Beta-blocker treatment in the critically ill: a systematic review and meta-analysis

Abstract

Background Critical illness may lead to activation of the sympathetic system. The sympathetic stimulation may be further increased by exogenous catecholamines, such as vasopressors and inotropes. Excessive adrenergic stress has been associated with organ dysfunction and higher mortality. β -Blockers may reduce the adrenergic burden, but they may also compromise perfusion to vital organs thus worsening organ dysfunction. To assess the effect of treatment with β -blockers in critically ill adults, we conducted a systematic review and meta-analysis of randomized controlled trials. Materials and methods We conducted a search from three major databases: Ovid Medline, the Cochrane Central Register for Controlled Trials and Scopus database. Two independent reviewers screened, selected, and assessed the included articles according to prespecified eligibility criteria. We assessed risk of bias of eligible articles according to the Cochrane guidelines. Quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Results Sixteen randomized controlled trials comprising 2410 critically ill patients were included in the final review. A meta-analysis of 11 trials including 2103 patients showed a significant reduction in mortality in patients treated with β -blockers compared to control (risk ratio 0.65, 95%CI 0.53–0.79; p < .0001). There was no significant difference in mean arterial pressure or vasopressor load. Quality of life, biventricular ejection fraction, blood lactate levels, cardiac biomarkers and mitochondrial function could not be included in meta-analysis due to heterogenous reporting of outcomes. Conclusions In this systematic review we found that β -blocker treatment reduced mortality in critical illness. Use of β -blockers in critical illness thus appears safe after initial hemodynamic stabilization. High-quality RCT’s are needed to answer the questions concerning optimal target group of patients, timing of β -blocker treatment, choice of β -blocker, and choice of physiological and hemodynamic parameters to target during β -blocker treatment in critical illness. KEY MESSAGES A potential outcome benefit of β -blocker treatment in critical illness exists according to the current review and meta-analysis. Administration of β -blockers to resuscitated patients in the ICU seems safe in terms of hemodynamic stability and outcome, even during concomitant vasopressor administration. However, further studies, preferably large RCTs on β -blocker tr...

The concomitant use of ultra short beta-blockers with vasopressors and inotropes in critically ill patients with septic shock: A systematic review and meta-analysis of randomized controlled trials

“… Wang et al, 2023 ). This result aligns with a prior meta-analysis, indicating no significant variance in vasopressor requirement at both 48 and 72 hours ( Heliste et al, 2022 ). The higher doses of vasopressor required by the esmolol-treated group can be attributed to the hypotensive effect of esmolol, however, the decline in vasopressor requirements along both studies' time points may be related to the disease remission and the improvement in the patient’s clinical status.…”

“…Indeed, this finding is consistent with a previous meta-analysis that included 11 randomized clinical trials and comprised 2103 critically ill patients, showing a lower mortality risk for more than 14 days in the beta-blockers group compared to the control group. However, there was no significant difference in the mortality risk in less than 14 days’ term ( Heliste et al, 2022 ). Another multicenter propensity score study included 1556 patients on beta-blocker therapy before ICU admission matched to 1556 patients with non-previous use of beta-blockers and found a lower 30-day mortality risk in patients who were on beta-blockers ( Christensen et al, 2011 ).…”

Incidence, risk factors and outcomes of acute kidney injury in surgical intensive care unit octogenarians at the Jordan University Hospital

“…Moreover, beta blockers can ameliorate renal function by reducing sympathetic activation and renal oxygen consumption [ 41 , 43 ]. Therefore, although beta blockers reduced mortality in critical ill patients [ 44 ], we recommend future randomized controlled trials on octogenarians to determine the optimal target group of patients, choice of beta blocker, timing of treatment, and the optimal hemodynamic targets.…”

Beta-blockers in cardiac arrhythmias–Clinical pharmacologist’s point of view

“…This is evidenced by the fact that β-blockers are widely used and have been included in both European and American guidelines for supraventricular and ventricular arrhythmias. There are also other benefits from the use of this group of drugs–it was noted that in hospitalized patients in severe clinical condition, treatment with beta-blockers reduced long-term mortality ( Heliste et al, 2022 ). Also in patients with sepsis, prior exposure to beta-blockers has been associated with reduced mortality ( Tan et al, 2019 ).…”