Combination Cuts Kidney Injury Risk Following Septic Shock Procedure

— Intraoperative dobutamine-norepinephrine reduced AKI risk by 36% after surgical source control

Adding dobutamine to intraoperative norepinephrine lowered the incidence of acute kidney injury (AKI) in adults with septic shock undergoing surgical source control, an open-label Chinese randomized trial showed.

New-onset or worsening AKI within 7 postoperative days occurred in 22.8% of those who received dobutamine plus norepinephrine compared with 34.7% of those who received norepinephrine alone (adjusted risk ratio 0.64, 95% CI 0.49-0.83), reported Nazrul Islam, MBBS, PhD, of the University of Southampton in England, and colleagues.

Patients in the combination group had significantly lower median Sequential Organ Failure Assessment (SOFA) scores on postoperative day 1 compared with the norepinephrine-alone group (5 vs 6, respectively) and higher median urine output 1 hour after starting the intervention (2.4 vs 1.9 mL/kg per hour).

No statistically significant differences were observed across nine other secondary outcomes, according to findings published in JAMAopens in a new tab or window and simultaneously presented at the European Society of Intensive Care Medicineopens in a new tab or window annual congress in Lisbon, Portugal.

"Timely source control with surgical intervention is a cornerstone of management in septic shock, necessary in 20% to 30% of patients, and associated with improved outcome," the authors noted. However, "hemodynamic instability in septic shock and surgical stress may compromise tissue perfusion and contribute to the development of AKI, despite intravenous fluids and vasopressor administration."

No specific intraoperative therapy has been established to counteract the combined insult, Islam and team noted, emphasizing that AKI "contributes substantially to morbidity and mortality."

While describing the findings as "hypothesis-generating," the authors concluded that "these data suggest an opportunity to explore dobutamine treatment response heterogeneity across different clinical subtypes."

Norepinephrine is a potent vasoconstrictor and can decrease regional renal blood flow, potentially increasing AKI risk. Conversely, the role of dobutamine in septic AKI prevention "has remained controversial," the researchers noted. While dobutamine can increase renal blood flow and glomerular filtration rate, some prior observational studies suggested an association with greater AKI progression or need for kidney replacement therapy (KRT).

To address the evidence gap, Islam and colleagues conducted the first large multicenter trial specifically testing the addition of intraoperative dobutamine during surgical source control.

The open-label trialopens in a new tab or window was conducted across 39 tertiary hospitals in China and randomized 584 adults with septic shock who were undergoing surgical source control from June 2024 to August 2025. The median patient age was 67.5 and a third were women.

Incidence of AKI within 7 days of surgery was the primary outcome. Secondary outcomes included SOFA scores on postoperative days 1, 3, and 7; mortality at 28 and 90 days; the percentage of patients requiring KRT within 7 days; postoperative intensive care and hospital length of stay; and postoperative mechanical ventilation duration.

Gastrointestinal perforation was the predominant indication for surgery (41.8%), followed by gastrointestinal obstruction (29.6%).

Patients in the intervention arm received a continuous dobutamine infusion initiated at 5 μg/kg per minute alongside norepinephrine during surgery. Norepinephrine in both arms was titrated to maintain a target mean arterial pressure of 65 mm Hg.

Postoperative AKI criteria were met via serum creatinine alone in 17.1% of all participants, urine output alone in 3.8%, and both criteria in 7.9%.

In post hoc exploratory analyses, the incidence of stage 2 and 3 AKI was lower in the dobutamine plus norepinephrine group compared with the norepinephrine-alone group (stage 2: 4.8% vs 9.9%; stage 3: 7.9% vs 13.6%). There was no difference in stage 1 AKI between the groups (10.0% vs 11.2%).

New-onset AKI occurred in 17.9% of the combination group and 28.6% of the norepinephrine group.

Worsening of preoperative AKI by at least 1 Kidney Disease: Improving Global Outcomes stage was similar between the groups. No statistically significant interactions were observed across the prespecified subgroups.

Tachycardia was more frequent in the dobutamine group (41% vs 29.9% in the norepinephrine-alone group). However, mean heart rate at the end of surgery and serious cardiac adverse events -- including ventricular tachycardia, atrial fibrillation, premature ventricular contractions, and cardiac arrest -- were comparable between groups.

Study limitations included inconsistent use of advanced hemodynamic monitoring and restriction of the intervention strictly to the intraoperative period.