Alan J. Jung, MD

In This Edition

Literature At A Glance

A guide to this month’s studies

1. Initial trophic feedings effective for patients with acute lung injury
2. IM vs. IV benzodiazepines in status epilepticus
3. CDI risk following antibiotic cessation
4. Acid suppression associated with increased complications in CDI patients
5. Perioperative statins and cardiac events in surgical patients
6. Enoxaparin vs. unfractionated heparin during PCI
7. Optimal serum potassium levels for AMI patients
8. PPIs superior to H2-blockers for lowering UGI bleeding following ACS and STEMI

Initial Lower-Volume Enteral Feeding Better Tolerated, but Has No Mortality Benefit

Clinical question: In mechanically ventilated patients with acute lung injury, do initial lower-volume enteral feedings (trophic feedings) improve clinical outcomes when compared with full enteral feedings?

Background: Malnutrition in critically ill patients is associated with poor outcomes, but conflicting data exist regarding the best timing, amount, and formulation of enteral nutrition to initiate. Initiation of lower-volume enteral feeding with periodic assessment of gastric residual volume is common practice, but the effects of this practice are unknown.

Study design: Multicenter randomized controlled open-label study.

Setting: Forty-four hospitals in the National Heart, Lung, and Blood Institute (NHLBI) Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network.

Synopsis: One thousand patients with acute lung injury receiving mechanical ventilation for longer than 72 hours were randomized using a Web-based system to receive either trophic or full enteric feedings for the first six days of mechanical ventilation. After the sixth day, a full enteric feeding protocol was used in all patients. All analyses were by intention-to-treat.

There was no significant difference between the trophic and full enteral feeding groups with regard to the primary outcome of ventilator-free days through Day 28 (14.9% vs. 15.0%, P=0.89). There were also no significant differences between groups in secondary outcomes, which included 60-day mortality, ICU-free days, organ-failure-free days, or the incidence of new infections. However, gastrointestinal intolerances occurred less often in the trophic feeding group, and these patients received fewer anti-diarrheal and prokinetic agents. The full feeding group gained 2.1 liters of fluid by Day 7, but this fluid gain did not cause significant differences in measures of circulatory or pulmonary physiology.

Limitations include open-label study design and inclusion of only critically ill adult medical patients with acute lung injury.

Bottom line: Initial lower-volume tube feedings in mechanically ventilated patients with acute lung injury did not improve clinical outcomes compared with full enteral feedings, but they were associated with fewer instances of gastrointestinal intolerance.

Citation: National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network. Initial trophic vs full enteral feeding in patients with acute lung injury: the EDEN randomized trial. JAMA. 2012;307:795-803.

Intramuscular Benzodiazepines as Good as IV Benzodiazepines in Status Epilepticus

Clinical question: Is intramuscular (IM) midazolam noninferior to intravenous lorazepam in patients in status epilepticus?

Background: Studies have shown that IV benzodiazepines, particularly lorazepam, are effective for patients in status epilepticus. Studies have not evaluated IM benzodiazepines. However, many emergency medical service (EMS) agencies use IM midazolam because IM administration is easier than IV administration, and midazolam has a longer nonrefrigerated shelf life than lorazepam does.

Study design: Randomized, double-blinded clinical trial.

Setting: Thirty-three EMS agencies across the United States.

Synopsis: Based on the 893 adults and children in status epilepticus included in this double-blind study, the researchers found IM midazolam to be noninferior to, and in fact superior to, IV lorazepam for treating seizures prior to arrival at EDs. Specifically, they found 10% more (95% CI 4.0% to 16.1%; P<0.001 for noninferiority and P<0.001 for superiority) seizure-free patients arriving at EDs when IM midazolam was administered. Seizures ceased in patients given IM midazolam in less time on average than it took for paramedics to administer IV lorazepam.

Hospitalists might be less inclined than EMS personnel to use IM midazolam because their patients have established IV access and refrigerated drugs are readily available. However, since IM midazolam was superior to IV lorazepam in this prehospital study, a similar trial in hospitalized patients is warranted. In subsequent trials, it would be useful to administer both midazolam and lorazepam via IM and IV routes, and IM injections by an autoinjector could be compared with the conventional manner.

Bottom line: In the prehospital setting, IM midazolam is at least as good as IV lorazepam in treating status epilepticus in children and adults.

Citation: Silbergleit R, Durkalski V, Lowenstein D, et al. Intramuscular versus intravenous therapy for prehospital status epilepticus. N Engl J Med. 2012;366:591-600.

Clostridium Difficile Infection Risk Remains High at Least Three Months after Antibiotics Are Stopped

Clinical question: How long are patients at higher risk for Clostridium difficile infection (CDI) after completing antibiotics?

Background: Studies have shown that patients given antibiotics are at higher risk for CDI than those who are not, particularly if they take multiple antibiotics at high doses for a prolonged period of time. However, it is not known how long a patient remains at high risk for CDI after completing antibiotic therapy.

Study design: Case-control study.

Setting: Nine hospitals in Netherlands.

Synopsis: The study compared 337 hospitalized patients who had CDI with 337 nondiarrheal controls and 227 non-CDI diarrheal controls. The study showed a seven- to tenfold increased risk for CDI during antibiotic treatment and in the 30 days following cessation of antibiotics. A 2.7-fold increased risk of CDI was seen in the one- to three-month period after antibiotic treatment was stopped.

Because researchers only obtained information about antibiotic use in the three months preceding the onset of diarrhea, it is unknown if CDI risk remains elevated longer than three months after antibiotics are stopped. Also of note, the enzyme immunoassays used in this study to diagnose C. diff had sensitivities of between 60% and 85%.

As hospitalists, this information can be used to advise patients about their continued risk for CDI after cessation of antibiotics. Further studies are needed to determine the risk after three months.

Bottom line: Patients are at highest risk for CDI up to one month after stopping antibiotics but continue to be at higher risk for at least two additional months.

Citation: Hensgens MPN, Goorhuis A, Dekkers OM, Kuijper EJ. Time interval of increased risk for Clostridium difficile infection after exposure to antibiotics. J Antimicrob Chemother. 2012;67:742-748.

Acid Suppression and Poor Outcomes in C. Diff Patients

Clinical question: What are potential modifiable risk factors associated with increased complications and mortality in patients hospitalized with C. diff infection (CDI)?

Background: CDI is a growing cause of morbidity and mortality in hospitalized patients. Evidence is growing for the association of acid suppression, among other modifiable risk factors, with complications and mortality in patients with CDI.

Study design: Retrospective case review.

Setting: Naval medical center.

Synopsis: A laboratory, medical record, and pharmacy database query found 485 patients with CDI. Complications of CDI were defined as ICU admission, surgery, and megacolon. Factors significantly associated with CDI complications and mortality were admission for CDI, corticosteroid use >5 mg per day, age ≥80 years, and prescription acid suppression (including H2-blockers and proton-pump inhibitors).

The latter two risk factors were associated with mortality alone. In multivariable regression, the odds of mortality among patients on acid suppression was more than four times the odds of those not on acid suppression (OR 4.74, 95% CI, 1.57 to 14.36).

Although this is a retrospective cohort study and cannot prove a causal relationship, the data add to a growing body of evidence supporting the risk of CDI complications and mortality for those on acid suppression.

Bottom line: In hospitalized patients with CDI, acid suppression is associated with increased complications and mortality and should be discontinued in this population when possible.

Citation: Morrison RH, Hall NS, Said M, et al. Risk factors associated with complications and mortality in patients with Clostridium difficile infection. Clin Infect Dis. 2011;53:1173-1178.

Perioperative Statins Reduce Cardiac Events for Surgical Patients

Clinical question: Does perioperative statin use improve cardiac outcomes (death, myocardial infarction, atrial fibrillation, and ICU and hospital lengths of stay) in statin-naive patients undergoing cardiac or non-cardiac surgery?

Background: Statins have been hypothesized to reduce perioperative cardiac complications because they reduce vascular and systemic inflammation caused by surgery, and several meta-analyses have demonstrated their efficacy. To date, no meta-analyses have specifically evaluated the benefits of perioperative statins in non-cardiac surgery from randomized controlled trials.

Study design: Systematic review of the literature and meta-analysis.

Setting: Fifteen randomized controlled trials of hospitalized surgical patients.

Synopsis: A systematic review examined the effects of statins on a variety of perioperative cardiac outcomes (death, myocardial infarction, atrial fibrillation, and ICU and hospital lengths of stay); 11 of the 15 patients were undergoing cardiac surgery.

Perioperative statins decreased the risk of atrial fibrillation in patients undergoing cardiac surgery (RR 0.56; 95% CI 0.45-0.69; number needed to treat [NNT], 6). In both cardiac and non-cardiac surgical patients, statins reduced the risk of myocardial infarction (RR 0.53; 95% CI 0.38 to 0.74; NNT 23). Statin treatment also reduced the mean length of hospital stay (in days, mean difference -0.32; 95% CI, -0.53 to -0.11) but did not reduce the length of ICU stay (mean difference -0.08; 95% CI, -0.25 to 0.10). Risk of death was not reduced with statin treatment (RR 0.62; 95% CI, 0.34 to 1.14).

Bottom line: Perioperative statins reduce the risk of postoperative atrial fibrillation in cardiac surgical patients, the risk of postoperative MI in cardiac and non-cardiac surgical patients, and the mean length of hospital stay.

Citation: Chopra V, Wesorick DH, Sussman JB, et al. Effect of perioperative statins on death, myocardial infarction, atrial fibrillation, and length of stay: a systematic review and meta-analysis. Arch Surg. 2012;147:181-188.

Enoxaparin Safe and Effective during Percutaneous Coronary Intervention

Clinical question: Is enoxaparin safe and efficacious compared with unfractionated heparin during percutaneous coronary intervention (PCI)?

Background: Despite problems with the use of unfractionated heparin during PCI, current guidelines give it a Class 1 recommendation for PCI in ST-elevation myocardial infarction (MI). There is growing evidence that enoxaparin can provide predictable, effective anticoagulation during PCI. Although several trials have examined this issue, none have been sufficiently powered to evaluate mortality.

Study design: Systematic review and meta-analysis.

Setting: Twenty-three trials or registries of patients undergoing PCI.

Synopsis: A systematic review found 23 trials representing 30,966 patients that examined the effects of enoxaparin versus unfractionated heparin on risk of mortality, MI, complications of MI, and major bleeding. Of these, 10,243 (33.1%) patients underwent primary PCI for ST elevation MI, 8,750 (28.2%) underwent PCI after fibrinolysis, and 11,973 (38.7%) patients had either scheduled PCI or PCI for non-ST elevation acute coronary syndrome.

Of all the patients, 13,943 (45%) received enoxaparin and 17,023 (55%) received unfractionated heparin. Enoxaparin was associated with significant reductions in all-cause mortality (RR 0.66; 95% CI, 0.57 to 0.76), composite of death or MI (RR 0.68; 95% CI, 0.57 to 0.81), and complications of MI (RR 0.75; 95% CI, 0.6 to 0.85). For patients who received primary PCI for ST elevation MI, enoxaparin reduced the risk of complications of MI by 44% (RR 0.56; 95% CI, 0.42 to 0.76). Enoxaparin also reduced the risk of major bleeding (RR 0.80, 95% CI, 0.68 to 0.95) with even more striking results for the 14 studies that compared intravenous enoxaparin to unfractionated heparin (RR 0.66; 95% CI, 0.52 to 0.83).

Bottom line: Enoxaparin is safe and efficacious when used during PCI. Patients who receive enoxaparin during PCI have reduced risk for death, MI, complications of MI, and major bleeding when compared with patients who receive unfractionated heparin.

Citation: Silvain J, Beygui F, Barthelmy O, et al. Efficacy and safety of enoxaparin versus unfractionated heparin during percutaneous coronary intervention: systematic review and meta-analysis. BMJ. 2012;344:e553.

Serum Potassium Levels and Mortality in Acute Myocardial Infarction

Clinical question: What is the relationship between serum potassium levels and mortality in acute myocardial infarction (AMI) patients?

Background: Several smaller studies in the pre-beta-blocker and pre-reperfusion era recommended maintaining serum potassium levels between 4.0 mEq/L and 5.0 mEq/L in AMI patients. However, current studies examining the relationship between potassium levels and mortality in AMI patients are lacking.

Study design: Retrospective cohort study.

Setting: Multicenter study involving 67 hospitals in the U.S.

Synopsis: Using the Cerner Health Facts database, which included 38,689 patients with biomarker-confirmed AMI, this study showed there was a U-shaped relationship between mean post-admission serum potassium level and in-hospital mortality.

Compared with the reference group of 3.5 mEq/L to less than 4.0 mEq/L (mortality rate 4.8%; 95% CI, 4.4% to 5.2%), mortality was comparable for those with mean post-admission potassium of 4.0 mEq/L to less than 4.5 mEq/L (5.0%; 95% CI, 4.7% to 5.3%). Mortality was twice as great for potassium of 4.5 mEq/L to less than 5.0 mEq/L (10.0%; 95% CI, 9.1% to 10.9%), and even greater for higher potassium strata. Similarly, mortality rates were higher for potassium levels of less than 3.5 mEq/L. Rates of ventricular fibrillation or cardiac arrest were higher among patients with potassium levels of less than 3.0 mEq/L or more than 5.0 mEq/L.

Bottom line: For inpatients with AMI, serum potassium levels of 3.5 mEq/L to 4.5 mEq/L should be maintained for the best outcomes. Repletion of serum potassium to levels greater than 4.5 mEq/L is associated with increased mortality and should be avoided.

Citation: Goyal A, Spertus JA, Gosch K, et al. Serum potassium levels and mortality in acute myocardial infarction. JAMA. 2012;307:157-164.

Proton-Pump Inhibitors Better than H2-Blockers in ACS and STEMI

Clinical question: Are proton-pump inhibitors (PPIs) better than H2-blockers at preventing UGI bleeding in patients after acute coronary syndrome (ACS) or ST-elevation myocardial infarction (STEMI)?

Background: It is not definitively known if PPIs are the same or better than H2-blockers in preventing UGI bleeding in patients on high-risk medications (aspirin, clopidogrel, and anticoagulants) after ACS or STEMI.

Study design: Randomized double-blinded controlled trial.

Setting: Single hospital.

Synopsis: Patients with ACS or STEMI were treated with aspirin, clopidogrel, and enoxaparin or thrombolytics. They were then randomized to either esomeprazole 20 mg or famotidine 40 mg, both administered nightly. They were followed throughout their hospital stay and were then followed between four and 52 weeks after discharge (mean duration: 19 weeks for esomeprazole, 18 weeks for famotidine). The primary end point was time to a composite outcome, consisting of UGI bleeding, obstruction, or perforation. Overall, 313 patients were randomized (164 to esomeprazole and 149 to famotidine).

The treatment groups were equivalent in baseline characteristics, and compliance in both groups was excellent (>98%). The primary endpoint occurred in three patients in the esomeprazole group and in 12 patients in the famotidine group (hazard ratio 0.21; 95% CI, 0.06 to 0.75; P=0.008).

Bottom line: PPIs are superior to H2-blockers in reducing UGI bleeding in patients on high-risk medications (aspirin, clopidogrel, and enoxaparin or thrombolytics) after ACS and STEMI. This confirms the recommendations of the 2010 ACCF/ACG/AHA Expert Consensus that PPIs should be used in those on dual antiplatelet therapy on anticoagulants.

Citation: Ng FH, Tunggal P, Chu WM, et al. Esomeprazole compared with famotidine in the prevention of upper gastrointestinal bleeding in patients with acute coronary syndrome or myocardial infarction. Am J Gastroenterol. 2012;107:389-396.

In This Edition

Literature At A Glance

A guide to this month’s studies

1. Initial trophic feedings effective for patients with acute lung injury
2. IM vs. IV benzodiazepines in status epilepticus
3. CDI risk following antibiotic cessation
4. Acid suppression associated with increased complications in CDI patients
5. Perioperative statins and cardiac events in surgical patients
6. Enoxaparin vs. unfractionated heparin during PCI
7. Optimal serum potassium levels for AMI patients
8. PPIs superior to H2-blockers for lowering UGI bleeding following ACS and STEMI

Initial Lower-Volume Enteral Feeding Better Tolerated, but Has No Mortality Benefit

Clinical question: In mechanically ventilated patients with acute lung injury, do initial lower-volume enteral feedings (trophic feedings) improve clinical outcomes when compared with full enteral feedings?

Background: Malnutrition in critically ill patients is associated with poor outcomes, but conflicting data exist regarding the best timing, amount, and formulation of enteral nutrition to initiate. Initiation of lower-volume enteral feeding with periodic assessment of gastric residual volume is common practice, but the effects of this practice are unknown.

Study design: Multicenter randomized controlled open-label study.

Setting: Forty-four hospitals in the National Heart, Lung, and Blood Institute (NHLBI) Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network.

Synopsis: One thousand patients with acute lung injury receiving mechanical ventilation for longer than 72 hours were randomized using a Web-based system to receive either trophic or full enteric feedings for the first six days of mechanical ventilation. After the sixth day, a full enteric feeding protocol was used in all patients. All analyses were by intention-to-treat.

There was no significant difference between the trophic and full enteral feeding groups with regard to the primary outcome of ventilator-free days through Day 28 (14.9% vs. 15.0%, P=0.89). There were also no significant differences between groups in secondary outcomes, which included 60-day mortality, ICU-free days, organ-failure-free days, or the incidence of new infections. However, gastrointestinal intolerances occurred less often in the trophic feeding group, and these patients received fewer anti-diarrheal and prokinetic agents. The full feeding group gained 2.1 liters of fluid by Day 7, but this fluid gain did not cause significant differences in measures of circulatory or pulmonary physiology.

Limitations include open-label study design and inclusion of only critically ill adult medical patients with acute lung injury.

Bottom line: Initial lower-volume tube feedings in mechanically ventilated patients with acute lung injury did not improve clinical outcomes compared with full enteral feedings, but they were associated with fewer instances of gastrointestinal intolerance.

Citation: National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network. Initial trophic vs full enteral feeding in patients with acute lung injury: the EDEN randomized trial. JAMA. 2012;307:795-803.

Intramuscular Benzodiazepines as Good as IV Benzodiazepines in Status Epilepticus

Clinical question: Is intramuscular (IM) midazolam noninferior to intravenous lorazepam in patients in status epilepticus?

Background: Studies have shown that IV benzodiazepines, particularly lorazepam, are effective for patients in status epilepticus. Studies have not evaluated IM benzodiazepines. However, many emergency medical service (EMS) agencies use IM midazolam because IM administration is easier than IV administration, and midazolam has a longer nonrefrigerated shelf life than lorazepam does.

Study design: Randomized, double-blinded clinical trial.

Setting: Thirty-three EMS agencies across the United States.

Synopsis: Based on the 893 adults and children in status epilepticus included in this double-blind study, the researchers found IM midazolam to be noninferior to, and in fact superior to, IV lorazepam for treating seizures prior to arrival at EDs. Specifically, they found 10% more (95% CI 4.0% to 16.1%; P<0.001 for noninferiority and P<0.001 for superiority) seizure-free patients arriving at EDs when IM midazolam was administered. Seizures ceased in patients given IM midazolam in less time on average than it took for paramedics to administer IV lorazepam.

Hospitalists might be less inclined than EMS personnel to use IM midazolam because their patients have established IV access and refrigerated drugs are readily available. However, since IM midazolam was superior to IV lorazepam in this prehospital study, a similar trial in hospitalized patients is warranted. In subsequent trials, it would be useful to administer both midazolam and lorazepam via IM and IV routes, and IM injections by an autoinjector could be compared with the conventional manner.

