Gastroenteritis aggressive versus slow treatment for rehydration (GASTRO): a phase II rehydration trial for severe dehydration: WHO plan C versus slow rehydration
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Background
World 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.
Methods
A 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.
Results
One 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).
Conclusion
Slower 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 registration
ISRCTN67518332. Date applied 31 August 2016.
World 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.
Methods
A 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.
Results
One 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).
Conclusion
Slower 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 registration
ISRCTN67518332. Date applied 31 August 2016.
Date Issued
2019-07-01
Date Acceptance
2019-05-30
Citation
BMC Medicine, 2019, 17 (1)
ISSN
1741-7015
Publisher
BioMed Central
Journal / Book Title
BMC Medicine
Volume
17
Issue
1
Copyright Statement
© The Author(s) 2019. Open Access. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Sponsor
Wellcome Trust
Wellcome Trust
Wellcome Trust
Grant Number
105603/Z/14/Z
100693/Z/12/Z
097816/Z/11/A
Subjects
Science & Technology
Life Sciences & Biomedicine
Medicine, General & Internal
General & Internal Medicine
Rehydration
Severe dehydration
Intravenous fluids
African children
Clinical trial
RAPID INTRAVENOUS REHYDRATION
GLOBAL ENTERIC MULTICENTER
HYPERTONIC DEHYDRATION
DEVELOPING-COUNTRIES
DIARRHEAL DISEASE
YOUNG-CHILDREN
TROPONIN-I
MORTALITY
MECHANISMS
THERAPY
African children
Clinical trial
Intravenous fluids
Rehydration
Severe dehydration
11 Medical and Health Sciences
General & Internal Medicine
Publication Status
Published
Article Number
122