened outcomes. Many are unable to tolerate enteral feeding. However, adding parenteral nutrition has risks, including overfeeding and hyperglycemia.

Study design: Prospective, multicenter, randomized controlled trial. Neither patients/families nor ICU physicians were blinded.

Setting: Two university hospitals in Belgium.

Synopsis: The study included 4,640 patients admitted to the ICU who were “at risk” for malnutrition (assessed using a Nutritional Risk Score of >3). They were randomized to early initiation of parenteral nutrition on Day 1 or late initiation of parenteral nutrition on Day 8, in both cases only if needed to supplement enteral feeding. Both groups received intensive IV insulin protocols to keep blood glucose at 80 mg/dL to 110 mg/dL. The study populations were well-matched, with similar APACHE II scores. Of the total patients, 42% were emergency admissions to the ICU (more than half of which had sepsis), while scheduled cardiac surgery patients made up the majority of the rest of the study participants.

Patients with late initiation of total parenteral nutrition (TPN) were more likely to be discharged alive from the ICU within eight days despite having increased risk of hypoglycemia and more elevation of inflammatory markers. They had shorter ICU and hospital stays, fewer days on the ventilator, fewer infectious complications, were less likely to develop renal failure, and had lower overall costs. The unblinded management of these patients raises concern in interpreting infectious outcomes because study investigators could have been biased to look for infection more often in the early initiation group.

Bottom line: In ICU patients at risk for malnutrition, delaying initiation of TPN to supplement enteral feeding shortens ICU stay and reduces infectious complications when compared with early initiation of TPN.

Citation: Casaer MP, Mesotten D, Hermans G, et al. Early versus late parenteral nutrition in critically ill adults. N Engl J Med. 2011;365:506-17.

Intrapleural Instillation of Combined DNase and t-PA Improve Outcomes in Patients with Empyema

Clinical question: Does the intrapleural administration of a fibrinolytic, a recombinant DNase, or a combination of the two improve outcomes in patients with pleural infections compared with placebo?

Background: Pleural-based infections confer high morbidity and mortality, especially in the one-third of cases in which chest tube drainage fails. Observational data suggest intrapleural administration of fibrinolytics can improve drainage; however, a large randomized trial (MIST1) failed to show improvement with streptokinase.

Study design: Randomized, double-blind, double-dummy, factorial, multicenter trial.

Setting: University hospitals in the U.K.

Synopsis: A total of 193 patients with clinical evidence of an infection as well as laboratory evidence of pleural infection were randomized in factorial design to placebo, DNase alone, t-PA alone, and DNase plus t-PA as a twice-daily, hourlong instillation into the pleural space on hospital days 1 through 3. The combination group had improvements in the size of the pleural effusion compared with placebo, the primary endpoint. This group also was less likely to be referred for surgery, had shorter hospital stays, had less fever, and had lower inflammatory markers by hospital Day 7. Neither of the single-agent groups were better than placebo. The confidence intervals for all outcomes besides radiographic size of the effusion were large, as the trial had limited power for secondary endpoints.

Bottom line: In patients with empyema, the addition of twice-daily instillations of DNase and tPA can improve drainage and decrease risk of treatment failure when combined with chest tube drainage and antibiotics.

Citation: Rahman NM, Maskell NA, West A, et al. Intrapleural use of tissue plasminogen activator and DNase in pleural infection. N Engl J Med. 2011;365:518-526.

Smoothing Admissions over the Week Improves Patient Flow

Clinical question: What is the difference between weekday and weekend hospital occupancy, and what might the effect be of redistributing, or “smoothing,” elective admissions across the week?

Background: Efforts to improve patient flow have largely focused on reducing the average length of stay (ALOS). As the ALOS decreases, though, further reductions have limited yield in improving patient flow and could occur at the expense of patient safety. Smoothing admissions is a recognized but underutilized tool to address patient flow and hospital overcrowding.

Study design: Retrospective cohort.

Setting: Thirty-nine freestanding, tertiary-care children’s hospitals in the U.S.

Synopsis: Hospital occupancy ranged from 70.9% to 108.1% for weekdays, and from 65.7% to 94.4% on weekends. The mean difference between weekday and weekend occupancy was 8.2%. Using a mathematical model to redistribute admissions from peak days to nonpeak days (within a one-week time frame), the investigators found that percent occupancy on average dropped by 6.6%—the same number of patients over the same time interval, but with lower average occupancy. And, while not projected by these authors, the correlate of lower average occupancy would be reduced waits and delays for admission and within-hospital services. Only 2.6%, or about 7.5 admissions per week per hospital, would need to be rescheduled in order to realize this gain.

Bottom line: Where feasible, reshuffling elective admissions to “smooth” demand across the week is associated with improved hospital flow.

Citation: Fieldston ES, Hall M, Shah SS, et al. Addressing inpatient crowding by smoothing occupancy at children’s hospitals. J Hosp Med. 2011;6:466-473.

Variability in Preferences, Experiences, and Expectations for Hospitalist Roles in Comanagement

Clinical question: Do provider expectations and experiences in comanagement differ from the traditional medical consultation model?

Background: Hospitalists participate in traditional medical consultation and, increasingly, a variety of comanagement with surgical and various medical specialists. It is uncertain what preferences and expectations on either side of the comanagement relationship might be. Learning more might lead to a better conceptual understanding and working definition of inpatient comanagement.

Study design: Baseline and follow-up surveys.

Setting: Large single-site academic medical center, hospitalist-hepatologist comanagement service.

Synopsis: All 41 respondents completed the baseline survey, with 32 respondents completing a total of 177 follow-up surveys. Respondents included hospitalists, hepatologists, nonphysician providers (NPPs), and GI fellows. Hospitalists were more likely than hepatologists to want to be informed about every patient care decision (83% versus 17%). The majority of respondents reported understanding their roles. At baseline, nearly all agreed that “comanagement tends to improve patient care.” However, at follow-up, fewer NPP and fewer GI fellows reported that patients on their service had received “better care than they would without comanagement.” At follow-up, fewer hospitalists than at baseline reported that there was one “physician leader to direct the overall management of the patient’s hospital course.”

Bottom line: Hospitalists were more likely than hepatologists, within a comanagement relationship, to want to be informed about every decision. Most expected—but fewer actually later reported—that the comanagement model improved patient care.

Citation: Hinami K, Whelan CT, Konetzka RT, and Meltzer DO. Provider expectations and experiences of comanagement. J Hosp Med. 2011;6:401-404.

In This Edition

Literature At A Glance

A guide to this month’s studies

1. Higher loading dose of clopidogrel in STEMI
2. Early vs. late surgery following hip fracture
3. Beta-blockers in chronic kidney disease
4. Long-term azithromycin in COPD
5. CT screening for lung cancer
6. Timing of parenteral nutrition in the ICU
7. Intrapleural management of empyema with DNase and t-PA
8. Effect of weekend elective admissions on hospital flow
9. Expectations and outcomes of medical comanagement

Higher-Dose Clopidogrel Improves Outcomes at 30 Days in STEMI Patients

Clinical question: Does a 600-mg loading dose of clopidogrel given before percutaneous coronary intervention (PCI) in patients with an ST-segment elevation myocardial infarction (STEMI) provide more protection from thrombotic complications at 30 days than a 300-mg dose?

Background: Clopidogrel at 600 mg is active more quickly (two hours versus 12 hours) and inhibits platelets more completely than does a 300-mg dose, but it has never been tested prospectively in patients undergoing percutaneous intervention with a STEMI.

Study design: Prospective, multicenter, randomized controlled trial.

Setting: Five hospitals in Italy, Belgium, Serbia, and Hungary.

Synopsis: Two-hundred-one patients with STEMI were randomized to either 600 mg or 300 mg of clopidogrel, given an average of 30 minutes before initial PCI, as well as other standard treatment for STEMI. The primary outcome was “infarct size,” judged as the area under the curve (AUC) of serial creatine kinase-MB (CK-MB) and troponin measurements. At 30 days, patients who received the 600-mg dose of clopidogrel had lower AUCs of cardiac biomarkers, statistically significant (though clinically small) improvement in left ventricle ejection fraction at discharge, lower incidence of severely impaired post-PCI thrombolitis in myocardial infarction (TIMI) flow, and fewer “major cardiovascular events,” driven mainly by a reduction in revascularizations. Measurement of biomarkers to calculate infarct size can be confounded by hypertrophy, and the trial was underpowered for cardiovascular events. However, there was no increase in bleeding events.

Bottom line: In patients with STEMI, treatment with a higher loading dose of clopidogrel before PCI reduces revascularizations and might decrease infarct size without an increase in adverse events.

Citation: Patti G, Bárczi G, Orlic D, et al. Outcome comparison of 600- and 300-mg loading doses of clopidogrel in patients undergoing primary percutaneous coronary intervention for ST-segment elevation myocardial infarction: results from the ARMYDA-6 MI (Antiplatelet therapy for Reduction of MYocardial Damage during Angioplasty-Myocardial Infarction) randomized study. J Am Coll Cardiol. 2011;58:1592-1599.

Medical Comorbidities Explain Most of Excess Risk Seen in Patients with Delayed Hip Fracture Repair

Clinical question: Could the increased mortality found with delays in hip fracture surgery be confounded by the premorbid functional status and medical comorbidities of patients whose surgery is more likely to be delayed?

Background: Guidelines recommend operating on patients with hip fracture within 24 hours, but the supporting evidence has not adjusted for underlying medical comorbidities, which could delay surgery and contribute to poor outcomes, making delays look harmful.

Study design: Prospective cohort, single-center design.

Setting: University hospital in Spain.

