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

Peters, M; Woolfall, K; Khan, I; Deja, E; Mouncey, P; Wulff, J; Mason, A; Agbecko, R; Draper, E; Fenn, B; Gould, D; Koelewyn, A; Klein, N; Mackerness, C; Martin, S; O'Neill, L; Ray, S; Ramnarayan, P; Tibby, S; Thorburn, K; Tume, LN; Watkins, J; Wellman, P; Harrison, D; Rowan, K

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.

Citation

clinical pilot trial. Critical Care, 23, 69. https://doi.org/10.1186/s13054-019-2354-4

• Journal Article Type: Article
• Acceptance Date: Feb 10, 2019
• Publication Date: Mar 7, 2019
• Deposit Date: Sep 4, 2019
• Publicly Available Date: Sep 4, 2019
• Journal: Critical Care
• Print ISSN: 1574-4280
• Electronic ISSN: 1466-609X
• Publisher: Springer Verlag
• Volume: 23
• Pages: 69
• DOI: https://doi.org/10.1186/s13054-019-2354-4
• Publisher URL: https://doi.org/10.1186/s13054-019-2354-4
• Related Public URLs: https://ccforum.biomedcentral.com/
• Additional Information: Projects : FEVER Study