Vasopressors for the Treatment of Septic Shock: Systematic Review and Meta-Analysis

Abstract

ObjectiveInternational guidelines recommend dopamine or norepinephrine as first-line vasopressor agents in septic shock. Phenylephrine, epinephrine, vasopressin and terlipressin are considered second-line agents. Our objective was to assess the evidence for the efficiency and safety of all vasopressors in septic shock.MethodsSystematic review and meta-analysis. We searched electronic database of MEDLINE, CENTRAL, LILACS and conference proceedings up to June 2014. We included randomized controlled trials comparing different vasopressors for the treatment of adult patients with septic shock. Primary outcome was all-cause mortality. Other clinical and hemodynamic measurements were extracted as secondary outcomes. Risk ratios (RR) and mean differences with 95% confidence intervals (CI) were pooled.ResultsThirty-two trials (3,544 patients) were included. Compared to dopamine (866 patients, 450 events), norepinephrine (832 patients, 376 events) was associated with decreased all-cause mortality, RR 0.89 (95% CI 0.81-0.98), corresponding to an absolute risk reduction of 11% and number needed to treat of 9. Norepinephrine was associated with lower risk for major adverse events and cardiac arrhythmias compared to dopamine. No other mortality benefit was demonstrated for the comparisons of norepinephrine to epinephrine, phenylephrine and vasopressin / terlipressin. Hemodynamic data were similar between the different vasopressors, with some advantage for norepinephrine in central venous pressure, urinary output and blood lactate levels.ConclusionsEvidence suggests a survival benefit, better hemodynamic profile and reduced adverse events rate for norepinephrine over dopamine. Norepinephrine should be regarded as the first line vasopressor in the treatment of septic shock.

Safe Use of Vasopressin and Angiotensin II for Patients with Circulatory Shock

“…Due to the previously mentioned vasoconstrictive properties of AVP, its use may be associated with digital, limb, and mesenteric ischemia. However, these effects are not limited to AVP and are associated with all vasoactive agents including catecholamines and angiotensin II . Because AVP has been used in clinical practice for the treatment of patients with shock for more than 20 years, many published studies provide granular insight into the risks associated with utilization of this agent at the bedside.…”

“…However, these effects are not limited to AVP and are associated with all vasoactive agents including catecholamines and angiotensin II. 1,2 Because AVP has been used in clinical practice for the treatment of patients with shock for more than 20 years, many published studies provide granular insight into the risks associated with utilization of this agent at the bedside. Similar to angiotensin II, it may be difficult to elucidate between an ADR due to AVP or the pathophysiologic consequences of the patient's underlying disease state.…”

Review article: Sepsis in the emergency department – Part 3: Treatment

“…Noradrenaline has been shown superior to dopamine and to cause less rhythm and metabolic derangements than adrenaline when used as a first‐line vasopressor in septic shock. Catecholamines are associated with significant adverse effects and evidence for use in sepsis is circumstantial; however, some reassurance might be gained with the observation that US hospitals affected by a noradrenaline shortage in 2011 reported an increase in septic shock‐related mortality .…”

Vasoactive agents for the treatment of sepsis

“…In a recent systematic review and meta-analysis, norepinephrine was found to be superior to dopamine in reduction of mortality rate [odds ratio ( reduction of 11% and number needed to treat (NNT) of 9. That means nine patients need to be treated to prevent one additional death (19). However, the Havel's review failed to identify beneficial effect of norepinephrine on mortality reduction over dopamine (20).…”

“…Similar to vasopressin, it can be used as a rescue therapy for septic shock when shock is refractory to conventional treatment (41). Following Obrien's seminal paper describing the use of terlipressin in clinical practice, many investigators began to explore the effectiveness of terlipressin in standard way (19,39,(42)(43)(44). Terlipressin was found to have equivalent effect on raising MAP, but it was associated with decreased cardiac index and oxygen consumption (42).…”