Synopsis: The study included 2,250 consecutive elderly patients admitted to the hospital for hip fracture who had their functional status and medical comorbidities assessed at enrollment. If their surgery was delayed beyond 24 hours, the reason was sought. Medical outcomes assessed daily while in hospital were delirium, pneumonia, heart failure, urinary tract infection, and new pressure sores, while the dose of pain medication, surgical complications, and in-hospital mortality were also compiled. No post-discharge data were available.

The median time to surgery was 72 hours. Patients with more medical comorbidities and poorer preoperative functional status had longer delays to operation, most commonly due to interrupting antiplatelet treatment or need for preoperative “echocardiography or other examinations.” When these medical factors were included in logistic regression analysis, the increased mortality seen with delays of surgery in the cohort was no longer statistically significant, suggesting the underlying comorbidities of these patients, rather than the delay to surgery itself, explained the increased mortality.

Bottom line: Delaying hip fracture surgery is less important than preoperative functional status and medical comorbidity in contributing to poor outcomes.

Citation: Vidán MT, Sánchez E, Gracia Y, Marañón E, Vaquero J, Serra JA. Causes and effects of surgical delay in patients with hip fracture: a cohort study. Ann Intern Med. 2011;155:226-233.

Beta-Blockers Decrease All-Cause and Cardiovascular Mortality in Patients with Chronic Kidney Disease

Clinical question: Are beta-blockers as effective in patients on dialysis and with end-stage chronic kidney disease (CKD) as they are in patients without severe renal disease?

Background: Patients with CKD have been largely excluded from trials of beta-blocker therapy even though they have high rates of cardiovascular disease and might be most likely to benefit. However, patients on dialysis might be predisposed to adverse complications of beta-blocker therapy, including hypotension.

Study design: Meta-analysis of eight trials of beta-blockade versus placebo (six heart failure trials) or ACE-I (two non-heart-failure trials) that included post-hoc analyses of CKD patients.

Setting: Varied, usually multinational RCTs.

Synopsis: The six congestive heart failure (CHF) studies were not designed to evaluate patients with CKD, and the two non-CHF studies were intended to evaluate progression of CKD, not cardiac outcomes. Thus, this is a meta-analysis of post-hoc CKD subgroups included in these trials. Compared with placebo, beta-blockers reduced all-cause and cardiovascular mortality without significant heterogeneity between trials. The magnitude of the effect was similar in CKD and non-CKD patients. Patients with CKD treated with beta-blockers were at increased risk of bradycardia and hypotension, but this did not lead to increased discontinuation of the drug. Only 114 dialysis patients were included in one of the eight trials (7,000 patients overall) and no outcomes were assessed.

Bottom line: Beta-blockers lower all-cause and cardiovascular mortality in patients with CKD similarly to patients without kidney disease but are associated with an increased risk for hypotension and bradycardia. Their effect in dialysis patients is unknown.

Citation: Badve SV, Roberts MA, Hawley CM, et al. Effects of beta-adrenergic antagonists in patients with chronic kidney disease: a systematic review and meta-analysis. J Am Coll Cardiol. 2011;58:1152-1161.

Daily Long-Term Azithromycin in COPD Patients Decreases Frequency of Exacerbations

Clinical question: Does long-term treatment with azithromycin decrease COPD exacerbations and improve quality of life with an acceptable risk profile?

Background: Patients with acute exacerbations of COPD have increased risks of death and more rapid decline in lung function. Macrolide antibiotics might decrease exacerbations via antibacterial and anti-inflammatory effects. Small studies of long-term treatment with macrolides in COPD have had conflicting results.

Study design: Prospective, multicenter, parallel-group, placebo-controlled trial.

Setting: Twelve U.S. academic health centers.

Synopsis: Eligible patients were those older than 40 with pulmonary function test-proven obstructive disease, a significant smoking history, a use of supplemental oxygen, or an oral glucocorticoid treatment in the previous year, and those who had previously come to healthcare attention for a COPD exacerbation. They were randomized to daily azithromycin (250 mg) or placebo. The primary outcome was time to first COPD exacerbation at one year. The investigators used deep nasopharyngeal swabs to evaluate the development of microbial resistance, and all patients were regularly screened for hearing loss. Time to first exacerbation and frequency of exacerbations decreased significantly with azithromycin treatment; the number needed to treat to prevent a COPD exacerbation was 2.86. More than half of nasopharyngeal samples had evidence of macrolide resistance at enrollment, and this increased to more than 80% at one year. Audiometric testing did show a decrease in hearing in those treated with azithromycin, but even those who did not stop their medication had recovery on subsequent testing.

Bottom line: Daily azithromycin decreases COPD exacerbations in those with a history of previous exacerbation at the cost of increased macrolide resistance and possible reversible decrements in hearing. The high degree of macrolide resistance at enrollment suggests non-antibacterial mechanisms might be responsible.

Citation: Albert RK, Connett J, Bailey WC, et al. Azithromycin for prevention of exacerbations of COPD. N Engl J Med. 2011;365:689-698.

Serial Low-Dose CT Scans Decrease Lung Cancer Mortality

Clinical question: Does annual screening with low-dose CT scans reduce mortality from lung cancer in current or former heavy smokers?

Background: Lung cancer is still the top cause of cancer death in the United States, and its prevalence is increasing in the developing world. Prior trials of screening chest radiography and sputum samples have not shown a decrease in lung cancer mortality, but CT scans could help identify lung cancer at an earlier, more treatable stage.

Study design: Prospective, multicenter, randomized trial of low-dose (roughly one-fifth the radiation of traditional CT) annual CT versus annual chest radiography.

Setting: Thirty-three U.S. medical institutions.

Synopsis: The study enrolled 53,454 current or prior smokers with a history of smoking more than 30 packs a year who were randomly assigned to undergo three annual CT scans or chest X-rays. Any CT scans that showed a noncalcified nodule greater than 4 mm and chest X-rays that showed a noncalcified nodule or mass of any size were classified as “positive,” but follow-up was left to the discretion of the treating physicians. Participants were followed for 6.5 years on average.

Of those screened with CT, 40% had a positive screening test at some point, more than three times the rate of chest radiography, and 96.4% of these were false-positives, which was similar to chest radiography. Adverse events as a result of workup of eventual false positives were uncommon, occurring in around 1% of those who did not have lung cancer and in 11% of those who did. Screening reduced lung cancer mortality by 20% compared with chest radiography, with a number needed to screen to prevent one lung cancer death of 320. Cost-effectiveness and effects of radiation were not assessed.

Bottom line: Serial screening with low-dose CT reduces lung cancer mortality at the cost of a high rate of false-positives. Questions remain about cost-effectiveness and radiation exposure.

Citation: National Lung Screening Trial Research Team, Aberle DR, Adams AM, Berg CD, et al. Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med. 2011;365:395-409.

One-Week Delay in Starting Parenteral Nutrition in ICU Patients Is Associated with Better Outcomes

Clinical question: In patients admitted to the ICU who are at risk for malnutrition, does supplementing enteral feeding with parenteral feeding on the day of admission improve outcomes when compared with supplementation starting on Day 8?

Background: Patients with critical illness are at risk for malnutrition, which may lead to worsened outcomes. Many are unable to tolerate enteral feeding. However, adding parenteral nutrition has risks, including overfeeding and hyperglycemia.

Study design: Prospective, multicenter, randomized controlled trial. Neither patients/families nor ICU physicians were blinded.

Setting: Two university hospitals in Belgium.

Synopsis: The study included 4,640 patients admitted to the ICU who were “at risk” for malnutrition (assessed using a Nutritional Risk Score of >3). They were randomized to early initiation of parenteral nutrition on Day 1 or late initiation of parenteral nutrition on Day 8, in both cases only if needed to supplement enteral feeding. Both groups received intensive IV insulin protocols to keep blood glucose at 80 mg/dL to 110 mg/dL. The study populations were well-matched, with similar APACHE II scores. Of the total patients, 42% were emergency admissions to the ICU (more than half of which had sepsis), while scheduled cardiac surgery patients made up the majority of the rest of the study participants.

Patients with late initiation of total parenteral nutrition (TPN) were more likely to be discharged alive from the ICU within eight days despite having increased risk of hypoglycemia and more elevation of inflammatory markers. They had shorter ICU and hospital stays, fewer days on the ventilator, fewer infectious complications, were less likely to develop renal failure, and had lower overall costs. The unblinded management of these patients raises concern in interpreting infectious outcomes because study investigators could have been biased to look for infection more often in the early initiation group.

Bottom line: In ICU patients at risk for malnutrition, delaying initiation of TPN to supplement enteral feeding shortens ICU stay and reduces infectious complications when compared with early initiation of TPN.

Citation: Casaer MP, Mesotten D, Hermans G, et al. Early versus late parenteral nutrition in critically ill adults. N Engl J Med. 2011;365:506-17.

Intrapleural Instillation of Combined DNase and t-PA Improve Outcomes in Patients with Empyema

Clinical question: Does the intrapleural administration of a fibrinolytic, a recombinant DNase, or a combination of the two improve outcomes in patients with pleural infections compared with placebo?

Background: Pleural-based infections confer high morbidity and mortality, especially in the one-third of cases in which chest tube drainage fails. Observational data suggest intrapleural administration of fibrinolytics can improve drainage; however, a large randomized trial (MIST1) failed to show improvement with streptokinase.

Study design: Randomized, double-blind, double-dummy, factorial, multicenter trial.

Setting: University hospitals in the U.K.

Synopsis: A total of 193 patients with clinical evidence of an infection as well as laboratory evidence of pleural infection were randomized in factorial design to placebo, DNase alone, t-PA alone, and DNase plus t-PA as a twice-daily, hourlong instillation into the pleural space on hospital days 1 through 3. The combination group had improvements in the size of the pleural effusion compared with placebo, the primary endpoint. This group also was less likely to be referred for surgery, had shorter hospital stays, had less fever, and had lower inflammatory markers by hospital Day 7. Neither of the single-agent groups were better than placebo. The confidence intervals for all outcomes besides radiographic size of the effusion were large, as the trial had limited power for secondary endpoints.

