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Relationship between norepinephrine dose and outcome in septic shock: a retrospective study
Lorenzo Antonino Calabrò1, Marco Pasetto2,3, Stefano Zorzi2,4
1Department of Intensive Care, Hôpital Erasme, Université Libre de Bruxelles, 1070, Brussels, Belgium. l.calabro@hubruxelles.be.
Journal of Anesthesia, Analgesia and Critical Care
|June 7, 2026
Summary
High-dose norepinephrine (NE) in septic shock is linked to increased mortality. While ischemic complications are rare, higher NE doses correlate with myocardial ischemia and cardiac arrest.
Area of Science:
- Critical Care Medicine
- Pharmacology
- Clinical Research
Background:
- Septic shock often necessitates high-dose norepinephrine (NE).
- The relationship between NE dosage and patient outcomes, including mortality and ischemic events, requires further clarification.
- Identifying clinically significant NE dose thresholds is crucial for patient management.
Purpose of the Study:
- To investigate the association between norepinephrine dosing and mortality in septic shock patients.
- To identify specific norepinephrine peak-dose ranges linked to increased ICU and in-hospital mortality.
- To evaluate the relationship between norepinephrine dose and the occurrence of ischemic complications.
Main Methods:
- Retrospective single-center cohort study of adult septic shock patients (2016-2022).
- Analysis of initial, highest 24-hour, and peak ICU norepinephrine doses.
- Utilized adjusted optimal binning for dose-response analysis and multivariable regression for outcome associations.
Main Results:
- A total of 506 patients were analyzed, with a median NE peak-dose of 0.5 µg/kg*min.
- Four NE peak-dose ranges were identified, showing a stepwise increase in ICU and in-hospital mortality from 20.7% to 100%.
- Higher NE doses were associated with increased ICU mortality (OR 2.55 for 1.2-3.0 µg/kg*min) and myocardial ischemia/cardiac arrest, but not other ischemic complications.
Conclusions:
- Increasing norepinephrine peak-doses in septic shock patients correlate with a significant, stepwise rise in mortality.
- Norepinephrine dosing is a critical factor in septic shock outcomes.
- Ischemic complications are generally infrequent and not strongly dose-dependent, with exceptions for myocardial ischemia and cardiac arrest.
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