Fever: An evaluation of the feasibility of conducting a randomised clinical trial to evaluate the clinical and cost-effectiveness of a more permissive temperature threshold for antipyretic intervention in critically ill children with fever due to infection
Background
Evidence in adults suggests that a high temperature (fever) could help recovery from infection. It is not known whether or not this applies to children in paediatric intensive care units (PICUs). Doctors and nurses (clinicians) usually cool children with fever. Before carrying out a trial to find whether or not cooling children at a higher temperature in PICU works, the FEVER feasibility study was conducted to answer the question ‘can this trial be done?’.
Design
Interviews and focus groups were held with parents and clinicians to find out their views. Twenty-five parents were interviewed and supported the study and the use of research without prior consent. Some were concerned about letting the temperature rise too high if a child was in pain or discomfort. Parents were asked about what outcomes are important. These were (1) long-term morbidity, (2) looking and behaving more normally, (3) length of time on breathing support, (4) time in a PICU and hospital and (5) how quickly vital statistics are back to normal. To find out how many children might take part in a large trial, information was collected on children with infection from 22 PICUs. This showed that each PICU should see > 10 patients per month.
Results
Finally, a pilot study was run to test if children could be recruited, to see if clinicians followed procedures and to interview people for feedback. Four hospitals recruited 100 participants. Children were randomly allocated to start cooling either at 37.5 °C or at 39.5 °C. Recruitment was higher than expected. There was concern among the children who experienced pain or discomfort. This led to parents declining consent more often in the 39.5 °C group than in the 37.5 °C group and cooling being started earlier than prescribed.
Conclusion
If the large trial focuses only on children receiving invasive ventilation (as these children will receive other medications for their discomfort), the FEVER trial is deemed feasible.
Who led the study?
Professor Mark Peters, Great Ormond Street Hospital for Children NHS Trust, London
This study was funded by the National Institute for Health Research (NIHR) – Health Technology Assessment (HTA) Programme (Project: 15/44/01)
Publications
Deja E, Peters MJ, Khan I, Mouncey PR, Agbeko R, Fenn B, Watkins J, Ramnarayan P, Tibby SM, Thorburn K, Tume LN, Rowan KM, Woolfall K. Establishing and augmenting views on the acceptability of a paediatric critical care randomised controlled trial (the FEVER trial): a mixed methods study. BMJ Open 2021; 11(3):e041952. http://dx.doi.org/10.1136/bmjopen-2020-041952 Woolfall K, O'Hara C, Deja E, Canter R, Khan I, Mouncey P, Carter A, Jones N, Watkins J, Lyttle MD, Tume L, Agbeko R, Tibby SM, Pappachan J, Thorburn K, Rowan KM, Peters MJ, Inwald D. Parents' prioritised outcomes for trials investigating treatments for paediatric severe infection: a qualitative synthesis. Arch Dis Child 2019; . http://dx.doi.org/10.1136/archdischild-2019-316807 Peters MJ, Woolfall K, Khan I, Deja E, Mouncey PR, Wulff J, Mason A, Agbeko RS, Draper ES, Fenn B, Gould DW, Koelewyn A, Klein N, Mackerness C, Martin S, O'Neill L, Ray S, Ramnarayan P, Tibby S, Thorburn K, Tume L, Watkins J, Wellman P, Harrison DA, Rowan KM. Permissive versus restrictive temperature thresholds in critically ill children with fever and infection: a multicentre randomized clinical pilot trial. Crit Care 2019; 23(1):69. http://dx.doi.org/10.1186/s13054-019-2354-4 Peters MJ, Khan I, Woolfall K, Deja E, Mouncey PR, Wulff J, Mason A, Agbeko R, Draper ES, Fenn B, Gould DW, Koelewyn A, Klein N, Mackerness C, Martin S, O’Neill L, Ramnarayan P, Tibby S, Tume L, Watkins J, Thorburn K, Wellman P, Harrison DA, Rowan KM. Different temperature thresholds for antipyretic intervention in critically ill children with fever due to infection: the FEVER feasibility RCT. Health Technol Assess 2019; 23:5. http://dx.doi.org/10.3310/hta23050