Bottom line: In patients with empyema, the addition of twice-daily instillations of DNase and tPA can improve drainage and decrease risk of treatment failure when combined with chest tube drainage and antibiotics.

Citation: Rahman NM, Maskell NA, West A, et al. Intrapleural use of tissue plasminogen activator and DNase in pleural infection. N Engl J Med. 2011;365:518-526.

Smoothing Admissions over the Week Improves Patient Flow

Clinical question: What is the difference between weekday and weekend hospital occupancy, and what might the effect be of redistributing, or “smoothing,” elective admissions across the week?

Background: Efforts to improve patient flow have largely focused on reducing the average length of stay (ALOS). As the ALOS decreases, though, further reductions have limited yield in improving patient flow and could occur at the expense of patient safety. Smoothing admissions is a recognized but underutilized tool to address patient flow and hospital overcrowding.

Study design: Retrospective cohort.

Setting: Thirty-nine freestanding, tertiary-care children’s hospitals in the U.S.

Synopsis: Hospital occupancy ranged from 70.9% to 108.1% for weekdays, and from 65.7% to 94.4% on weekends. The mean difference between weekday and weekend occupancy was 8.2%. Using a mathematical model to redistribute admissions from peak days to nonpeak days (within a one-week time frame), the investigators found that percent occupancy on average dropped by 6.6%—the same number of patients over the same time interval, but with lower average occupancy. And, while not projected by these authors, the correlate of lower average occupancy would be reduced waits and delays for admission and within-hospital services. Only 2.6%, or about 7.5 admissions per week per hospital, would need to be rescheduled in order to realize this gain.

Bottom line: Where feasible, reshuffling elective admissions to “smooth” demand across the week is associated with improved hospital flow.

Citation: Fieldston ES, Hall M, Shah SS, et al. Addressing inpatient crowding by smoothing occupancy at children’s hospitals. J Hosp Med. 2011;6:466-473.

Variability in Preferences, Experiences, and Expectations for Hospitalist Roles in Comanagement

Clinical question: Do provider expectations and experiences in comanagement differ from the traditional medical consultation model?

Background: Hospitalists participate in traditional medical consultation and, increasingly, a variety of comanagement with surgical and various medical specialists. It is uncertain what preferences and expectations on either side of the comanagement relationship might be. Learning more might lead to a better conceptual understanding and working definition of inpatient comanagement.

Study design: Baseline and follow-up surveys.

Setting: Large single-site academic medical center, hospitalist-hepatologist comanagement service.

Synopsis: All 41 respondents completed the baseline survey, with 32 respondents completing a total of 177 follow-up surveys. Respondents included hospitalists, hepatologists, nonphysician providers (NPPs), and GI fellows. Hospitalists were more likely than hepatologists to want to be informed about every patient care decision (83% versus 17%). The majority of respondents reported understanding their roles. At baseline, nearly all agreed that “comanagement tends to improve patient care.” However, at follow-up, fewer NPP and fewer GI fellows reported that patients on their service had received “better care than they would without comanagement.” At follow-up, fewer hospitalists than at baseline reported that there was one “physician leader to direct the overall management of the patient’s hospital course.”

Bottom line: Hospitalists were more likely than hepatologists, within a comanagement relationship, to want to be informed about every decision. Most expected—but fewer actually later reported—that the comanagement model improved patient care.

Citation: Hinami K, Whelan CT, Konetzka RT, and Meltzer DO. Provider expectations and experiences of comanagement. J Hosp Med. 2011;6:401-404.

Clinical question: What is the relative efficacy of trimethoprim/sulfamethoxazole (TMP/sulfa) versus ciprofloxacin for the treatment of severe exacerbations of COPD?

Background: The use of antimicrobials in the treatment of COPD exacerbations is well accepted, with the original studies using amoxicillin, TMP/sulfa, and tetracyclines. Whether newer antimicrobial agents offer greater efficacy versus these standard agents remains uncertain.

Study design: Randomized, double-blind, placebo-controlled (double-dummy), noninferiority trial.

Setting: Two academic medical ICUs in Tunisia.

Synopsis: Consecutive patients (n=170) with severe exacerbations of COPD requiring mechanical ventilation were randomized to standard medical therapy plus either TMP/sulfa or ciprofloxacin. Patients had a prior diagnosis of COPD and the clinical presence of purulent sputum and respiratory failure. The study excluded those who were immunosuppressed, had significant hepatic or renal disease, pneumonia, recent antibiotic use, active cancer, or inability to take oral medications.

The primary endpoint of hospital death and the need for an additional course of antibiotics was no different between the groups (16.4% with TMP/sulfa versus 15.3% with ciprofloxacin). The mean exacerbation-free interval, days of mechanical ventilation, and length of stay were no different. Noninferiority was defined as <10% relative difference.

Bottom line: TMP/sulfa was noninferior to ciprofloxacin in the treatment of severe exacerbations of COPD requiring mechanical ventilation.

Citation: Nouira S, Marghli S, Besbes L, et al. Standard versus newer antibacterial agents in the treatment of severe acute exacerbations of chronic obstructive pulmonary disease: a randomized trial of trimethoprim-sulfamethoxazole versus ciprofloxacin. Clin Inf Dis. 2010;51:143-149.

For more physician reviews of HM-related research, visit our website.

Clinical question: What is the relative efficacy of trimethoprim/sulfamethoxazole (TMP/sulfa) versus ciprofloxacin for the treatment of severe exacerbations of COPD?

Background: The use of antimicrobials in the treatment of COPD exacerbations is well accepted, with the original studies using amoxicillin, TMP/sulfa, and tetracyclines. Whether newer antimicrobial agents offer greater efficacy versus these standard agents remains uncertain.

Study design: Randomized, double-blind, placebo-controlled (double-dummy), noninferiority trial.

Setting: Two academic medical ICUs in Tunisia.

Synopsis: Consecutive patients (n=170) with severe exacerbations of COPD requiring mechanical ventilation were randomized to standard medical therapy plus either TMP/sulfa or ciprofloxacin. Patients had a prior diagnosis of COPD and the clinical presence of purulent sputum and respiratory failure. The study excluded those who were immunosuppressed, had significant hepatic or renal disease, pneumonia, recent antibiotic use, active cancer, or inability to take oral medications.

The primary endpoint of hospital death and the need for an additional course of antibiotics was no different between the groups (16.4% with TMP/sulfa versus 15.3% with ciprofloxacin). The mean exacerbation-free interval, days of mechanical ventilation, and length of stay were no different. Noninferiority was defined as <10% relative difference.

Bottom line: TMP/sulfa was noninferior to ciprofloxacin in the treatment of severe exacerbations of COPD requiring mechanical ventilation.

Citation: Nouira S, Marghli S, Besbes L, et al. Standard versus newer antibacterial agents in the treatment of severe acute exacerbations of chronic obstructive pulmonary disease: a randomized trial of trimethoprim-sulfamethoxazole versus ciprofloxacin. Clin Inf Dis. 2010;51:143-149.

For more physician reviews of HM-related research, visit our website.

Clinical question: What is the relative efficacy of trimethoprim/sulfamethoxazole (TMP/sulfa) versus ciprofloxacin for the treatment of severe exacerbations of COPD?

Background: The use of antimicrobials in the treatment of COPD exacerbations is well accepted, with the original studies using amoxicillin, TMP/sulfa, and tetracyclines. Whether newer antimicrobial agents offer greater efficacy versus these standard agents remains uncertain.

Study design: Randomized, double-blind, placebo-controlled (double-dummy), noninferiority trial.

Setting: Two academic medical ICUs in Tunisia.

Synopsis: Consecutive patients (n=170) with severe exacerbations of COPD requiring mechanical ventilation were randomized to standard medical therapy plus either TMP/sulfa or ciprofloxacin. Patients had a prior diagnosis of COPD and the clinical presence of purulent sputum and respiratory failure. The study excluded those who were immunosuppressed, had significant hepatic or renal disease, pneumonia, recent antibiotic use, active cancer, or inability to take oral medications.

The primary endpoint of hospital death and the need for an additional course of antibiotics was no different between the groups (16.4% with TMP/sulfa versus 15.3% with ciprofloxacin). The mean exacerbation-free interval, days of mechanical ventilation, and length of stay were no different. Noninferiority was defined as <10% relative difference.

Bottom line: TMP/sulfa was noninferior to ciprofloxacin in the treatment of severe exacerbations of COPD requiring mechanical ventilation.

Citation: Nouira S, Marghli S, Besbes L, et al. Standard versus newer antibacterial agents in the treatment of severe acute exacerbations of chronic obstructive pulmonary disease: a randomized trial of trimethoprim-sulfamethoxazole versus ciprofloxacin. Clin Inf Dis. 2010;51:143-149.

For more physician reviews of HM-related research, visit our website.

In This Edition

Literature at a Glance

A guide to this month’s studies

• Characteristics of CA-MRSA
• Association of gurgling with morbidity and mortality
• Antibiotics for active ulcerative colitis
• TIPS for cirrhosis-induced variceal bleeding
• Steroid dose, route in COPD exacerbations
• Effect of reminders and stop orders on urinary catheter use
• Outcomes of chest-compression-only CPR
• Albumin levels and risk of surgical-site infections

Characteristics of Community-Acquired methicillin-resistant Staphylococcus aureus Pneumonia in an Academic Medical Center

Clinical question: What are the clinical features and epidemiology of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) pneumonia?

Background: CA-MRSA is an emerging cause of pneumonia. The genetic makeup of most CA-MRSA strains is different than that of nosocomial MRSA. Typically, CA-MRSA is resistant to methicillin, beta-lactams, and erythromycin, but it retains susceptibility to trimethoprim-sulfamethoxazole (TMP/sulfa) and clindamycin.

