In adults with septic shock undergoing surgical source control, a new study found that adding intraoperative dobutamine to norepinephrine reduces the risk of acute kidney injury (AKI) over norepinephrine alone.
International guidelines recommend dobutamine for management of septic shock and cardiac dysfunction with persistent hypoperfusion in adults, but this is based on very low–certainty evidence, and there is even less for dobutamine plus norepinephrine.
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 in their study published in JAMA. 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).
Open-label randomised clinical trial
The researchers therefore conducted a multicentre, open-label, randomised clinical trial conducted across 39 tertiary hospitals in China, from June 2024 to August 2025). Adults with septic shock requiring surgical source control of anticipated duration > 1 hour were eligible. Key exclusions included recent use of dobutamine, levosimendan, epinephrine, or recombinant human B-type natriuretic peptide.
Of 714 patients screened, 584 were randomised 1:1 (stratified by site): 290 to dobutamine plus norepinephrine and 294 to norepinephrine alone. Median age was 67.5 years (IQR 55–76); 32.9% were female. Most patients had preoperative septic shock; common procedures involved gastrointestinal perforation (41.8%) or obstruction (29.6%).
Norepinephrine was titrated in both arms to a target mean arterial pressure of 65 mm Hg. In the intervention arm, dobutamine was initiated at 5 µg/kg/min intraoperatively (with dose reduction or discontinuation for tachycardia or arrhythmia). Treatment began after induction for preoperative shock or after recognition of intraoperative shock.
The primary outcome was New-onset AKI or worsening of preoperative AKI (by ≥1 Kidney Disease: Improving Global Outcomes [KDIGO] stage) within 7 postoperative days. This occurred in 66/290 (22.8%) patients receiving dobutamine plus norepinephrine versus 102/294 (34.7%) receiving norepinephrine alone (adjusted risk ratio 0.64; 95% CI 0.49–0.83; P = .001). Absolute risk reduction was approximately 11.9 percentage points.
The benefit was driven mainly by reductions in stage 2 (4.8% vs 9.9%; ARR 0.48) and stage 3 (7.9% vs 13.6%; ARR 0.56) AKI. Stage 1 rates were similar. Secondary outcomes: SOFA score on postoperative day 1 was lower (adjusted difference −0.53; 95% CI −0.98 to −0.07) and urine output 1 hour after intervention start was higher (adjusted difference +0.55 mL/kg/h; 95% CI 0.03–1.07) with combination therapy. No significant differences were seen in most other secondary outcomes, including mortality, kidney replacement therapy, or length of stay.
Adverse events included tachycardia being more common (≈41% with dobutamine plus norepinephrine vs 30%). Other reported cardiovascular events were similar between groups.
The researchers concluded that “While hypothesis generating, these data suggest an opportunity to explore dobutamine treatment response heterogeneity across different clinical subtypes.”
Limitations of the study include being an open-label trial and largely restricted to Chinese patients and settings.
