Different temperature thresholds for antipyretic intervention in critically ill children with fever due to infection: the FEVER feasibility RCT

BACKGROUND: Fever accelerates host immune system control of pathogens but at a high metabolic cost. The optimal approach to fever management and the optimal temperature thresholds used for treatment in critically ill children are unknown. OBJECTIVES: To determine the feasibility of conducting a definitive randomised controlled trial (RCT) to evaluate the clinical effectiveness and cost-effectiveness of different temperature thresholds for antipyretic management. DESIGN: A mixed-methods feasibility study comprising three linked studies - (1) a qualitative study exploring parent and clinician views, (2) an observational study of the epidemiology of fever in children with infection in paediatric intensive care units (PICUs) and (3) a pilot RCT with an integrated-perspectives study. SETTING: Participants were recruited from (1) four hospitals in England via social media (for the FEVER qualitative study), (2) 22 PICUs in the UK (for the FEVER observational study) and (3) four PICUs in England (for the FEVER pilot RCT). PARTICIPANTS: (1) Parents of children with relevant experience were recruited to the FEVER qualitative study, (2) patients who were unplanned admissions to PICUs were recruited to the FEVER observational study and (3) children admitted with infection requiring mechanical ventilation were recruited to the FEVER pilot RCT. Parents of children and clinicians involved in the pilot RCT. INTERVENTIONS: The FEVER qualitative study and the FEVER observational study had no interventions. In the FEVER pilot RCT, children were randomly allocated (1 : 1) using research without prior consent (RWPC) to permissive (39.5 °C) or restrictive (37.5 °C) temperature thresholds for antipyretics during their PICU stay while mechanically ventilated. MAIN OUTCOME MEASURES: (1) The acceptability of FEVER, RWPC and potential outcomes (in the FEVER qualitative study), (2) the size of the potentially eligible population and the temperature thresholds used (in the FEVER observational study) and (3) recruitment and retention rates, protocol adherence and separation between groups and distribution of potential outcomes (in the FEVER pilot RCT). RESULTS: In the FEVER qualitative study, 25 parents were interviewed and 56 clinicians took part in focus groups. Both the parents and the clinicians found the study acceptable. Clinicians raised concerns regarding temperature thresholds and not using paracetamol for pain/discomfort. In the FEVER observational study, 1853 children with u