In addition, the most common strain of CA-MRSA carries the Panton-Valentine leukocidin (PVL) toxin, which is associated with necrotizing pneumonia and high mortality rates.

Study design: Retrospective case series.

Setting: A 1,100-bed teaching hospital in Chicago.

Synopsis: Of the 5,955 discharges with a diagnosis-related group (DRG) code of pneumonia, 15 met criteria for CA-MRSA, or <1% of all inpatient community-acquired pneumonia cases. All 15 CA-MRSA strains were positive for PVL.

Seven of the 15 patients never were admitted to the ICU, while seven patients required mechanical ventilation. Seven patients were immunocompromised; one patient presented with preceding influenza; seven patients presented with hemoptysis; and eight patients demonstrated findings of lung necrosis on CT scan. Two patients died; both were immunocompromised.

Although the initial antibiotic regimen varied considerably, 14 patients ultimately received either clindamycin or linezolid.

Bottom line: CA-MRSA pneumonia is an uncommon subset of community-acquired pneumonia admissions. Approximately half the patients admitted with CA-MRSA presented with features of severe pneumonia. Nearly all were treated with antibiotics that inhibit exotoxin production, and the associated mortality rate of 13% was lower than previously reported.

Citation: Lobo JL, Reed KD, Wunderink RG. Expanded clinical presentation of community-acquired methicillin-resistant Staphylococcus aureus pneumonia. Chest. 2010;138(1):130-136.

Gurgling Breath Sounds in Hospitalized Patients Might Predict Subsequent Pneumonia Development

Clinical question: Can gurgling sounds over the glottis during speech or quiet breathing predict hospital-acquired pneumonia (HAP)?

Background: HAP is a relatively frequent complication of hospitalization. HAP usually portends an increase in morbidity and mortality. Patients in the hospital might have disease states that inhibit the reflexes that normally eliminate secretions from above or below their glottis, increasing the risk of pneumonia.

Study design: Prospective cohort.

Setting: A 350-bed community teaching hospital in Bridgeport, Conn.

Synopsis: All patients admitted to a respiratory-care unit and general medical ward from December 2008 to April 2009 underwent auscultation over their glottis by study personnel. Patients with gurgles heard during speech or quiet breathing on auscultation and patients without gurgles were entered into the study in a 1:3 fashion, until 20 patients with gurgles and 60 patients without gurgles had been enrolled. Patients were followed for the development of clinical and radiographic evidence of HAP, ICU transfer, and in-hospital death.

Both dementia and treatment with opiates were independent predictors of gurgle in multivariate analysis. HAP occurred in 55% of the patients with gurgle versus 1.7% of patients without gurgle. In addition, 50% of the patients with gurgle required transfer to the ICU, compared with only 3.3% of patients without gurgle. In-hospital mortality was 30% among patients with gurgle versus 11.7% among patients without gurgle.

Bottom line: In patients admitted to the medical service of a community teaching hospital, gurgling sounds heard over the glottis during speech or quiet inspiration are independently associated with the development of HAP, ICU transfer, and in-hospital mortality.

Citation: Vazquez R, Gheorghe C, Ramos F, Dadu R, Amoateng-Adjepong Y, Manthous CA. Gurgling breath sounds may predict hospital-acquired pneumonia. Chest. 2010;138(2):284-288.

Treatment of Active Ulcerative Colitis with Triple Antibiotic Therapy Provides Better Response than Placebo

Clinical question: Does combination antibiotic therapy induce and/or maintain remission of active ulcerative colitis (UC)?

Background: Mouse models and other experimental evidence have suggested a pathogenic role for microbes in the development and/or exacerbation of ulcerative colitis, although antibiotic human trials have produced conflicting results. Recently, Fusobacterium varium was shown to be present in the gastrointestinal (GI) tract of most UC patients, and a pilot study using targeted antibacterials demonstrated efficacy in treating active UC.

Study design: Randomized, double-blind, placebo-controlled, multicenter trial.

Setting: Eleven hospitals in Japan.

Synopsis: Patients with mild to severe chronic relapsing UC were randomly assigned to either combination antibiotic therapy or placebo. All previous UC treatment regimens were continued in study patients, with the exception of steroids, which were tapered slowly if possible. Patients in the antibiotic group received a two-week combination therapy of amoxicillin, tetracycline, and metronidazole. Patients were followed weekly or monthly and underwent periodic exams and colonoscopies to assess clinical and endoscopic improvement for 12 months.

One hundred five patients were enrolled in each group. The clinical response rate at one year in patients treated with antibiotics was 44.8% versus 22.8% in the placebo group. Remission at one year was achieved in 26.7% of patients treated with antibiotics versus 14.9% of placebo patients. Endoscopic response rates and steroid discontinuation rates were higher in the antibiotic-treated groups. Effects were most pronounced in the group of patients with active disease.

Bottom line: Triple antibiotic therapy with amoxicillin, tetracycline, and metronidazole, when compared with placebo, was associated with improvement in clinical symptoms, endoscopic findings, remission rates, and steroid withdrawal in patients with active ulcerative colitis.

Citation: Ohkusa T, Kato K, Terao S, et al. Newly developed antibiotic combination therapy for ulcerative colitis: a double-blind placebo-controlled multicenter trial. Am J Gastroenterol. 2010;105(8):1820-1829.

Early TIPS Outperformed Optimal Medical Therapy in Patients with Advanced Cirrhosis and Variceal Bleeding

Clinical question: Does early treatment with a transjugular intrahepatic portosystemic shunt (TIPS) improve outcomes in patients with advanced cirrhosis and variceal bleeding?

Background: Current management guidelines for variceal bleeding include treatment with vasoactive drugs and serial endoscopy, yet treatment failure occurs in 10% to 15% of patients. TIPS is highly effective in controlling bleeding in such patients, but it historically has been reserved for patients who repeatedly fail preventive strategies.

Study design: Randomized controlled trial.

Setting: Nine European centers.

Synopsis: Sixty-three patients with advanced cirrhosis and acute esophageal variceal bleeding treated with optimal medical therapy were randomized within 24 hours of admission to either 1) early TIPS (polytetrafluoroethylene-covered stents) within 72 hours of randomization, or 2) ongoing optimal medical therapy with vasoactive drugs, treatment with a nonselective beta-blocker, and endoscopic band ligation.

During the median 16-month follow-up, rebleeding or failure to control bleeding occurred in 45% of patients in the optimal medical therapy group versus 3% of patients in the early TIPS group. One-year actuarial survival was 61% in the optimal medical therapy group versus 86% in the early-TIPS group. Remarkably, encephalopathy was less common in the early-TIPS group, and adverse events as a whole were similar in both groups.

Bottom line: Early use of TIPS was superior to optimal medical therapy for patients with advanced cirrhosis hospitalized for acute variceal bleeding at high risk for treatment failure.

Citation: García-Pagán JC, Caca K, Bureau C, et al. Early use of TIPS in patients with cirrhosis and variceal bleeding. N Engl J Med. 2010;362(25):2370-2379.

Low-Dose Oral Corticosteroids As Effective As High-Dose Intravenous Therapy in COPD Exacerbations

Clinical question: In patients hospitalized with acute exacerbation of chronic obstructive pulmonary disease (COPD), what are the outcomes of those initially treated with low doses of steroids administered orally compared with those initially treated with higher doses intravenously?

Background: COPD affects 6% of adults in the U.S., and acute exacerbation of COPD is one of the leading causes of hospitalization nationwide. Systemic corticosteroids are beneficial for patients hospitalized with acute exacerbation of COPD; however, optimal dose and route of administration are uncertain.

Study design: Retrospective cohort.

Setting: Four hundred fourteen U.S. acute-care hospitals; most were small to midsize nonteaching facilities serving urban patient populations.

Synopsis: Almost 80,000 patients admitted to a non-ICU setting with a diagnosis of acute exacerbation of COPD from 2006 to 2007, and who received systemic corticosteroids during the first two hospital days, were included in the study. In contrast to clinical guidelines recommending the use of low-dose oral corticosteroids, 92% of study participants were treated initially with intravenous steroids, whereas 8% received oral treatment. The primary composite outcome measure—need for mechanical ventilation after the second hospital day, inpatient mortality, or readmission for COPD within 30 days—was no worse in patients treated with oral steroids. Risk of treatment failure, length of stay, and cost were significantly lower among orally treated patients.

Bottom line: High-dose intravenous steroids appear to be no more effective than low-dose oral steroids for acute exacerbation of COPD. The authors recommend a randomized controlled trial be conducted to compare these two management strategies.

Citation: Lindenauer PK, Pekow PS, Lahti MC, Lee Y, Benjamin EM, Rothberg MB. Association of corticosteroid dose and route of administration with risk of treatment failure in acute exacerbation of chronic obstructive pulmonary disease. JAMA. 2010;303(23):2359-2367.

Reminders and Stop Orders Reduce Catheter-Associated Urinary Tract Infections

Clinical question: Do interventions that remind clinicians of the presence of urinary catheters and prompt timely removal decrease the rate of catheter-associated urinary tract infections (CA-UTI)?

Background: CA-UTI is a common yet preventable hospital-acquired infection. Many catheters are placed unnecessarily, remain in use without physician awareness, and are not removed promptly when no longer needed.

Study design: Systematic review and meta-analysis of 13 preintervention and postintervention quasi-experimental trials and one randomized controlled trial.

Setting: Studies conducted in the U.S., Canada, Europe, and Asia.

Synopsis: This literature search revealed 14 articles that used a reminder or stop-order intervention to prompt removal of urinary catheters and reported pre- and postintervention outcomes for CA-UTI rates, duration of urinary catheter use, and recatheterization need. Five studies used stop orders and nine studies used reminder interventions.

