A systematic review and meta-analysis of noradrenaline compared to adrenaline in the management of septic shock

Abstract

Background: Septic shock is associated with significant mortality. The International Surviving Sepsis Campaign guidelines recommend noradrenaline as first-line vasopressor, whilst South African guidelines recommend adrenaline. Clinical trials show similar efficacy but suggest safety advantages for noradrenaline. We reviewed the evidence comparing noradrenaline and adrenaline in the initial management of adult patients with septic shock.

Methods: We searched PubMed, Epistemonikos, Cochrane Library, and clinical trial registries for clinical practice guidelines, health technology assessments, and systematic reviews of randomised controlled trials (RCTs) through July 2024. We appraised these using AGREE II and AMSTAR 2 tools and assessed eligible RCTs extracted from systematic reviews with Cochrane's Risk of Bias 2.0 Tool. We estimated random-effects rate ratios (RR) and mean differences (MD) with 95 % confidence intervals and rated certainty of evidence using GRADE. Key outcomes included mortality, time to shock reversal, and adverse effects. (PROSPERO: CRD42022368373).

Results: We identified three guidelines, one systematic review, from which five RCTs were extracted. Comparing adrenaline to noradrenaline, we found little to no difference in mortality (RR 0.99, 0.83 to 1.18), time to improvement of mean arterial pressure (MD 7.17 min, -16.74 to 31.08), vasopressor-free days (MD -0.05 days, -4.07 to 3.96), or dysrhythmias (RR 0.92, 0.59 to 1.45). Change in lactate concentrations 24 h after resuscitation was lower for noradrenaline than adrenaline. The certainty of evidence was assessed as low to very low.

Conclusion: Adrenaline and noradrenaline are associated with similar outcomes in managing septic shock. The choice of vasopressor should be based on availability, patient population, and cost.