Epinephrine vs Norepinephrine as the Initial Vasoactive Agent in Pediatric Septic Shock: A Feasibility Randomized Controlled Trial for Recruitment Rates and Protocol Adherence, the Epinephrine vs Norepinephrine in Pediatric Septic Shock Trial

Background and aims: Pediatric guidelines recommend initial resuscitation of septic shock using either epinephrine or norepinephrine as first-line support. However, there are no trials comparing these two agents. The primary aim of this randomized controlled trial was to test the feasibility of a study protocol, specifically in terms of recruitment rates and protocol adherence, comparing epinephrine and norepinephrine as first-line vasoactive agents in pediatric septic shock. Patients and methods: A double-blinded, randomized controlled single-center study was conducted in the Emergency Medicine Department (ED) and pediatric intensive care unit (PICU) at a tertiary referral hospital in India. Thirty children aged between 1 month and 17 years with suspected septic shock, in whom signs of shock persisted after the initial fluid bolus, were recruited. Participants were randomized: 1:1 to receive either epinephrine or norepinephrine (each 15), initiated at 0.05-0.1 µg/kg/min. Feasibility outcomes were recruitment rates, randomization to study-drug initiation time, and adherence to protocol. Exploratory clinical outcomes included proportion of shock resolution, adverse events, and hospital mortality. Results: Of 44 screened patients, 10 met exclusion criteria and 4 declined consents, with a recruitment rate of 3.2 patients/month. The median time to vasoactive initiation after randomization was 12 minutes (IQR 8-15). The median time for shock resolution was 31 hours (IQR 10.8-51.2) and 14 hours (IQR 11.5-16.5) in the epinephrine and norepinephrine groups, respectively. Adverse events meeting pre-determined stopping criteria occurred in 7/16 and 1/15 in the epinephrine and norepinephrine groups, respectively. One patient in each group died. Conclusions: A protocol randomizing children with septic shock to epinephrine vs norepinephrine was feasible in terms of protocol adherence and recruitment rates. These findings can inform the design of a definitive multicenter trial powered for patient-centered endpoints.