Gastroenteritis: rehydration for children with severe acute malnutrition (GASTRO-SAM)

在非洲，经常住院的患有严重急性营养不良（SAM）的儿童（50%）患有腹泻（每天3次水样便）。当这些儿童按照世界卫生组织（世卫组织）SAM治疗指南进行管理时，其结果非常差，超过20%的儿童在住院期间死亡。导致脱水的腹泻的一种标准治疗方法是“补液”疗法，对那些因水样腹泻而失去约10%或更多体重的严重脱水患者使用点滴（静脉注射）。另一种治疗方法是口服补液盐（ORS）溶液，用于脱水不太严重的人，或作为儿童在接受滴注（静脉注射）治疗后的后续补液治疗。然而，世卫组织严重脱水急性呼吸窘迫症儿童指南建议，只有在出现晚期晚期休克（血压较低）的情况下才限制静脉注射治疗，并专门强调使用低钠（盐）口服补液溶液（ORS），以免引起心力衰竭和给予过多的盐（钠）。因此，对于需要补液的儿童，指南推荐低钠补液，称为ReSoMal。这些指南非常有争议，因为它们是基于专家意见，没有相关的临床研究或临床试验来支持这些建议的证据。由于预后非常差，因此我们的目标是在一项名为GASTROSAM的临床试验中评估对营养良好的儿童进行的通常标准治疗是否比静脉注射和口服补液推荐治疗对患有腹泻的SAM儿童更好和更安全。我们将进行一项小型试验，测试严重脱水的SAM儿童静脉补液100毫升/公斤（相当于补充失去的体积）是否安全，目前推荐用于无营养不良的儿童。我们将以两种方式进行输液，要么快速输液（超过3- 5小时），要么缓慢输液（超过8小时），并将其与目前推荐的方法进行比较（目前推荐使用口服补液盐治疗，只有在发生休克时才开始滴注治疗）。我们还将测试给没有严重营养不良的儿童的标准补液（含更多钠）是否比目前的补液（称为ReSoMal）更安全，有害影响更小，后者的钠含量要低得多，过去的研究表明，它会导致儿童的钠含量非常低，这可能会造成伤害。试验的结果将帮助我们设计一个更大的试验，我们的目标是比较所有入院儿童的快速补液和缓慢补液，而不考虑他们的营养状况（即营养良好和营养不良）。我们目前正在进行另一项名为GASTRO的小型试验，对患有严重腹泻但没有营养不良的儿童进行快速（标准推荐治疗）和缓慢补液的比较，因为即使对于没有营养不良的儿童，结果也很差。该试验的数据也将帮助我们设计未来的大型试验。

Children with severe acute malnutrition (SAM) who are admitted to a hospital in Africa frequently (>50%) have diarrhoea (3 watery stools/day). The outcome in such children when they managed in accordance to World Health Organization (WHO) SAM treatment guideline is very poor with over 20% dying during hospital admission. One standard treatment of diarrhoea that causes dehydration is 'rehydration' therapy either by using a drip (intravenous) for those who have developed severe dehydration, where approximately 10% or more of the body weight has been lost from watery diarrhoea. The other treatment is oral rehydration salt (ORS) solutions which is given to those with less severe dehydration or as a follow-on rehydration treatment for children after they have received their drip (intravenous) treatment. However, the WHO guidelines for SAM children with severe dehydration recommend restriction of intravenous therapy only to cases with late stage advanced shock (where the blood pressure is low) and focus exclusively on the use of low sodium (salt) oral rehydration solutions (ORS) for fear of causing heart failure and giving too much salt (sodium). Therefore, for children requiring ORS guidelines recommend a low sodium ORS called ReSoMal. These guidelines are very controversial since they are based on expert opinion, and do not have the relevant clinical studies or clinical trials to back up the evidence to support these recommendations. Owing to the very poor outcomes, we therefore aim to evaluate in a clinical trial called GASTROSAM whether the usual standard treatment that is given to children who are well nourished is better and safer that the intravenous and oral rehydration recommended treatments for SAM children with diarrhoea. We will conduct a small trial that will test whether it is safe to give intravenous rehydration for SAM children with severe dehydration of 100mls/kg (the equivalent volume to replace what has been lost) which is currently recommended for children without malnutrition. We will do this in two ways by either infusing the fluid rapidly (over 3- 5 hours), or more slowly (over 8 hours) and compare this to what is currently being recommended (which largely recommends to treat this with oral rehydration salts and only to start drip treatment if shock occurs). We will also test whether the standard ORS (with a higher amount of sodium) given for children without severe malnutrition is safer and has less harmful effects that the current ORS called ReSoMal which has a much lower sodium content and has in the past has been shown to result in children developing very low sodium levels which can cause harm. The results of the trial will help us design a much larger trial in which we aim to compare rapid rehydration versus slower rehydration in all children who are admitted to hospital irrespective of their nutritional status (i.e. well-nourished and malnourished). We are currently conducting another small trial called GASTRO in children with severe diarrhoea who do not have malnutrition comparing rapid (standard recommended treatment) versus slower rehydration as the outcomes even for children who are not malnourished is also very poor. The data from this trial will also help us design a future large trial.