Use of a stop order or reminder reduced the rate of CA-UTI (episodes per 1,000 catheter days) by 52%. Mean duration of catheterization decreased by 37%, which resulted in 2.61 fewer days of catheterization per patient in the intervention versus control groups. Recatheterization rates were similar in the control and intervention groups.

Bottom line: Urinary catheter reminders and stop orders are low-cost strategies that appear to reduce the rate of CA-UTI.

Citation: Meddings J, Rogers MA, Macy M, Saint S. Systematic review and meta-analysis: reminder systems to reduce catheter-associated urinary tract infections and urinary catheter use in hospitalized patients. Clin Infect Dis. 2010;51(5):550-560.

Chest-Compression-Only Bystander CPR Increases Survival

Clinical question: Is bystander cardiopulmonary resuscitation (CPR) with chest compressions alone or chest compressions with rescue breathing superior in out-of-hospital adult cardiac arrest?

Background: Out-of-hospital cardiac arrest claims hundreds of thousands of lives each year. Early initiation of CPR by a layperson can increase a patient’s chances of surviving and having a favorable long-term neurologic recovery. Although traditional CPR consists of chest compression with rescue breathing, chest compression alone might be more acceptable to many laypersons and has the potential advantage of fewer compression interruptions.

Study design: Multicenter randomized trial.

Setting: Two EMSs in Washington state and one in London.

Synopsis: Patients were initially eligible for this study if a dispatcher determined that the patient was unconscious and not breathing, and that bystander CPR was not yet under way. If the caller was willing to undertake CPR with the dispatcher’s assistance, a randomization envelope containing CPR instructions was opened. Patients with arrest due to trauma, drowning, or asphyxiation were excluded, as were those under 18 years of age.

No significant difference was observed between the two groups in the percentage of patients who survived to hospital discharge or who survived with a favorable neurologic outcome. However, subgroup analyses showed a trend toward a higher percentage of patients surviving to hospital discharge with chest compressions alone, as compared with chest compressions with rescue breathing for patients with a cardiac cause of arrest and for those with shockable rhythms.

Bottom line: Dispatcher CPR instruction consisting of chest compression alone was noninferior to conventional CPR with rescue breathing, and it showed a trend toward better outcomes in cardiac cause of arrest.

Citation: Rea TD, Fahrenbruch C, Culley L, et al. CPR with chest compression alone or with rescue breathing. N Engl J Med. 2010;363(5):423-433.

Low Albumin Is Associated with Postoperative Wound Infections

Clinical question: What is the relationship between preoperative serum albumin levels and postoperative surgical-site infections (SSI)?

Background: Poor nutritional status is associated with adverse surgical outcomes. Serum albumin can both reflect nutritional status and function as a negative acute phase reactant, i.e., decreases in the setting of inflammation. It is uncertain whether low preoperative albumin levels are associated with postoperative SSI risk.

Study design: Retrospective cohort with multivariate analysis.

Setting: Four centers in Ireland.

Synopsis: Patients undergoing GI surgery (n=524) were prospectively followed as part of an SSI database. Demographic data, American Society of Anesthesia class, serum albumin levels, and presence and severity of SSI data were collected on all patients. Follow-up extended to 30 days.

SSI developed in 20% of patients. Patients who developed a SSI had lower serum albumin levels (mean 3.0 g/dL versus 3.6 g/dL). A serum albumin level less than 3.0 g/dL was associated with greater risk of SSI (relative risk 5.68), deeper SSI, and prolonged length of stay.

Bottom line: After controlling for other variables, serum albumin lower than 3.0 g/dL is independently associated with SSI frequency and severity.

Citation: Hennessey DB, Burke JP, Ni-Dhonochu T, Shields C, Winter DC, Mealy K. Preoperative hypoalbuminemia is an independent risk factor for the development of surgical site infection following gastrointestinal surgery: a multi-institutional study. Ann Surg. 2010;252 (2):325-329. TH

Pediatric HM Literature

Nebulized Hypertonic Saline Alone Safe to Study in Bronchiolitis

Reviewed by Pediatric Editor Mark Shen, MD, medical director of hospital medicine at Dell Children’s Medical Center, Austin, Texas.

Clinical question: Is nebulized 3% saline solution safe to use alone in infants with bronchiolitis?

Background: Nebulized 3% (hypertonic) saline is increasingly used in the treatment of infants hospitalized with bronchiolitis. Studies to date have primarily investigated its efficacy in conjunction with bronchodilators due to a theoretical risk of bronchospasm. The safety profile of hypertonic saline alone in bronchiolitis is unknown.

Study design: Retrospective cohort study.

Setting: A single children’s hospital.

Synopsis: An existing QI database was reviewed during one winter season. One hundred fifty-four records were analyzed, comprising previously healthy infants with acute bronchiolitis. Hypertonic (3%) saline delivered more than four hours before and after albuterol was considered to have been given alone. Adverse events were not defined a priori, and documentation of symptoms related to medication administration was encouraged via a new comment section of a pathway scoring system.

Sixty-eight patients received 444 doses of hypertonic saline, 377 (85%) of which were administered alone. Four adverse events (1.0%) occurred in the group without adjunctive bronchodilator therapy; one adverse event (1.1%) occurred after concomitant delivery of albuterol and 3% saline. Rates of readmission and transfer to higher level of care were similar between those that did and did not receive hypertonic saline.

The potential for under-ascertainment of adverse events is significant with the retrospective design and frequency of underreporting in most hospitals. In addition, adverse events related to medication administration might be particularly difficult to assess in such dynamic diseases as bronchiolitis. Nevertheless, this study does suggest that adverse event rates are low with hypertonic saline alone, paving the way for future studies to assess its efficacy without bronchodilators clouding the picture.

Bottom line: Nebulized 3% saline has a low rate of adverse events in infants with acute bronchiolitis.

Citation: Ralston S, Hill V, Martinez M. Nebulized hypertonic saline without adjunctive bronchodilators for children with bronchiolitis. Pediatrics. 2010;126(3):e520-e525.

In This Edition

Literature at a Glance

A guide to this month’s studies

• Characteristics of CA-MRSA
• Association of gurgling with morbidity and mortality
• Antibiotics for active ulcerative colitis
• TIPS for cirrhosis-induced variceal bleeding
• Steroid dose, route in COPD exacerbations
• Effect of reminders and stop orders on urinary catheter use
• Outcomes of chest-compression-only CPR
• Albumin levels and risk of surgical-site infections

Characteristics of Community-Acquired methicillin-resistant Staphylococcus aureus Pneumonia in an Academic Medical Center

Clinical question: What are the clinical features and epidemiology of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) pneumonia?

Background: CA-MRSA is an emerging cause of pneumonia. The genetic makeup of most CA-MRSA strains is different than that of nosocomial MRSA. Typically, CA-MRSA is resistant to methicillin, beta-lactams, and erythromycin, but it retains susceptibility to trimethoprim-sulfamethoxazole (TMP/sulfa) and clindamycin.

In addition, the most common strain of CA-MRSA carries the Panton-Valentine leukocidin (PVL) toxin, which is associated with necrotizing pneumonia and high mortality rates.

Study design: Retrospective case series.

Setting: A 1,100-bed teaching hospital in Chicago.

Synopsis: Of the 5,955 discharges with a diagnosis-related group (DRG) code of pneumonia, 15 met criteria for CA-MRSA, or <1% of all inpatient community-acquired pneumonia cases. All 15 CA-MRSA strains were positive for PVL.

Seven of the 15 patients never were admitted to the ICU, while seven patients required mechanical ventilation. Seven patients were immunocompromised; one patient presented with preceding influenza; seven patients presented with hemoptysis; and eight patients demonstrated findings of lung necrosis on CT scan. Two patients died; both were immunocompromised.

Although the initial antibiotic regimen varied considerably, 14 patients ultimately received either clindamycin or linezolid.

Bottom line: CA-MRSA pneumonia is an uncommon subset of community-acquired pneumonia admissions. Approximately half the patients admitted with CA-MRSA presented with features of severe pneumonia. Nearly all were treated with antibiotics that inhibit exotoxin production, and the associated mortality rate of 13% was lower than previously reported.

Citation: Lobo JL, Reed KD, Wunderink RG. Expanded clinical presentation of community-acquired methicillin-resistant Staphylococcus aureus pneumonia. Chest. 2010;138(1):130-136.

Gurgling Breath Sounds in Hospitalized Patients Might Predict Subsequent Pneumonia Development

Clinical question: Can gurgling sounds over the glottis during speech or quiet breathing predict hospital-acquired pneumonia (HAP)?

Background: HAP is a relatively frequent complication of hospitalization. HAP usually portends an increase in morbidity and mortality. Patients in the hospital might have disease states that inhibit the reflexes that normally eliminate secretions from above or below their glottis, increasing the risk of pneumonia.

Study design: Prospective cohort.

Setting: A 350-bed community teaching hospital in Bridgeport, Conn.

Synopsis: All patients admitted to a respiratory-care unit and general medical ward from December 2008 to April 2009 underwent auscultation over their glottis by study personnel. Patients with gurgles heard during speech or quiet breathing on auscultation and patients without gurgles were entered into the study in a 1:3 fashion, until 20 patients with gurgles and 60 patients without gurgles had been enrolled. Patients were followed for the development of clinical and radiographic evidence of HAP, ICU transfer, and in-hospital death.

Both dementia and treatment with opiates were independent predictors of gurgle in multivariate analysis. HAP occurred in 55% of the patients with gurgle versus 1.7% of patients without gurgle. In addition, 50% of the patients with gurgle required transfer to the ICU, compared with only 3.3% of patients without gurgle. In-hospital mortality was 30% among patients with gurgle versus 11.7% among patients without gurgle.

Bottom line: In patients admitted to the medical service of a community teaching hospital, gurgling sounds heard over the glottis during speech or quiet inspiration are independently associated with the development of HAP, ICU transfer, and in-hospital mortality.

