Continuous Terlipressin Infusion as Rescue Treatment in a Case Series of Children with Refractory Septic Shock

BACKGROUND: Despite intensive therapy, refractory pediatric septic shock has a high rate of morbidity and mortality. Additional treatments are needed to improve outcomes in such cases. OBJECTIVE: To report the clinical effects of continuous terlipressin infusion as rescue treatment for children with septic shock refractory to high catecholamine doses. METHODS: Sixteen episodes of catecholamine-resistant septic shock were recorded in 15 children (aged from newborn to 15 years) who received compassionate rescue treatment with terlipressin at 6 pediatric intensive care units. Terlipressin treatment consisted of a loading dose (20 mu g/kg) followed by continuous infusion at a rate of 4-20 mu g/kg/h. Terlipressin was titrated at increases of 1 mu g/kg/h to maintain mean arterial pressure (MAP) in normal range for age and to reduce catecholamine dosage. The main outcome was survival of the episode. Secondary outcomes included hemodynamic effects, ischemia, and terlipressin-related adverse events. RESULTS: Terlipressin increased median MAP from 48 (range 42-63) to 68 (45-115) mm Hg 30 minutes after terlipressin administration (p < 0.01). MAP was subsequently sustained, which allowed for the reduction of norepinephrine infusion from 2 mu g/kg/min (1-4) at baseline to 1.5 mu g/kg/min (0.4-4) at 1 hour, 1.3 mu g/kg/min (0-8) at 4 hours, 1 mu g/kg/min (0-2) at 12 hours, 0.45 mu g/kg/min (0-1.4) at 24 hours, and 0 mu g/kg/min (0-0.6) at 48 hours (p < 0.05 vs baseline in all cases). In 8 (50%) of the 16 septic shock episodes the patients survived, 7 (44%) without sequelae. One patient survived with sequelae (minor amputation and mild cutaneous ischemia). Eight patients had signs of ischemia at admission; terlipressin induced reversible ischemia in another 4 patients. Meningococcal infection, prior ischemia, and MAP were risk factors for mortality. CONCLUSIONS: Continuous terlipressin infusion may improve hemodynamics and survival in some children with refractory septic shock. Terlipressin could contribute to tissue ischemia.