Abstract
INTRODUCTION: Fluid bolus during initial resuscitation of septic shock is administered with the aim to restore effective circulating volume and improve organ perfusion. Despite its widespread practice, bolus fluid therapy is not backed by high-quality evidence in critically ill children. After the FEAST trial suggested harm, recent recommendations consider health care systems and the availability of mechanical ventilation before prescribing bolus administration. Up to 40 mL/kg bolus fluids over the first hour is suggested for settings with intensive care, however, there is a lack of data on optimal bolus volume (from 5 to 20 mL/kg) contributing to considerable practice variability. OBJECTIVES: This study aimed to compare the safety and efficacy of two fluid bolus volumes (10 mL/kg vs 20 mL/kg of normal saline) for initial resuscitation of children with septic shock. Primary objective: To compare the incidence of new invasive ventilation and/or 25% worsening in oxygenation at 6 hours. Secondary objectives: To compare the resolution of shock at 6 and 24 hours, fluid overload % (FO%), and hospital mortality.(,) METHODS: This was an unblinded superiority randomized controlled trial conducted from December 2021 to November 2023 in a tertiary Pediatric Emergency Department in north India. We enrolled consecutive children aged 1 month to 12 years presenting with clinical signs of septic shock defined as acute febrile illness complicated with impaired perfusion, as evidenced by one or more of the following: hypotension (systolic blood pressure < 5th centile for age), capillary refill time of > 3 seconds, weak radial pulse volume or other signs of poor perfusion as decided by the treating clinician. Enrolled children were randomized to receive either 10 mL/kg of 0.9% saline or 20 mL/kg of 0.9% saline over 10 – 20 minutes. The bolus fluid was repeated with the same volume if necessary. Continuous monitoring and 2 hourly data were recorded in a pre-designed case record form. We hypothesized that the primary outcome, the incidence of new invasive ventilation and/or 25% worsening of oxygenation at 6 hours would be lower with a reduced bolus volume (10 mL/kg). RESULTS: Of 227 screened, 123 were enrolled; 62 in 10 mL/kg and 61 in 20 mL/kg group. Median(IQR) age was 3(0.6, 7)y. Fifty-eight (47%) children had weight<2SD for age. Gastrointestinal(29%), respiratory (17%), and tropical infections(12%) were common etiologies. Eleven(9%) had confirmed bloodstream infections. Half (n = 57) presented in hypotensive shock. Volume of fluid (mL/kg) received at 1 hour [13(10, 20) vs 24.7(22, 40); p < 0.001], 6 hours [37(28, 55) vs 53(39, 104); p = 0.006] and FO% at 24 hours [2.3(0.5, 5.9) vs 4.9(2.3, 9.6); p=0.001] were significantly lower in 10 mL/kg group.(,) Children initiated on vasoactives(adrenaline/noradrenaline) [41(65%) vs 36(59%)] and time of initiation [22.5(20, 172) vs 20 (20, 105) minutes] were comparable. Primary outcome occurred in 20(32.2%) children in 10 mL/kg group and 23(37.7%) children in 20 mL/kg group, the difference being not significant [RR (95% CI): 0.85(0.53, 1.38); p = 0.52]. There was trend towards lower new intubation in 10 mL/kg group [21 (34%) vs 31(51%), p = 0.058]. Resolution of shock at 6 hours [17(27%) vs 15(25%)] and 24 hours [34(56%) vs 36(59%)] were similar. Unfavourable outcome (29 deaths, 19 discontinued care), was comparable [26(41%) vs 22(36%); p=0.50] between the groups. CONCLUSION: Among children with septic shock, administration of 10 mL/kg bolus as compared to 20 mL/kg bolus did not result in a lower risk of intubation in the initial 6 hours of resuscitation. Both fluid bolus strategies have comparable efficacy. The lower cumulative fluid balance and the tendency towards lesser new intubation beyond 6 hours of resuscitation in children receiving 10 mL/kg bolus may be explored in larger trials. GRANT ACKNOWLEDGEMENT: The authors acknowledge the financial support from Indian Council of Medical Research (ICMR) under the Centre for Advanced Research (CAR) scheme.