Eight studies (n=1,271) were included in the review: one prospective randomised trial and seven before-and-after studies. None of the studies was blinded. Four before-and-after studies reported imbalances in study group criteria at baseline.
Bundled care increased the odds of survival compared to controls (OR 1.91, 95% CI 1.49 to 2.45, I2=0%; eight studies, n=1,271); the difference was statistically significant. Bundled care significantly decreased the time to administration of antibiotics (WMD -0.58 hours, 95% CI -0.85 to -0.33, I2=0%; four studies) and increased the odds of receiving appropriate antibiotics compared with controls (OR 3.05, 95% CI 1.69 to 5.53, I2=0%; five studies).
There was significant statistical heterogeneity among studies that reported on timely administration of antibiotics (I2=77%) and crystalloid use (I2=89%) and studies that reported the number of patients who received vasopressors (I2=84%), inotropes (I2=67%), packed red blood cell transfusions (I2=73%), corticosteroids (I2=87%) and rhAPC (I2=88%).
Sensitivity analyses reduced statistical heterogeneity among studies that reported timely administration of antibiotics, use of inotropes and packed red blood cell transfusions, which indicated that bundle care signficantly increased the odds of receiving timely antibiotics compared with controls (OR 3.89, 95% CI 1.98 to 7.64, I2=0%; five studies) and use of inotropes (OR 6.89, 95% CI 2.33 to 20.38, I2=0%; six studies). There were no statistically significant differences between treatment groups in occurrence of packed red blood cell transfusions.