Article of the month

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 

Rajeshwari Nataraj , Parth Dalal, Bharath KT Vijayaraghavan, Priyavarthini Venkatachalam, Vasanth Kumar, Chidambaram Lakshmanan, Luregn J Schlapbach, Niranjan Kissoon, Suchitra Ranjit

https://www.ijccm.org/doi/pdf/10.5005/jp-journals-10071-25043

Abstract

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. 

Keywords: Child, Epinephrine, Feasibility, Norepinephrine, Septic shock, Sepsis, Trial. 

Indian Journal of Critical Care Medicine (2025): 10.5005/jp-journals-10071-25043