Citation: Vazquez R, Gheorghe C, Ramos F, Dadu R, Amoateng-Adjepong Y, Manthous CA. Gurgling breath sounds may predict hospital-acquired pneumonia. Chest. 2010;138(2):284-288.

Treatment of Active Ulcerative Colitis with Triple Antibiotic Therapy Provides Better Response than Placebo

Clinical question: Does combination antibiotic therapy induce and/or maintain remission of active ulcerative colitis (UC)?

Background: Mouse models and other experimental evidence have suggested a pathogenic role for microbes in the development and/or exacerbation of ulcerative colitis, although antibiotic human trials have produced conflicting results. Recently, Fusobacterium varium was shown to be present in the gastrointestinal (GI) tract of most UC patients, and a pilot study using targeted antibacterials demonstrated efficacy in treating active UC.

Study design: Randomized, double-blind, placebo-controlled, multicenter trial.

Setting: Eleven hospitals in Japan.

Synopsis: Patients with mild to severe chronic relapsing UC were randomly assigned to either combination antibiotic therapy or placebo. All previous UC treatment regimens were continued in study patients, with the exception of steroids, which were tapered slowly if possible. Patients in the antibiotic group received a two-week combination therapy of amoxicillin, tetracycline, and metronidazole. Patients were followed weekly or monthly and underwent periodic exams and colonoscopies to assess clinical and endoscopic improvement for 12 months.

One hundred five patients were enrolled in each group. The clinical response rate at one year in patients treated with antibiotics was 44.8% versus 22.8% in the placebo group. Remission at one year was achieved in 26.7% of patients treated with antibiotics versus 14.9% of placebo patients. Endoscopic response rates and steroid discontinuation rates were higher in the antibiotic-treated groups. Effects were most pronounced in the group of patients with active disease.

Bottom line: Triple antibiotic therapy with amoxicillin, tetracycline, and metronidazole, when compared with placebo, was associated with improvement in clinical symptoms, endoscopic findings, remission rates, and steroid withdrawal in patients with active ulcerative colitis.

Citation: Ohkusa T, Kato K, Terao S, et al. Newly developed antibiotic combination therapy for ulcerative colitis: a double-blind placebo-controlled multicenter trial. Am J Gastroenterol. 2010;105(8):1820-1829.

Early TIPS Outperformed Optimal Medical Therapy in Patients with Advanced Cirrhosis and Variceal Bleeding

Clinical question: Does early treatment with a transjugular intrahepatic portosystemic shunt (TIPS) improve outcomes in patients with advanced cirrhosis and variceal bleeding?

Background: Current management guidelines for variceal bleeding include treatment with vasoactive drugs and serial endoscopy, yet treatment failure occurs in 10% to 15% of patients. TIPS is highly effective in controlling bleeding in such patients, but it historically has been reserved for patients who repeatedly fail preventive strategies.

Study design: Randomized controlled trial.

Setting: Nine European centers.

Synopsis: Sixty-three patients with advanced cirrhosis and acute esophageal variceal bleeding treated with optimal medical therapy were randomized within 24 hours of admission to either 1) early TIPS (polytetrafluoroethylene-covered stents) within 72 hours of randomization, or 2) ongoing optimal medical therapy with vasoactive drugs, treatment with a nonselective beta-blocker, and endoscopic band ligation.

During the median 16-month follow-up, rebleeding or failure to control bleeding occurred in 45% of patients in the optimal medical therapy group versus 3% of patients in the early TIPS group. One-year actuarial survival was 61% in the optimal medical therapy group versus 86% in the early-TIPS group. Remarkably, encephalopathy was less common in the early-TIPS group, and adverse events as a whole were similar in both groups.

Bottom line: Early use of TIPS was superior to optimal medical therapy for patients with advanced cirrhosis hospitalized for acute variceal bleeding at high risk for treatment failure.

Citation: García-Pagán JC, Caca K, Bureau C, et al. Early use of TIPS in patients with cirrhosis and variceal bleeding. N Engl J Med. 2010;362(25):2370-2379.

Low-Dose Oral Corticosteroids As Effective As High-Dose Intravenous Therapy in COPD Exacerbations

Clinical question: In patients hospitalized with acute exacerbation of chronic obstructive pulmonary disease (COPD), what are the outcomes of those initially treated with low doses of steroids administered orally compared with those initially treated with higher doses intravenously?

Background: COPD affects 6% of adults in the U.S., and acute exacerbation of COPD is one of the leading causes of hospitalization nationwide. Systemic corticosteroids are beneficial for patients hospitalized with acute exacerbation of COPD; however, optimal dose and route of administration are uncertain.

Study design: Retrospective cohort.

Setting: Four hundred fourteen U.S. acute-care hospitals; most were small to midsize nonteaching facilities serving urban patient populations.

Synopsis: Almost 80,000 patients admitted to a non-ICU setting with a diagnosis of acute exacerbation of COPD from 2006 to 2007, and who received systemic corticosteroids during the first two hospital days, were included in the study. In contrast to clinical guidelines recommending the use of low-dose oral corticosteroids, 92% of study participants were treated initially with intravenous steroids, whereas 8% received oral treatment. The primary composite outcome measure—need for mechanical ventilation after the second hospital day, inpatient mortality, or readmission for COPD within 30 days—was no worse in patients treated with oral steroids. Risk of treatment failure, length of stay, and cost were significantly lower among orally treated patients.

Bottom line: High-dose intravenous steroids appear to be no more effective than low-dose oral steroids for acute exacerbation of COPD. The authors recommend a randomized controlled trial be conducted to compare these two management strategies.

Citation: Lindenauer PK, Pekow PS, Lahti MC, Lee Y, Benjamin EM, Rothberg MB. Association of corticosteroid dose and route of administration with risk of treatment failure in acute exacerbation of chronic obstructive pulmonary disease. JAMA. 2010;303(23):2359-2367.

Reminders and Stop Orders Reduce Catheter-Associated Urinary Tract Infections

Clinical question: Do interventions that remind clinicians of the presence of urinary catheters and prompt timely removal decrease the rate of catheter-associated urinary tract infections (CA-UTI)?

Background: CA-UTI is a common yet preventable hospital-acquired infection. Many catheters are placed unnecessarily, remain in use without physician awareness, and are not removed promptly when no longer needed.

Study design: Systematic review and meta-analysis of 13 preintervention and postintervention quasi-experimental trials and one randomized controlled trial.

Setting: Studies conducted in the U.S., Canada, Europe, and Asia.

Synopsis: This literature search revealed 14 articles that used a reminder or stop-order intervention to prompt removal of urinary catheters and reported pre- and postintervention outcomes for CA-UTI rates, duration of urinary catheter use, and recatheterization need. Five studies used stop orders and nine studies used reminder interventions.

Use of a stop order or reminder reduced the rate of CA-UTI (episodes per 1,000 catheter days) by 52%. Mean duration of catheterization decreased by 37%, which resulted in 2.61 fewer days of catheterization per patient in the intervention versus control groups. Recatheterization rates were similar in the control and intervention groups.

Bottom line: Urinary catheter reminders and stop orders are low-cost strategies that appear to reduce the rate of CA-UTI.

Citation: Meddings J, Rogers MA, Macy M, Saint S. Systematic review and meta-analysis: reminder systems to reduce catheter-associated urinary tract infections and urinary catheter use in hospitalized patients. Clin Infect Dis. 2010;51(5):550-560.

Chest-Compression-Only Bystander CPR Increases Survival

Clinical question: Is bystander cardiopulmonary resuscitation (CPR) with chest compressions alone or chest compressions with rescue breathing superior in out-of-hospital adult cardiac arrest?

Background: Out-of-hospital cardiac arrest claims hundreds of thousands of lives each year. Early initiation of CPR by a layperson can increase a patient’s chances of surviving and having a favorable long-term neurologic recovery. Although traditional CPR consists of chest compression with rescue breathing, chest compression alone might be more acceptable to many laypersons and has the potential advantage of fewer compression interruptions.

Study design: Multicenter randomized trial.

Setting: Two EMSs in Washington state and one in London.

Synopsis: Patients were initially eligible for this study if a dispatcher determined that the patient was unconscious and not breathing, and that bystander CPR was not yet under way. If the caller was willing to undertake CPR with the dispatcher’s assistance, a randomization envelope containing CPR instructions was opened. Patients with arrest due to trauma, drowning, or asphyxiation were excluded, as were those under 18 years of age.

No significant difference was observed between the two groups in the percentage of patients who survived to hospital discharge or who survived with a favorable neurologic outcome. However, subgroup analyses showed a trend toward a higher percentage of patients surviving to hospital discharge with chest compressions alone, as compared with chest compressions with rescue breathing for patients with a cardiac cause of arrest and for those with shockable rhythms.

Bottom line: Dispatcher CPR instruction consisting of chest compression alone was noninferior to conventional CPR with rescue breathing, and it showed a trend toward better outcomes in cardiac cause of arrest.

Citation: Rea TD, Fahrenbruch C, Culley L, et al. CPR with chest compression alone or with rescue breathing. N Engl J Med. 2010;363(5):423-433.

Low Albumin Is Associated with Postoperative Wound Infections

Clinical question: What is the relationship between preoperative serum albumin levels and postoperative surgical-site infections (SSI)?

Background: Poor nutritional status is associated with adverse surgical outcomes. Serum albumin can both reflect nutritional status and function as a negative acute phase reactant, i.e., decreases in the setting of inflammation. It is uncertain whether low preoperative albumin levels are associated with postoperative SSI risk.

Study design: Retrospective cohort with multivariate analysis.

Setting: Four centers in Ireland.