Bottom line: In the prehospital setting, IM midazolam is at least as good as IV lorazepam in treating status epilepticus in children and adults.

Citation: Silbergleit R, Durkalski V, Lowenstein D, et al. Intramuscular versus intravenous therapy for prehospital status epilepticus. N Engl J Med. 2012;366:591-600.

Clostridium Difficile Infection Risk Remains High at Least Three Months after Antibiotics Are Stopped

Clinical question: How long are patients at higher risk for Clostridium difficile infection (CDI) after completing antibiotics?

Background: Studies have shown that patients given antibiotics are at higher risk for CDI than those who are not, particularly if they take multiple antibiotics at high doses for a prolonged period of time. However, it is not known how long a patient remains at high risk for CDI after completing antibiotic therapy.

Study design: Case-control study.

Setting: Nine hospitals in Netherlands.

Synopsis: The study compared 337 hospitalized patients who had CDI with 337 nondiarrheal controls and 227 non-CDI diarrheal controls. The study showed a seven- to tenfold increased risk for CDI during antibiotic treatment and in the 30 days following cessation of antibiotics. A 2.7-fold increased risk of CDI was seen in the one- to three-month period after antibiotic treatment was stopped.

Because researchers only obtained information about antibiotic use in the three months preceding the onset of diarrhea, it is unknown if CDI risk remains elevated longer than three months after antibiotics are stopped. Also of note, the enzyme immunoassays used in this study to diagnose C. diff had sensitivities of between 60% and 85%.

As hospitalists, this information can be used to advise patients about their continued risk for CDI after cessation of antibiotics. Further studies are needed to determine the risk after three months.

Bottom line: Patients are at highest risk for CDI up to one month after stopping antibiotics but continue to be at higher risk for at least two additional months.

Citation: Hensgens MPN, Goorhuis A, Dekkers OM, Kuijper EJ. Time interval of increased risk for Clostridium difficile infection after exposure to antibiotics. J Antimicrob Chemother. 2012;67:742-748.

Acid Suppression and Poor Outcomes in C. Diff Patients

Clinical question: What are potential modifiable risk factors associated with increased complications and mortality in patients hospitalized with C. diff infection (CDI)?

Background: CDI is a growing cause of morbidity and mortality in hospitalized patients. Evidence is growing for the association of acid suppression, among other modifiable risk factors, with complications and mortality in patients with CDI.

Study design: Retrospective case review.

Setting: Naval medical center.

Synopsis: A laboratory, medical record, and pharmacy database query found 485 patients with CDI. Complications of CDI were defined as ICU admission, surgery, and megacolon. Factors significantly associated with CDI complications and mortality were admission for CDI, corticosteroid use >5 mg per day, age ≥80 years, and prescription acid suppression (including H2-blockers and proton-pump inhibitors).

The latter two risk factors were associated with mortality alone. In multivariable regression, the odds of mortality among patients on acid suppression was more than four times the odds of those not on acid suppression (OR 4.74, 95% CI, 1.57 to 14.36).

Although this is a retrospective cohort study and cannot prove a causal relationship, the data add to a growing body of evidence supporting the risk of CDI complications and mortality for those on acid suppression.

Bottom line: In hospitalized patients with CDI, acid suppression is associated with increased complications and mortality and should be discontinued in this population when possible.

Citation: Morrison RH, Hall NS, Said M, et al. Risk factors associated with complications and mortality in patients with Clostridium difficile infection. Clin Infect Dis. 2011;53:1173-1178.

Perioperative Statins Reduce Cardiac Events for Surgical Patients

Clinical question: Does perioperative statin use improve cardiac outcomes (death, myocardial infarction, atrial fibrillation, and ICU and hospital lengths of stay) in statin-naive patients undergoing cardiac or non-cardiac surgery?

Background: Statins have been hypothesized to reduce perioperative cardiac complications because they reduce vascular and systemic inflammation caused by surgery, and several meta-analyses have demonstrated their efficacy. To date, no meta-analyses have specifically evaluated the benefits of perioperative statins in non-cardiac surgery from randomized controlled trials.

Study design: Systematic review of the literature and meta-analysis.

Setting: Fifteen randomized controlled trials of hospitalized surgical patients.

Synopsis: A systematic review examined the effects of statins on a variety of perioperative cardiac outcomes (death, myocardial infarction, atrial fibrillation, and ICU and hospital lengths of stay); 11 of the 15 patients were undergoing cardiac surgery.

Perioperative statins decreased the risk of atrial fibrillation in patients undergoing cardiac surgery (RR 0.56; 95% CI 0.45-0.69; number needed to treat [NNT], 6). In both cardiac and non-cardiac surgical patients, statins reduced the risk of myocardial infarction (RR 0.53; 95% CI 0.38 to 0.74; NNT 23). Statin treatment also reduced the mean length of hospital stay (in days, mean difference -0.32; 95% CI, -0.53 to -0.11) but did not reduce the length of ICU stay (mean difference -0.08; 95% CI, -0.25 to 0.10). Risk of death was not reduced with statin treatment (RR 0.62; 95% CI, 0.34 to 1.14).

Bottom line: Perioperative statins reduce the risk of postoperative atrial fibrillation in cardiac surgical patients, the risk of postoperative MI in cardiac and non-cardiac surgical patients, and the mean length of hospital stay.

Citation: Chopra V, Wesorick DH, Sussman JB, et al. Effect of perioperative statins on death, myocardial infarction, atrial fibrillation, and length of stay: a systematic review and meta-analysis. Arch Surg. 2012;147:181-188.

Enoxaparin Safe and Effective during Percutaneous Coronary Intervention

Clinical question: Is enoxaparin safe and efficacious compared with unfractionated heparin during percutaneous coronary intervention (PCI)?

Background: Despite problems with the use of unfractionated heparin during PCI, current guidelines give it a Class 1 recommendation for PCI in ST-elevation myocardial infarction (MI). There is growing evidence that enoxaparin can provide predictable, effective anticoagulation during PCI. Although several trials have examined this issue, none have been sufficiently powered to evaluate mortality.

Study design: Systematic review and meta-analysis.

Setting: Twenty-three trials or registries of patients undergoing PCI.

Synopsis: A systematic review found 23 trials representing 30,966 patients that examined the effects of enoxaparin versus unfractionated heparin on risk of mortality, MI, complications of MI, and major bleeding. Of these, 10,243 (33.1%) patients underwent primary PCI for ST elevation MI, 8,750 (28.2%) underwent PCI after fibrinolysis, and 11,973 (38.7%) patients had either scheduled PCI or PCI for non-ST elevation acute coronary syndrome.

Of all the patients, 13,943 (45%) received enoxaparin and 17,023 (55%) received unfractionated heparin. Enoxaparin was associated with significant reductions in all-cause mortality (RR 0.66; 95% CI, 0.57 to 0.76), composite of death or MI (RR 0.68; 95% CI, 0.57 to 0.81), and complications of MI (RR 0.75; 95% CI, 0.6 to 0.85). For patients who received primary PCI for ST elevation MI, enoxaparin reduced the risk of complications of MI by 44% (RR 0.56; 95% CI, 0.42 to 0.76). Enoxaparin also reduced the risk of major bleeding (RR 0.80, 95% CI, 0.68 to 0.95) with even more striking results for the 14 studies that compared intravenous enoxaparin to unfractionated heparin (RR 0.66; 95% CI, 0.52 to 0.83).

Bottom line: Enoxaparin is safe and efficacious when used during PCI. Patients who receive enoxaparin during PCI have reduced risk for death, MI, complications of MI, and major bleeding when compared with patients who receive unfractionated heparin.

Citation: Silvain J, Beygui F, Barthelmy O, et al. Efficacy and safety of enoxaparin versus unfractionated heparin during percutaneous coronary intervention: systematic review and meta-analysis. BMJ. 2012;344:e553.

Serum Potassium Levels and Mortality in Acute Myocardial Infarction

Clinical question: What is the relationship between serum potassium levels and mortality in acute myocardial infarction (AMI) patients?

Background: Several smaller studies in the pre-beta-blocker and pre-reperfusion era recommended maintaining serum potassium levels between 4.0 mEq/L and 5.0 mEq/L in AMI patients. However, current studies examining the relationship between potassium levels and mortality in AMI patients are lacking.

Study design: Retrospective cohort study.

Setting: Multicenter study involving 67 hospitals in the U.S.

Synopsis: Using the Cerner Health Facts database, which included 38,689 patients with biomarker-confirmed AMI, this study showed there was a U-shaped relationship between mean post-admission serum potassium level and in-hospital mortality.

Compared with the reference group of 3.5 mEq/L to less than 4.0 mEq/L (mortality rate 4.8%; 95% CI, 4.4% to 5.2%), mortality was comparable for those with mean post-admission potassium of 4.0 mEq/L to less than 4.5 mEq/L (5.0%; 95% CI, 4.7% to 5.3%). Mortality was twice as great for potassium of 4.5 mEq/L to less than 5.0 mEq/L (10.0%; 95% CI, 9.1% to 10.9%), and even greater for higher potassium strata. Similarly, mortality rates were higher for potassium levels of less than 3.5 mEq/L. Rates of ventricular fibrillation or cardiac arrest were higher among patients with potassium levels of less than 3.0 mEq/L or more than 5.0 mEq/L.

Bottom line: For inpatients with AMI, serum potassium levels of 3.5 mEq/L to 4.5 mEq/L should be maintained for the best outcomes. Repletion of serum potassium to levels greater than 4.5 mEq/L is associated with increased mortality and should be avoided.

Citation: Goyal A, Spertus JA, Gosch K, et al. Serum potassium levels and mortality in acute myocardial infarction. JAMA. 2012;307:157-164.

Proton-Pump Inhibitors Better than H2-Blockers in ACS and STEMI

Clinical question: Are proton-pump inhibitors (PPIs) better than H2-blockers at preventing UGI bleeding in patients after acute coronary syndrome (ACS) or ST-elevation myocardial infarction (STEMI)?

Background: It is not definitively known if PPIs are the same or better than H2-blockers in preventing UGI bleeding in patients on high-risk medications (aspirin, clopidogrel, and anticoagulants) after ACS or STEMI.

Study design: Randomized double-blinded controlled trial.

Setting: Single hospital.

Synopsis: Patients with ACS or STEMI were treated with aspirin, clopidogrel, and enoxaparin or thrombolytics. They were then randomized to either esomeprazole 20 mg or famotidine 40 mg, both administered nightly. They were followed throughout their hospital stay and were then followed between four and 52 weeks after discharge (mean duration: 19 weeks for esomeprazole, 18 weeks for famotidine). The primary end point was time to a composite outcome, consisting of UGI bleeding, obstruction, or perforation. Overall, 313 patients were randomized (164 to esomeprazole and 149 to famotidine).

The treatment groups were equivalent in baseline characteristics, and compliance in both groups was excellent (>98%). The primary endpoint occurred in three patients in the esomeprazole group and in 12 patients in the famotidine group (hazard ratio 0.21; 95% CI, 0.06 to 0.75; P=0.008).

Bottom line: PPIs are superior to H2-blockers in reducing UGI bleeding in patients on high-risk medications (aspirin, clopidogrel, and enoxaparin or thrombolytics) after ACS and STEMI. This confirms the recommendations of the 2010 ACCF/ACG/AHA Expert Consensus that PPIs should be used in those on dual antiplatelet therapy on anticoagulants.

Citation: Ng FH, Tunggal P, Chu WM, et al. Esomeprazole compared with famotidine in the prevention of upper gastrointestinal bleeding in patients with acute coronary syndrome or myocardial infarction. Am J Gastroenterol. 2012;107:389-396.

In This Edition

Literature At A Glance

A guide to this month’s studies

1. Initial trophic feedings effective for patients with acute lung injury
2. IM vs. IV benzodiazepines in status epilepticus
3. CDI risk following antibiotic cessation
4. Acid suppression associated with increased complications in CDI patients
5. Perioperative statins and cardiac events in surgical patients
6. Enoxaparin vs. unfractionated heparin during PCI
7. Optimal serum potassium levels for AMI patients
8. PPIs superior to H2-blockers for lowering UGI bleeding following ACS and STEMI

Initial Lower-Volume Enteral Feeding Better Tolerated, but Has No Mortality Benefit

Clinical question: In mechanically ventilated patients with acute lung injury, do initial lower-volume enteral feedings (trophic feedings) improve clinical outcomes when compared with full enteral feedings?

Background: Malnutrition in critically ill patients is associated with poor outcomes, but conflicting data exist regarding the best timing, amount, and formulation of enteral nutrition to initiate. Initiation of lower-volume enteral feeding with periodic assessment of gastric residual volume is common practice, but the effects of this practice are unknown.

Study design: Multicenter randomized controlled open-label study.

Setting: Forty-four hospitals in the National Heart, Lung, and Blood Institute (NHLBI) Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network.

Synopsis: One thousand patients with acute lung injury receiving mechanical ventilation for longer than 72 hours were randomized using a Web-based system to receive either trophic or full enteric feedings for the first six days of mechanical ventilation. After the sixth day, a full enteric feeding protocol was used in all patients. All analyses were by intention-to-treat.

There was no significant difference between the trophic and full enteral feeding groups with regard to the primary outcome of ventilator-free days through Day 28 (14.9% vs. 15.0%, P=0.89). There were also no significant differences between groups in secondary outcomes, which included 60-day mortality, ICU-free days, organ-failure-free days, or the incidence of new infections. However, gastrointestinal intolerances occurred less often in the trophic feeding group, and these patients received fewer anti-diarrheal and prokinetic agents. The full feeding group gained 2.1 liters of fluid by Day 7, but this fluid gain did not cause significant differences in measures of circulatory or pulmonary physiology.

Limitations include open-label study design and inclusion of only critically ill adult medical patients with acute lung injury.

Bottom line: Initial lower-volume tube feedings in mechanically ventilated patients with acute lung injury did not improve clinical outcomes compared with full enteral feedings, but they were associated with fewer instances of gastrointestinal intolerance.

Citation: National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network. Initial trophic vs full enteral feeding in patients with acute lung injury: the EDEN randomized trial. JAMA. 2012;307:795-803.

Intramuscular Benzodiazepines as Good as IV Benzodiazepines in Status Epilepticus

Clinical question: Is intramuscular (IM) midazolam noninferior to intravenous lorazepam in patients in status epilepticus?

Background: Studies have shown that IV benzodiazepines, particularly lorazepam, are effective for patients in status epilepticus. Studies have not evaluated IM benzodiazepines. However, many emergency medical service (EMS) agencies use IM midazolam because IM administration is easier than IV administration, and midazolam has a longer nonrefrigerated shelf life than lorazepam does.

Study design: Randomized, double-blinded clinical trial.

Setting: Thirty-three EMS agencies across the United States.

Synopsis: Based on the 893 adults and children in status epilepticus included in this double-blind study, the researchers found IM midazolam to be noninferior to, and in fact superior to, IV lorazepam for treating seizures prior to arrival at EDs. Specifically, they found 10% more (95% CI 4.0% to 16.1%; P<0.001 for noninferiority and P<0.001 for superiority) seizure-free patients arriving at EDs when IM midazolam was administered. Seizures ceased in patients given IM midazolam in less time on average than it took for paramedics to administer IV lorazepam.

Hospitalists might be less inclined than EMS personnel to use IM midazolam because their patients have established IV access and refrigerated drugs are readily available. However, since IM midazolam was superior to IV lorazepam in this prehospital study, a similar trial in hospitalized patients is warranted. In subsequent trials, it would be useful to administer both midazolam and lorazepam via IM and IV routes, and IM injections by an autoinjector could be compared with the conventional manner.

Bottom line: In the prehospital setting, IM midazolam is at least as good as IV lorazepam in treating status epilepticus in children and adults.

Citation: Silbergleit R, Durkalski V, Lowenstein D, et al. Intramuscular versus intravenous therapy for prehospital status epilepticus. N Engl J Med. 2012;366:591-600.

Clostridium Difficile Infection Risk Remains High at Least Three Months after Antibiotics Are Stopped

Clinical question: How long are patients at higher risk for Clostridium difficile infection (CDI) after completing antibiotics?

Background: Studies have shown that patients given antibiotics are at higher risk for CDI than those who are not, particularly if they take multiple antibiotics at high doses for a prolonged period of time. However, it is not known how long a patient remains at high risk for CDI after completing antibiotic therapy.

Study design: Case-control study.

Setting: Nine hospitals in Netherlands.

Synopsis: The study compared 337 hospitalized patients who had CDI with 337 nondiarrheal controls and 227 non-CDI diarrheal controls. The study showed a seven- to tenfold increased risk for CDI during antibiotic treatment and in the 30 days following cessation of antibiotics. A 2.7-fold increased risk of CDI was seen in the one- to three-month period after antibiotic treatment was stopped.

Because researchers only obtained information about antibiotic use in the three months preceding the onset of diarrhea, it is unknown if CDI risk remains elevated longer than three months after antibiotics are stopped. Also of note, the enzyme immunoassays used in this study to diagnose C. diff had sensitivities of between 60% and 85%.

As hospitalists, this information can be used to advise patients about their continued risk for CDI after cessation of antibiotics. Further studies are needed to determine the risk after three months.

Bottom line: Patients are at highest risk for CDI up to one month after stopping antibiotics but continue to be at higher risk for at least two additional months.

Citation: Hensgens MPN, Goorhuis A, Dekkers OM, Kuijper EJ. Time interval of increased risk for Clostridium difficile infection after exposure to antibiotics. J Antimicrob Chemother. 2012;67:742-748.

Acid Suppression and Poor Outcomes in C. Diff Patients

Clinical question: What are potential modifiable risk factors associated with increased complications and mortality in patients hospitalized with C. diff infection (CDI)?

Background: CDI is a growing cause of morbidity and mortality in hospitalized patients. Evidence is growing for the association of acid suppression, among other modifiable risk factors, with complications and mortality in patients with CDI.

Study design: Retrospective case review.

Setting: Naval medical center.

Synopsis: A laboratory, medical record, and pharmacy database query found 485 patients with CDI. Complications of CDI were defined as ICU admission, surgery, and megacolon. Factors significantly associated with CDI complications and mortality were admission for CDI, corticosteroid use >5 mg per day, age ≥80 years, and prescription acid suppression (including H2-blockers and proton-pump inhibitors).

The latter two risk factors were associated with mortality alone. In multivariable regression, the odds of mortality among patients on acid suppression was more than four times the odds of those not on acid suppression (OR 4.74, 95% CI, 1.57 to 14.36).

Although this is a retrospective cohort study and cannot prove a causal relationship, the data add to a growing body of evidence supporting the risk of CDI complications and mortality for those on acid suppression.

Bottom line: In hospitalized patients with CDI, acid suppression is associated with increased complications and mortality and should be discontinued in this population when possible.

Citation: Morrison RH, Hall NS, Said M, et al. Risk factors associated with complications and mortality in patients with Clostridium difficile infection. Clin Infect Dis. 2011;53:1173-1178.

Perioperative Statins Reduce Cardiac Events for Surgical Patients

Clinical question: Does perioperative statin use improve cardiac outcomes (death, myocardial infarction, atrial fibrillation, and ICU and hospital lengths of stay) in statin-naive patients undergoing cardiac or non-cardiac surgery?

