Fluid-Refractory Septic Shock in Children and Milrinone: Outcomes in a Two-Center, Retrospective Cohort in France, 2011–2021

Objectives: We have examined the associated outcomes of milrinone treatment for fluid-refractory septic shock. Design: Two-center, retrospective cohort from France. Setting: Two PICUs, both within tertiary care teaching hospitals. Patients: Children of 1 month to 18 years hospitalized between May 2011 and April 2021 with an episode of fluid-refractory septic shock treated with at least one vasoactive or inotropic agent. Intervention: None. Measurements and Main Results: We compared survival and PICU outcomes (organ support, length of stay) between patients who received milrinone and those who did not. We compared adverse events in the two groups, and we described the frequency and dosing of milrinone. We identified 290 patients with fluid-refractory septic shock with a median (interquartile range [IQR]) age of 48 months (IQR, 13–148 mo), of whom 46 of 290 (16%) received milrinone, with a median dose of 0.5 µg kg –1 min –1 (IQR, 0.5–0.8 µg kg –1 min –1 ). Overall mortality was 55 of 290 (19%). Use of milrinone was associated with a greater hazard (hazard ratio [HR], and 95% CI) of 30-day mortality (HR, 2.57 [95% CI, 1.15–5.75]; p = 0.021). Receiving milrinone, as opposed to not, was associated with greater volume of fluid boluses per case (16.8 [IQR, 0–50] vs. 10 [IQR, 0–29] mL kg –1 ; p = 0.04) and greater proportion undergoing mechanical ventilation (41/46 vs. 174/244; mean percentage difference, 17.8% [95% CI, 4.5–26.4%]; p = 0.011). Milrinone grouping, as opposed to not, was associated with greater proportion having cardiac arrests in the PICU (22/46 vs. 28/244; mean percentage difference, 36.3% [95% CI, 21.8–50.7%]; p < 0.001) and greater proportion with adverse events (17/46 vs. 24/244; mean percentage difference, 27.1% [95% CI, 13.9–41.9%]; p < 0.001). Conclusions: In our 2011–2021 cohort of children, milrinone was used in around one-in-six cases with fluid-refractory septic shock. Patients treated with milrinone had an associated greater hazard of mortality; and, proportionately, worse PICU outcomes, and greater adverse events.