Highlights
– In a randomized trial of older, higher‑risk patients undergoing major abdominal surgery, a prophylactic, titrated norepinephrine infusion started at induction markedly reduced episodes of intraoperative hypotension compared with reactive ephedrine boluses.
– The intervention group experienced fewer 30‑day medico‑surgical complications (Clavien‑Dindo ≥1) and fewer pulmonary complications; other secondary outcomes (AKI, length of stay, 1‑month mortality) were not statistically different.
– Results support a physiologic rationale for preventing early intraoperative hypotension, but single‑center design, potential reporting inconsistencies, and composite primary outcome composition warrant cautious interpretation and external validation.
Background
Intraoperative hypotension (IOH) is strongly associated with adverse perioperative outcomes, including acute kidney injury (AKI), myocardial injury, and increased mortality. Episodes of hypotension occurring during induction of general anesthesia are common but less well studied than hypotension later in the intraoperative period. Traditional management frequently relies on reactive bolus vasopressors (e.g., ephedrine) when hypotension occurs. An alternative strategy is the prophylactic administration of a continuous, low‑dose vasopressor started at induction to maintain arterial pressure and preserve organ perfusion. The randomized trial summarized here tests whether early prevention of postinduction hypotension using norepinephrine reduces postoperative complications in high‑risk patients undergoing major abdominal surgery.
Study design
This single‑center randomized controlled trial was conducted at Amiens University Hospital (Amiens, France). Adults older than 50 years with American Society of Anesthesiologists Physical Status II or higher who were scheduled for major abdominal surgery were randomized to one of two intraoperative hemodynamic strategies:
- Ephedrine group: reactive treatment of hypotension after induction using iterative boluses of ephedrine (3 mg · ml‑1).
- Norepinephrine group: prophylactic continuous intravenous norepinephrine infusion started at induction (0.016 mg · ml‑1 solution initiated at 0.48 mg · h‑1) with titration for hypotension.
The primary endpoint was any medico‑surgical complication within 30 days, defined as Clavien‑Dindo score ≥1. Secondary endpoints included hospital length of stay, development of AKI, 1‑month mortality, and domain‑specific complications (cardiovascular, respiratory, neurologic, infectious). Outcome assessment was performed by blinded evaluators. A total of 500 patients were randomized and 473 were included in the intention‑to‑treat analysis.
Key findings
The trial reported a substantial reduction in intraoperative hypotension with the prophylactic norepinephrine strategy. Cumulative episodes of IOH were markedly lower in the norepinephrine group than in the ephedrine group (35 [15%] vs. 176 [74%]; P < 0.001).
Primary outcome. The composite primary outcome (Clavien‑Dindo ≥1 within 30 days) occurred in 137 patients (58%) in the ephedrine group and 103 patients (44%) in the norepinephrine group (reported relative risk 0.58; 95% CI, 0.40–0.83; P = 0.004). This represents an absolute risk reduction of 14 percentage points and a number needed to treat (NNT) of approximately 7 to prevent one patient having any complication under the study definition. Notably, there appears to be an inconsistency between the reported absolute rates and the relative risk estimate; the percentages (58% vs. 44%) would typically correspond to a relative risk around 0.76. This discrepancy should prompt readers to consult the full published paper for clarification of the figures and analytic approach.
Secondary outcomes. There were no statistically significant differences between groups for overall hospital length of stay, AKI incidence, or 1‑month mortality. Pulmonary complications were lower in the norepinephrine group (40 [17%]) than in the ephedrine group (74 [31%]) with a reported relative risk 0.46 (95% CI, 0.29–0.70; P < 0.001). Cardiovascular, neurologic, and infectious complications did not differ significantly in the reported summary.
Safety and hemodynamics. No major safety signals were reported in the abstracted summary; the norepinephrine regimen used a low starting rate (0.48 mg/h) equivalent to approximately 8 μg/min, a dose consistent with low‑dose vasopressor therapy used to maintain mean arterial pressure (MAP). Detailed adverse event reporting, vasopressor‑related complications (e.g., ischemia), and access site considerations are reported in the full article and should be reviewed before widespread translation of the approach.
Mechanistic plausibility
Preventing drops in MAP at induction preserves organ perfusion during a period when anesthetic agents (and often positive‑pressure ventilation) reduce systemic vascular resistance and venous return. Norepinephrine provides alpha‑adrenergic vasoconstriction with modest beta‑adrenergic support, typically increasing arterial pressure without marked tachycardia. By contrast, ephedrine has mixed direct and indirect adrenergic effects with tachycardia and potential tachyphylaxis after repeated boluses. Continuous, titrated norepinephrine limits the amplitude and duration of hypotensive episodes, plausibly reducing ischemic insults to the lungs, kidneys, and heart and lowering postoperative complication rates. The reduction in pulmonary complications seen in this trial may reflect improved hemodynamic stability limiting pulmonary edema and hypoperfusion‑related inflammatory sequelae, or fewer episodes of aggressive fluid loading used to treat hypotension reactively.
