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

在非洲，患有严重急性营养不良的儿童经常（>50%）出现腹泻（每天3次水样便）。当这些儿童按照世界卫生组织（WHO）SAM治疗指南进行治疗时，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是“补液”疗法，对于已经发展为严重脱水的人，其中大约10%或更多的体重已经从水样腹泻中损失。另一种治疗方法是口服补液盐（ORS）溶液，给那些脱水不太严重的人服用，或者作为儿童接受滴注（静脉注射）治疗后的后续补液治疗。然而，世卫组织关于严重脱水的SAM儿童的指南建议仅对晚期晚期休克（血压低）的病例限制静脉治疗，并专门关注低钠（盐）口服补液溶液（ORS）的使用，以免引起心力衰竭和给予过多的盐（钠）。因此，对于需要口服补液盐的儿童，指南推荐一种低钠口服补液盐，称为ReSoMal。这些指南是非常有争议的，因为它们是基于专家的意见，并没有相关的临床研究或临床试验来支持这些建议的证据。由于结果非常差，因此，我们的目标是在一项名为GASTROSAM的临床试验中评估，给予营养良好的儿童的常规标准治疗是否比推荐用于SAM腹泻儿童的静脉和口服补液治疗更好和更安全。我们将进行一项小型试验，测试对严重脱水100 mls/kg（相当于补充损失的体积）的SAM儿童进行静脉补液是否安全，目前推荐用于无营养不良的儿童。我们将以两种方式进行，快速输注液体（超过3- 5小时）或更慢（超过8小时），并将其与目前推荐的方法进行比较（主要建议使用口服补液盐治疗，只有在发生休克时才开始滴注治疗）。我们还将测试为没有严重营养不良的儿童提供的标准ORS（钠含量较高）是否比目前称为ReSoMal的ORS更安全，有害影响更小，ReSoMal的钠含量要低得多，过去已被证明会导致儿童的钠水平非常低，这可能会造成伤害。该试验的结果将帮助我们设计一个更大的试验，我们的目标是在所有入院的儿童中比较快速补液与慢速补液，无论其营养状况如何（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，在没有营养不良的严重腹泻儿童中比较快速（标准推荐治疗）与较慢的补液，因为即使对于没有营养不良的儿童，结果也很差。这项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.