Phase II trial of isotonic fluid resuscitation in Kenyan children with severe malnutrition and hypovolaemia

Abstract

BackgroundChildren with severe malnutrition who develop shock have a high mortality. Contrary to contemporaneous paediatric practice, current guidelines recommend use of low dose hypotonic fluid resuscitation (half-strength Darrows/5% dextrose (HSD/5D). We evaluated the safety and efficacy of this guideline compared to resuscitation with a standard isotonic solution.MethodsA Phase II randomised controlled, safety and efficacy trial in Kenyan children aged over 6 months with severe malnutrition and shock including children with severe dehydration/shock and presumptive septic shock (non-diarrhoeal shock). Eligible children were randomised to HSD/5D or Ringer's Lactate (RL). A maximum of two boluses of 15 ml/kg of HSD/5D were given over two hours (as recommended by guidelines) while those randomised to RL received 10 ml/kg aliquots half hourly (maximum 40 ml/kg). Primary endpoint was resolution of shock at 8 and 24 hours. Secondary outcomes included resolution of acidosis, adverse events and mortality.Results61 children were enrolled: 41 had shock and severe dehydrating diarrhoea, 20 had presumptive septic shock; 69% had decompensated shock. By 8 hours response to volume resuscitation was poor with shock persisting in most children:-HSD/5D 15/22 (68%) and RL14/25 (52%), p = 0.39. Oliguria was more prevalent at 8 hours in the HSD/5D group, 9/22 (41%), compared to RL-3/25 (12%), p = 0.02. Mortality was high, HSD/5D-15/26(58%) and RL 13/29(45%); p = 0.42. Most deaths occurred within 48 hours of admission. Neither pulmonary oedema nor cardiogenic failure was detected.ConclusionsOutcome was universally poor characterised by persistence of shock, oliguria and high case fatality. Isotonic fluid was associated with modest improvement in shock and survival when compared to HSD/5D but inconclusive due to the limitations of design and effectiveness of either resuscitation strategy. Although isotonic fluid resuscitation did not result in cardiogenic heart failure, as previously feared, we conclude that the modest volumes used and rate of infusion were insufficient to promptly correct shock. The adverse performance of the recommended fluid resuscitation guideline for severe malnutrition should prompt clinical investigation of isotonic fluids for resuscitation of compensated shock, defining rate and volumes required to inform future guidelines.Trial RegistrationThe trial is registered as ISCRTN: 61146418

Fluid Bolus Therapy-Based Resuscitation for Severe Sepsis in Hospitalized Children

“…Yet the scarce data from a broad hospitalized population with sepsis from resourcerich settings require attention-particularly in light of the FEAST trial which challenged current practice and triggered discussion and debate (28)(29)(30)(31)(32)(33)(34). Finally, our findings are coherent with a recent systematic review of fluid resuscitation in adults (34).…”

“…The majority of trials of FBT-based resuscitation in children with septic shock have occurred outside of Europe or North America in the context of dengue shock syndrome (24)(25)(26), malaria (27)(28)(29), or malnutrition (30), thus limiting their broader applicability to developed countries. We excluded these studies based on their focused populations and lack of advanced therapeutic interventions such as mechanical ventilation and vasoactive support.…”

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“…This may be even more relevant in children with significant malnutrition, although the evidence base for this is extremely limited [81,82].…”

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“…Isotonic fluid was associated with modest improvement in shock and survival when compared to HSD/ 5D but results were inconclusive. 31 What is clear from the literature is that very few studies linked clinical status, physiological investigation and response to treatment in representative cohorts of children with severe malnutrition. Few have drawn on modern technology and contemporary understanding of paediatric critical illness to study myocardial status and haemodynamic response to fluid expansion.…”

“…The trial included 41 children with shock and severe dehydrating diarrhoea and 20 with presumptive septic shock; overall 69% of the trial cohort had decompensated hypotensive shock. 31 Outcome was universally poor, characterised by persistence of shock, oliguria and high case fatality. No episodes of pulmonary oedema or fluid overload were reported.…”