Association of noradrenaline dose with mortality in critically ill patients: a systematic review and dose-response...

Noradrenaline is currently the first-line vasopressor in treatment of circulatory failure. Its dose reflects illness severity, and together with dopamine, dobutamine and adrenaline, it is used in the Sequential Organ Failure Assessment (SOFA) score to grade cardiovascular dysfunction. Over the years, noradrenaline use has increased and it has largely replaced dopamine. As part of the SOFA-2 update, we conducted a systematic review and dose-response meta-analysis to assess the association between noradrenaline dose and mortality.

We searched MEDLINE, Embase, and Web of Science from 1 January 2013 to 30 October 2024 for studies reporting mortality by noradrenaline dose in critically ill adults. The primary outcome was mortality. We generated pooled relative risks (RR) and assessed linear and non-linear dose-response relationships. Mortality was also analysed by SOFA-2 noradrenaline categories. The study followed PRISMA guidelines and was registered with PROSPERO (CRD42024501533).

Nineteen studies, including totally 29,935 patients, were included in the systematic review, and six in the meta-analysis. We observed a consistent increase in mortality: the relative risk escalated by a factor of 1.5 for every 0.1 µg/kg/min increase in peak noradrenaline dose. We did not find inflection points in the dose-mortality curve. In SOFA-2 categories, hospital mortality was 16.5% in the dose category ≤ 0.2 µg/kg/min, 31.9% in the category > 0.2 to 0.4 µg/kg/min, and 40.3% in the category > 0.4 µg/kg/min (p < 0.001).

In critically ill patients, escalating doses of noradrenaline correlate with an exponentially rising relative risk of mortality. This dose-dependent pattern reinforces the role of noradrenaline dose as a marker of cardiovascular failure severity.