Administration of fluid bolus over 15-20 minutes versus 5-10 minutes in children with septic shock in the ‘first hour’ of resuscitation– A Randomized Controlled Trial

Septic shock in children is most commonly associated with severe hypovolemia. Studies on pediatric septic shock have shown that early and aggressive resuscitation including administration of fluid volumes up to 60ml/kg in the first hour of resuscitation results in 9 fold reduction in mortality in these children. Therefore the management guidelines for septic shock in children advocates aggressive fluid resuscitation of up to 60 ml/kg as boluses of 20ml/kg each over a total duration of 20-30 minutes to achieve desired heart rates, and blood pressure. Although advocated, this duration of administration may not be practical in all types of setups for 2 important reasons a) due to logistics of administering such large volumes in 5-10 minutes (thin veins) and b) due to the fear of fluid overload as most of these facilities may not be equipped to ventilate these children in case fluid overload develops. Not surprisingly therefore, the average time duration reported in pediatric literature till date of administering each bolus has ranged from anywhere between 15-30 minutes per bolus to 45-60 minutes per bolus. Given this background, we decided to compare these two time durations- that is the one proposed (5-10minutes) versus the one commonly used (15-20 minutes) of individual bolus administration on immediate effects such as proportion developing fluid overload and/or proportion requiring mechanical ventilation and critical outcomes such as mortality. There is a plan to enroll 220 subjects over a period of 2 years. The bolus will be administered by manual push in the 5-10 minutes group and by infusion pump timed for 15 minutes in the 15 minute group soon after enrollment. This study will provide an answer to the duration of administration of each fluid bolus in children with septic shock in the first hour of resuscitation. If proven to be superior or similar in terms of primary outcomes the 15-20 minutes time duration may be recommended instead of the 5-10 minutes duration for administration of each fluid bolus thereby ensuring better compliance with the guidelines and improved outcomes in children with septic shock.

In August 2014, we performed interim analysis after enrolling ~ 50% of patients (n=96) and found that fewer children receiving fluid boluses over 15-20 minutes required mechanical ventilation than those receiving boluses over 5-10 minutes. Due to safety concerns in the group receiving boluses over 5-10 minutes we had to stop the study as per the mandate of the IEC.