Wellcome Trust Centre for Clinical Tropical Medicine, Department of Paediatrics, Faculty of Medicine, St Marys Campus, Norfolk Place, Imperial College, London W2 1PG, UK.
BMC Med. 2013 Mar 14;11:68. doi: 10.1186/1741-7015-11-68.
Early rapid fluid resuscitation (boluses) in African children with severe febrile illnesses increases the 48-hour mortality by 3.3% compared with controls (no bolus). We explored the effect of boluses on 48-hour all-cause mortality by clinical presentation at enrolment, hemodynamic changes over the first hour, and on different modes of death, according to terminal clinical events. We hypothesize that boluses may cause excess deaths from neurological or respiratory events relating to fluid overload.
Pre-defined presentation syndromes (PS; severe acidosis or severe shock, respiratory, neurological) and predominant terminal clinical events (cardiovascular collapse, respiratory, neurological) were described by randomized arm (bolus versus control) in 3,141 severely ill febrile children with shock enrolled in the Fluid Expansion as Supportive Therapy (FEAST) trial. Landmark analyses were used to compare early mortality in treatment groups, conditional on changes in shock and hypoxia parameters. Competing risks methods were used to estimate cumulative incidence curves and sub-hazard ratios to compare treatment groups in terms of terminal clinical events.
Of 2,396 out of 3,141 (76%) classifiable participants, 1,647 (69%) had a severe metabolic acidosis or severe shock PS, 625 (26%) had a respiratory PS and 976 (41%) had a neurological PS, either alone or in combination. Mortality was greatest among children fulfilling criteria for all three PS (28% bolus, 21% control) and lowest for lone respiratory (2% bolus, 5% control) or neurological (3% bolus, 0% control) presentations. Excess mortality in bolus arms versus control was apparent for all three PS, including all their component features. By one hour, shock had resolved (responders) more frequently in bolus versus control groups (43% versus 32%, P <0.001), but excess mortality with boluses was evident in responders (relative risk 1.98, 95% confidence interval 0.94 to 4.17, P = 0.06) and 'non-responders' (relative risk 1.67, 95% confidence interval 1.23 to 2.28, P = 0.001), with no evidence of heterogeneity (P = 0.68). The major difference between bolus and control arms was the higher proportion of cardiogenic or shock terminal clinical events in bolus arms (n = 123; 4.6% versus 2.6%, P = 0.008) rather than respiratory (n = 61; 2.2% versus 1.3%, P = 0.09) or neurological (n = 63, 2.1% versus 1.8%, P = 0.6) terminal clinical events.
Excess mortality from boluses occurred in all subgroups of children. Contrary to expectation, cardiovascular collapse rather than fluid overload appeared to contribute most to excess deaths with rapid fluid resuscitation. These results should prompt a re-evaluation of evidence on fluid resuscitation for shock and a re-appraisal of the rate, composition and volume of resuscitation fluids.
ISRCTN69856593.
与对照组（不推注）相比，在非洲患有严重发热疾病的儿童中早期快速液体复苏（推注）会使 48 小时死亡率增加 3.3%。我们通过登记时的临床表现、第 1 小时内的血液动力学变化以及根据终末临床事件不同的死亡方式，探讨了推注对 48 小时全因死亡率的影响。我们假设推注可能会导致因与液体过载相关的神经或呼吸事件而导致额外死亡。
在 3141 名患有休克的严重发热儿童中，根据预先定义的表现综合征（PS；严重酸中毒或严重休克、呼吸、神经）和主要终末临床事件（心血管衰竭、呼吸、神经），按随机分组（推注组与对照组）进行描述。使用 landmark 分析比较治疗组的早期死亡率，条件是休克和缺氧参数的变化。使用竞争风险方法估计累积发病率曲线和亚危险比，以比较治疗组的终末临床事件。
在 3141 名可分类参与者中的 2396 名（76%）中，1647 名（69%）患有严重代谢性酸中毒或严重休克 PS，625 名（26%）患有呼吸 PS，976 名（41%）患有神经 PS，单独或组合存在。同时符合所有三种 PS 标准的儿童死亡率最高（推注组 28%，对照组 21%），而仅存在呼吸（推注组 2%，对照组 5%）或神经（推注组 3%，对照组 0%）表现的儿童死亡率最低。在推注组与对照组中，所有三种 PS 均表现出明显的超额死亡率，包括其所有组成特征。到第 1 小时，与对照组相比，推注组中休克得到缓解（应答者）的频率更高（43%比 32%，P <0.001），但推注组中仍存在额外的死亡率（相对风险 1.98，95%置信区间 0.94 至 4.17，P = 0.06），在应答者（相对风险 1.67，95%置信区间 1.23 至 2.28，P = 0.001）和“非应答者”（相对风险 1.67，95%置信区间 1.23 至 2.28，P = 0.001）中，且无组间差异（P = 0.68）。推注组和对照组之间的主要区别是推注组中心源性或休克终末临床事件的比例较高（n = 123；4.6%比 2.6%，P = 0.008），而呼吸终末临床事件（n = 61；2.2%比 1.3%，P = 0.09）或神经终末临床事件（n = 63，2.1%比 1.8%，P = 0.6）的比例较低。
推注导致所有亚组儿童的死亡率增加。与预期相反，心血管衰竭而不是液体过载似乎是快速液体复苏导致额外死亡的主要原因。这些结果应促使人们重新评估有关休克液体复苏的证据，并重新评估复苏液的速度、组成和容量。
ISRCTN69856593。