Background: Statins have been hypothesized to reduce perioperative cardiac complications because they reduce vascular and systemic inflammation caused by surgery, and several meta-analyses have demonstrated their efficacy. To date, no meta-analyses have specifically evaluated the benefits of perioperative statins in non-cardiac surgery from randomized controlled trials.

Study design: Systematic review of the literature and meta-analysis.

Setting: Fifteen randomized controlled trials of hospitalized surgical patients.

Synopsis: A systematic review examined the effects of statins on a variety of perioperative cardiac outcomes (death, myocardial infarction, atrial fibrillation, and ICU and hospital lengths of stay); 11 of the 15 patients were undergoing cardiac surgery.

Perioperative statins decreased the risk of atrial fibrillation in patients undergoing cardiac surgery (RR 0.56; 95% CI 0.45-0.69; number needed to treat [NNT], 6). In both cardiac and non-cardiac surgical patients, statins reduced the risk of myocardial infarction (RR 0.53; 95% CI 0.38 to 0.74; NNT 23). Statin treatment also reduced the mean length of hospital stay (in days, mean difference -0.32; 95% CI, -0.53 to -0.11) but did not reduce the length of ICU stay (mean difference -0.08; 95% CI, -0.25 to 0.10). Risk of death was not reduced with statin treatment (RR 0.62; 95% CI, 0.34 to 1.14).

Bottom line: Perioperative statins reduce the risk of postoperative atrial fibrillation in cardiac surgical patients, the risk of postoperative MI in cardiac and non-cardiac surgical patients, and the mean length of hospital stay.

Citation: Chopra V, Wesorick DH, Sussman JB, et al. Effect of perioperative statins on death, myocardial infarction, atrial fibrillation, and length of stay: a systematic review and meta-analysis. Arch Surg. 2012;147:181-188.

Enoxaparin Safe and Effective during Percutaneous Coronary Intervention

Clinical question: Is enoxaparin safe and efficacious compared with unfractionated heparin during percutaneous coronary intervention (PCI)?

Background: Despite problems with the use of unfractionated heparin during PCI, current guidelines give it a Class 1 recommendation for PCI in ST-elevation myocardial infarction (MI). There is growing evidence that enoxaparin can provide predictable, effective anticoagulation during PCI. Although several trials have examined this issue, none have been sufficiently powered to evaluate mortality.

Study design: Systematic review and meta-analysis.

Setting: Twenty-three trials or registries of patients undergoing PCI.

Synopsis: A systematic review found 23 trials representing 30,966 patients that examined the effects of enoxaparin versus unfractionated heparin on risk of mortality, MI, complications of MI, and major bleeding. Of these, 10,243 (33.1%) patients underwent primary PCI for ST elevation MI, 8,750 (28.2%) underwent PCI after fibrinolysis, and 11,973 (38.7%) patients had either scheduled PCI or PCI for non-ST elevation acute coronary syndrome.

Of all the patients, 13,943 (45%) received enoxaparin and 17,023 (55%) received unfractionated heparin. Enoxaparin was associated with significant reductions in all-cause mortality (RR 0.66; 95% CI, 0.57 to 0.76), composite of death or MI (RR 0.68; 95% CI, 0.57 to 0.81), and complications of MI (RR 0.75; 95% CI, 0.6 to 0.85). For patients who received primary PCI for ST elevation MI, enoxaparin reduced the risk of complications of MI by 44% (RR 0.56; 95% CI, 0.42 to 0.76). Enoxaparin also reduced the risk of major bleeding (RR 0.80, 95% CI, 0.68 to 0.95) with even more striking results for the 14 studies that compared intravenous enoxaparin to unfractionated heparin (RR 0.66; 95% CI, 0.52 to 0.83).

Bottom line: Enoxaparin is safe and efficacious when used during PCI. Patients who receive enoxaparin during PCI have reduced risk for death, MI, complications of MI, and major bleeding when compared with patients who receive unfractionated heparin.

Citation: Silvain J, Beygui F, Barthelmy O, et al. Efficacy and safety of enoxaparin versus unfractionated heparin during percutaneous coronary intervention: systematic review and meta-analysis. BMJ. 2012;344:e553.

Serum Potassium Levels and Mortality in Acute Myocardial Infarction

Clinical question: What is the relationship between serum potassium levels and mortality in acute myocardial infarction (AMI) patients?

Background: Several smaller studies in the pre-beta-blocker and pre-reperfusion era recommended maintaining serum potassium levels between 4.0 mEq/L and 5.0 mEq/L in AMI patients. However, current studies examining the relationship between potassium levels and mortality in AMI patients are lacking.

Study design: Retrospective cohort study.

Setting: Multicenter study involving 67 hospitals in the U.S.

Synopsis: Using the Cerner Health Facts database, which included 38,689 patients with biomarker-confirmed AMI, this study showed there was a U-shaped relationship between mean post-admission serum potassium level and in-hospital mortality.

Compared with the reference group of 3.5 mEq/L to less than 4.0 mEq/L (mortality rate 4.8%; 95% CI, 4.4% to 5.2%), mortality was comparable for those with mean post-admission potassium of 4.0 mEq/L to less than 4.5 mEq/L (5.0%; 95% CI, 4.7% to 5.3%). Mortality was twice as great for potassium of 4.5 mEq/L to less than 5.0 mEq/L (10.0%; 95% CI, 9.1% to 10.9%), and even greater for higher potassium strata. Similarly, mortality rates were higher for potassium levels of less than 3.5 mEq/L. Rates of ventricular fibrillation or cardiac arrest were higher among patients with potassium levels of less than 3.0 mEq/L or more than 5.0 mEq/L.

Bottom line: For inpatients with AMI, serum potassium levels of 3.5 mEq/L to 4.5 mEq/L should be maintained for the best outcomes. Repletion of serum potassium to levels greater than 4.5 mEq/L is associated with increased mortality and should be avoided.

Citation: Goyal A, Spertus JA, Gosch K, et al. Serum potassium levels and mortality in acute myocardial infarction. JAMA. 2012;307:157-164.

Proton-Pump Inhibitors Better than H2-Blockers in ACS and STEMI

Clinical question: Are proton-pump inhibitors (PPIs) better than H2-blockers at preventing UGI bleeding in patients after acute coronary syndrome (ACS) or ST-elevation myocardial infarction (STEMI)?

Background: It is not definitively known if PPIs are the same or better than H2-blockers in preventing UGI bleeding in patients on high-risk medications (aspirin, clopidogrel, and anticoagulants) after ACS or STEMI.

Study design: Randomized double-blinded controlled trial.

Setting: Single hospital.

Synopsis: Patients with ACS or STEMI were treated with aspirin, clopidogrel, and enoxaparin or thrombolytics. They were then randomized to either esomeprazole 20 mg or famotidine 40 mg, both administered nightly. They were followed throughout their hospital stay and were then followed between four and 52 weeks after discharge (mean duration: 19 weeks for esomeprazole, 18 weeks for famotidine). The primary end point was time to a composite outcome, consisting of UGI bleeding, obstruction, or perforation. Overall, 313 patients were randomized (164 to esomeprazole and 149 to famotidine).

The treatment groups were equivalent in baseline characteristics, and compliance in both groups was excellent (>98%). The primary endpoint occurred in three patients in the esomeprazole group and in 12 patients in the famotidine group (hazard ratio 0.21; 95% CI, 0.06 to 0.75; P=0.008).

Bottom line: PPIs are superior to H2-blockers in reducing UGI bleeding in patients on high-risk medications (aspirin, clopidogrel, and enoxaparin or thrombolytics) after ACS and STEMI. This confirms the recommendations of the 2010 ACCF/ACG/AHA Expert Consensus that PPIs should be used in those on dual antiplatelet therapy on anticoagulants.

Citation: Ng FH, Tunggal P, Chu WM, et al. Esomeprazole compared with famotidine in the prevention of upper gastrointestinal bleeding in patients with acute coronary syndrome or myocardial infarction. Am J Gastroenterol. 2012;107:389-396.

Literature at a Glance

A guide to this month’s studies

1. Risks of preoperative tobacco use
2. Timing of perioperative beta-blocker use and outcomes
3. Continuous vs. bolus dose diuretics in CHF
4. Outcomes of carotid endearterectomy and carotid artery stenting
5. Protocol for low-risk chest pain
6. Effect of esomeprazole on recurrent ulcer rates in clopidogrel users
7. Effect of ICU QI project on hospital mortality
8. Acute kidney injury risks after coronary angiography

Smokers Have Worse Perioperative Outcomes

Clinical question: Do current smokers have worse 30-day postoperative outcomes than nonsmokers after noncardiac surgery?

Background: Approximately 20% of adults in the U.S. smoke cigarettes, and a significant fraction of surgical patients are current smokers. Despite concerns that smoking is associated with worse postoperative outcomes, these increased risks have not been quantified across multiple outcomes.

Study design: Retrospective cohort study.

Setting: Surgical patients in 200 centers throughout the United States.

Synopsis: Data from the American College of Surgeons National Surgical Quality Improvement Program from 2005 to 2008 were acquired, and 391,006 patient records were reviewed. Postoperative morbidity and mortality were significantly greater in smokers. Current smokers had a 40% increased odds of death at 30 days compared to people who had never smoked (OR 1.38, 95% CI, 1.11-1.72). Current smokers also had significantly greater odds of pulmonary complications, including pneumonia (OR 2.09, 95% CI, 1.80-2.43), unplanned intubation (OR 1.87, 95% CI, 1.58-2.21), and mechanical ventilation (OR 1.53, 95% CI, 1.31-1.79).

Furthermore, current smokers had significantly greater odds of postoperative cardiac arrest (OR 1.57, 95% CI, 1.10-2.25), myocardial infarction (OR 1.80, 95% CI, 1.11-2.25), and stroke (OR 1.73, 95% CI, 1.18-2.53). Odds of infectious complications were increased in current smokers, including deep incisional infections (OR 1.42, 95% CI, 1.21-1.68), sepsis (OR 1.30, 95% CI, 1.20-1.60), and septic shock (OR 1.55, 95% CI, 1.29-1.87).

Limitations of this study include self-reporting of smoking habits and absence of detailed smoking history just before and after surgery.

Bottom line: Current smokers have significantly increased postoperative morbidity and mortality after noncardiac surgery.

Citation: Turan A, Mascha EJ, Roberman D, et al. Smoking and perioperative outcomes. Anesthesiology. 2011;114(4):837-846.

Chronic Beta-Blockade Reduces Postoperative Myocardial Ischemia

Clinical question: Does the timing of beta-blocker exposure affect cardiovascular outcomes in patients undergoing elective, noncardiac surgery?

Background: Several studies have demonstrated that beta-blockers are associated with decreased perioperative cardiovascular morbidity and mortality. Study designs have varied greatly, and differences in dosing and timing of beta-blocker administration have caused conflicting results. The question of when to initiate beta-blockers prior to surgery remains controversial.

Study design: Prospective cohort study.

Setting: Three academic medical centers in Canada.

Synopsis: Data from 1,398 patients who had elective, noncardiac surgery with either acute (n=436) or chronic (n=962) beta-blocker exposure were analyzed. Acute exposure was defined as receiving a beta-blocker for the first time within 48 hours after surgery, whereas chronic beta-blocker exposure was defined as receiving a beta-blocker seven to 10 days prior to surgery.

Patients with chronic beta-blocker exposure were more likely to have a history of coronary disease, heart failure, or hypertension and were more likely to be receiving statins, antiplatelet agents, and angiotensin-converting enzyme inhibitors. The primary outcome was a composite of major cardiac events, including myocardial infarction, nonfatal cardiac arrest, and 30-day mortality.

Major cardiac events occurred more often in patients with acute versus chronic beta-blocker exposure in both the entire cohort (8.3% vs. 4.7%) and in the propensity-matched cohort (8.0% vs. 3.0%). Myocardial infarction accounted for the majority of cardiac events.

There are several limitations of this study: The sample size was small, the beta-blocker and dosage used varied, and the indication and exact duration of chronic beta-blocker therapy was unknown.

Bottom line: Chronic beta-blocker therapy reduces major cardiac events compared with acute beta-blocker therapy in patients undergoing elective, noncardiac surgery.

Citation: Ellenberger C, Tait G, Beattie WS. Chronic beta-blockade is associated with a better outcome after elective noncardiac surgery than acute beta-blockade: a single-center propensity-matched cohort study. Anesthesiology. 2011;114(4):817-823.

Continuous and Bolus Dosing of Furosemide Provides Similar Outcomes in Heart Failure

Clinical question: Does continuous infusion compared to bolus dosing of furosemide improve clinical outcomes in patients with acute decompensated heart failure?

Background: Diuresis with furosemide is commonly used to manage acute decompensated heart failure, but it is uncertain which dosing strategy is optimal. Continuous infusion of furosemide has been proposed as a more effective method of diuresis compared with bolus dosing, especially when higher doses are required, but data comparing the two strategies are limited.

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

Setting: Twenty-six clinical sites in the U.S. and Canada.

Synopsis: Researchers randomized 308 patients with acute decompensated heart failure to either continuous or bolus intravenous dosing, which was calculated as either the equivalent of their daily oral dose (low-dose strategy) or 2.5 times their daily dose (high-dose strategy). Mean ejection fraction was 35%. Primary endpoints were patients’ assessment of symptoms based on a visual-analogue scale quantified as area under the curve, as well as change in serum creatinine level at 72 hours.

No significant differences between the continuous and bolus dosing groups were evidenced in primary endpoints at 72 hours. Patients in the bolus group had more dose increases at 48 hours (21% vs. 11%, P=0.01). Patients in the high-dose group were more likely to change from intravenous to oral doses at 48 hours (31% vs. 17%, P<0.001) and had greater net fluid loss (4.9L vs. 3.6L, P=0.01). More patients in the high-dose versus low-dose group had an increase in creatinine ≥0.3 mg/dL (23% vs. 14%, P=0.04). Hospital length of stay, readmission, and mortality rates were similar between the groups.

Bottom line: Diuretic therapy administered by continuous infusion or bolus dosing in patients with acute decompensated heart failure have equivocal effects on patients’ symptoms and kidney function.

Citation: Felker GM, Lee KL, Bull DA, et al. Diuretic strategies in patients with acute decompensated heart failure. N Engl J Med. 2011;364(9):797-805.

Carotid Endarterectomy Is Better than Carotid Artery Stenting

Clinical question: How do the clinical outcomes of carotid artery stenting compare with those of carotid endarterectomy?

Background: Whether carotid artery stenting or carotid endarterectomy is the preferred therapy for patients with carotid artery stenosis has been highly controversial. This study was a meta-analysis of all available data from randomized trials comparing carotid endarterectomy to carotid artery stenting.

Study design: Meta-analysis.

Setting: Teaching and nonteaching hospitals.

Synopsis: Thirteen randomized trials were identified with 3,723 patients who had undergone endarterectomy and 3,754 patients who had undergone carotid artery stenting. Outcomes included stroke, myocardial infarction, cranial nerve injury, and death or stroke, and these outcomes were divided as either short-term (<30 days) or long-term (>1 year) outcomes.

Patients who had undergone carotid artery stenting had less risk of short-term myocardial infarction (OR 0.48, 95% CI, 0.29–9.78, P=0.003) and less risk of cranial nerve injury (OR 0.09, 95% CI, 0.05–0.16, P<0.001). However, carotid artery stenting had a significantly higher risk of short-term stroke and combined death or stroke, and also significantly higher long-term risk of stroke and combined death or stroke. The association between carotid artery stenting and stroke was stronger in the subgroup of patients >68 years but not in patients <68 years. There was no significant heterogeneity, and no significant modifying associations were revealed by meta-regression analysis.

Limitations include potentially unpublished small studies favoring carotid endarterectomy and a significant publication bias regarding short-term death.

Bottom line: Although carotid artery stenting has less short-term risk of myocardial infarction and cranial nerve injury, carotid endarterectomy has less short-term and long-term risks of stroke and death.

Citation: Economopoulus KP, Sergentanis TN, Tsivgoulis G, Mariolis AD, Stefanadis C. Carotid artery stenting versus carotid endarterectomy: a comprehensive meta-analysis of short-term and long-term outcomes. Stroke. 2011;42:687-692.

Chest Pain Protocol Can Identify Low-Risk Chest Pain in Emergency Departments

Clinical question: Can a two-hour accelerated diagnostic protocol (ADP) based on electrocardiogram, point-of-care biomarkers, and Thrombolysis in Myocardial Infarction (TIMI) score safely identify patients with chest pain at very low short-term risk of major cardiac events?

Background: Evaluation of patients presenting to EDs with chest pain utilize significant amounts of hospital resources. A safe, reproducible, and expeditious process to identify patients at low risk for short-term cardiac events is desired.

Study design: Prospective cohort study.

Setting: Fourteen urban EDs in nine countries across the Asia-Pacific region.

Synopsis: The study included 3,582 patients presenting to an ED with at least five minutes of chest pain suggestive of an acute coronary syndrome and for whom further evaluation with serial cardiac biomarkers was planned. A negative ADP was defined as TIMI score of 0, no new ischemic changes on initial electrocardiogram, and normal cardiac biomarkers at zero and two hours after arrival.

All components of the ADP were negative for 352 patients (9.8%). Only three low-risk patients (0.9%) by ADP had a major cardiac event during the 30-day follow-up period, yielding a negative predictive value of 99.1% (95% CI, 97.3-99.8%). Mean hospital stay for the low-risk group with a negative ADP was 43 hours with a median of 26 hours. The authors suggest that a 10% reduction in prolonged workups of patients with chest pain could be seen with implementation of this protocol.

Potential limitations include applicability only to a select cohort of patients with chest pain and the low specificity of the protocol.

Bottom line: A two-hour diagnostic protocol can help expedite discharge of patients with very-low-risk chest pain.

Citation: Than T, Cullen L, Reid CM, et al. A 2-h diagnostic protocol to assess patients with chest pain symptoms in the Asia-Pacific region (ASPECT): a prospective observational validation study. Lancet. 2011;337:1077-1084.

Esomeprazole Reduces Peptic Ulcer Recurrence in Patients on Clopidogrel

Clinical question: Does esomeprazole prevent recurrent peptic ulcers in patients with atherosclerosis on clopidogrel?

Background: Although clopidogrel is sometimes used as an alternative antiplatelet agent to aspirin, a significant rate of recurrent ulcer bleeding on clopidogrel has been described. No previous prospective trial has studied whether a proton-pump inhibitor (PPI) can reduce the risk of peptic ulcer recurrence or bleeding in atherosclerotic patients on clopidogrel.

Study design: Randomized controlled trial.

Setting: A single veterans hospital in Taiwan.

Synopsis: One hundred sixty-five patients were enrolled with a past history of peptic ulcer disease, no signs of ulcer recurrence by endoscopy, and current use of clopidogrel 37.5 mg to 75 mg per day. All patients had atherosclerosis and had been on clopidogrel for at least two weeks, without aspirin, corticosteroids, anticoagulants, or recent treatment with a PPI. Patients were randomized to clopidogrel 75 mg at night (n=82) or clopidogrel 75 mg at night plus esomeprazole 20 mg before breakfast. Follow-up endoscopy was performed at six months or as needed for symptoms.

Recurrence of ulcer was found in 1.2% of patients on clopidogrel plus esomeprazole versus 11.0% in patients on clopidogrel alone (95% CI, 2.6-17.0%; P=0.009). The pharmacodynamic study revealed no significant differences in platelet aggregation within or between treatment groups on day 1 or day 28. No significant differences were seen on the incidence of ischemic events in this setting, but the trial was underpowered to draw conclusions on this outcome.

