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Crit Care. 2019 Mar 7;23(1):69. doi: 10.1186/s13054-019-2354-4.

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

Author information

1
Respiratory, Critical Care and Anaesthesia Unit, Paediatric Intensive Care, UCL Great Ormond Street Institute of Child Health, 30 Guildford Street, London, WC1N 1EH, UK. mark.peters@ucl.ac.uk.
2
Paediatric Intensive Care Unit, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK. mark.peters@ucl.ac.uk.
3
Department of Psychological Sciences, North West Hub for Trials Methodology, University of Liverpool, Liverpool, UK.
4
Clinical Trials Unit, Intensive Care National Audit and Research Centre, London, UK.
5
NHS Foundation Trust, Newcastle, UK.
6
Institute of Cellular Medicine, Newcastle University, Newcastle, UK.
7
Department of Health Sciences, University of Leicester, Leicester, UK.
8
Patient and Parent representative, London, UK.
9
Infection, Inflammation and Rheumatology, UCL Great Ormond Street Institute of Child Health, London, UK.
10
Paediatric Intensive Care Unit, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
11
Respiratory, Critical Care and Anaesthesia Unit, Paediatric Intensive Care, UCL Great Ormond Street Institute of Child Health, 30 Guildford Street, London, WC1N 1EH, UK.
12
Children's Acute Transport Service, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
13
Evelina Children's Hospital, Guy's and St Thomas' NHS Foundation Trust, London, UK.
14
Alder Hey Children's Hospital NHS Foundation Trust, Liverpool, UK.
15
Faculty of Health and Applied Sciences, University of the West of England, Glenside Campus, Bristol, UK.

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.

KEYWORDS:

Antipyretics; Clinical trial; Fever; Infection; Paediatric intensive care; Paracetamol; Sepsis

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