The Efficacy and Safety of Vasopressors for Septic Shock Patients: A Systemic Review and Network Meta-Analysis

Abstract

Background Septic shock is a distributive shock with decreased systemic vascular resistance and mean arterial pressure (MAP). Septic shock contributes to the most common causes of death in the intensive care unit (ICU). Current guidelines recommend the use of norepinephrine as the first-line vasopressor, while adrenergic agonists and vasopressin analogs are also commonly used by physicians. To date, very few studies have synthetically compared the effects of multiple types of vasoactive medications. The aim of this study is to systemically evaluate the efficacy of vasoactive agents both individually and in combination to treat septic shock. Methods The PubMed, MEDLINE, Embase, Web of Science and Cochrane Central Register for Controlled Trials (CENTRAL) were searched up to May 12, 2022, to identify relevant randomized controlled trials. A network meta-analysis was performed to evaluate the effect of different types of vasopressors. The primary outcome was 28-day all-cause mortality. The secondary outcome was the ICU length of stay. Adverse events are defined as any undesirable outcomes, including myocardial infarction, cardiac arrhythmia, peripheral ischemia or stroke and cerebrovascular events. Findings Thirty-three RCTs comprising 4966 patients and assessing 8 types of vasoactive treatments were included in the network meta-analysis. The surface under the cumulative ranking curve (SUCRA) provided a ranking of vasoactive medications in terms of 28-day all-cause mortality from most effective to least effective: norepinephrine plus dobutamine, epinephrine, vasopressin, terlipressin, norepinephrine, norepinephrine plus vasopressin, dopamine and dobutamine. Dopamine was associated with a significantly shorter ICU stay than norepinephrine, terlipressin and vasopressin, while other vasoactive medications showed no definite difference in ICU length of stay. Regarding adverse events, norepinephrine was associated with the highest incidences of myocardial infarction and peripheral ischemia. Dopamine was associated with the highest incidence of cardiac arrhythmia. Epinephrine and terlipressin were associated with the highest incidences of myocardial infarction and peripheral ischemia. Interpretation The results of this network meta-analysis suggest that norepinephrine plus dobutamine is associated with a lower risk of 28-day mortality in septic shock patients than other vasoactive medications, and the use of dopamine is associated with a higher risk of 28-day mortality due to septic shock than norepinephrine, terlipressin and vasopressin.

Impact of High-Dose Vasopressor During Endotoxic Shock on the Cerebral, Lingual, Hepatic, and Renal Microcirculation Evaluated by Near-Infrared Spectroscopy in Swine

“…Because the MAP increased only near that before lipopolysaccharide administration at a maximum dose of 6 U/min, the response to further increases in dose and blood pressure is unknown. Recent clinical investigations have reported that vasopressor combination therapy does not decrease mortality more than that associated with monotherapy (30) and that vasopressin in combination with norepinephrine does not decrease the mortality rates (31); however, in practice, vasopressin is often used in combination with norepinephrine, and its effect on microcirculation is unknown. In addition, vasopressin was administered after norepinephrine, and the response would have been different if vasopressin had been administered first.…”

Sex- and Gender-Based Analysis on Norepinephrine Use in Septic Shock: Why Is It Still a Male World?

“…Moreover, its β-1 adrenergic receptor activity can lead to cardiac arrhythmias, limiting its use [2]. In a recent systematic review and network meta-analysis on thirty-three randomized controlled trials (RCTs) comprising 4966 patients, DA was associated with the highest incidence of cardiac arrhythmia and a higher risk of 28-day mortality due to septic shock compared to the other vasopressors [20].…”