An important limitation is that the findings of this study are applicable only to patients on clopidogrel monotherapy and not dual antiplatelet therapy.

Bottom line: A significant reduction in recurrent peptic ulcers is seen with the combination of esomeprazole plus clopidogrel, versus clopidogrel alone, in patients with atherosclerosis and a history of peptic ulcer disease.

Citation: Hsu PI, Lai KH, Liu CP. Esomeprazole with clopidogrel reduces peptic ulcer recurrence, compared with clopidogrel alone, in patients with atherosclerosis. Gastroenterology. 2011;140:791-798.

ICU Quality-Improvement Project Reduces Hospital Mortality

Clinical question: Does a quality-improvement (QI) project in the ICU reduce in-hospital mortality and length of stay among elderly adults?

Background: Previous studies have shown that ICU-acquired infections are associated with increased morbidity and mortality, and QI initiatives reduce hospital-acquired infections. However, it has not been demonstrated that QI projects in the ICU reduce in-hospital mortality or length of stay.

Study design: Retrospective cohort study.

Setting: Four hundred fifty-nine Midwestern hospitals.

Synopsis: This study included 238,937 adults age >65 who were hospitalized in an ICU from 2001 to 2006 at one of 95 hospitals invited to implement the Keystone ICU Project. The control group included 1,091,547 elderly adults at one of 364 hospitals not invited to participate in the project. The Keystone ICU Project implements evidence-based practices to reduce rates of catheter-related bloodstream infections and ventilator-associated pneumonia.

Hospital mortality was not significantly reduced during initiation or implementation of the project; however, a significant reduction in hospital mortality occurred in the study group during one to 12 months post-implementation (OR=0.83 vs. 0.88, P=0.041) and 13 to 22 months post-implementation (OR=0.76 vs. 0.84, P=0.007). In contrast, length of stay did not differ significantly between the two groups, but the study was underpowered for this outcome.

The study is limited by the complexity of the Keystone ICU Project, as well as the exclusion of smaller hospitals and nonelderly adults. The study is promising because implementing a QI project in the ICU is associated with no known harms and might confer a mortality benefit at a relatively low cost.

Bottom line: Elderly adults had lower in-hospital mortality after implementation of the Keystone QI project in ICUs.

Citation: Lipitz-Snyderman A, Steinwachs D, Needham DM, Colantuoni E, Morlock LL, Pronovost PJ. Impact of a statewide intensive care unit quality improvement initiative on hospital mortality and length of stay: retrospective comparative analysis. BMJ. 2011;342:d219.

Serious Long-Term Risks with Acute Kidney Injury after Coronary Angiography

Clinical question: Does postcoronary angiography acute kidney injury (AKI) increase the risk of poor long-term clinical outcomes?

Background: Previous studies have shown that AKI following coronary angiography increases the risk of poor short-term clinical outcomes, such as in-hospital myocardial infarction, prolonged hospital stay, and early mortality. Little is known about the long-term cardiovascular and renal outcomes following post-coronary angiography AKI.

Study design: Retrospective cohort study.

Setting: All coronary angiography centers in Alberta, Canada.

Synopsis: The study included 14,782 adults who were ≥18 years of age, underwent coronary angiography, had a baseline creatinine measurement, did not have end-stage renal disease (ESRD), and had a creatinine measurement within seven days after coronary angiography.

During a median follow-up period of 19.7 months, 1,099 (7.4%) patients developed stage 1 AKI and 321 (2.2%) developed stage 2 or 3 AKI. Mortality increased twofold with stage 1 AKI and >3-fold with stage 2 or 3 AKI. Risk of ESRD increased substantially by >11-fold in patients with stage 2 or 3 AKI. Risk of hospitalization for subsequent AKI, myocardial infarction, and heart failure also increased significantly following post-coronary angiography AKI.

Patients who experienced AKI were older, had more severe CAD, were more likely to have such comorbidities as DM, HTN, and heart failure, and had lower baseline GFRs. However, the underlying comorbidities do not completely explain the increased risk of poor long-term outcomes in the adjusted analysis.

Limitations include missing or underestimating mild cases of AKI, residual confounding from unmeasured variables, and inability of retrospective comparative studies to establish causality.

Bottom line: Adults with post-coronary angiography AKI are at increased risk of poor long-term cardiovascular and renal outcomes.

Citation: James MT, Ghali WA, Knudtson ML, et al. Associations between acute kidney injury and cardiovascular and renal outcomes after coronary angiography. Circulation. 2011;123(4):409-416. TH

Pediatric HM Literature

Proton-Pump Inhibitors Ineffective for Gastroesophageal Reflux Disease in Children

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

Clinical question: What is the efficacy of proton-pump inhibitors (PPIs) in children with gastroesophageal reflux disease (GERD)?

Background: Gastroesophageal reflux is both a common and normal phenomenon in infants. GERD refers to the presence of abnormal symptoms ascribed to the reflux and frequently is treated in children in a manner similar to adults with reflux esophagitis. PPIs often are prescribed as front-line treatment, and their use has increased dramatically in recent years, though their effectiveness in children remains unclear.

Study design: Systematic review of the literature.

Setting: Hawaii’s largest health insurer.

Synopsis: Medline, Embase, and the Cochrane Database of Systematic Reviews were searched for randomized controlled trials (RCTs) and crossover studies performed to evaluate the efficacy of PPIs in children 0-17 years with GERD and no complicating diseases. Ten RCTs and two crossover studies were analyzed and rated independently by two reviewers.

Due to significant heterogeneity between the studies, a meta-analysis was not possible; studies were discussed separately. PPIs offered no advantage when compared with controls (alginates, ranitidine, different dosages of PPIs), and similar rates of adverse events were reported between treatment groups.

This study is hampered by notable heterogeneity of patient type, symptoms, and study design in many of the trials. However, the results are in line with discussions at a recent FDA Gastrointestinal Drugs Advisory Committee meeting, which reviewed the lack of efficacy of PPIs in infants in four recent Phase 3 clinical trials.

Bottom line: Little evidence supports the widespread use of PPIs in children.

Citation: Van der Pol RJ, Smits MJ, van Wijk MP, Omari TI, Tabbers MM, Benninga MA. Efficacy of proton-pump inhibitors in children with gastroesophageal reflux disease: a systematic review. Pediatrics. 2011;127:925-935.

Literature at a Glance

A guide to this month’s studies

1. Risks of preoperative tobacco use
2. Timing of perioperative beta-blocker use and outcomes
3. Continuous vs. bolus dose diuretics in CHF
4. Outcomes of carotid endearterectomy and carotid artery stenting
5. Protocol for low-risk chest pain
6. Effect of esomeprazole on recurrent ulcer rates in clopidogrel users
7. Effect of ICU QI project on hospital mortality
8. Acute kidney injury risks after coronary angiography

Smokers Have Worse Perioperative Outcomes

Clinical question: Do current smokers have worse 30-day postoperative outcomes than nonsmokers after noncardiac surgery?

Background: Approximately 20% of adults in the U.S. smoke cigarettes, and a significant fraction of surgical patients are current smokers. Despite concerns that smoking is associated with worse postoperative outcomes, these increased risks have not been quantified across multiple outcomes.

Study design: Retrospective cohort study.

Setting: Surgical patients in 200 centers throughout the United States.

Synopsis: Data from the American College of Surgeons National Surgical Quality Improvement Program from 2005 to 2008 were acquired, and 391,006 patient records were reviewed. Postoperative morbidity and mortality were significantly greater in smokers. Current smokers had a 40% increased odds of death at 30 days compared to people who had never smoked (OR 1.38, 95% CI, 1.11-1.72). Current smokers also had significantly greater odds of pulmonary complications, including pneumonia (OR 2.09, 95% CI, 1.80-2.43), unplanned intubation (OR 1.87, 95% CI, 1.58-2.21), and mechanical ventilation (OR 1.53, 95% CI, 1.31-1.79).

Furthermore, current smokers had significantly greater odds of postoperative cardiac arrest (OR 1.57, 95% CI, 1.10-2.25), myocardial infarction (OR 1.80, 95% CI, 1.11-2.25), and stroke (OR 1.73, 95% CI, 1.18-2.53). Odds of infectious complications were increased in current smokers, including deep incisional infections (OR 1.42, 95% CI, 1.21-1.68), sepsis (OR 1.30, 95% CI, 1.20-1.60), and septic shock (OR 1.55, 95% CI, 1.29-1.87).

Limitations of this study include self-reporting of smoking habits and absence of detailed smoking history just before and after surgery.

Bottom line: Current smokers have significantly increased postoperative morbidity and mortality after noncardiac surgery.

Citation: Turan A, Mascha EJ, Roberman D, et al. Smoking and perioperative outcomes. Anesthesiology. 2011;114(4):837-846.

Chronic Beta-Blockade Reduces Postoperative Myocardial Ischemia

Clinical question: Does the timing of beta-blocker exposure affect cardiovascular outcomes in patients undergoing elective, noncardiac surgery?

Background: Several studies have demonstrated that beta-blockers are associated with decreased perioperative cardiovascular morbidity and mortality. Study designs have varied greatly, and differences in dosing and timing of beta-blocker administration have caused conflicting results. The question of when to initiate beta-blockers prior to surgery remains controversial.

Study design: Prospective cohort study.

Setting: Three academic medical centers in Canada.

Synopsis: Data from 1,398 patients who had elective, noncardiac surgery with either acute (n=436) or chronic (n=962) beta-blocker exposure were analyzed. Acute exposure was defined as receiving a beta-blocker for the first time within 48 hours after surgery, whereas chronic beta-blocker exposure was defined as receiving a beta-blocker seven to 10 days prior to surgery.

Patients with chronic beta-blocker exposure were more likely to have a history of coronary disease, heart failure, or hypertension and were more likely to be receiving statins, antiplatelet agents, and angiotensin-converting enzyme inhibitors. The primary outcome was a composite of major cardiac events, including myocardial infarction, nonfatal cardiac arrest, and 30-day mortality.

Major cardiac events occurred more often in patients with acute versus chronic beta-blocker exposure in both the entire cohort (8.3% vs. 4.7%) and in the propensity-matched cohort (8.0% vs. 3.0%). Myocardial infarction accounted for the majority of cardiac events.

There are several limitations of this study: The sample size was small, the beta-blocker and dosage used varied, and the indication and exact duration of chronic beta-blocker therapy was unknown.

Bottom line: Chronic beta-blocker therapy reduces major cardiac events compared with acute beta-blocker therapy in patients undergoing elective, noncardiac surgery.

Citation: Ellenberger C, Tait G, Beattie WS. Chronic beta-blockade is associated with a better outcome after elective noncardiac surgery than acute beta-blockade: a single-center propensity-matched cohort study. Anesthesiology. 2011;114(4):817-823.

Continuous and Bolus Dosing of Furosemide Provides Similar Outcomes in Heart Failure

Clinical question: Does continuous infusion compared to bolus dosing of furosemide improve clinical outcomes in patients with acute decompensated heart failure?

Background: Diuresis with furosemide is commonly used to manage acute decompensated heart failure, but it is uncertain which dosing strategy is optimal. Continuous infusion of furosemide has been proposed as a more effective method of diuresis compared with bolus dosing, especially when higher doses are required, but data comparing the two strategies are limited.

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

Setting: Twenty-six clinical sites in the U.S. and Canada.

Synopsis: Researchers randomized 308 patients with acute decompensated heart failure to either continuous or bolus intravenous dosing, which was calculated as either the equivalent of their daily oral dose (low-dose strategy) or 2.5 times their daily dose (high-dose strategy). Mean ejection fraction was 35%. Primary endpoints were patients’ assessment of symptoms based on a visual-analogue scale quantified as area under the curve, as well as change in serum creatinine level at 72 hours.

No significant differences between the continuous and bolus dosing groups were evidenced in primary endpoints at 72 hours. Patients in the bolus group had more dose increases at 48 hours (21% vs. 11%, P=0.01). Patients in the high-dose group were more likely to change from intravenous to oral doses at 48 hours (31% vs. 17%, P<0.001) and had greater net fluid loss (4.9L vs. 3.6L, P=0.01). More patients in the high-dose versus low-dose group had an increase in creatinine ≥0.3 mg/dL (23% vs. 14%, P=0.04). Hospital length of stay, readmission, and mortality rates were similar between the groups.

Bottom line: Diuretic therapy administered by continuous infusion or bolus dosing in patients with acute decompensated heart failure have equivocal effects on patients’ symptoms and kidney function.

Citation: Felker GM, Lee KL, Bull DA, et al. Diuretic strategies in patients with acute decompensated heart failure. N Engl J Med. 2011;364(9):797-805.

Carotid Endarterectomy Is Better than Carotid Artery Stenting

Clinical question: How do the clinical outcomes of carotid artery stenting compare with those of carotid endarterectomy?

Background: Whether carotid artery stenting or carotid endarterectomy is the preferred therapy for patients with carotid artery stenosis has been highly controversial. This study was a meta-analysis of all available data from randomized trials comparing carotid endarterectomy to carotid artery stenting.

Study design: Meta-analysis.

Setting: Teaching and nonteaching hospitals.

Synopsis: Thirteen randomized trials were identified with 3,723 patients who had undergone endarterectomy and 3,754 patients who had undergone carotid artery stenting. Outcomes included stroke, myocardial infarction, cranial nerve injury, and death or stroke, and these outcomes were divided as either short-term (<30 days) or long-term (>1 year) outcomes.

Patients who had undergone carotid artery stenting had less risk of short-term myocardial infarction (OR 0.48, 95% CI, 0.29–9.78, P=0.003) and less risk of cranial nerve injury (OR 0.09, 95% CI, 0.05–0.16, P<0.001). However, carotid artery stenting had a significantly higher risk of short-term stroke and combined death or stroke, and also significantly higher long-term risk of stroke and combined death or stroke. The association between carotid artery stenting and stroke was stronger in the subgroup of patients >68 years but not in patients <68 years. There was no significant heterogeneity, and no significant modifying associations were revealed by meta-regression analysis.

Limitations include potentially unpublished small studies favoring carotid endarterectomy and a significant publication bias regarding short-term death.

Bottom line: Although carotid artery stenting has less short-term risk of myocardial infarction and cranial nerve injury, carotid endarterectomy has less short-term and long-term risks of stroke and death.

Citation: Economopoulus KP, Sergentanis TN, Tsivgoulis G, Mariolis AD, Stefanadis C. Carotid artery stenting versus carotid endarterectomy: a comprehensive meta-analysis of short-term and long-term outcomes. Stroke. 2011;42:687-692.

Chest Pain Protocol Can Identify Low-Risk Chest Pain in Emergency Departments

Clinical question: Can a two-hour accelerated diagnostic protocol (ADP) based on electrocardiogram, point-of-care biomarkers, and Thrombolysis in Myocardial Infarction (TIMI) score safely identify patients with chest pain at very low short-term risk of major cardiac events?

Background: Evaluation of patients presenting to EDs with chest pain utilize significant amounts of hospital resources. A safe, reproducible, and expeditious process to identify patients at low risk for short-term cardiac events is desired.

Study design: Prospective cohort study.

Setting: Fourteen urban EDs in nine countries across the Asia-Pacific region.

Synopsis: The study included 3,582 patients presenting to an ED with at least five minutes of chest pain suggestive of an acute coronary syndrome and for whom further evaluation with serial cardiac biomarkers was planned. A negative ADP was defined as TIMI score of 0, no new ischemic changes on initial electrocardiogram, and normal cardiac biomarkers at zero and two hours after arrival.

All components of the ADP were negative for 352 patients (9.8%). Only three low-risk patients (0.9%) by ADP had a major cardiac event during the 30-day follow-up period, yielding a negative predictive value of 99.1% (95% CI, 97.3-99.8%). Mean hospital stay for the low-risk group with a negative ADP was 43 hours with a median of 26 hours. The authors suggest that a 10% reduction in prolonged workups of patients with chest pain could be seen with implementation of this protocol.

Potential limitations include applicability only to a select cohort of patients with chest pain and the low specificity of the protocol.

Bottom line: A two-hour diagnostic protocol can help expedite discharge of patients with very-low-risk chest pain.

Citation: Than T, Cullen L, Reid CM, et al. A 2-h diagnostic protocol to assess patients with chest pain symptoms in the Asia-Pacific region (ASPECT): a prospective observational validation study. Lancet. 2011;337:1077-1084.

Esomeprazole Reduces Peptic Ulcer Recurrence in Patients on Clopidogrel

Clinical question: Does esomeprazole prevent recurrent peptic ulcers in patients with atherosclerosis on clopidogrel?

Background: Although clopidogrel is sometimes used as an alternative antiplatelet agent to aspirin, a significant rate of recurrent ulcer bleeding on clopidogrel has been described. No previous prospective trial has studied whether a proton-pump inhibitor (PPI) can reduce the risk of peptic ulcer recurrence or bleeding in atherosclerotic patients on clopidogrel.

Study design: Randomized controlled trial.

Setting: A single veterans hospital in Taiwan.

Synopsis: One hundred sixty-five patients were enrolled with a past history of peptic ulcer disease, no signs of ulcer recurrence by endoscopy, and current use of clopidogrel 37.5 mg to 75 mg per day. All patients had atherosclerosis and had been on clopidogrel for at least two weeks, without aspirin, corticosteroids, anticoagulants, or recent treatment with a PPI. Patients were randomized to clopidogrel 75 mg at night (n=82) or clopidogrel 75 mg at night plus esomeprazole 20 mg before breakfast. Follow-up endoscopy was performed at six months or as needed for symptoms.

Recurrence of ulcer was found in 1.2% of patients on clopidogrel plus esomeprazole versus 11.0% in patients on clopidogrel alone (95% CI, 2.6-17.0%; P=0.009). The pharmacodynamic study revealed no significant differences in platelet aggregation within or between treatment groups on day 1 or day 28. No significant differences were seen on the incidence of ischemic events in this setting, but the trial was underpowered to draw conclusions on this outcome.

An important limitation is that the findings of this study are applicable only to patients on clopidogrel monotherapy and not dual antiplatelet therapy.

Bottom line: A significant reduction in recurrent peptic ulcers is seen with the combination of esomeprazole plus clopidogrel, versus clopidogrel alone, in patients with atherosclerosis and a history of peptic ulcer disease.

Citation: Hsu PI, Lai KH, Liu CP. Esomeprazole with clopidogrel reduces peptic ulcer recurrence, compared with clopidogrel alone, in patients with atherosclerosis. Gastroenterology. 2011;140:791-798.

ICU Quality-Improvement Project Reduces Hospital Mortality

Clinical question: Does a quality-improvement (QI) project in the ICU reduce in-hospital mortality and length of stay among elderly adults?

Background: Previous studies have shown that ICU-acquired infections are associated with increased morbidity and mortality, and QI initiatives reduce hospital-acquired infections. However, it has not been demonstrated that QI projects in the ICU reduce in-hospital mortality or length of stay.

Study design: Retrospective cohort study.

Setting: Four hundred fifty-nine Midwestern hospitals.

Synopsis: This study included 238,937 adults age >65 who were hospitalized in an ICU from 2001 to 2006 at one of 95 hospitals invited to implement the Keystone ICU Project. The control group included 1,091,547 elderly adults at one of 364 hospitals not invited to participate in the project. The Keystone ICU Project implements evidence-based practices to reduce rates of catheter-related bloodstream infections and ventilator-associated pneumonia.

