Gastroenteritis aggressive versus slow treatment for rehydration (GASTRO): a phase II rehydration trial for severe dehydration: WHO plan C versus slow rehydration

BMC Medicine

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[1] 0000 0001 0155 5938, grid.33058.3d, KEMRI-Wellcome Trust Research Programme, PO Box 230, Kilifi, Kenya;0000 0001 0169 7725, grid.241103.5, Department of Paediatrics, University Hospital of Wales, Heath Park, CF14 4XW, Cardiff, Wales, UK;0000 0004 0512 5005, grid.461221.2, Mbale Clinical Research Institute, PO Box 291, Pallisa Road, Mbale, Uganda;0000 0004 0512 5005, grid.461221.2, Mbale Regional Referral Hospital, PO Box 291, Pallisa Road, Mbale, Uganda;0000 0004 0514 9699, grid.461268.f, Soroti Regional Referral Hospital, PO Box 289, Soroti, Uganda;0000 0004 0606 323X, grid.415052.7, MRC Clinical Trials Unit at UCL 90 High Holborn, 2nd Floor, WC1V 6LJ, London, UK;Department of Paediatrics, Faculty of Medicine, St Mary’s Campus, Norfolk Place, Imperial College, W2 1PG, London, UK;0000 0001 0155 5938, grid.33058.3d, KEMRI-Wellcome Trust Research Programme, PO Box 230, Kilifi, Kenya;

关键词: Rehydration;    Severe dehydration;    Intravenous fluids;    African children;    Clinical trial;   

DOI  :  10.1186/s12916-019-1356-z

来源: publisher

【 摘 要 】

BackgroundWorld Health Organization rehydration management guidelines (plan C) for severe dehydration are widely practiced in resource-poor settings, but never formally evaluated in a trial. The Fluid Expansion as a Supportive Therapy trial raised concerns regarding the safety of bolus therapy for septic shock, warranting a formal evaluation of rehydration therapy for gastroenteritis.MethodsA multi-centre open-label phase II randomised controlled trial evaluated two rehydration strategies in 122 Ugandan/Kenyan children aged 60 days to 12 years with severe dehydration secondary to gastroenteritis. We compared the safety and efficacy of standard rapid rehydration using Ringer’s lactate (100 ml/kg over 3 h (6 h if < 1 year), incorporating 0.9% saline boluses for children with shock (plan C) versus slower rehydration: 100 ml/kg Ringer’s lactate over 8 h (all ages) without boluses (slow: experimental). The primary outcome was the frequency of serious adverse events (SAE) within 48 h including cardiovascular, respiratory and neurological complications. Secondary outcomes included clinical, biochemical and physiological measures of response to treatment by intravenous rehydration.ResultsOne hundred twenty-two eligible children (median (IQR) age 8 (6–12) months) were randomised to plan C (n = 61) or slow (n = 61), with two (2%) lost to follow-up at day 7). Following randomisation mean (SD) time to start intravenous rehydration started was 15 min (18) in both arms. Mean (SD) fluid received by 1 hour was greater in plan C (mean 20.2 ml/kg (12.2) and 33.1 ml/kg (17) for children < 1 year and >− 1 year respectively) versus 10.4 ml/kg (6.6) in slow arm. By 8 hours volume received were similar mean (SD) plan C: 96.3 ml/kg (15.6) and 97.8 ml/kg (10.0) for children < 1 and ≥ 1 year respectively vs 93.2 ml/kg (12.2) in slow arm. By 48-h, three (5%) plan C vs two (3%) slow had an SAE (risk ratio 0.67, 95% CI 0.12–3.85, p = 0.65). There was no difference in time to the correction of dehydration (p = 0.9) or time to discharge (p = 0.8) between groups. Atrial natriuretic peptide levels rose substantially by 8 hours in both arms, which persisted to day 7. Day 7 weights suggested only 33 (29%) could be retrospectively classified as severely dehydration (≥ 10% weight loss).ConclusionSlower rehydration over 8 hours appears to be safe, easier to implement than plan C. Future large trials with mortality as the primary endpoint are warranted.Trial registrationISRCTN67518332. Date applied 31 August 2016.

【 授权许可】

CC BY