• Luregn J Schlapbach, Sainath Raman, David Buckley, Shane George, Megan King, Roberta Ridolfi, Amanda Harley, Michele Cree, Debbie Long, Simon Erickson, Puneet Singh, Marino Festa, Kristen Gibbons, Rinaldo Bellomo, and Resuscitation in Paediatric Sepsis Randomized Controlled Pilot Platform in the Paediatric Intensive Care Unit (RESPOND PICU) Study Investigators and the Australian and New Zealand Intensive Care Society Paediatric Study Group.
• Child Health Research Centre, The University of Queensland, Brisbane, QLD, Australia.
• Pediatr Crit Care Me. 2024 Feb 1; 25 (2): 159170159-170.

ObjectivesAdjunctive therapy with vitamin C, hydrocortisone, and thiamin has been evaluated in adults, but randomized controlled trial (RCT) data in children are lacking. We aimed to test the feasibility of vitamin C, hydrocortisone, and thiamin in PICU patients with septic shock; and to explore whether the intervention is associated with increased survival free of organ dysfunction.DesignOpen-label parallel, pilot RCT multicenter study. The primary endpoint was feasibility. Clinical endpoints included survival free of organ dysfunction censored at 28 days and nine secondary outcomes, shock reversal, and two proxy measures of intervention efficacy.SettingSix PICUs in Australia and New Zealand.PatientsChildren of age between 28 days and 18 years requiring vasoactive drugs for septic shock between August 2019 and March 2021.InterventionsPatients were assigned 1:1 to receive 1 mg/kg hydrocortisone every 6 hours (q6h), 30 mg/kg ascorbic acid q6h, and 4 mg/kg thiamin every 12 hours (n = 27), or standard septic shock management (n = 33).Measurements And Main ResultsSixty of 77 (78%) eligible patients consented with 91% of approached parents providing consent. The median time from randomization to intervention was 44 (interquartile range [IQR] 29-120) min. Seventy of seventy-seven (28%) patients had received IV steroids before randomization. Median survival alive and free of organ dysfunction was 20.0 (0.0-26.0) days in the intervention and 21.0 (0.0-25.0) days in the standard care group. Median PICU length of stay was 5.3 (2.5-11.3) days in the intervention group versus 6.9 (3.0-11.5) days in the control group. Shock reversal occurred at a median of 35.2 (14.6-101.2) hours in the intervention group versus 47.3 (22.4-106.8) hours in the standard care group (median difference -12 hr; 95% CI, -56.8 to 32.7 hr).ConclusionsIn children requiring vasopressors for septic shock, a protocol comparing adjunctive treatment with high-dose vitamin C, hydrocortisone, and thiamin versus standard care was feasible. These findings assist in making modifications to the trial protocol to enable a better-designed larger RCT.Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.

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