Hospital mortality was not significantly reduced during initiation or implementation of the project; however, a significant reduction in hospital mortality occurred in the study group during one to 12 months post-implementation (OR=0.83 vs. 0.88, P=0.041) and 13 to 22 months post-implementation (OR=0.76 vs. 0.84, P=0.007). In contrast, length of stay did not differ significantly between the two groups, but the study was underpowered for this outcome.

The study is limited by the complexity of the Keystone ICU Project, as well as the exclusion of smaller hospitals and nonelderly adults. The study is promising because implementing a QI project in the ICU is associated with no known harms and might confer a mortality benefit at a relatively low cost.

Bottom line: Elderly adults had lower in-hospital mortality after implementation of the Keystone QI project in ICUs.

Citation: Lipitz-Snyderman A, Steinwachs D, Needham DM, Colantuoni E, Morlock LL, Pronovost PJ. Impact of a statewide intensive care unit quality improvement initiative on hospital mortality and length of stay: retrospective comparative analysis. BMJ. 2011;342:d219.

Serious Long-Term Risks with Acute Kidney Injury after Coronary Angiography

Clinical question: Does postcoronary angiography acute kidney injury (AKI) increase the risk of poor long-term clinical outcomes?

Background: Previous studies have shown that AKI following coronary angiography increases the risk of poor short-term clinical outcomes, such as in-hospital myocardial infarction, prolonged hospital stay, and early mortality. Little is known about the long-term cardiovascular and renal outcomes following post-coronary angiography AKI.

Study design: Retrospective cohort study.

Setting: All coronary angiography centers in Alberta, Canada.

Synopsis: The study included 14,782 adults who were ≥18 years of age, underwent coronary angiography, had a baseline creatinine measurement, did not have end-stage renal disease (ESRD), and had a creatinine measurement within seven days after coronary angiography.

During a median follow-up period of 19.7 months, 1,099 (7.4%) patients developed stage 1 AKI and 321 (2.2%) developed stage 2 or 3 AKI. Mortality increased twofold with stage 1 AKI and >3-fold with stage 2 or 3 AKI. Risk of ESRD increased substantially by >11-fold in patients with stage 2 or 3 AKI. Risk of hospitalization for subsequent AKI, myocardial infarction, and heart failure also increased significantly following post-coronary angiography AKI.

Patients who experienced AKI were older, had more severe CAD, were more likely to have such comorbidities as DM, HTN, and heart failure, and had lower baseline GFRs. However, the underlying comorbidities do not completely explain the increased risk of poor long-term outcomes in the adjusted analysis.

Limitations include missing or underestimating mild cases of AKI, residual confounding from unmeasured variables, and inability of retrospective comparative studies to establish causality.

Bottom line: Adults with post-coronary angiography AKI are at increased risk of poor long-term cardiovascular and renal outcomes.

Citation: James MT, Ghali WA, Knudtson ML, et al. Associations between acute kidney injury and cardiovascular and renal outcomes after coronary angiography. Circulation. 2011;123(4):409-416. TH

Pediatric HM Literature

Proton-Pump Inhibitors Ineffective for Gastroesophageal Reflux Disease in Children

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

Clinical question: What is the efficacy of proton-pump inhibitors (PPIs) in children with gastroesophageal reflux disease (GERD)?

Background: Gastroesophageal reflux is both a common and normal phenomenon in infants. GERD refers to the presence of abnormal symptoms ascribed to the reflux and frequently is treated in children in a manner similar to adults with reflux esophagitis. PPIs often are prescribed as front-line treatment, and their use has increased dramatically in recent years, though their effectiveness in children remains unclear.

Study design: Systematic review of the literature.

Setting: Hawaii’s largest health insurer.

Synopsis: Medline, Embase, and the Cochrane Database of Systematic Reviews were searched for randomized controlled trials (RCTs) and crossover studies performed to evaluate the efficacy of PPIs in children 0-17 years with GERD and no complicating diseases. Ten RCTs and two crossover studies were analyzed and rated independently by two reviewers.

Due to significant heterogeneity between the studies, a meta-analysis was not possible; studies were discussed separately. PPIs offered no advantage when compared with controls (alginates, ranitidine, different dosages of PPIs), and similar rates of adverse events were reported between treatment groups.

This study is hampered by notable heterogeneity of patient type, symptoms, and study design in many of the trials. However, the results are in line with discussions at a recent FDA Gastrointestinal Drugs Advisory Committee meeting, which reviewed the lack of efficacy of PPIs in infants in four recent Phase 3 clinical trials.

Bottom line: Little evidence supports the widespread use of PPIs in children.

Citation: Van der Pol RJ, Smits MJ, van Wijk MP, Omari TI, Tabbers MM, Benninga MA. Efficacy of proton-pump inhibitors in children with gastroesophageal reflux disease: a systematic review. Pediatrics. 2011;127:925-935.

Literature at a Glance

A guide to this month’s studies

1. Risks of preoperative tobacco use
2. Timing of perioperative beta-blocker use and outcomes
3. Continuous vs. bolus dose diuretics in CHF
4. Outcomes of carotid endearterectomy and carotid artery stenting
5. Protocol for low-risk chest pain
6. Effect of esomeprazole on recurrent ulcer rates in clopidogrel users
7. Effect of ICU QI project on hospital mortality
8. Acute kidney injury risks after coronary angiography

Smokers Have Worse Perioperative Outcomes

Clinical question: Do current smokers have worse 30-day postoperative outcomes than nonsmokers after noncardiac surgery?

Background: Approximately 20% of adults in the U.S. smoke cigarettes, and a significant fraction of surgical patients are current smokers. Despite concerns that smoking is associated with worse postoperative outcomes, these increased risks have not been quantified across multiple outcomes.

Study design: Retrospective cohort study.

Setting: Surgical patients in 200 centers throughout the United States.

Synopsis: Data from the American College of Surgeons National Surgical Quality Improvement Program from 2005 to 2008 were acquired, and 391,006 patient records were reviewed. Postoperative morbidity and mortality were significantly greater in smokers. Current smokers had a 40% increased odds of death at 30 days compared to people who had never smoked (OR 1.38, 95% CI, 1.11-1.72). Current smokers also had significantly greater odds of pulmonary complications, including pneumonia (OR 2.09, 95% CI, 1.80-2.43), unplanned intubation (OR 1.87, 95% CI, 1.58-2.21), and mechanical ventilation (OR 1.53, 95% CI, 1.31-1.79).

Furthermore, current smokers had significantly greater odds of postoperative cardiac arrest (OR 1.57, 95% CI, 1.10-2.25), myocardial infarction (OR 1.80, 95% CI, 1.11-2.25), and stroke (OR 1.73, 95% CI, 1.18-2.53). Odds of infectious complications were increased in current smokers, including deep incisional infections (OR 1.42, 95% CI, 1.21-1.68), sepsis (OR 1.30, 95% CI, 1.20-1.60), and septic shock (OR 1.55, 95% CI, 1.29-1.87).

Limitations of this study include self-reporting of smoking habits and absence of detailed smoking history just before and after surgery.

Bottom line: Current smokers have significantly increased postoperative morbidity and mortality after noncardiac surgery.

Citation: Turan A, Mascha EJ, Roberman D, et al. Smoking and perioperative outcomes. Anesthesiology. 2011;114(4):837-846.

Chronic Beta-Blockade Reduces Postoperative Myocardial Ischemia

Clinical question: Does the timing of beta-blocker exposure affect cardiovascular outcomes in patients undergoing elective, noncardiac surgery?

Background: Several studies have demonstrated that beta-blockers are associated with decreased perioperative cardiovascular morbidity and mortality. Study designs have varied greatly, and differences in dosing and timing of beta-blocker administration have caused conflicting results. The question of when to initiate beta-blockers prior to surgery remains controversial.

Study design: Prospective cohort study.

Setting: Three academic medical centers in Canada.

Synopsis: Data from 1,398 patients who had elective, noncardiac surgery with either acute (n=436) or chronic (n=962) beta-blocker exposure were analyzed. Acute exposure was defined as receiving a beta-blocker for the first time within 48 hours after surgery, whereas chronic beta-blocker exposure was defined as receiving a beta-blocker seven to 10 days prior to surgery.

Patients with chronic beta-blocker exposure were more likely to have a history of coronary disease, heart failure, or hypertension and were more likely to be receiving statins, antiplatelet agents, and angiotensin-converting enzyme inhibitors. The primary outcome was a composite of major cardiac events, including myocardial infarction, nonfatal cardiac arrest, and 30-day mortality.

Major cardiac events occurred more often in patients with acute versus chronic beta-blocker exposure in both the entire cohort (8.3% vs. 4.7%) and in the propensity-matched cohort (8.0% vs. 3.0%). Myocardial infarction accounted for the majority of cardiac events.

There are several limitations of this study: The sample size was small, the beta-blocker and dosage used varied, and the indication and exact duration of chronic beta-blocker therapy was unknown.

Bottom line: Chronic beta-blocker therapy reduces major cardiac events compared with acute beta-blocker therapy in patients undergoing elective, noncardiac surgery.

Citation: Ellenberger C, Tait G, Beattie WS. Chronic beta-blockade is associated with a better outcome after elective noncardiac surgery than acute beta-blockade: a single-center propensity-matched cohort study. Anesthesiology. 2011;114(4):817-823.

Continuous and Bolus Dosing of Furosemide Provides Similar Outcomes in Heart Failure

Clinical question: Does continuous infusion compared to bolus dosing of furosemide improve clinical outcomes in patients with acute decompensated heart failure?

Background: Diuresis with furosemide is commonly used to manage acute decompensated heart failure, but it is uncertain which dosing strategy is optimal. Continuous infusion of furosemide has been proposed as a more effective method of diuresis compared with bolus dosing, especially when higher doses are required, but data comparing the two strategies are limited.

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

Setting: Twenty-six clinical sites in the U.S. and Canada.

Synopsis: Researchers randomized 308 patients with acute decompensated heart failure to either continuous or bolus intravenous dosing, which was calculated as either the equivalent of their daily oral dose (low-dose strategy) or 2.5 times their daily dose (high-dose strategy). Mean ejection fraction was 35%. Primary endpoints were patients’ assessment of symptoms based on a visual-analogue scale quantified as area under the curve, as well as change in serum creatinine level at 72 hours.

No significant differences between the continuous and bolus dosing groups were evidenced in primary endpoints at 72 hours. Patients in the bolus group had more dose increases at 48 hours (21% vs. 11%, P=0.01). Patients in the high-dose group were more likely to change from intravenous to oral doses at 48 hours (31% vs. 17%, P<0.001) and had greater net fluid loss (4.9L vs. 3.6L, P=0.01). More patients in the high-dose versus low-dose group had an increase in creatinine ≥0.3 mg/dL (23% vs. 14%, P=0.04). Hospital length of stay, readmission, and mortality rates were similar between the groups.

Bottom line: Diuretic therapy administered by continuous infusion or bolus dosing in patients with acute decompensated heart failure have equivocal effects on patients’ symptoms and kidney function.

Citation: Felker GM, Lee KL, Bull DA, et al. Diuretic strategies in patients with acute decompensated heart failure. N Engl J Med. 2011;364(9):797-805.

Carotid Endarterectomy Is Better than Carotid Artery Stenting

Clinical question: How do the clinical outcomes of carotid artery stenting compare with those of carotid endarterectomy?

Background: Whether carotid artery stenting or carotid endarterectomy is the preferred therapy for patients with carotid artery stenosis has been highly controversial. This study was a meta-analysis of all available data from randomized trials comparing carotid endarterectomy to carotid artery stenting.

Study design: Meta-analysis.

Setting: Teaching and nonteaching hospitals.

Synopsis: Thirteen randomized trials were identified with 3,723 patients who had undergone endarterectomy and 3,754 patients who had undergone carotid artery stenting. Outcomes included stroke, myocardial infarction, cranial nerve injury, and death or stroke, and these outcomes were divided as either short-term (<30 days) or long-term (>1 year) outcomes.

Patients who had undergone carotid artery stenting had less risk of short-term myocardial infarction (OR 0.48, 95% CI, 0.29–9.78, P=0.003) and less risk of cranial nerve injury (OR 0.09, 95% CI, 0.05–0.16, P<0.001). However, carotid artery stenting had a significantly higher risk of short-term stroke and combined death or stroke, and also significantly higher long-term risk of stroke and combined death or stroke. The association between carotid artery stenting and stroke was stronger in the subgroup of patients >68 years but not in patients <68 years. There was no significant heterogeneity, and no significant modifying associations were revealed by meta-regression analysis.

Limitations include potentially unpublished small studies favoring carotid endarterectomy and a significant publication bias regarding short-term death.

Bottom line: Although carotid artery stenting has less short-term risk of myocardial infarction and cranial nerve injury, carotid endarterectomy has less short-term and long-term risks of stroke and death.

Citation: Economopoulus KP, Sergentanis TN, Tsivgoulis G, Mariolis AD, Stefanadis C. Carotid artery stenting versus carotid endarterectomy: a comprehensive meta-analysis of short-term and long-term outcomes. Stroke. 2011;42:687-692.

Chest Pain Protocol Can Identify Low-Risk Chest Pain in Emergency Departments

Clinical question: Can a two-hour accelerated diagnostic protocol (ADP) based on electrocardiogram, point-of-care biomarkers, and Thrombolysis in Myocardial Infarction (TIMI) score safely identify patients with chest pain at very low short-term risk of major cardiac events?

Background: Evaluation of patients presenting to EDs with chest pain utilize significant amounts of hospital resources. A safe, reproducible, and expeditious process to identify patients at low risk for short-term cardiac events is desired.

Study design: Prospective cohort study.

Setting: Fourteen urban EDs in nine countries across the Asia-Pacific region.

Synopsis: The study included 3,582 patients presenting to an ED with at least five minutes of chest pain suggestive of an acute coronary syndrome and for whom further evaluation with serial cardiac biomarkers was planned. A negative ADP was defined as TIMI score of 0, no new ischemic changes on initial electrocardiogram, and normal cardiac biomarkers at zero and two hours after arrival.

All components of the ADP were negative for 352 patients (9.8%). Only three low-risk patients (0.9%) by ADP had a major cardiac event during the 30-day follow-up period, yielding a negative predictive value of 99.1% (95% CI, 97.3-99.8%). Mean hospital stay for the low-risk group with a negative ADP was 43 hours with a median of 26 hours. The authors suggest that a 10% reduction in prolonged workups of patients with chest pain could be seen with implementation of this protocol.

Potential limitations include applicability only to a select cohort of patients with chest pain and the low specificity of the protocol.

Bottom line: A two-hour diagnostic protocol can help expedite discharge of patients with very-low-risk chest pain.

Citation: Than T, Cullen L, Reid CM, et al. A 2-h diagnostic protocol to assess patients with chest pain symptoms in the Asia-Pacific region (ASPECT): a prospective observational validation study. Lancet. 2011;337:1077-1084.

Esomeprazole Reduces Peptic Ulcer Recurrence in Patients on Clopidogrel

Clinical question: Does esomeprazole prevent recurrent peptic ulcers in patients with atherosclerosis on clopidogrel?

Background: Although clopidogrel is sometimes used as an alternative antiplatelet agent to aspirin, a significant rate of recurrent ulcer bleeding on clopidogrel has been described. No previous prospective trial has studied whether a proton-pump inhibitor (PPI) can reduce the risk of peptic ulcer recurrence or bleeding in atherosclerotic patients on clopidogrel.

Study design: Randomized controlled trial.

Setting: A single veterans hospital in Taiwan.

Synopsis: One hundred sixty-five patients were enrolled with a past history of peptic ulcer disease, no signs of ulcer recurrence by endoscopy, and current use of clopidogrel 37.5 mg to 75 mg per day. All patients had atherosclerosis and had been on clopidogrel for at least two weeks, without aspirin, corticosteroids, anticoagulants, or recent treatment with a PPI. Patients were randomized to clopidogrel 75 mg at night (n=82) or clopidogrel 75 mg at night plus esomeprazole 20 mg before breakfast. Follow-up endoscopy was performed at six months or as needed for symptoms.

Recurrence of ulcer was found in 1.2% of patients on clopidogrel plus esomeprazole versus 11.0% in patients on clopidogrel alone (95% CI, 2.6-17.0%; P=0.009). The pharmacodynamic study revealed no significant differences in platelet aggregation within or between treatment groups on day 1 or day 28. No significant differences were seen on the incidence of ischemic events in this setting, but the trial was underpowered to draw conclusions on this outcome.

An important limitation is that the findings of this study are applicable only to patients on clopidogrel monotherapy and not dual antiplatelet therapy.

Bottom line: A significant reduction in recurrent peptic ulcers is seen with the combination of esomeprazole plus clopidogrel, versus clopidogrel alone, in patients with atherosclerosis and a history of peptic ulcer disease.

Citation: Hsu PI, Lai KH, Liu CP. Esomeprazole with clopidogrel reduces peptic ulcer recurrence, compared with clopidogrel alone, in patients with atherosclerosis. Gastroenterology. 2011;140:791-798.

ICU Quality-Improvement Project Reduces Hospital Mortality

Clinical question: Does a quality-improvement (QI) project in the ICU reduce in-hospital mortality and length of stay among elderly adults?

Background: Previous studies have shown that ICU-acquired infections are associated with increased morbidity and mortality, and QI initiatives reduce hospital-acquired infections. However, it has not been demonstrated that QI projects in the ICU reduce in-hospital mortality or length of stay.

Study design: Retrospective cohort study.

Setting: Four hundred fifty-nine Midwestern hospitals.

Synopsis: This study included 238,937 adults age >65 who were hospitalized in an ICU from 2001 to 2006 at one of 95 hospitals invited to implement the Keystone ICU Project. The control group included 1,091,547 elderly adults at one of 364 hospitals not invited to participate in the project. The Keystone ICU Project implements evidence-based practices to reduce rates of catheter-related bloodstream infections and ventilator-associated pneumonia.

Hospital mortality was not significantly reduced during initiation or implementation of the project; however, a significant reduction in hospital mortality occurred in the study group during one to 12 months post-implementation (OR=0.83 vs. 0.88, P=0.041) and 13 to 22 months post-implementation (OR=0.76 vs. 0.84, P=0.007). In contrast, length of stay did not differ significantly between the two groups, but the study was underpowered for this outcome.

The study is limited by the complexity of the Keystone ICU Project, as well as the exclusion of smaller hospitals and nonelderly adults. The study is promising because implementing a QI project in the ICU is associated with no known harms and might confer a mortality benefit at a relatively low cost.

Bottom line: Elderly adults had lower in-hospital mortality after implementation of the Keystone QI project in ICUs.

Citation: Lipitz-Snyderman A, Steinwachs D, Needham DM, Colantuoni E, Morlock LL, Pronovost PJ. Impact of a statewide intensive care unit quality improvement initiative on hospital mortality and length of stay: retrospective comparative analysis. BMJ. 2011;342:d219.

Serious Long-Term Risks with Acute Kidney Injury after Coronary Angiography

Clinical question: Does postcoronary angiography acute kidney injury (AKI) increase the risk of poor long-term clinical outcomes?

Background: Previous studies have shown that AKI following coronary angiography increases the risk of poor short-term clinical outcomes, such as in-hospital myocardial infarction, prolonged hospital stay, and early mortality. Little is known about the long-term cardiovascular and renal outcomes following post-coronary angiography AKI.

Study design: Retrospective cohort study.

Setting: All coronary angiography centers in Alberta, Canada.