Critical appraisal and limitations
Strengths of the trial include randomized design, a clinically relevant high‑risk population, and blinded outcome assessment. The effect on a clinically meaningful composite endpoint and the large reduction in IOH episodes reinforce the physiologic rationale for prevention rather than reaction.
However, several limitations must be acknowledged:
- Single‑center design limits generalizability. Practice patterns (anesthesia induction agents, fluid management, surgical case mix, use of goal‑directed therapy) may differ across centers and may interact with the effect of a prophylactic vasopressor.
- Primary endpoint composition: Clavien‑Dindo ≥1 includes a range of complications from minor to severe. While reducing any complication is desirable, the clinical significance of changes in minor complications differs from changes in major events (e.g., AKI requiring dialysis, myocardial infarction).
- Incomplete reporting in the summarized abstract: the apparent mismatch between reported absolute event rates and the presented relative risk and confidence intervals should be reconciled by reviewing the full manuscript and supplementary data.
- Blinding: intraoperative clinicians could not be blinded to the vasopressor strategy, introducing potential performance bias in fluid administration and other cointerventions. Although outcome assessors were blinded, intraoperative management differences may have contributed to outcomes.
- Safety details: while no major safety signals are highlighted in the abstracted results, comprehensive reporting of vasopressor‑related adverse events (local ischemia, arrhythmia, excessive hypertension) and access considerations (peripheral vs central administration) is necessary before routine adoption.
- External validity: enrolled patients were older than 50 with at least ASA II status undergoing major abdominal procedures. Results may not apply to younger, lower‑risk patients, minor procedures, or cardiac surgery populations.
Implications for practice
This trial supports a strategy of prophylactic, low‑dose, titrated norepinephrine infusion started at induction to reduce early intraoperative hypotension in older, higher‑risk patients undergoing major abdominal surgery. For clinicians considering implementation, recommendations include:
- Use standardized protocols specifying starting dose, titration steps, MAP targets, and thresholds for additional interventions (e.g., fluid bolus, inotropic support).
- Ensure monitoring and safety infrastructure: continuous invasive or high‑fidelity noninvasive BP monitoring, clear contingency plans for excessive vasoconstriction, and vascular access suitable for vasopressor infusion.
- Integrate the strategy with established enhanced recovery and goal‑directed fluid therapy pathways to avoid unnecessary fluid administration driven by reactive hypotension management.
- Anticipate the need for local validation and audit of outcomes (e.g., rates of IOH, AKI, pulmonary complications) before declaring the strategy standard of care.
Research gaps and next steps
Important unanswered questions include the reproducibility of these findings in multicenter settings, the optimal norepinephrine dosing strategy and MAP targets, comparisons with other vasopressor agents or combined approaches, and the net effect on clinically important major outcomes (e.g., severe AKI, myocardial infarction, long‑term mortality). Cost‑effectiveness, feasibility of peripheral administration, and safety in settings without continuous invasive monitoring also merit study. A larger, multicenter pragmatic trial with stratified analyses by baseline risk and surgical subtype would clarify generalizability and inform guideline recommendations.
Conclusion
The randomized trial from Amiens University Hospital provides compelling evidence that a prophylactic, titrated norepinephrine infusion begun at induction reduces intraoperative hypotension and may lower the incidence of postoperative medico‑surgical complications — particularly pulmonary complications — in older, higher‑risk patients undergoing major abdominal surgery. While physiologically plausible and clinically attractive, these findings should be confirmed in multicenter studies, and implementation should proceed with attention to local protocols, monitoring, and safety reporting.
Funding and clinicaltrials.gov
Funding sources and trial registration details were not included in the abstracted summary provided here. Readers should consult the full published article for funding declarations, conflicts of interest, and trial registry identifiers.
Reference
Trocheris‑Fumery O, Flet T, Scetbon C, Tarpin P, Meynier J, Badaoui R, De Broca B, Sabbagh C, Régimbeau JM, De Sousa P, Foulon A, Josse E, Dupont H, Bar S, Abou‑Arab O. Early Use of Norepinephrine in High‑risk Patients Undergoing Major Abdominal Surgery: A Randomized Controlled Trial. Anesthesiology. 2025 Nov 1;143(5):1160‑1170. doi: 10.1097/ALN.0000000000005704. Epub 2025 Aug 4. PMID: 40758953; PMCID: PMC12513051.