Simon J Erickson1, Johnny Millar2,3, Brian J Anderson4,5, Marino S Festa6, Lahn Straney7, Yahya Shehabi8,9, Debbie A Long10,11. 1. Paediatric Critical Care, Perth Children's Hospital, Perth, WA, Australia. 2. Paediatric Intensive Care Unit, Royal Children's Hospital, Melbourne, VIC, Australia. 3. Murdoch Children's Research Institute, University of Melbourne, Melbourne, VIC, Australia. 4. Paediatric Intensive Care Unit, Starship Children's Hospital, Auckland, New Zealand. 5. Department of Anaesthesiology, University of Auckland, Auckland, New Zealand. 6. Kids Critical Care Research, The Children's Hospital at Westmead, Westmead, NSW, Australia. 7. Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC, Australia. 8. School of Clinical Sciences, Monash University, Melbourne, VIC, Australia. 9. Clinical School of Medicine, University of New South Wales, Sydney, NSW, Australia. 10. Paediatric Intensive Care Unit, Queensland Children's Hospital, Brisbane, QLD, Australia. 11. Children's Health Research Centre, The University of Queensland, Brisbane, QLD, Australia.
Abstract
OBJECTIVES: To assess the feasibility, safety, and efficacy of a sedation protocol using dexmedetomidine as the primary sedative in mechanically ventilated critically ill children. DESIGN: Open-label, pilot, prospective, multicenter, randomized, controlled trial. The primary outcome was the proportion of sedation scores in the target sedation range in the first 48 hours. Safety outcomes included device removal, adverse events, and vasopressor use. Feasibility outcomes included time to randomization and protocol fidelity. SETTING:Six tertiary PICUs in Australia and New Zealand. PATIENTS: Critically ill children, younger than 16 years old, requiring intubation and mechanical ventilation and expected to be mechanically ventilated for at least 24 hours. INTERVENTIONS: Children randomized to dexmedetomidine received a dexmedetomidine-based algorithm targeted to light sedation (State Behavioral Scale -1 to +1). Children randomized to usual care received sedation as determined by the treating clinician (but not dexmedetomidine), also targeted to light sedation. MEASUREMENTS AND MAIN RESULTS: Sedation with dexmedetomidine as the primary sedative resulted in a greater proportion of sedation measurements in the light sedation range (State Behavioral Scale -1 to +1) over the first 48 hours (229/325 [71%] vs 181/331 [58%]; p = 0.04) and the first 24 hours (66/103 [64%] vs 48/116 [41%]; p < 0.001) compared with usual care. Cumulative midazolam dosage was significantly reduced in the dexmedetomidine arm compared with usual care (p = 0.002).There were more episodes of hypotension and bradycardia with dexmedetomidine (including one serious adverse event) but no difference in vasopressor requirements. Median time to randomization after intubation was 6.0 hours (interquartile range, 2.0-9.0 hr) in the dexmedetomidine arm compared with 3.0 hours (interquartile range, 1.0-7.0 hr) in the usual care arm (p = 0.24). CONCLUSIONS: A sedation protocol using dexmedetomidine as the primary sedative was feasible, appeared safe, achieved early, light sedation, and reduced midazolam requirements. The findings of this pilot study justify further studies of sedative agents in critically ill children.
RCT Entities:
OBJECTIVES: To assess the feasibility, safety, and efficacy of a sedation protocol using dexmedetomidine as the primary sedative in mechanically ventilated critically illchildren. DESIGN: Open-label, pilot, prospective, multicenter, randomized, controlled trial. The primary outcome was the proportion of sedation scores in the target sedation range in the first 48 hours. Safety outcomes included device removal, adverse events, and vasopressor use. Feasibility outcomes included time to randomization and protocol fidelity. SETTING: Six tertiary PICUs in Australia and New Zealand. PATIENTS: Critically illchildren, younger than 16 years old, requiring intubation and mechanical ventilation and expected to be mechanically ventilated for at least 24 hours. INTERVENTIONS:Children randomized to dexmedetomidine received a dexmedetomidine-based algorithm targeted to light sedation (State Behavioral Scale -1 to +1). Children randomized to usual care received sedation as determined by the treating clinician (but not dexmedetomidine), also targeted to light sedation. MEASUREMENTS AND MAIN RESULTS: Sedation with dexmedetomidine as the primary sedative resulted in a greater proportion of sedation measurements in the light sedation range (State Behavioral Scale -1 to +1) over the first 48 hours (229/325 [71%] vs 181/331 [58%]; p = 0.04) and the first 24 hours (66/103 [64%] vs 48/116 [41%]; p < 0.001) compared with usual care. Cumulative midazolam dosage was significantly reduced in the dexmedetomidine arm compared with usual care (p = 0.002).There were more episodes of hypotension and bradycardia with dexmedetomidine (including one serious adverse event) but no difference in vasopressor requirements. Median time to randomization after intubation was 6.0 hours (interquartile range, 2.0-9.0 hr) in the dexmedetomidine arm compared with 3.0 hours (interquartile range, 1.0-7.0 hr) in the usual care arm (p = 0.24). CONCLUSIONS: A sedation protocol using dexmedetomidine as the primary sedative was feasible, appeared safe, achieved early, light sedation, and reduced midazolam requirements. The findings of this pilot study justify further studies of sedative agents in critically illchildren.
Authors: Morten H Møller; Waleed Alhazzani; Kimberley Lewis; Emilie Belley-Cote; Anders Granholm; John Centofanti; William B McIntyre; Jessica Spence; Zainab Al Duhailib; Dale M Needham; Laura Evans; Annika Reintam Blaser; Margaret A Pisani; Frederick D'Aragon; Manu Shankar-Hari; Mohammed Alshahrani; Giuseppe Citerio; Rakesh C Arora; Sangeeta Mehta; Timothy D Girard; Otavio T Ranzani; Naomi Hammond; John W Devlin; Yahya Shehabi; Pratik Pandharipande; Marlies Ostermann Journal: Intensive Care Med Date: 2022-05-19 Impact factor: 41.787
Authors: Marco Daverio; Florian von Borell; Angela Amigoni; Erwin Ista; Anne-Sylvie Ramelet; Francesca Sperotto; Paula Pokorna; Sebastian Brenner; Maria Cristina Mondardini; Dick Tibboel Journal: Crit Care Date: 2022-03-31 Impact factor: 9.097