Synopsis: The study included 14,782 adults who were ≥18 years of age, underwent coronary angiography, had a baseline creatinine measurement, did not have end-stage renal disease (ESRD), and had a creatinine measurement within seven days after coronary angiography.

During a median follow-up period of 19.7 months, 1,099 (7.4%) patients developed stage 1 AKI and 321 (2.2%) developed stage 2 or 3 AKI. Mortality increased twofold with stage 1 AKI and >3-fold with stage 2 or 3 AKI. Risk of ESRD increased substantially by >11-fold in patients with stage 2 or 3 AKI. Risk of hospitalization for subsequent AKI, myocardial infarction, and heart failure also increased significantly following post-coronary angiography AKI.

Patients who experienced AKI were older, had more severe CAD, were more likely to have such comorbidities as DM, HTN, and heart failure, and had lower baseline GFRs. However, the underlying comorbidities do not completely explain the increased risk of poor long-term outcomes in the adjusted analysis.

Limitations include missing or underestimating mild cases of AKI, residual confounding from unmeasured variables, and inability of retrospective comparative studies to establish causality.

Bottom line: Adults with post-coronary angiography AKI are at increased risk of poor long-term cardiovascular and renal outcomes.

Citation: James MT, Ghali WA, Knudtson ML, et al. Associations between acute kidney injury and cardiovascular and renal outcomes after coronary angiography. Circulation. 2011;123(4):409-416. TH

Pediatric HM Literature

Proton-Pump Inhibitors Ineffective for Gastroesophageal Reflux Disease in Children

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

Clinical question: What is the efficacy of proton-pump inhibitors (PPIs) in children with gastroesophageal reflux disease (GERD)?

Background: Gastroesophageal reflux is both a common and normal phenomenon in infants. GERD refers to the presence of abnormal symptoms ascribed to the reflux and frequently is treated in children in a manner similar to adults with reflux esophagitis. PPIs often are prescribed as front-line treatment, and their use has increased dramatically in recent years, though their effectiveness in children remains unclear.

Study design: Systematic review of the literature.

Setting: Hawaii’s largest health insurer.

Synopsis: Medline, Embase, and the Cochrane Database of Systematic Reviews were searched for randomized controlled trials (RCTs) and crossover studies performed to evaluate the efficacy of PPIs in children 0-17 years with GERD and no complicating diseases. Ten RCTs and two crossover studies were analyzed and rated independently by two reviewers.

Due to significant heterogeneity between the studies, a meta-analysis was not possible; studies were discussed separately. PPIs offered no advantage when compared with controls (alginates, ranitidine, different dosages of PPIs), and similar rates of adverse events were reported between treatment groups.

This study is hampered by notable heterogeneity of patient type, symptoms, and study design in many of the trials. However, the results are in line with discussions at a recent FDA Gastrointestinal Drugs Advisory Committee meeting, which reviewed the lack of efficacy of PPIs in infants in four recent Phase 3 clinical trials.

Bottom line: Little evidence supports the widespread use of PPIs in children.

Citation: Van der Pol RJ, Smits MJ, van Wijk MP, Omari TI, Tabbers MM, Benninga MA. Efficacy of proton-pump inhibitors in children with gastroesophageal reflux disease: a systematic review. Pediatrics. 2011;127:925-935.

Clinical question: Does the mortality rate differ between patients treated perioperatively with atenolol versus metoprolol?

Background: Perioperative beta-blockers have been shown to reduce mortality in patients with significant cardiac risk factors. Different beta-blockers have been used in the studies demonstrating benefit, and it is uncertain which beta-blocker is the preferred agent. The purpose of this study was to compare the perioperative benefits of metoprolol versus atenolol.

Study design: Retrospective cohort study.

Setting: San Francisco Veterans Affairs Medical Center.

Synopsis: Computerized records of patients who underwent surgery from 1996 to 2008 were extracted into a database, and patients who received inpatient beta-blockers after surgery were included. Of these patients, 3,787 received beta-blockade exclusively with either atenolol (n=1,011) or metoprolol (n=2,776) during hospitalization. Perioperative risk reduction was better with atenolol versus metoprolol. Mortality rates were 1% versus 3% at 30 days (P=0.0008), and 7% versus 13% at one year (P=<0.0001) with atenolol and metoprolol, respectively. Similar results were found in the analysis of 1,871 patients who were on their respective beta-blocker as an outpatient before surgery.

Because the metoprolol group had higher prevalence of risk factors, such as coronary artery disease, peripheral vascular disease, and congestive heart failure, a propensity-matched analysis was performed to remove differences in risk factors between the groups. After propensity matching, the metoprolol group still had statistically significant higher mortality at 30 days and one year, even though causality cannot be established in this retrospective study.

Bottom line: Atenolol was associated with fewer cases of perioperative mortality compared with metoprolol in patients with cardiac risk factors or established cardiovascular disease.

Citation: Wallace AW, Au S, Cason BA. Perioperative ß-blockade: atenolol is associated with reduced mortality when compared to metoprolol. Anesthesiology. 2011;114:824-836.

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

Clinical question: Does the mortality rate differ between patients treated perioperatively with atenolol versus metoprolol?

Background: Perioperative beta-blockers have been shown to reduce mortality in patients with significant cardiac risk factors. Different beta-blockers have been used in the studies demonstrating benefit, and it is uncertain which beta-blocker is the preferred agent. The purpose of this study was to compare the perioperative benefits of metoprolol versus atenolol.

Study design: Retrospective cohort study.

Setting: San Francisco Veterans Affairs Medical Center.

Synopsis: Computerized records of patients who underwent surgery from 1996 to 2008 were extracted into a database, and patients who received inpatient beta-blockers after surgery were included. Of these patients, 3,787 received beta-blockade exclusively with either atenolol (n=1,011) or metoprolol (n=2,776) during hospitalization. Perioperative risk reduction was better with atenolol versus metoprolol. Mortality rates were 1% versus 3% at 30 days (P=0.0008), and 7% versus 13% at one year (P=<0.0001) with atenolol and metoprolol, respectively. Similar results were found in the analysis of 1,871 patients who were on their respective beta-blocker as an outpatient before surgery.

Because the metoprolol group had higher prevalence of risk factors, such as coronary artery disease, peripheral vascular disease, and congestive heart failure, a propensity-matched analysis was performed to remove differences in risk factors between the groups. After propensity matching, the metoprolol group still had statistically significant higher mortality at 30 days and one year, even though causality cannot be established in this retrospective study.

Bottom line: Atenolol was associated with fewer cases of perioperative mortality compared with metoprolol in patients with cardiac risk factors or established cardiovascular disease.

Citation: Wallace AW, Au S, Cason BA. Perioperative ß-blockade: atenolol is associated with reduced mortality when compared to metoprolol. Anesthesiology. 2011;114:824-836.

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

Clinical question: Does the mortality rate differ between patients treated perioperatively with atenolol versus metoprolol?

Background: Perioperative beta-blockers have been shown to reduce mortality in patients with significant cardiac risk factors. Different beta-blockers have been used in the studies demonstrating benefit, and it is uncertain which beta-blocker is the preferred agent. The purpose of this study was to compare the perioperative benefits of metoprolol versus atenolol.

Study design: Retrospective cohort study.

Setting: San Francisco Veterans Affairs Medical Center.

Synopsis: Computerized records of patients who underwent surgery from 1996 to 2008 were extracted into a database, and patients who received inpatient beta-blockers after surgery were included. Of these patients, 3,787 received beta-blockade exclusively with either atenolol (n=1,011) or metoprolol (n=2,776) during hospitalization. Perioperative risk reduction was better with atenolol versus metoprolol. Mortality rates were 1% versus 3% at 30 days (P=0.0008), and 7% versus 13% at one year (P=<0.0001) with atenolol and metoprolol, respectively. Similar results were found in the analysis of 1,871 patients who were on their respective beta-blocker as an outpatient before surgery.

Because the metoprolol group had higher prevalence of risk factors, such as coronary artery disease, peripheral vascular disease, and congestive heart failure, a propensity-matched analysis was performed to remove differences in risk factors between the groups. After propensity matching, the metoprolol group still had statistically significant higher mortality at 30 days and one year, even though causality cannot be established in this retrospective study.

Bottom line: Atenolol was associated with fewer cases of perioperative mortality compared with metoprolol in patients with cardiac risk factors or established cardiovascular disease.

Citation: Wallace AW, Au S, Cason BA. Perioperative ß-blockade: atenolol is associated with reduced mortality when compared to metoprolol. Anesthesiology. 2011;114:824-836.

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

• ICU volume and outcomes
• Bicarbonate and contrast-induced nephropathy
• Rate of incidental findings in chest CT angiography
• Consequences of adverse-event reporting by physicians
• Hip fracture comanagement
• Niacin vs. ezetimibe in atherosclerosis
• Effect of hospital pharmacists on readmission rates
• Antibiotics in acute exacerbations of COPD

Higher Patient ICU Inflow Volumes Are Associated with Unplanned Readmissions to ICU

Clinical question: Do higher rates of unplanned ICU readmissions occur on days with high patient inflow volumes?

Background: Patients readmitted to ICUs have longer lengths of stay (LOS) and higher rates of in-hospital mortality. Previous studies suggest many ICU readmissions might be due to premature discharge, but there is little evidence evaluating the impact of patient inflow volumes on the incidence of ICU readmissions.

Study design: Retrospective, cohort study.

Setting: Large, urban, tertiary-care academic medical center in Baltimore.

Synopsis: A retrospective review of 3,233 discharges from a neurosciences critical-care unit revealed 95 unplanned readmissions to the ICU setting within 72 hours of discharge to lower level of care. The odds of one or more discharges becoming an unplanned readmission became significantly higher on days when ≥8 patients were admitted to the ICU (OR, 1.66; 95% CI, 1.03-2.68), and the odds of an unplanned readmission were almost five times higher on days when ≥10 patients were admitted, compared with days when ≤9 patients were admitted (OR, 4.99; 95% CI, 2.45-10.17).

After adjusting for patient complexity, patients discharged on days with ≥10 admissions had higher than twice the odds of becoming an unplanned readmission than patients discharged on days with ≤9 admissions (OR, 2.34; 95% CI, 1.27-4.34).

This study was limited to patients in a neurosciences critical-care unit at a single academic medical center. Further research is needed to better understand how high admission volumes lead to increased unplanned readmission rates.

Bottom line: Days with high patient inflow volumes to the ICU are associated with higher rates of unplanned readmissions to the ICU, and the rate of unplanned readmissions becomes significant once a daily threshold of eight admissions is reached.

Citation: Baker DR, Pronovost PJ, Morlock LL, Geocadin RG, Holzmueller CG. Patient flow variability and unplanned readmissions to an intensive care unit. Crit Care Med. 2009;37(11):2882-2887.

Effectiveness of Sodium Bicarbonate in Contrast-Induced Nephropathy Prevention

Clinical question: Is IV sodium bicarbonate effective for prevention of contrast-induced nephropathy (CIN) in high-risk patients?

Background: CIN is a leading cause of acute kidney injury in the hospital setting. Some studies have suggested IV sodium bicarbonate might reduce risk for CIN; other studies challenge this conclusion.

Study design: Systematic review.

Setting: Published and unpublished randomized, controlled trials performed worldwide.

Synopsis: The research examined in this study was composed of randomized, controlled trials that investigated CIN prevention and included IV sodium bicarbonate in one of the treatment groups. Nine published and 15 unpublished trials were selected for a total of 3,563 patients studied. The overall pooled relative risk of CIN in patients treated with IV sodium bicarbonate compared with normal saline was 0.62 (95% CI, 0.45-0.86), though the strength of this evidence was questioned.

Significant heterogeneity across studies was found (I²=49.1%; P=0.004), partially related to substantially greater treatment effect in published (RR 0.43, 95% CI, 0.25-0.75) versus unpublished (RR 0.78, 95% CI, 0.52-1.17) studies. Publication bias was confirmed statistically. Among the published studies, greater treatment effect favoring bicarbonate over saline tended to be reported in those published before 2008, had fewer patients (<200) and events (<15), had measured events within 48 hours, and were studies of lower quality.

No effects regarding the risk of heart failure, the need for dialysis, or mortality were found, though the studies were not specifically designed to investigate those clinical outcomes. Larger studies are needed to better assess these questions.

Bottom line: IV sodium bicarbonate for CIN prevention in high-risk patients could be less effective than previous reports have suggested.

Citation: Zoungas S, Ninomiya T, Huxley R, et al. Systematic review: sodium bicarbonate treatment regimens for the prevention of contrast-induced nephropathy. Ann Intern Med. 2009;151(9):631-638.

Incidental Findings More Frequent than PE in Chest CT Angiograms

Clinical question: What is the prevalence of incidental findings on chest-computed tomographic angiograms (CTAs) ordered by an ED to evaluate for pulmonary embolism (PE)?

Background: CTAs commonly are ordered by ED physicians to assess for PE. While CTAs might yield findings to support an alternate diagnosis to PE, incidental findings might be found that often require further radiographic or clinical followup. The workup of these incidental findings can be burdensome and low-yield.

Study design: Retrospective chart review.

Setting: Single, academic, tertiary-care hospital in North Carolina.

Synopsis: All patients who underwent CTA evaluation for PE in the ED over two enrollment periods were selected; radiographic findings were compiled and their medical records reviewed. Fifty-five of 589 CTAs (9%) were positive for PE. New incidental findings requiring radiographic or clinical followup were found in 141 cases (24%).

Overall, pulmonary nodules were most common, requiring followup in 73 (13%) cases. Adenopathy requiring followup was seen in 51 cases (9%), and new masses requiring followup were found in 12 cases (2%). Findings to support alternate diagnoses for shortness of breath, hypoxemia, or tachycardia were found in 195 patients (33%), most commonly pleural effusion (19%) and infiltrates (11%). Other incidental findings that required less-urgent clinical attention were common with 615 total findings, most frequently nonmalignant bone findings in 144 cases (24%), mild dependent atelectasis in 137 cases (23%), and emphysema in 69 cases (12%).

Bottom line: Incidental findings requiring followup were more than twice as common as PE (24% vs. 9%) in CTAs ordered to evaluate for PE in an ED.

Citation: Hall WB, Truitt SG, Scheunemann LP, et al. The prevalence of clinically relevant incidental findings on chest computed tomographic angiograms ordered to diagnose pulmonary embolism. Arch Intern Med. 2009;169(21):1961-1965.

Patients Don’t Penalize for Adverse-Outcome Disclosure

Clinical question: What patient or clinical characteristics affect the likelihood of physician reporting of an adverse outcome, and how does adverse-outcome disclosure affect patient perceptions of quality of care?

Background: Harmful adverse events (AE), injuries caused by medical management rather than by the underlying condition of the patient, are common in the U.S. Previous studies have focused on physician and provider attitudes about disclosure. Little is known about how characteristics of the AE affect disclosure, and how disclosure affects patients’ perceptions of quality of care.

Study design: Retrospective cohort study.

Setting: Acute-care hospitals in Massachusetts.

Synopsis: Of 4,143 eligible patients, 2,582 (62%) agreed to a telephone interview that asked about patient experiences with adverse events during their hospital stay. Respondents reporting an AE were asked about disclosure by medical staff, effects of adverse events on their hospital course, and the quality of their hospital care.

Of the 845 AEs reported by 608 patients, only 40% were disclosed, defined as “anyone from the hospital explaining why the negative effects occurred.” The majority of the AEs were related to newly prescribed medications (40%) and surgical procedures (34%). Researchers determined that 31% of the AEs were preventable and 75% were severe. In multivariate analysis, disclosure was less likely if the AE was preventable or if patients had long-term effects from the AE. Patients with an AE were more likely to rate the quality of their hospitalization higher if there had been disclosure.

Bottom line: Disclosure of adverse events by medical personnel is low (40%) in hospitalized patients, even though disclosure of adverse events increases patients’ ratings of quality of care.

Citation: López L, Weismann JS, Schneider EC, Weingart SN, Cohen AP, Epstein AM. Disclosure of hospital adverse events and its association with patients’ ratings of the quality of care. Arch Intern Med. 2009;169(20):1888-1894.

Comanagement of Hip-Fracture Patients by Geriatricians Decreases Time to Surgery, LOS, and Complications

Clinical question: Does comanagement of hip-fracture patients by geriatricians and orthopedic surgeons improve short-term outcomes?

Background: Hip fractures in older adults are associated with considerable morbidity and mortality. A model at a single center, where hip fracture patients are comanaged by geriatricians and orthopedic surgeons, demonstrated decreased LOS, readmission rates, and mortality when compared with national data. This study compares results to a usual-care site.

Study design: Retrospective cohort study.

Setting: Community-based teaching hospital and a tertiary-care hospital in Rochester, N.Y.

Synopsis: Researchers enrolled 314 patients with hip fractures. The 193 patients in the intervention group were comanaged by geriatricians and orthopedic surgeons. The 121 patients in the usual-care group were admitted under the care of orthopedic surgeons, and hospitalists were consulted when deemed necessary. Retrospective chart reviews were performed; complications were defined a priori.

When compared with usual care, patients in the intervention group had significantly shorter times to surgery (24.1 hours vs. 37.4 hours), shorter LOS (4.6 days vs. 8.3 days), fewer complications (30.6% vs. 46.3%), including fewer postoperative infections (2.3% vs. 19.8%), cardiac complications (1.0% vs. 7.4%), cases of thromboembolism (0.5% vs. 5.0%), episodes of bleeding (0% vs. 3.3%), and episodes of hypoxia (6.7% vs. 14.1%). There was no difference in inpatient mortality or 30-day readmission rates.

Further assessment comanagement by hospitalists and comanagement by geriatricians is needed.

Bottom line: Perioperative comanagement of hip-fracture patients by geriatricians and orthopedic surgeons significantly improves short-term outcomes.

Citation: Friedman SM, Mendelson DA, Bingham KW, Kates SL. Impact of a comanaged geriatric fracture center on short-term hip fracture outcomes. Arch Intern Med. 2009;169 (18):1712-1717.

Niacin Is Superior to Ezetimibe in Causing Significant Regression of Carotid Intima-Media Thickness when Combined with a Statin

Clinical question: Is ezetimibe superior to niacin for reducing carotid intima-media thickness (CIMT) in patients with coronary artery disease (CAD) already on statin monotherapy?

Background: Statin montherapy significantly reduces the risk of cardiovascular events, and further lowering of this risk can be achieved by reducing the LDL, using statin intensification, or adding ezetimibe, or by raising the HDL levels by adding niacin therapy. This comparative-effectiveness trial compared the efficacy of these two approaches.

Study design: Prospective, randomized, parallel-group, open-label study.

Setting: Tertiary-care military medical center, and private tertiary-care hospital in Washington, D.C.

Synopsis: Three hundred sixty-three patients with known CAD or CAD equivalent were enrolled, and all of the patients were maintained on statin therapy with LDL <100 and HDL <50. Patients were randomized to ezetimibe 10 mg/day or niacin, starting at 500 mg at bedtime and titrated to 2 g/day. Primary endpoint was a mean change in CIMT after 14 months. Secondary endpoints were change in lipid levels, composite of major cardiovascular events, drug discontinuation, and quality of life.

The trial was terminated early after 208 patients had completed the trial. Although ezetimibe showed greater reduction of LDL, niacin showed significantly greater reduction in the progression of CIMT. Patients receiving niacin experienced fewer cardiovascular events (1% vs. 5%) but had higher rates of withdrawal (15% vs. 9%) due to flushing.