Synopsis: Patients undergoing GI surgery (n=524) were prospectively followed as part of an SSI database. Demographic data, American Society of Anesthesia class, serum albumin levels, and presence and severity of SSI data were collected on all patients. Follow-up extended to 30 days.

SSI developed in 20% of patients. Patients who developed a SSI had lower serum albumin levels (mean 3.0 g/dL versus 3.6 g/dL). A serum albumin level less than 3.0 g/dL was associated with greater risk of SSI (relative risk 5.68), deeper SSI, and prolonged length of stay.

Bottom line: After controlling for other variables, serum albumin lower than 3.0 g/dL is independently associated with SSI frequency and severity.

Citation: Hennessey DB, Burke JP, Ni-Dhonochu T, Shields C, Winter DC, Mealy K. Preoperative hypoalbuminemia is an independent risk factor for the development of surgical site infection following gastrointestinal surgery: a multi-institutional study. Ann Surg. 2010;252 (2):325-329. TH

Pediatric HM Literature

Nebulized Hypertonic Saline Alone Safe to Study in Bronchiolitis

Reviewed by Pediatric Editor Mark Shen, MD, medical director of hospital medicine at Dell Children’s Medical Center, Austin, Texas.

Clinical question: Is nebulized 3% saline solution safe to use alone in infants with bronchiolitis?

Background: Nebulized 3% (hypertonic) saline is increasingly used in the treatment of infants hospitalized with bronchiolitis. Studies to date have primarily investigated its efficacy in conjunction with bronchodilators due to a theoretical risk of bronchospasm. The safety profile of hypertonic saline alone in bronchiolitis is unknown.

Study design: Retrospective cohort study.

Setting: A single children’s hospital.

Synopsis: An existing QI database was reviewed during one winter season. One hundred fifty-four records were analyzed, comprising previously healthy infants with acute bronchiolitis. Hypertonic (3%) saline delivered more than four hours before and after albuterol was considered to have been given alone. Adverse events were not defined a priori, and documentation of symptoms related to medication administration was encouraged via a new comment section of a pathway scoring system.

Sixty-eight patients received 444 doses of hypertonic saline, 377 (85%) of which were administered alone. Four adverse events (1.0%) occurred in the group without adjunctive bronchodilator therapy; one adverse event (1.1%) occurred after concomitant delivery of albuterol and 3% saline. Rates of readmission and transfer to higher level of care were similar between those that did and did not receive hypertonic saline.

The potential for under-ascertainment of adverse events is significant with the retrospective design and frequency of underreporting in most hospitals. In addition, adverse events related to medication administration might be particularly difficult to assess in such dynamic diseases as bronchiolitis. Nevertheless, this study does suggest that adverse event rates are low with hypertonic saline alone, paving the way for future studies to assess its efficacy without bronchodilators clouding the picture.

Bottom line: Nebulized 3% saline has a low rate of adverse events in infants with acute bronchiolitis.

Citation: Ralston S, Hill V, Martinez M. Nebulized hypertonic saline without adjunctive bronchodilators for children with bronchiolitis. Pediatrics. 2010;126(3):e520-e525.

In This Edition

Literature at a Glance

A guide to this month’s studies

• Characteristics of CA-MRSA
• Association of gurgling with morbidity and mortality
• Antibiotics for active ulcerative colitis
• TIPS for cirrhosis-induced variceal bleeding
• Steroid dose, route in COPD exacerbations
• Effect of reminders and stop orders on urinary catheter use
• Outcomes of chest-compression-only CPR
• Albumin levels and risk of surgical-site infections

Characteristics of Community-Acquired methicillin-resistant Staphylococcus aureus Pneumonia in an Academic Medical Center

Clinical question: What are the clinical features and epidemiology of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) pneumonia?

Background: CA-MRSA is an emerging cause of pneumonia. The genetic makeup of most CA-MRSA strains is different than that of nosocomial MRSA. Typically, CA-MRSA is resistant to methicillin, beta-lactams, and erythromycin, but it retains susceptibility to trimethoprim-sulfamethoxazole (TMP/sulfa) and clindamycin.

In addition, the most common strain of CA-MRSA carries the Panton-Valentine leukocidin (PVL) toxin, which is associated with necrotizing pneumonia and high mortality rates.

Study design: Retrospective case series.

Setting: A 1,100-bed teaching hospital in Chicago.

Synopsis: Of the 5,955 discharges with a diagnosis-related group (DRG) code of pneumonia, 15 met criteria for CA-MRSA, or <1% of all inpatient community-acquired pneumonia cases. All 15 CA-MRSA strains were positive for PVL.

Seven of the 15 patients never were admitted to the ICU, while seven patients required mechanical ventilation. Seven patients were immunocompromised; one patient presented with preceding influenza; seven patients presented with hemoptysis; and eight patients demonstrated findings of lung necrosis on CT scan. Two patients died; both were immunocompromised.

Although the initial antibiotic regimen varied considerably, 14 patients ultimately received either clindamycin or linezolid.

Bottom line: CA-MRSA pneumonia is an uncommon subset of community-acquired pneumonia admissions. Approximately half the patients admitted with CA-MRSA presented with features of severe pneumonia. Nearly all were treated with antibiotics that inhibit exotoxin production, and the associated mortality rate of 13% was lower than previously reported.

Citation: Lobo JL, Reed KD, Wunderink RG. Expanded clinical presentation of community-acquired methicillin-resistant Staphylococcus aureus pneumonia. Chest. 2010;138(1):130-136.

Gurgling Breath Sounds in Hospitalized Patients Might Predict Subsequent Pneumonia Development

Clinical question: Can gurgling sounds over the glottis during speech or quiet breathing predict hospital-acquired pneumonia (HAP)?

Background: HAP is a relatively frequent complication of hospitalization. HAP usually portends an increase in morbidity and mortality. Patients in the hospital might have disease states that inhibit the reflexes that normally eliminate secretions from above or below their glottis, increasing the risk of pneumonia.

Study design: Prospective cohort.

Setting: A 350-bed community teaching hospital in Bridgeport, Conn.

Synopsis: All patients admitted to a respiratory-care unit and general medical ward from December 2008 to April 2009 underwent auscultation over their glottis by study personnel. Patients with gurgles heard during speech or quiet breathing on auscultation and patients without gurgles were entered into the study in a 1:3 fashion, until 20 patients with gurgles and 60 patients without gurgles had been enrolled. Patients were followed for the development of clinical and radiographic evidence of HAP, ICU transfer, and in-hospital death.

Both dementia and treatment with opiates were independent predictors of gurgle in multivariate analysis. HAP occurred in 55% of the patients with gurgle versus 1.7% of patients without gurgle. In addition, 50% of the patients with gurgle required transfer to the ICU, compared with only 3.3% of patients without gurgle. In-hospital mortality was 30% among patients with gurgle versus 11.7% among patients without gurgle.

Bottom line: In patients admitted to the medical service of a community teaching hospital, gurgling sounds heard over the glottis during speech or quiet inspiration are independently associated with the development of HAP, ICU transfer, and in-hospital mortality.

Citation: Vazquez R, Gheorghe C, Ramos F, Dadu R, Amoateng-Adjepong Y, Manthous CA. Gurgling breath sounds may predict hospital-acquired pneumonia. Chest. 2010;138(2):284-288.

Treatment of Active Ulcerative Colitis with Triple Antibiotic Therapy Provides Better Response than Placebo

Clinical question: Does combination antibiotic therapy induce and/or maintain remission of active ulcerative colitis (UC)?

Background: Mouse models and other experimental evidence have suggested a pathogenic role for microbes in the development and/or exacerbation of ulcerative colitis, although antibiotic human trials have produced conflicting results. Recently, Fusobacterium varium was shown to be present in the gastrointestinal (GI) tract of most UC patients, and a pilot study using targeted antibacterials demonstrated efficacy in treating active UC.

Study design: Randomized, double-blind, placebo-controlled, multicenter trial.

Setting: Eleven hospitals in Japan.

Synopsis: Patients with mild to severe chronic relapsing UC were randomly assigned to either combination antibiotic therapy or placebo. All previous UC treatment regimens were continued in study patients, with the exception of steroids, which were tapered slowly if possible. Patients in the antibiotic group received a two-week combination therapy of amoxicillin, tetracycline, and metronidazole. Patients were followed weekly or monthly and underwent periodic exams and colonoscopies to assess clinical and endoscopic improvement for 12 months.

One hundred five patients were enrolled in each group. The clinical response rate at one year in patients treated with antibiotics was 44.8% versus 22.8% in the placebo group. Remission at one year was achieved in 26.7% of patients treated with antibiotics versus 14.9% of placebo patients. Endoscopic response rates and steroid discontinuation rates were higher in the antibiotic-treated groups. Effects were most pronounced in the group of patients with active disease.

Bottom line: Triple antibiotic therapy with amoxicillin, tetracycline, and metronidazole, when compared with placebo, was associated with improvement in clinical symptoms, endoscopic findings, remission rates, and steroid withdrawal in patients with active ulcerative colitis.

Citation: Ohkusa T, Kato K, Terao S, et al. Newly developed antibiotic combination therapy for ulcerative colitis: a double-blind placebo-controlled multicenter trial. Am J Gastroenterol. 2010;105(8):1820-1829.

Early TIPS Outperformed Optimal Medical Therapy in Patients with Advanced Cirrhosis and Variceal Bleeding

Clinical question: Does early treatment with a transjugular intrahepatic portosystemic shunt (TIPS) improve outcomes in patients with advanced cirrhosis and variceal bleeding?

Background: Current management guidelines for variceal bleeding include treatment with vasoactive drugs and serial endoscopy, yet treatment failure occurs in 10% to 15% of patients. TIPS is highly effective in controlling bleeding in such patients, but it historically has been reserved for patients who repeatedly fail preventive strategies.

Study design: Randomized controlled trial.

Setting: Nine European centers.

