Beta-blocker use in severe sepsis and septic shock: a systematic review

Abstract

Objective:

Recent growing evidence suggests that beta-blocker treatment could improve cardiovascular dynamics and possibly the outcome of patients admitted to intensive care with severe sepsis or septic shock.

Design:

Systematic review.

Data sources:

MEDLINE and EMBASE healthcare databases.

Review methods:

To investigate this topic, we conducted a systematic review of the above databases up to 31 May 2015. Due to the clinical novelty of the subject, we also included non-randomized clinical studies. We focused on the impact of beta-blocker treatment on mortality, also investigating its effects on cardiovascular, immune and metabolic function. Evidence from experimental studies was reviewed as well.

Results:

From the initial search we selected 10 relevant clinical studies. Five prospective studies (two randomized) assessed the hemodynamic effects of the beta₁-blocker esmolol. Heart rate decreased significantly in all, but the impact on other parameters differed. The imbalance between prospective studies’ size (10 to 144 patients) and the differences in their design disfavor a meta-analysis. One retrospective study showed improved hemodynamics combining metoprolol and milrinone in septic patients, and another retrospective study found no association between beta-blocker administration and mortality. We also found three case series. Twenty-one experimental studies evaluated the hemodynamic, immune and/or metabolic effects of selective and/or non-selective beta-blockers in animal models of sepsis (dogs, mice, pigs, rats, sheep), yielding conflicting results.

Conclusions:

Whilst there is not enough prospective data to conduct a meta-analysis, the available clinical data are promising. We discuss the ability of beta blockade to modulate sepsis-induced alterations at cardiovascular, metabolic, immunologic and coagulation levels.

Keywords::

• Critical care
• Esmolol
• Hemodynamics
• Infection
• Intensive care
• Systemic Inflammatory Response Syndrome

Transparency

Declaration of funding

There was no financial support for this study.

Declaration of financial/other relationships

F.S. and C.S. have disclosed that they have no significant relationships with or financial interests in any commercial companies related to this study or article. A.M. has disclosed that she was the principal investigator of the largest randomized controlled trial to date on the use of beta-blockade in septic patients (Effect of heart rate control with esmolol on hemodynamic and clinical outcomes in patients with septic shock: a randomized clinical trial. JAMA. 2013;310:1683-91). She has also disclosed that she is the author of other studies on the use of beta blockade in this population of critically ill patients. P.F. has disclosed that he was an investigator of the POISE trial (Effects of extended-release metoprolol succinate in patients undergoing non-cardiac surgery (POISE trial): a randomized controlled trial’. Lancet 2008;371:1839-47).

CMRO peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgment

The authors thank Ms Tatjana Petrinic (Senior Librarian – Bodleian Libraries, Oxford, United Kingdom) for her continuous support and kind guidance in the advanced literature search. The current work has been performed initially at Nuffield Department of Anaesthetics, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom.