Background The effect of premorbid β-blocker exposure on clinical outcomes in patients with sepsis is not well characterized. We aimed to examine the association between premorbid β-blocker exposure and mortality in sepsis. Methods EMBase, MEDLINE, and Cochrane databases were searched for all studies of premorbid β-blocker and sepsis. The search was last updated on 22 June 2019. Two reviewers independently assessed, selected, and abstracted data from studies reporting chronic β-blocker use prior to sepsis and mortality. Main data extracted were premorbid β-blocker exposure, mortality, study design, and patient data. Two reviewers independently assessed the risk of bias and quality of evidence. Results In total, nine studies comprising 56,414 patients with sepsis including 6576 patients with premorbid exposure to β-blockers were eligible. For the primary outcome of mortality, two retrospective studies reported adjusted odds ratios showing a reduction in mortality with premorbid β-blocker exposure. One study showed that premorbid β-blocker exposure decreases mortality in patients with septic shock. Another study showed that continued β-blockade during sepsis is associated with decreased mortality. Conclusion This systematic review suggests that β-blocker exposure prior to sepsis is associated with reduced mortality. There was insufficient data to conduct a bona fide meta-analysis. Whether the apparent reduction in mortality may be attributed to the mitigation of catecholamine excess is unclear. Trial registration PROSPERO, CRD42019130558 registered June 12, 2019. Electronic supplementary material The online version of this article (10.1186/s13054-019-2562-y) contains supplementary material, which is available to authorized users.

OBJECTIVES: To examine the effect of premorbid β-blocker exposure on mortality and organ dysfunction in sepsis. DESIGN: Retrospective observational study. SETTING: ICUs in Australia, the Czech Republic, and the United States. PATIENTS: Total of 4,086 critical care patients above 18 years old with sepsis between January 2014 and December 2018. INTERVENTION: Premorbid beta-blocker exposure. MEASUREMENTS AND MAIN RESULTS: One thousand five hundred fifty-six patients (38%) with premorbid β-blocker exposure were identified. Overall ICU mortality rate was 15.1%. In adjusted models, premorbid β-blocker exposure was associated with decreased ICU (adjusted odds ratio, 0.80; 95% CI, 0.66–0.97; p = 0.025) and hospital (adjusted odds ratio, 0.83; 95% CI, 0.71–0.99; p = 0.033) mortality. The risk reduction in ICU mortality of 16% was significant (hazard ratio, 0.84, 95% CI, 0.71–0.99; p = 0.037). In particular, exposure to noncardioselective β-blocker before septic episode was associated with decreased mortality. Sequential Organ Failure Assessment score analysis showed that premorbid β-blocker exposure had potential benefits in reducing respiratory and neurologic dysfunction. CONCLUSIONS: This study suggests that β-blocker exposure prior to sepsis, especially to noncardioselective β blockers, may be associated with better outcome. The findings suggest prospective evaluation of β-blocker use in the management of sepsis.

Objectives: To examine the association between premorbid metformin exposure and mortality, hyperlactatemia, and organ dysfunction in sepsis. Data Sources: PubMed and EMBASE (with Medline via Ovid) databases were searched for all studies of premorbid metformin exposure and sepsis published between January 1974 and August 2018. Study Selection: Studies of at least 20 patients with sepsis that reported data on metformin use, mortality, and/or organ dysfunction were independently selected. Data Extraction: Two reviewers abstracted data on study design, settings, study quality, participants, metformin exposure, mortality, initial lactate levels, and organ dysfunction. Risk of bias was independently assessed. Data Synthesis: Eight observational studies fulfilled our criteria, comprising 4,144 patients with sepsis including 562 diabetics on metformin. Premorbid metformin exposure was associated with reduced mortality in sepsis (odds ratio, 0.57; 95% CI, 0.40–0.80). Between studies heterogeneity was low (i 2 = 43%; τ2 = 0.1; p = 0.09). Premorbid metformin exposure was not significantly associated with initial lactate levels (mean difference, 0.39 [–0.50 to 1.28]; i 2 = 72%; p = 0.39). Conclusions: The meta-analysis suggests that premorbid metformin exposure is associated with decreased mortality in sepsis but not with hyperlactatemia. What are the potential mechanisms and whether there is any effect on organ dysfunction remain unclear.