Intraoperative Dobutamine Plus Norepinephrine to Prevent Postoperative Acute Kidney Injury in Septic Shock

IMPORTANCE International guidelines recommend dobutamine for management of septic shock and cardiac dysfunction with persistent hypoperfusion in adults based on very low–certainty evidence. Randomized trials are lacking on the effect of intraoperative dobutamine combined with norepinephrine vs norepinephrine on postoperative outcomes in patients with septic shock undergoing surgical source control. OBJECTIVE To determine whether intraoperative dobutamine combined with norepinephrine reduces acute kidney injury (AKI) within 7 postoperative days in patients with septic shock undergoing surgical source control. DESIGN, SETTING, AND PARTICIPANTS This randomized, open-label clinical trial in 39 tertiary hospitals in China enrolled adults with septic shock who were undergoing surgical source control between June 2024 and August 2025. Follow-up ended on November 15, 2025. INTERVENTION Intraoperative, intravenous infusion of dobutamine (up to 5 µg/kg/min) combined with norepinephrine vs norepinephrine alone. MAIN OUTCOMES AND MEASURES The primary outcome was new-onset AKI or worsening of preoperative AKI within 7 days after surgery, defined using Kidney Disease: Improving Global Outcomes (KDIGO) criteria. The 11 secondary outcomes included Sequential Organ Failure Assessment (SOFA) score on postoperative day 1 and urine output 1 hour post intervention. RESULTS Among 584 patients (median [IQR] age, 67.5 [55.0-76.0] years; 192 [32.9%] females), new-onset or worsening AKI within 7 postoperative days occurred in 22.8% (66/290) randomized to receive dobutamine plus norepinephrine vs 34.7% (102/294) randomized to receive norepinephrine alone (adjusted risk ratio [ARR], 0.64 [95% CI, 0.49-0.83]). No significant differences were observed in 9 of the 11 secondary outcomes. SOFA scores on postoperative day 1 (adjusted difference, −0.53 [95% CI, −0.98 to −0.07]) were lower and urine output 1 hour post intervention (adjusted difference, 0.55 [95% CI, 0.03 to 1.07] mL/kg/h) was higher in the dobutamine plus norepinephrine group. Stage 2 and 3 AKI were lower in the dobutamine plus norepinephrine group compared with the norepinephrine alone group (stage 2: 4.8% vs 9.9%; ARR, 0.48 [95% CI, 0.26-0.88]; stage 3: 7.9% vs 13.6%; ARR, 0.56 [95% CI, 0.35-0.91]). Tachycardia (heart rate >100/min) occurred more frequently in patients receiving dobutamine and norepinephrine than norepinephrine alone. CONCLUSIONS AND RELEVANCE Among adult patients with septic shock undergoing surgical source control, intraoperative dobutamine combined with norepinephrine reduced the incidence of new-onset or worsening AKI within 7 postoperative days compared with norepinephrine. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT06462313