Permissive versus restrictive temperature thresholds in critically ill children with fever and infection: A multicentre randomized clinical pilot trial

Peters, Mark J.; Woolfall, Kerry; Khan, Imran; Deja, Elisabeth; Mouncey, Paul R.; Wulff, Jerome; Mason, Alexina; Agbeko, Rachel S.; Draper, Elizabeth S.; Fenn, Blaise; Gould, Doug W.; Koelewyn, Abby; Klein, Nigel; Mackerness, Christine; Martin, Sian; O'Neill, Lauran; Ray, Samiran; Ramnarayan, Padmanabhan; Tibby, Shane; Thorburn, Kentigern; Tume, Lyvonne N.; Watkins, Jason; Wellman, Paul; Harrison, David A.; Rowan, Kathryn M.

Abstract

Background: Fever improves pathogen control at a significant metabolic cost. No randomized clinical trials (RCT) have compared fever treatment thresholds in critically ill children. We performed a pilot RCT to determine whether a definitive trial of a permissive approach to fever in comparison to current restrictive practice is feasible in critically ill children with suspected infection. Methods: An open, parallel-group pilot RCT with embedded mixed methods perspectives study in four UK paediatric intensive care units (PICUs) and associated retrieval services. Participants were emergency PICU admissions aged > 28 days to < 16 years receiving respiratory support and supplemental oxygen. Subjects were randomly assigned to permissive (antipyretic interventions only at ≥ 39.5 °C) or restrictive groups (antipyretic interventions at ≥ 37.5 °C) whilst on respiratory support. Parents were invited to complete a questionnaire or take part in an interview. Focus groups were conducted with staff at each unit. Outcomes were measures of feasibility: recruitment rate, protocol adherence and acceptability, between group separation of temperature and safety. Results: One hundred thirty-eight children met eligibility criteria of whom 100 (72%) were randomized (11.1 patients per month per site) without prior consent (RWPC). Consent to continue in the trial was obtained in 87 cases (87%). The mean maximum temperature (95% confidence interval) over the first 48 h was 38.4 °C (38.2-38.6) in the restrictive group and 38.8 °C (38.6-39.1) in the permissive group, a mean difference of 0.5 °C (0.2-0.8). Protocol deviations were observed in 6.8% (99/1438) of 6-h time periods and largely related to patient comfort in the recovery phase. Length of stay, duration of organ support and mortality were similar between groups. No pre-specified serious adverse events occurred. Staff (n = 48) and parents (n = 60) were supportive of the trial, including RWPC. Suggestions were made to only include invasively ventilated children for the duration of intubation. Conclusion: Uncertainty around the optimal fever threshold for antipyretic intervention is relevant to many emergency PICU admissions. A more permissive approach was associated with a modest increase in mean maximum temperature. A definitive trial should focus on the most seriously ill cases in whom antipyretics are rarely used for their analgesic effects alone. Trial registration: ISRCTN16022198. Registered on 14 August 2017.

• Journal Article Type: Article
• Acceptance Date: Feb 6, 2019
• Online Publication Date: Mar 7, 2019
• Publication Date: Mar 7, 2019
• Deposit Date: Feb 8, 2019
• Publicly Available Date: Feb 8, 2019
• Journal: Critical Care
• Print ISSN: 1574-4280
• Electronic ISSN: 1875-7081
• Publisher: Bohn Stafleu van Loghum
• Peer Reviewed: Peer Reviewed
• Volume: 23
• Issue: 1
• DOI: https://doi.org/10.1186/s13054-019-2354-4
• Keywords: fever, intensive care, children, infection, temperature
• Public URL: https://uwe-repository.worktribe.com/output/850918
• Publisher URL: https://doi.org/10.1186/s13054-019-2354-4
• Contract Date: Feb 8, 2019