Synopsis: Sixty-three patients with advanced cirrhosis and acute esophageal variceal bleeding treated with optimal medical therapy were randomized within 24 hours of admission to either 1) early TIPS (polytetrafluoroethylene-covered stents) within 72 hours of randomization, or 2) ongoing optimal medical therapy with vasoactive drugs, treatment with a nonselective beta-blocker, and endoscopic band ligation.

During the median 16-month follow-up, rebleeding or failure to control bleeding occurred in 45% of patients in the optimal medical therapy group versus 3% of patients in the early TIPS group. One-year actuarial survival was 61% in the optimal medical therapy group versus 86% in the early-TIPS group. Remarkably, encephalopathy was less common in the early-TIPS group, and adverse events as a whole were similar in both groups.

Bottom line: Early use of TIPS was superior to optimal medical therapy for patients with advanced cirrhosis hospitalized for acute variceal bleeding at high risk for treatment failure.

Citation: García-Pagán JC, Caca K, Bureau C, et al. Early use of TIPS in patients with cirrhosis and variceal bleeding. N Engl J Med. 2010;362(25):2370-2379.

Low-Dose Oral Corticosteroids As Effective As High-Dose Intravenous Therapy in COPD Exacerbations

Clinical question: In patients hospitalized with acute exacerbation of chronic obstructive pulmonary disease (COPD), what are the outcomes of those initially treated with low doses of steroids administered orally compared with those initially treated with higher doses intravenously?

Background: COPD affects 6% of adults in the U.S., and acute exacerbation of COPD is one of the leading causes of hospitalization nationwide. Systemic corticosteroids are beneficial for patients hospitalized with acute exacerbation of COPD; however, optimal dose and route of administration are uncertain.

Study design: Retrospective cohort.

Setting: Four hundred fourteen U.S. acute-care hospitals; most were small to midsize nonteaching facilities serving urban patient populations.

Synopsis: Almost 80,000 patients admitted to a non-ICU setting with a diagnosis of acute exacerbation of COPD from 2006 to 2007, and who received systemic corticosteroids during the first two hospital days, were included in the study. In contrast to clinical guidelines recommending the use of low-dose oral corticosteroids, 92% of study participants were treated initially with intravenous steroids, whereas 8% received oral treatment. The primary composite outcome measure—need for mechanical ventilation after the second hospital day, inpatient mortality, or readmission for COPD within 30 days—was no worse in patients treated with oral steroids. Risk of treatment failure, length of stay, and cost were significantly lower among orally treated patients.

Bottom line: High-dose intravenous steroids appear to be no more effective than low-dose oral steroids for acute exacerbation of COPD. The authors recommend a randomized controlled trial be conducted to compare these two management strategies.

Citation: Lindenauer PK, Pekow PS, Lahti MC, Lee Y, Benjamin EM, Rothberg MB. Association of corticosteroid dose and route of administration with risk of treatment failure in acute exacerbation of chronic obstructive pulmonary disease. JAMA. 2010;303(23):2359-2367.

Reminders and Stop Orders Reduce Catheter-Associated Urinary Tract Infections

Clinical question: Do interventions that remind clinicians of the presence of urinary catheters and prompt timely removal decrease the rate of catheter-associated urinary tract infections (CA-UTI)?

Background: CA-UTI is a common yet preventable hospital-acquired infection. Many catheters are placed unnecessarily, remain in use without physician awareness, and are not removed promptly when no longer needed.

Study design: Systematic review and meta-analysis of 13 preintervention and postintervention quasi-experimental trials and one randomized controlled trial.

Setting: Studies conducted in the U.S., Canada, Europe, and Asia.

Synopsis: This literature search revealed 14 articles that used a reminder or stop-order intervention to prompt removal of urinary catheters and reported pre- and postintervention outcomes for CA-UTI rates, duration of urinary catheter use, and recatheterization need. Five studies used stop orders and nine studies used reminder interventions.

Use of a stop order or reminder reduced the rate of CA-UTI (episodes per 1,000 catheter days) by 52%. Mean duration of catheterization decreased by 37%, which resulted in 2.61 fewer days of catheterization per patient in the intervention versus control groups. Recatheterization rates were similar in the control and intervention groups.

Bottom line: Urinary catheter reminders and stop orders are low-cost strategies that appear to reduce the rate of CA-UTI.

Citation: Meddings J, Rogers MA, Macy M, Saint S. Systematic review and meta-analysis: reminder systems to reduce catheter-associated urinary tract infections and urinary catheter use in hospitalized patients. Clin Infect Dis. 2010;51(5):550-560.

Chest-Compression-Only Bystander CPR Increases Survival

Clinical question: Is bystander cardiopulmonary resuscitation (CPR) with chest compressions alone or chest compressions with rescue breathing superior in out-of-hospital adult cardiac arrest?

Background: Out-of-hospital cardiac arrest claims hundreds of thousands of lives each year. Early initiation of CPR by a layperson can increase a patient’s chances of surviving and having a favorable long-term neurologic recovery. Although traditional CPR consists of chest compression with rescue breathing, chest compression alone might be more acceptable to many laypersons and has the potential advantage of fewer compression interruptions.

Study design: Multicenter randomized trial.

Setting: Two EMSs in Washington state and one in London.

Synopsis: Patients were initially eligible for this study if a dispatcher determined that the patient was unconscious and not breathing, and that bystander CPR was not yet under way. If the caller was willing to undertake CPR with the dispatcher’s assistance, a randomization envelope containing CPR instructions was opened. Patients with arrest due to trauma, drowning, or asphyxiation were excluded, as were those under 18 years of age.

No significant difference was observed between the two groups in the percentage of patients who survived to hospital discharge or who survived with a favorable neurologic outcome. However, subgroup analyses showed a trend toward a higher percentage of patients surviving to hospital discharge with chest compressions alone, as compared with chest compressions with rescue breathing for patients with a cardiac cause of arrest and for those with shockable rhythms.

Bottom line: Dispatcher CPR instruction consisting of chest compression alone was noninferior to conventional CPR with rescue breathing, and it showed a trend toward better outcomes in cardiac cause of arrest.

Citation: Rea TD, Fahrenbruch C, Culley L, et al. CPR with chest compression alone or with rescue breathing. N Engl J Med. 2010;363(5):423-433.

Low Albumin Is Associated with Postoperative Wound Infections

Clinical question: What is the relationship between preoperative serum albumin levels and postoperative surgical-site infections (SSI)?

Background: Poor nutritional status is associated with adverse surgical outcomes. Serum albumin can both reflect nutritional status and function as a negative acute phase reactant, i.e., decreases in the setting of inflammation. It is uncertain whether low preoperative albumin levels are associated with postoperative SSI risk.

Study design: Retrospective cohort with multivariate analysis.

Setting: Four centers in Ireland.

Synopsis: Patients undergoing GI surgery (n=524) were prospectively followed as part of an SSI database. Demographic data, American Society of Anesthesia class, serum albumin levels, and presence and severity of SSI data were collected on all patients. Follow-up extended to 30 days.

SSI developed in 20% of patients. Patients who developed a SSI had lower serum albumin levels (mean 3.0 g/dL versus 3.6 g/dL). A serum albumin level less than 3.0 g/dL was associated with greater risk of SSI (relative risk 5.68), deeper SSI, and prolonged length of stay.

Bottom line: After controlling for other variables, serum albumin lower than 3.0 g/dL is independently associated with SSI frequency and severity.

Citation: Hennessey DB, Burke JP, Ni-Dhonochu T, Shields C, Winter DC, Mealy K. Preoperative hypoalbuminemia is an independent risk factor for the development of surgical site infection following gastrointestinal surgery: a multi-institutional study. Ann Surg. 2010;252 (2):325-329. TH

Pediatric HM Literature

Nebulized Hypertonic Saline Alone Safe to Study in Bronchiolitis

Reviewed by Pediatric Editor Mark Shen, MD, medical director of hospital medicine at Dell Children’s Medical Center, Austin, Texas.

Clinical question: Is nebulized 3% saline solution safe to use alone in infants with bronchiolitis?

Background: Nebulized 3% (hypertonic) saline is increasingly used in the treatment of infants hospitalized with bronchiolitis. Studies to date have primarily investigated its efficacy in conjunction with bronchodilators due to a theoretical risk of bronchospasm. The safety profile of hypertonic saline alone in bronchiolitis is unknown.

Study design: Retrospective cohort study.

Setting: A single children’s hospital.

Synopsis: An existing QI database was reviewed during one winter season. One hundred fifty-four records were analyzed, comprising previously healthy infants with acute bronchiolitis. Hypertonic (3%) saline delivered more than four hours before and after albuterol was considered to have been given alone. Adverse events were not defined a priori, and documentation of symptoms related to medication administration was encouraged via a new comment section of a pathway scoring system.

Sixty-eight patients received 444 doses of hypertonic saline, 377 (85%) of which were administered alone. Four adverse events (1.0%) occurred in the group without adjunctive bronchodilator therapy; one adverse event (1.1%) occurred after concomitant delivery of albuterol and 3% saline. Rates of readmission and transfer to higher level of care were similar between those that did and did not receive hypertonic saline.

The potential for under-ascertainment of adverse events is significant with the retrospective design and frequency of underreporting in most hospitals. In addition, adverse events related to medication administration might be particularly difficult to assess in such dynamic diseases as bronchiolitis. Nevertheless, this study does suggest that adverse event rates are low with hypertonic saline alone, paving the way for future studies to assess its efficacy without bronchodilators clouding the picture.

Bottom line: Nebulized 3% saline has a low rate of adverse events in infants with acute bronchiolitis.

Citation: Ralston S, Hill V, Martinez M. Nebulized hypertonic saline without adjunctive bronchodilators for children with bronchiolitis. Pediatrics. 2010;126(3):e520-e525.