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.