Limitations of the study are small sample size, short follow-up period, and use of CIMT as a surrogate marker for clinical endpoint.

Bottom line: Niacin is superior to ezetimibe in reducing CIMT and raising HDL levels and might be more efficacious in reducing cardiovascular risk.

Citation: Taylor AJ, Villines TC, Stanek EJ, et al. Extended-release niacin or ezetimibe and carotid intima-media thickness. N Engl J Med. 2009;361(22):2113-2122.

Pharmacist-Facilitated Hospital Discharge Program Didn’t Reduce Post-Discharge Healthcare Resource Utilization

Clinical question: Does pharmacist-facilitated hospital discharge reduce hospital readmission rates?

Background: Medication discrepancies at the time of discharge often lead to confusion, medical errors, and readmission to the hospital. Patients who are at high risk of medication errors often are on multiple medications and experience adverse drug events upon discharge.

Study design: Prospective cohort study.

Setting: Tertiary-care, academic teaching hospital in Michigan.

Synopsis: One pharmacist alternated between the resident service and hospitalist service every month. The pharmacist monitored the patients being discharged for appropriateness and accuracy of medications. The pharmacist assessed medication therapy, reconciled medications, screened for adherence concerns, counseled and educated patients, and performed post-discharge telephone follow-up.

Primary outcomes were ED visits within 72 hours and readmission rates by day 14 and day 30.

The study found high numbers of medication discrepancies in the control (33.5%) and intervention (59.6%) groups, and these discrepancies were resolved prior to discharge; however, there was no significant impact on post-discharge ED visits, or 14- and 30-day readmission rates. Post-discharge telephone calls reduced 14-day readmission rates.

Bottom line: Pharmacist-facilitated hospital discharge did not significantly reduce post-discharge ED visits or readmissions.

Citation: Walker PC, Bernstein SJ, Jones JN, et al. Impact of a pharmacist-facilitated hospital discharge program. Arch Intern Med. 2009;169(21):2003-2010.

Questionable Antibiotic Benefit for Patients with Acute COPD Exacerbations

Clinical question: Does the addition of antibiotics to systemic corticosteroids provide additional benefits for patients hospitalized with acute exacerbations of chronic obstructive pulmonary disease (AECOPD)?

Background: The role of antibiotics in the treatment of AECOPD is unclear, particularly in addition to systemic corticosteroids. Many of the studies demonstrating the benefit of antibiotics were conducted several decades before systemic steroids were used routinely for the treatment of AECOPD.

Study design: Randomized, double-blinded, placebo-controlled study.

Setting: Two academic teaching hospitals in the Netherlands.

Synopsis: Two hundred sixty-five acute exacerbations of COPD were enrolled in the study, and patients were randomized to a seven-day course of 200 mg/day of doxycycline or placebo. All patients received systemic corticosteroids, nebulized bronchodilator therapy, and physiotherapy. The study found that doxycycline was equivalent to placebo for the primary endpoint of clinical success on day 30; however, doxycycline was superior to placebo for secondary outcomes of clinical success, clinical cure, symptomatic improvement, microbiological success, and reducing open label antibiotic use on day 10, but not on day 30.

Because the population studied had low levels of advanced antimicrobial resistance, the findings might not be generalizable. Results suggested a difference of treatment effect between subgroups based on C-reactive protein values, but further research is needed.

Bottom line: Patients treated with doxycycline for acute exacerbation of COPD had improved clinical outcomes at day 10, but the benefits were not significant at day 30. Data are still equivocal regarding benefits of antibiotics in patients with acute exacerbations of COPD.

Citation: Daniels JM, Snijders D, de Graaff CS, Vlaspolder F, Jansen HM, Boersma WG. Antibiotics in addition to systemic corticosteroids for acute exacerbations of chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2010;181(2):150-157. TH

PEDIATRIC HM LITERATURE

By Mark Shen, MD

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

Less Is More in the Management of Acute Gastroenteritis

Clinical question: What is the effect of a guideline-training program for pediatricians on the management of acute gastroenteritis (AGE)?

Background: Guidelines recommending oral rehydration, early refeeding, and limited interventions have been developed for AGE management, but uptake by pediatricians has been slow. While individual components of these guidelines have been shown to be effective in comparison to other resource-intensive interventions, outcomes of global guideline implementation have not been studied well.

Study design: Prospective, randomized, controlled trial.

Setting: One hundred forty-nine primary-care pediatricians in Italy.

Synopsis: Pediatricians from the Italian national healthcare system were randomized to AGE guideline training or no training (usual practice; control group). The physicians enrolled 1,309 children in the study. Parents completed daily forms documenting the interventions for, and outcomes of, each illness.

Management by the trained group of pediatricians was in full compliance with the guidelines 66% of the time, as opposed to 33% of the time in the untrained group.

Significant differences between the groups were noted for each basic tenet of the guidelines: oral rehydration use, restrictive diets, medication use, and microbiologic testing. Notably, by both intention-to-treat and per-protocol analysis, the mean duration of diarrhea was shorter in children managed by the trained group of pediatricians.

As underadherence to evidence-based guidelines remains commonplace, effective implementation will become a greater area of focus. Despite a modest effect in an ambulatory population, these investigators demonstrated a clear improvement in outcomes with a simple, two-hour training program. While not studied, it is likely that the cost of care was significantly lower in the guideline group, given the dramatic differences in medication use and testing.

Bottom line: Effective implementation of AGE guidelines will improve outcomes and reduce costs.

Citation: Albano F, Lo Vecchio A, Guarino A. The applicability and efficacy of guidelines for the management of acute gastroenteritis in outpatient children: a field-randomized trial on primary care pediatricians. J Pediatr. 2010;156(2):226-230.

In This Edition

Literature at a Glance

A guide to this month’s studies

• ICU volume and outcomes
• Bicarbonate and contrast-induced nephropathy
• Rate of incidental findings in chest CT angiography
• Consequences of adverse-event reporting by physicians
• Hip fracture comanagement
• Niacin vs. ezetimibe in atherosclerosis
• Effect of hospital pharmacists on readmission rates
• Antibiotics in acute exacerbations of COPD

Higher Patient ICU Inflow Volumes Are Associated with Unplanned Readmissions to ICU

Clinical question: Do higher rates of unplanned ICU readmissions occur on days with high patient inflow volumes?

Background: Patients readmitted to ICUs have longer lengths of stay (LOS) and higher rates of in-hospital mortality. Previous studies suggest many ICU readmissions might be due to premature discharge, but there is little evidence evaluating the impact of patient inflow volumes on the incidence of ICU readmissions.

Study design: Retrospective, cohort study.

Setting: Large, urban, tertiary-care academic medical center in Baltimore.

Synopsis: A retrospective review of 3,233 discharges from a neurosciences critical-care unit revealed 95 unplanned readmissions to the ICU setting within 72 hours of discharge to lower level of care. The odds of one or more discharges becoming an unplanned readmission became significantly higher on days when ≥8 patients were admitted to the ICU (OR, 1.66; 95% CI, 1.03-2.68), and the odds of an unplanned readmission were almost five times higher on days when ≥10 patients were admitted, compared with days when ≤9 patients were admitted (OR, 4.99; 95% CI, 2.45-10.17).

After adjusting for patient complexity, patients discharged on days with ≥10 admissions had higher than twice the odds of becoming an unplanned readmission than patients discharged on days with ≤9 admissions (OR, 2.34; 95% CI, 1.27-4.34).

This study was limited to patients in a neurosciences critical-care unit at a single academic medical center. Further research is needed to better understand how high admission volumes lead to increased unplanned readmission rates.

Bottom line: Days with high patient inflow volumes to the ICU are associated with higher rates of unplanned readmissions to the ICU, and the rate of unplanned readmissions becomes significant once a daily threshold of eight admissions is reached.

Citation: Baker DR, Pronovost PJ, Morlock LL, Geocadin RG, Holzmueller CG. Patient flow variability and unplanned readmissions to an intensive care unit. Crit Care Med. 2009;37(11):2882-2887.

Effectiveness of Sodium Bicarbonate in Contrast-Induced Nephropathy Prevention

Clinical question: Is IV sodium bicarbonate effective for prevention of contrast-induced nephropathy (CIN) in high-risk patients?

Background: CIN is a leading cause of acute kidney injury in the hospital setting. Some studies have suggested IV sodium bicarbonate might reduce risk for CIN; other studies challenge this conclusion.

Study design: Systematic review.

Setting: Published and unpublished randomized, controlled trials performed worldwide.

Synopsis: The research examined in this study was composed of randomized, controlled trials that investigated CIN prevention and included IV sodium bicarbonate in one of the treatment groups. Nine published and 15 unpublished trials were selected for a total of 3,563 patients studied. The overall pooled relative risk of CIN in patients treated with IV sodium bicarbonate compared with normal saline was 0.62 (95% CI, 0.45-0.86), though the strength of this evidence was questioned.

Significant heterogeneity across studies was found (I²=49.1%; P=0.004), partially related to substantially greater treatment effect in published (RR 0.43, 95% CI, 0.25-0.75) versus unpublished (RR 0.78, 95% CI, 0.52-1.17) studies. Publication bias was confirmed statistically. Among the published studies, greater treatment effect favoring bicarbonate over saline tended to be reported in those published before 2008, had fewer patients (<200) and events (<15), had measured events within 48 hours, and were studies of lower quality.

No effects regarding the risk of heart failure, the need for dialysis, or mortality were found, though the studies were not specifically designed to investigate those clinical outcomes. Larger studies are needed to better assess these questions.

Bottom line: IV sodium bicarbonate for CIN prevention in high-risk patients could be less effective than previous reports have suggested.

Citation: Zoungas S, Ninomiya T, Huxley R, et al. Systematic review: sodium bicarbonate treatment regimens for the prevention of contrast-induced nephropathy. Ann Intern Med. 2009;151(9):631-638.

Incidental Findings More Frequent than PE in Chest CT Angiograms

Clinical question: What is the prevalence of incidental findings on chest-computed tomographic angiograms (CTAs) ordered by an ED to evaluate for pulmonary embolism (PE)?

Background: CTAs commonly are ordered by ED physicians to assess for PE. While CTAs might yield findings to support an alternate diagnosis to PE, incidental findings might be found that often require further radiographic or clinical followup. The workup of these incidental findings can be burdensome and low-yield.

Study design: Retrospective chart review.

Setting: Single, academic, tertiary-care hospital in North Carolina.

Synopsis: All patients who underwent CTA evaluation for PE in the ED over two enrollment periods were selected; radiographic findings were compiled and their medical records reviewed. Fifty-five of 589 CTAs (9%) were positive for PE. New incidental findings requiring radiographic or clinical followup were found in 141 cases (24%).

Overall, pulmonary nodules were most common, requiring followup in 73 (13%) cases. Adenopathy requiring followup was seen in 51 cases (9%), and new masses requiring followup were found in 12 cases (2%). Findings to support alternate diagnoses for shortness of breath, hypoxemia, or tachycardia were found in 195 patients (33%), most commonly pleural effusion (19%) and infiltrates (11%). Other incidental findings that required less-urgent clinical attention were common with 615 total findings, most frequently nonmalignant bone findings in 144 cases (24%), mild dependent atelectasis in 137 cases (23%), and emphysema in 69 cases (12%).

Bottom line: Incidental findings requiring followup were more than twice as common as PE (24% vs. 9%) in CTAs ordered to evaluate for PE in an ED.

Citation: Hall WB, Truitt SG, Scheunemann LP, et al. The prevalence of clinically relevant incidental findings on chest computed tomographic angiograms ordered to diagnose pulmonary embolism. Arch Intern Med. 2009;169(21):1961-1965.

Patients Don’t Penalize for Adverse-Outcome Disclosure

Clinical question: What patient or clinical characteristics affect the likelihood of physician reporting of an adverse outcome, and how does adverse-outcome disclosure affect patient perceptions of quality of care?

Background: Harmful adverse events (AE), injuries caused by medical management rather than by the underlying condition of the patient, are common in the U.S. Previous studies have focused on physician and provider attitudes about disclosure. Little is known about how characteristics of the AE affect disclosure, and how disclosure affects patients’ perceptions of quality of care.

Study design: Retrospective cohort study.

Setting: Acute-care hospitals in Massachusetts.

Synopsis: Of 4,143 eligible patients, 2,582 (62%) agreed to a telephone interview that asked about patient experiences with adverse events during their hospital stay. Respondents reporting an AE were asked about disclosure by medical staff, effects of adverse events on their hospital course, and the quality of their hospital care.

Of the 845 AEs reported by 608 patients, only 40% were disclosed, defined as “anyone from the hospital explaining why the negative effects occurred.” The majority of the AEs were related to newly prescribed medications (40%) and surgical procedures (34%). Researchers determined that 31% of the AEs were preventable and 75% were severe. In multivariate analysis, disclosure was less likely if the AE was preventable or if patients had long-term effects from the AE. Patients with an AE were more likely to rate the quality of their hospitalization higher if there had been disclosure.

Bottom line: Disclosure of adverse events by medical personnel is low (40%) in hospitalized patients, even though disclosure of adverse events increases patients’ ratings of quality of care.

Citation: López L, Weismann JS, Schneider EC, Weingart SN, Cohen AP, Epstein AM. Disclosure of hospital adverse events and its association with patients’ ratings of the quality of care. Arch Intern Med. 2009;169(20):1888-1894.

Comanagement of Hip-Fracture Patients by Geriatricians Decreases Time to Surgery, LOS, and Complications

Clinical question: Does comanagement of hip-fracture patients by geriatricians and orthopedic surgeons improve short-term outcomes?

Background: Hip fractures in older adults are associated with considerable morbidity and mortality. A model at a single center, where hip fracture patients are comanaged by geriatricians and orthopedic surgeons, demonstrated decreased LOS, readmission rates, and mortality when compared with national data. This study compares results to a usual-care site.

Study design: Retrospective cohort study.

Setting: Community-based teaching hospital and a tertiary-care hospital in Rochester, N.Y.

Synopsis: Researchers enrolled 314 patients with hip fractures. The 193 patients in the intervention group were comanaged by geriatricians and orthopedic surgeons. The 121 patients in the usual-care group were admitted under the care of orthopedic surgeons, and hospitalists were consulted when deemed necessary. Retrospective chart reviews were performed; complications were defined a priori.

When compared with usual care, patients in the intervention group had significantly shorter times to surgery (24.1 hours vs. 37.4 hours), shorter LOS (4.6 days vs. 8.3 days), fewer complications (30.6% vs. 46.3%), including fewer postoperative infections (2.3% vs. 19.8%), cardiac complications (1.0% vs. 7.4%), cases of thromboembolism (0.5% vs. 5.0%), episodes of bleeding (0% vs. 3.3%), and episodes of hypoxia (6.7% vs. 14.1%). There was no difference in inpatient mortality or 30-day readmission rates.

Further assessment comanagement by hospitalists and comanagement by geriatricians is needed.

Bottom line: Perioperative comanagement of hip-fracture patients by geriatricians and orthopedic surgeons significantly improves short-term outcomes.

Citation: Friedman SM, Mendelson DA, Bingham KW, Kates SL. Impact of a comanaged geriatric fracture center on short-term hip fracture outcomes. Arch Intern Med. 2009;169 (18):1712-1717.

Niacin Is Superior to Ezetimibe in Causing Significant Regression of Carotid Intima-Media Thickness when Combined with a Statin

Clinical question: Is ezetimibe superior to niacin for reducing carotid intima-media thickness (CIMT) in patients with coronary artery disease (CAD) already on statin monotherapy?

Background: Statin montherapy significantly reduces the risk of cardiovascular events, and further lowering of this risk can be achieved by reducing the LDL, using statin intensification, or adding ezetimibe, or by raising the HDL levels by adding niacin therapy. This comparative-effectiveness trial compared the efficacy of these two approaches.

Study design: Prospective, randomized, parallel-group, open-label study.

Setting: Tertiary-care military medical center, and private tertiary-care hospital in Washington, D.C.

Synopsis: Three hundred sixty-three patients with known CAD or CAD equivalent were enrolled, and all of the patients were maintained on statin therapy with LDL <100 and HDL <50. Patients were randomized to ezetimibe 10 mg/day or niacin, starting at 500 mg at bedtime and titrated to 2 g/day. Primary endpoint was a mean change in CIMT after 14 months. Secondary endpoints were change in lipid levels, composite of major cardiovascular events, drug discontinuation, and quality of life.

The trial was terminated early after 208 patients had completed the trial. Although ezetimibe showed greater reduction of LDL, niacin showed significantly greater reduction in the progression of CIMT. Patients receiving niacin experienced fewer cardiovascular events (1% vs. 5%) but had higher rates of withdrawal (15% vs. 9%) due to flushing.

Limitations of the study are small sample size, short follow-up period, and use of CIMT as a surrogate marker for clinical endpoint.

Bottom line: Niacin is superior to ezetimibe in reducing CIMT and raising HDL levels and might be more efficacious in reducing cardiovascular risk.

Citation: Taylor AJ, Villines TC, Stanek EJ, et al. Extended-release niacin or ezetimibe and carotid intima-media thickness. N Engl J Med. 2009;361(22):2113-2122.

Pharmacist-Facilitated Hospital Discharge Program Didn’t Reduce Post-Discharge Healthcare Resource Utilization

Clinical question: Does pharmacist-facilitated hospital discharge reduce hospital readmission rates?

Background: Medication discrepancies at the time of discharge often lead to confusion, medical errors, and readmission to the hospital. Patients who are at high risk of medication errors often are on multiple medications and experience adverse drug events upon discharge.

Study design: Prospective cohort study.

Setting: Tertiary-care, academic teaching hospital in Michigan.

Synopsis: One pharmacist alternated between the resident service and hospitalist service every month. The pharmacist monitored the patients being discharged for appropriateness and accuracy of medications. The pharmacist assessed medication therapy, reconciled medications, screened for adherence concerns, counseled and educated patients, and performed post-discharge telephone follow-up.

Primary outcomes were ED visits within 72 hours and readmission rates by day 14 and day 30.

The study found high numbers of medication discrepancies in the control (33.5%) and intervention (59.6%) groups, and these discrepancies were resolved prior to discharge; however, there was no significant impact on post-discharge ED visits, or 14- and 30-day readmission rates. Post-discharge telephone calls reduced 14-day readmission rates.

Bottom line: Pharmacist-facilitated hospital discharge did not significantly reduce post-discharge ED visits or readmissions.

Citation: Walker PC, Bernstein SJ, Jones JN, et al. Impact of a pharmacist-facilitated hospital discharge program. Arch Intern Med. 2009;169(21):2003-2010.

Questionable Antibiotic Benefit for Patients with Acute COPD Exacerbations

Clinical question: Does the addition of antibiotics to systemic corticosteroids provide additional benefits for patients hospitalized with acute exacerbations of chronic obstructive pulmonary disease (AECOPD)?

Background: The role of antibiotics in the treatment of AECOPD is unclear, particularly in addition to systemic corticosteroids. Many of the studies demonstrating the benefit of antibiotics were conducted several decades before systemic steroids were used routinely for the treatment of AECOPD.

Study design: Randomized, double-blinded, placebo-controlled study.

Setting: Two academic teaching hospitals in the Netherlands.

