Septic shock is a serious and concerning cause of morbidity and mortality in children. Fluid resuscitation is an important step in the early management of septic shock in children. Crystalloid solutions are recommended for initial fluid resuscitation;  saline (0.9% sodium chloride) is commonly used, as it is inexpensive and readily available with an efficacy similar to colloids with respect to shock resolution and mortality. Balanced crystalloids (BC)  have a composition resembling plasma with a lower chloride concentration than saline. Some balanced crystalloids (e.g., multiple electrolytes solution (MES) also known as Plasma-Lyte A) have been reported to be associated with decreased risk of metabolic disturbances such as hyperchloremia and metabolic acidosis as compared to saline in children from diverse patient settings. In a recently published systematic review in children, the authors tried to compare the effect of balanced versus unbalanced fluid on change in bicarbonate or pH within 24 hours in critically ill children. In the meta-analysis of 3 RCTs, the authors observed higher change in serum bicarbonate levels and pH level in the first 24 hours with balanced crystalloids.  However, the 3 studies pooled for the primary outcomes included children with gastroenteritis and compared Ringers Lactate with Saline or Plasmalyte with Saline.  The authors highlighted the need for larger pediatric trials to answer the clinically relevant questions pertaining to choice of fluid in critically ill children.

In a previous study by our group of 708 children, we observed lower risk of new or progressive AKI in the first 7 days after fluid resuscitation with the use of MES as compared to saline in children with septic shock. With this study we gained experience in conducting multicentre RCT addressing fluid resuscitation in children. However, in this study we compared only one type of balanced crystalloid with saline i.e. MES. The cost of MES is twice that of saline while that of Ringers lactate is similar to that of saline. Not only the cost, there are important differences between the different types of crystalloids available in the market. There are no studies comparing Ringers Acetate and Lactate amongst each other or with MES on metabolic parameters or AKI in children. The limited data available comparing these solutions in adult patients have found Ringers’ Acetate to have the advantage of extrahepatic metabolism with less oxygen demand compared to Lactate which is heavily dependent on liver for its metabolism. Using solutions in large volumes and/or rapid speed as is used in resuscitation may cause added burden on the already compromised liver and worsen its functions.  Multiorgan dysfunction carries high mortality and morbidity in children with septic shock. Finally, most studies comparing balanced crystalloids have evaluated the acid-base status and electrolyte abnormalities resulting from their infusion and there is a dearth of information on the impact of using various balanced crystalloids on patient-important outcomes such as mortality, hospital length of stay, and receipt or duration of life support and therefore the need for this study.

The Pediatric Surviving Sepsis Campaign (SSC) recently issued a recommendation to use balanced crystalloids, rather than saline, for the initial resuscitation in septic shock. This suggestion, however, was based on evidence of limited quality, prompting the SSC committee to comment in their report that the ‘type of fluid’ to be used for resuscitation should be a research priority.  The findings of this study would help address this research priority and provide important data with regard to choice of fluid in children with septic shock between various types of crystalloids. We plan to enrol 408 children (102 per group) in the study to address this important research question.