Bystander cardiopulmonary resuscitation, early and aggressive advanced life support, rewarming, and the combination of intravenous epinephrine and vasopressin were associated with sustained return of spontaneous circulation following hypothermic submersion-associated cardiac arrest.

Data Extraction: Study design, mortality/clinical response, and other variables were extracted independently by two reviewers. When possible, study datasets were split into mutually exclusive groups with and without shock or critical illness.Data Synthesis: Although a pooled odds ratio indicated no overall mortality/clinical response benefit with combination therapy (odds ratio, 0.856; 95% confidence interval, 0.71-1.03; p ‫؍‬ .0943; I 2 ‫؍‬ 45.1%), stratification of datasets by monotherapy mortality risk demonstrated substantial benefit in the most severely ill subset (monotherapy risk of death >25%; odds ratio of death, 0.51; 95% confidence interval, 0.41-0.64; I 2 ‫؍‬ 8.6%). Of those datasets that could be stratified by the presence of shock/critical illness, the more severely ill group consistently demonstrated increased efficacy of a combination therapy strategy (odds ratio, 0.49; 95% confidence interval, 0.35-0.70; p < .0001; I 2 ‫؍‬ 0%). An increased risk of death was found in low-risk patients (risk of death <15% in the monotherapy arm) exposed to combination therapy (odds ratio, 1.53; 95% confidence interval, 1.16 -2.03; p ‫؍‬ .003; I 2 ‫؍‬ 8.2%). Meta-regression indicated that efficacy of combination therapy was dependent only on the risk of death in the monotherapy group.Conclusion: Combination antibiotic therapy improves survival and clinical response of high-risk, life-threatening infections, particularly those associated with septic shock but may be detrimental to low-risk patients. (Crit Care Med 2010; 38:1651-1664) KEY WORDS: sepsis; septic shock; outcome; serious infection; combination therapy; infectious diseases; antibiotic; critically ill LEARNING OBJECTIVESAfter participating in this educational activity, the participant should be better able to:1. Select antibiotic choices for treatment of patients with sepsis.2. Evaluate efficacy of combination antibiotic therapy in patient with sepsis and septic shock.3. Prescribe appropriate antibiotic regimens for critically ill patients with sepsis.