Monday 9th September 2013
Time: 1.00-2.00pm (tea/coffee available from 12.40pm)
Kennedy Lecture Theatre, UCL Institute of Child Health.
If you would like to suggest someone as a speaker, please contact the OWL Committee Chair, Professor Christine Kinnon.
For any administrative questions, please contact Nicole Hofmans.
Why fluid resuscitation in the FEAST trial was harmful: more than just wet
Part of the Otto Wolff Lecture series 2013
Professor Kathryn Maitland
Professor of Tropical Paediatric Infectious Diseases, Imperial College London
Over the last 13 years Prof Maitland has been based full-time at the KEMRI-Wellcome Trust Research Programme, Kilifi, Kenya where she has led a research group whose major research portfolio includes studies of severe malaria, bacterial sepsis, severe anaemia and severe malnutrition and built collaborations across Africa including a network of clinical trial sites with the capacity to undertake high quality large clinical trials. This network conducted the MRC-funded FEAST trial (Fluid Expansion As a Supportive Therapy), which was the largest trial of critically children ever undertaken in Africa (FEAST trial).
Shock affects around one in ten children admitted to African hospitals, with 15-22% dying, often within hours of admission. Fluid resuscitation has been regarded as standard approach to treating shock in well-resourced countries for the last two decades -albeit based on a weak level of evidence– however, it has been unclear whether this approach could be safely adopted into practice in Africa children. FEAST was initiated to address this treatment gap and its design was informed by over a decade of preparatory clinical research in Kenya. It was the first controlled trial of fluid resuscitation ever undertaken. The trial was conducted in six centres in three countries (Kenya, Tanzania and Uganda) involving 3,141 children with range of severe febrile illness (including severe malaria, sepsis, pneumonia, meningitis) who presented with impaired perfusion. It was conducted in hospitals, with limited infrastructure, representing the realities of acute paediatric care in Africa.
Findings: The trial was stopped early by the committee overseeing safety since children randomised to receive early rapid fluid boluses (20-40ml/kg) with normal saline or 5% human albumin had a 45% increased relative risk of death by 48 hours compared with children receiving no boluses. Mortality patterns were remarkably consistent across all centres and subgroups (including malaria, coma, sepsis, acidosis, severe anaemia and severity of shock) Maitland, K., et al. NEJM (2011). Further analysis showed that the increased risk of death was due to cardiovascular collapse at 48 hours, rather than fluid overload, and further challenges the widely held belief that early and rapid reversal of shock by fluid resuscitation translates into longer-term survival benefits (Maitland, K. et al, BMC Medicine 2013).
FEAST trial publications[1-7]:
1. Maitland K, Kiguli S, Opoka RO, Engoru C, Olupot-Olupot P, Akech SO, Nyeko R, Mtove G, Reyburn H, Lang T, Brent B, Evans JA, Tibenderana JK, Crawley J, Russell EC, Levin M, Babiker AG, Gibb DM: Mortality after fluid bolus in African children with severe infection. The New England journal of medicine 2011, 364:2483-2495.
2. Maitland K, Akech SO, Russell EC: Mortality after Fluid Bolus in African Children with Sepsis: Reply. The New England journal of medicine 2011, 365:1348-1353.
3. Maitland K, Molyneux S, Boga M, Kiguli S, Lang T: Use of deferred consent for severely ill children in a multi-centre phase III trial. Trials 2011, 12:90.
4. Maitland K, Babiker A, Kiguli S, Molyneux E: The FEAST trial of fluid bolus in African children with severe infection. Lancet 2012, 379:613; author reply 613-614.
5. Molyneux S, Njue M, Boga M, Akello L, Olupot-Olupot P, Engoru C, Kiguli S, Maitland K: 'The words will pass with the blowing wind': staff and parent views of the deferred consent process, with prior assent, used in an emergency fluids trial in two african hospitals. PloS one 2013, 8:e54894.
6. Maitland K, George EC, Evans JA, Kiguli S, Olupot-Olupot P, Akech SO, Opoka RO, Engoru C, Nyeko R, Mtove G, Reyburn H, Brent B, Nteziyaremye J, Mpoya A, Prevatt N, Dambisya CM, Semakula D, Ddungu A, Okuuny V, Wokulira R, Timbwa M, Otii B, Levin M, Crawley J, Babiker AG, Gibb DM: Exploring mechanisms of excess mortality with early fluid resuscitation: insights from the FEAST trial. BMC Med 2013, 11:68.
7. Todd J, Heyderman RS, Musoke P, Peto T: When enough is enough: how the decision was made to stop the FEAST trial: data and safety monitoring in an African trial of Fluid Expansion As Supportive Therapy (FEAST) for critically ill children. Trials 2013, 14:85.
Professor Maitland is Professor of Tropical Paediatric Infectious Disease at the Faculty of Medicine, Imperial College, London and Honorary Consultant in Paediatric Infectious Disease at St Marys Hospital, London. She is also Honorary Clinician Researcher at the MRC Clinical trials Unit, London.