Effects of saline or albumin fluid bolus in resuscitation: evidence from re-analysis of the FEAST trial

Abstract

Summary Background Fluid resuscitation is the recommended management of shock, but increased mortality in febrile African children in the FEAST trial. We hypothesised that fluid bolus-induced deaths in FEAST would be associated with detectable changes in cardiovascular, neurological, or respiratory function, oxygen carrying capacity, and blood biochemistry. Methods We developed composite scores for respiratory, cardiovascular, and neurological function using vital sign data from the FEAST trial, and used them to compare participants from FEAST with those from four other cohorts and to identify differences between the bolus (n=2097) and no bolus (n=1044) groups of FEAST. We calculated the odds of adverse outcome for each ten-unit increase in baseline score using logistic regression for each cohort. Within FEAST participants, we also compared haemoglobin and plasma biochemistry between bolus and non-bolus patients, assessed the effects of these factors along with the vital sign scores on the contribution of bolus to mortality using Cox proportional hazard models, and used Bayesian clustering to identify subgroups that differed in response to bolus. The FEAST trial is registered with ISRCTN, number ISRCTN69856593. Findings Increasing respiratory (odds ratio 1·09, 95% CI 1·07–1·11), neurological (1·26, 1·21–1·31), and cardiovascular scores (1·09, 1·05–1·14) were associated with death in FEAST (all p<0·0001), and with adverse outcomes for specific scores in the four other cohorts. In FEAST, fluid bolus increased respiratory and neurological scores and decreased cardiovascular score at 1 h after commencement of the infusion. Fluid bolus recipients had mean 0·33 g/dL (95% CI 0·20–0·46) reduction in haemoglobin concentration after 8 h (p<0·0001), and at 24 h had a decrease of 1·41 mEq/L (95% CI 0·76–2·06; p=0·0002) in mean base excess and increase of 1·65 mmol/L (0·47–2·8; p=0·0070) in mean chloride, and a decrease of 0·96 mmol/L (0·45 to 1·47; p=0·0003) in bicarbonate. There were similar effects of fluid bolus in three patient subgroups, identified on the basis of their baseline characteristics. Hyperchloraemic acidosis and respiratory and neurological dysfunction induced by saline or albumin bolus explained the excess mortality due to bolus in Cox survival models. Interpretation In the resuscitation of febrile children, albumin and saline boluses can cause respiratory and neurological dysfunction, hyperchloraemic acidosis, and reduction in haemoglobin concentration. The findings support the notion that fluid resuscitation with unbuffered electrolyte solutions may cause harm and their use should be cautioned. The effects of lower volumes of buffered solutions should be evaluated further. Funding Medical Research Council, Department for International Development, National Institute for Health Research, Imperial College Biomedical Research Centre.

Phases of fluid management and the roles of human albumin solution in perioperative and critically ill patients

“…The FEAST trial evaluated the role of fluid bolus therapy in the resuscitation of children in Africa with shock and life-threatening infections with severe febrile illness and impaired perfusion (mostly malaria), and reported higher 48-h mortality in those who received boluses of either saline or 5% albumin, as compared with a no bolus control group who received maintenance fluids 127 . A recent reanalysis of the FEAST trial found that worsening hyperchloremic acidosis, due to the chloride content of the saline or 5% albumin boluses, was a major contributor to the increased mortality risk 128 . This raises the possibility that lower-volume fluid therapy with buffered solution or higher-percentage HSA solution might help to minimize mortality in this setting, although this requires further study 128,129 .…”

“…A recent reanalysis of the FEAST trial found that worsening hyperchloremic acidosis, due to the chloride content of the saline or 5% albumin boluses, was a major contributor to the increased mortality risk 128 . This raises the possibility that lower-volume fluid therapy with buffered solution or higher-percentage HSA solution might help to minimize mortality in this setting, although this requires further study 128,129 .…”

Accuracy of a Modified qSOFA Score for Predicting Critical Care Admission in Febrile Children

“…A recent secondary analysis of the Fluid Expansion as Supportive Therapy study demonstrated the relevance of respiratory, cardiovascular, and central nervous system dysfunction in identifying patients at a greater risk of mortality, further supporting this approach. 18 The 2005 Pediatric Sepsis Consensus 19 thresholds for abnormal HR and RR, used in both SIRS and the age-adjusted qSOFA, were based on values that were likely determined through clinical consensus. 20 In contrast, evidencebased sets of reference ranges have since been developed, on ED 21 and hospitalized patients, 22 which may be more discriminative in the febrile ED population.…”

Epidemiology and effects of fluid bolus administration in the paediatric emergency department

“…In one of the conditions known to cause dehydration without systemic inflammation, diabetic ketoacidosis, Kuppermann and Glaser found that large volume fluid resuscitation was not associated with an increased risk of developing cerebral oedema (injury). This stands in contrast to the finding that FBT in children with a febrile illness and poor perfusion was associated with cerebral and pulmonary oedema . Further study is needed to define the patient groups that may benefit or that may be harmed by FBT.…”