Synopsis: Two hundred sixty-five acute exacerbations of COPD were enrolled in the study, and patients were randomized to a seven-day course of 200 mg/day of doxycycline or placebo. All patients received systemic corticosteroids, nebulized bronchodilator therapy, and physiotherapy. The study found that doxycycline was equivalent to placebo for the primary endpoint of clinical success on day 30; however, doxycycline was superior to placebo for secondary outcomes of clinical success, clinical cure, symptomatic improvement, microbiological success, and reducing open label antibiotic use on day 10, but not on day 30.

Because the population studied had low levels of advanced antimicrobial resistance, the findings might not be generalizable. Results suggested a difference of treatment effect between subgroups based on C-reactive protein values, but further research is needed.

Bottom line: Patients treated with doxycycline for acute exacerbation of COPD had improved clinical outcomes at day 10, but the benefits were not significant at day 30. Data are still equivocal regarding benefits of antibiotics in patients with acute exacerbations of COPD.

Citation: Daniels JM, Snijders D, de Graaff CS, Vlaspolder F, Jansen HM, Boersma WG. Antibiotics in addition to systemic corticosteroids for acute exacerbations of chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2010;181(2):150-157. TH

PEDIATRIC HM LITERATURE

By Mark Shen, MD

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

Less Is More in the Management of Acute Gastroenteritis

Clinical question: What is the effect of a guideline-training program for pediatricians on the management of acute gastroenteritis (AGE)?

Background: Guidelines recommending oral rehydration, early refeeding, and limited interventions have been developed for AGE management, but uptake by pediatricians has been slow. While individual components of these guidelines have been shown to be effective in comparison to other resource-intensive interventions, outcomes of global guideline implementation have not been studied well.

Study design: Prospective, randomized, controlled trial.

Setting: One hundred forty-nine primary-care pediatricians in Italy.

Synopsis: Pediatricians from the Italian national healthcare system were randomized to AGE guideline training or no training (usual practice; control group). The physicians enrolled 1,309 children in the study. Parents completed daily forms documenting the interventions for, and outcomes of, each illness.

Management by the trained group of pediatricians was in full compliance with the guidelines 66% of the time, as opposed to 33% of the time in the untrained group.

Significant differences between the groups were noted for each basic tenet of the guidelines: oral rehydration use, restrictive diets, medication use, and microbiologic testing. Notably, by both intention-to-treat and per-protocol analysis, the mean duration of diarrhea was shorter in children managed by the trained group of pediatricians.

As underadherence to evidence-based guidelines remains commonplace, effective implementation will become a greater area of focus. Despite a modest effect in an ambulatory population, these investigators demonstrated a clear improvement in outcomes with a simple, two-hour training program. While not studied, it is likely that the cost of care was significantly lower in the guideline group, given the dramatic differences in medication use and testing.

Bottom line: Effective implementation of AGE guidelines will improve outcomes and reduce costs.

Citation: Albano F, Lo Vecchio A, Guarino A. The applicability and efficacy of guidelines for the management of acute gastroenteritis in outpatient children: a field-randomized trial on primary care pediatricians. J Pediatr. 2010;156(2):226-230.

In This Edition

Literature at a Glance

A guide to this month’s studies

• ICU volume and outcomes
• Bicarbonate and contrast-induced nephropathy
• Rate of incidental findings in chest CT angiography
• Consequences of adverse-event reporting by physicians
• Hip fracture comanagement
• Niacin vs. ezetimibe in atherosclerosis
• Effect of hospital pharmacists on readmission rates
• Antibiotics in acute exacerbations of COPD

Higher Patient ICU Inflow Volumes Are Associated with Unplanned Readmissions to ICU

Clinical question: Do higher rates of unplanned ICU readmissions occur on days with high patient inflow volumes?

Background: Patients readmitted to ICUs have longer lengths of stay (LOS) and higher rates of in-hospital mortality. Previous studies suggest many ICU readmissions might be due to premature discharge, but there is little evidence evaluating the impact of patient inflow volumes on the incidence of ICU readmissions.

Study design: Retrospective, cohort study.

Setting: Large, urban, tertiary-care academic medical center in Baltimore.

Synopsis: A retrospective review of 3,233 discharges from a neurosciences critical-care unit revealed 95 unplanned readmissions to the ICU setting within 72 hours of discharge to lower level of care. The odds of one or more discharges becoming an unplanned readmission became significantly higher on days when ≥8 patients were admitted to the ICU (OR, 1.66; 95% CI, 1.03-2.68), and the odds of an unplanned readmission were almost five times higher on days when ≥10 patients were admitted, compared with days when ≤9 patients were admitted (OR, 4.99; 95% CI, 2.45-10.17).

After adjusting for patient complexity, patients discharged on days with ≥10 admissions had higher than twice the odds of becoming an unplanned readmission than patients discharged on days with ≤9 admissions (OR, 2.34; 95% CI, 1.27-4.34).

This study was limited to patients in a neurosciences critical-care unit at a single academic medical center. Further research is needed to better understand how high admission volumes lead to increased unplanned readmission rates.

Bottom line: Days with high patient inflow volumes to the ICU are associated with higher rates of unplanned readmissions to the ICU, and the rate of unplanned readmissions becomes significant once a daily threshold of eight admissions is reached.

Citation: Baker DR, Pronovost PJ, Morlock LL, Geocadin RG, Holzmueller CG. Patient flow variability and unplanned readmissions to an intensive care unit. Crit Care Med. 2009;37(11):2882-2887.

Effectiveness of Sodium Bicarbonate in Contrast-Induced Nephropathy Prevention

Clinical question: Is IV sodium bicarbonate effective for prevention of contrast-induced nephropathy (CIN) in high-risk patients?

Background: CIN is a leading cause of acute kidney injury in the hospital setting. Some studies have suggested IV sodium bicarbonate might reduce risk for CIN; other studies challenge this conclusion.

Study design: Systematic review.

Setting: Published and unpublished randomized, controlled trials performed worldwide.

Synopsis: The research examined in this study was composed of randomized, controlled trials that investigated CIN prevention and included IV sodium bicarbonate in one of the treatment groups. Nine published and 15 unpublished trials were selected for a total of 3,563 patients studied. The overall pooled relative risk of CIN in patients treated with IV sodium bicarbonate compared with normal saline was 0.62 (95% CI, 0.45-0.86), though the strength of this evidence was questioned.

Significant heterogeneity across studies was found (I²=49.1%; P=0.004), partially related to substantially greater treatment effect in published (RR 0.43, 95% CI, 0.25-0.75) versus unpublished (RR 0.78, 95% CI, 0.52-1.17) studies. Publication bias was confirmed statistically. Among the published studies, greater treatment effect favoring bicarbonate over saline tended to be reported in those published before 2008, had fewer patients (<200) and events (<15), had measured events within 48 hours, and were studies of lower quality.

No effects regarding the risk of heart failure, the need for dialysis, or mortality were found, though the studies were not specifically designed to investigate those clinical outcomes. Larger studies are needed to better assess these questions.

Bottom line: IV sodium bicarbonate for CIN prevention in high-risk patients could be less effective than previous reports have suggested.

Citation: Zoungas S, Ninomiya T, Huxley R, et al. Systematic review: sodium bicarbonate treatment regimens for the prevention of contrast-induced nephropathy. Ann Intern Med. 2009;151(9):631-638.

Incidental Findings More Frequent than PE in Chest CT Angiograms

Clinical question: What is the prevalence of incidental findings on chest-computed tomographic angiograms (CTAs) ordered by an ED to evaluate for pulmonary embolism (PE)?

Background: CTAs commonly are ordered by ED physicians to assess for PE. While CTAs might yield findings to support an alternate diagnosis to PE, incidental findings might be found that often require further radiographic or clinical followup. The workup of these incidental findings can be burdensome and low-yield.

Study design: Retrospective chart review.

Setting: Single, academic, tertiary-care hospital in North Carolina.

Synopsis: All patients who underwent CTA evaluation for PE in the ED over two enrollment periods were selected; radiographic findings were compiled and their medical records reviewed. Fifty-five of 589 CTAs (9%) were positive for PE. New incidental findings requiring radiographic or clinical followup were found in 141 cases (24%).

Overall, pulmonary nodules were most common, requiring followup in 73 (13%) cases. Adenopathy requiring followup was seen in 51 cases (9%), and new masses requiring followup were found in 12 cases (2%). Findings to support alternate diagnoses for shortness of breath, hypoxemia, or tachycardia were found in 195 patients (33%), most commonly pleural effusion (19%) and infiltrates (11%). Other incidental findings that required less-urgent clinical attention were common with 615 total findings, most frequently nonmalignant bone findings in 144 cases (24%), mild dependent atelectasis in 137 cases (23%), and emphysema in 69 cases (12%).

Bottom line: Incidental findings requiring followup were more than twice as common as PE (24% vs. 9%) in CTAs ordered to evaluate for PE in an ED.

Citation: Hall WB, Truitt SG, Scheunemann LP, et al. The prevalence of clinically relevant incidental findings on chest computed tomographic angiograms ordered to diagnose pulmonary embolism. Arch Intern Med. 2009;169(21):1961-1965.

Patients Don’t Penalize for Adverse-Outcome Disclosure

Clinical question: What patient or clinical characteristics affect the likelihood of physician reporting of an adverse outcome, and how does adverse-outcome disclosure affect patient perceptions of quality of care?

Background: Harmful adverse events (AE), injuries caused by medical management rather than by the underlying condition of the patient, are common in the U.S. Previous studies have focused on physician and provider attitudes about disclosure. Little is known about how characteristics of the AE affect disclosure, and how disclosure affects patients’ perceptions of quality of care.

Study design: Retrospective cohort study.

Setting: Acute-care hospitals in Massachusetts.

Synopsis: Of 4,143 eligible patients, 2,582 (62%) agreed to a telephone interview that asked about patient experiences with adverse events during their hospital stay. Respondents reporting an AE were asked about disclosure by medical staff, effects of adverse events on their hospital course, and the quality of their hospital care.

Of the 845 AEs reported by 608 patients, only 40% were disclosed, defined as “anyone from the hospital explaining why the negative effects occurred.” The majority of the AEs were related to newly prescribed medications (40%) and surgical procedures (34%). Researchers determined that 31% of the AEs were preventable and 75% were severe. In multivariate analysis, disclosure was less likely if the AE was preventable or if patients had long-term effects from the AE. Patients with an AE were more likely to rate the quality of their hospitalization higher if there had been disclosure.

Bottom line: Disclosure of adverse events by medical personnel is low (40%) in hospitalized patients, even though disclosure of adverse events increases patients’ ratings of quality of care.

Citation: López L, Weismann JS, Schneider EC, Weingart SN, Cohen AP, Epstein AM. Disclosure of hospital adverse events and its association with patients’ ratings of the quality of care. Arch Intern Med. 2009;169(20):1888-1894.

Comanagement of Hip-Fracture Patients by Geriatricians Decreases Time to Surgery, LOS, and Complications

Clinical question: Does comanagement of hip-fracture patients by geriatricians and orthopedic surgeons improve short-term outcomes?

Background: Hip fractures in older adults are associated with considerable morbidity and mortality. A model at a single center, where hip fracture patients are comanaged by geriatricians and orthopedic surgeons, demonstrated decreased LOS, readmission rates, and mortality when compared with national data. This study compares results to a usual-care site.

Study design: Retrospective cohort study.

Setting: Community-based teaching hospital and a tertiary-care hospital in Rochester, N.Y.

Synopsis: Researchers enrolled 314 patients with hip fractures. The 193 patients in the intervention group were comanaged by geriatricians and orthopedic surgeons. The 121 patients in the usual-care group were admitted under the care of orthopedic surgeons, and hospitalists were consulted when deemed necessary. Retrospective chart reviews were performed; complications were defined a priori.

When compared with usual care, patients in the intervention group had significantly shorter times to surgery (24.1 hours vs. 37.4 hours), shorter LOS (4.6 days vs. 8.3 days), fewer complications (30.6% vs. 46.3%), including fewer postoperative infections (2.3% vs. 19.8%), cardiac complications (1.0% vs. 7.4%), cases of thromboembolism (0.5% vs. 5.0%), episodes of bleeding (0% vs. 3.3%), and episodes of hypoxia (6.7% vs. 14.1%). There was no difference in inpatient mortality or 30-day readmission rates.

Further assessment comanagement by hospitalists and comanagement by geriatricians is needed.

Bottom line: Perioperative comanagement of hip-fracture patients by geriatricians and orthopedic surgeons significantly improves short-term outcomes.

Citation: Friedman SM, Mendelson DA, Bingham KW, Kates SL. Impact of a comanaged geriatric fracture center on short-term hip fracture outcomes. Arch Intern Med. 2009;169 (18):1712-1717.

Niacin Is Superior to Ezetimibe in Causing Significant Regression of Carotid Intima-Media Thickness when Combined with a Statin

Clinical question: Is ezetimibe superior to niacin for reducing carotid intima-media thickness (CIMT) in patients with coronary artery disease (CAD) already on statin monotherapy?

Background: Statin montherapy significantly reduces the risk of cardiovascular events, and further lowering of this risk can be achieved by reducing the LDL, using statin intensification, or adding ezetimibe, or by raising the HDL levels by adding niacin therapy. This comparative-effectiveness trial compared the efficacy of these two approaches.

Study design: Prospective, randomized, parallel-group, open-label study.

Setting: Tertiary-care military medical center, and private tertiary-care hospital in Washington, D.C.

Synopsis: Three hundred sixty-three patients with known CAD or CAD equivalent were enrolled, and all of the patients were maintained on statin therapy with LDL <100 and HDL <50. Patients were randomized to ezetimibe 10 mg/day or niacin, starting at 500 mg at bedtime and titrated to 2 g/day. Primary endpoint was a mean change in CIMT after 14 months. Secondary endpoints were change in lipid levels, composite of major cardiovascular events, drug discontinuation, and quality of life.

The trial was terminated early after 208 patients had completed the trial. Although ezetimibe showed greater reduction of LDL, niacin showed significantly greater reduction in the progression of CIMT. Patients receiving niacin experienced fewer cardiovascular events (1% vs. 5%) but had higher rates of withdrawal (15% vs. 9%) due to flushing.

Limitations of the study are small sample size, short follow-up period, and use of CIMT as a surrogate marker for clinical endpoint.

Bottom line: Niacin is superior to ezetimibe in reducing CIMT and raising HDL levels and might be more efficacious in reducing cardiovascular risk.

Citation: Taylor AJ, Villines TC, Stanek EJ, et al. Extended-release niacin or ezetimibe and carotid intima-media thickness. N Engl J Med. 2009;361(22):2113-2122.

Pharmacist-Facilitated Hospital Discharge Program Didn’t Reduce Post-Discharge Healthcare Resource Utilization

Clinical question: Does pharmacist-facilitated hospital discharge reduce hospital readmission rates?

Background: Medication discrepancies at the time of discharge often lead to confusion, medical errors, and readmission to the hospital. Patients who are at high risk of medication errors often are on multiple medications and experience adverse drug events upon discharge.

Study design: Prospective cohort study.

Setting: Tertiary-care, academic teaching hospital in Michigan.

Synopsis: One pharmacist alternated between the resident service and hospitalist service every month. The pharmacist monitored the patients being discharged for appropriateness and accuracy of medications. The pharmacist assessed medication therapy, reconciled medications, screened for adherence concerns, counseled and educated patients, and performed post-discharge telephone follow-up.

Primary outcomes were ED visits within 72 hours and readmission rates by day 14 and day 30.

The study found high numbers of medication discrepancies in the control (33.5%) and intervention (59.6%) groups, and these discrepancies were resolved prior to discharge; however, there was no significant impact on post-discharge ED visits, or 14- and 30-day readmission rates. Post-discharge telephone calls reduced 14-day readmission rates.

Bottom line: Pharmacist-facilitated hospital discharge did not significantly reduce post-discharge ED visits or readmissions.

Citation: Walker PC, Bernstein SJ, Jones JN, et al. Impact of a pharmacist-facilitated hospital discharge program. Arch Intern Med. 2009;169(21):2003-2010.

Questionable Antibiotic Benefit for Patients with Acute COPD Exacerbations

Clinical question: Does the addition of antibiotics to systemic corticosteroids provide additional benefits for patients hospitalized with acute exacerbations of chronic obstructive pulmonary disease (AECOPD)?

Background: The role of antibiotics in the treatment of AECOPD is unclear, particularly in addition to systemic corticosteroids. Many of the studies demonstrating the benefit of antibiotics were conducted several decades before systemic steroids were used routinely for the treatment of AECOPD.

Study design: Randomized, double-blinded, placebo-controlled study.

Setting: Two academic teaching hospitals in the Netherlands.

Synopsis: Two hundred sixty-five acute exacerbations of COPD were enrolled in the study, and patients were randomized to a seven-day course of 200 mg/day of doxycycline or placebo. All patients received systemic corticosteroids, nebulized bronchodilator therapy, and physiotherapy. The study found that doxycycline was equivalent to placebo for the primary endpoint of clinical success on day 30; however, doxycycline was superior to placebo for secondary outcomes of clinical success, clinical cure, symptomatic improvement, microbiological success, and reducing open label antibiotic use on day 10, but not on day 30.

Because the population studied had low levels of advanced antimicrobial resistance, the findings might not be generalizable. Results suggested a difference of treatment effect between subgroups based on C-reactive protein values, but further research is needed.

Bottom line: Patients treated with doxycycline for acute exacerbation of COPD had improved clinical outcomes at day 10, but the benefits were not significant at day 30. Data are still equivocal regarding benefits of antibiotics in patients with acute exacerbations of COPD.

Citation: Daniels JM, Snijders D, de Graaff CS, Vlaspolder F, Jansen HM, Boersma WG. Antibiotics in addition to systemic corticosteroids for acute exacerbations of chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2010;181(2):150-157. TH

PEDIATRIC HM LITERATURE

By Mark Shen, MD

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

Less Is More in the Management of Acute Gastroenteritis

Clinical question: What is the effect of a guideline-training program for pediatricians on the management of acute gastroenteritis (AGE)?

Background: Guidelines recommending oral rehydration, early refeeding, and limited interventions have been developed for AGE management, but uptake by pediatricians has been slow. While individual components of these guidelines have been shown to be effective in comparison to other resource-intensive interventions, outcomes of global guideline implementation have not been studied well.

Study design: Prospective, randomized, controlled trial.

Setting: One hundred forty-nine primary-care pediatricians in Italy.

Synopsis: Pediatricians from the Italian national healthcare system were randomized to AGE guideline training or no training (usual practice; control group). The physicians enrolled 1,309 children in the study. Parents completed daily forms documenting the interventions for, and outcomes of, each illness.

Management by the trained group of pediatricians was in full compliance with the guidelines 66% of the time, as opposed to 33% of the time in the untrained group.

Significant differences between the groups were noted for each basic tenet of the guidelines: oral rehydration use, restrictive diets, medication use, and microbiologic testing. Notably, by both intention-to-treat and per-protocol analysis, the mean duration of diarrhea was shorter in children managed by the trained group of pediatricians.

As underadherence to evidence-based guidelines remains commonplace, effective implementation will become a greater area of focus. Despite a modest effect in an ambulatory population, these investigators demonstrated a clear improvement in outcomes with a simple, two-hour training program. While not studied, it is likely that the cost of care was significantly lower in the guideline group, given the dramatic differences in medication use and testing.

Bottom line: Effective implementation of AGE guidelines will improve outcomes and reduce costs.

Citation: Albano F, Lo Vecchio A, Guarino A. The applicability and efficacy of guidelines for the management of acute gastroenteritis in outpatient children: a field-randomized trial on primary care pediatricians. J Pediatr. 2010;156(2):226-230.