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For clinicians

Approximately 2,500 non-newborn children die from septic shock each year in the US and thousands more die worldwide.  Despite widespread implementation of resuscitation protocols, contemporary studies still report 2-6% mortality for children with septic shock treated in the paediatric ED.

Crystalloids are the standard resuscitative fluid for septic shock. 0.9% Saline and Balanced Fluids (Plasma-Lyte 148, Ringer’s Lactate, and Hartmann’s Solution) are inexpensive, stable at room temperature, and nearly universally available with identical storage volumes and dosing strategies. Notably, both are also of proven clinical benefit in septic shock.  However, 0.9% Saline is used in 80-95% of cases of paediatric septic shock, despite data supporting that Balanced Fluid resuscitation may have superior efficacy and safety.

0.9% Saline contains a supra-physiologic concentration of chloride (1.5X that of plasma) and a strong ion difference (SID) of zero but is isotonic compared to extracellular fluid.  Balanced Fluids have less chloride, small amounts of additional electrolytes, and a higher SID due to the presence of an anion buffer.  The high chloride content and low SID of 0.9% Saline has been associated with acute kidney injury (AKI), acidemia, hyperkalaemia, vascular permeability, inflammation, coagulopathy, fluid overload, and death.

Balanced Fluids have demonstrated a 1-4% absolute mortality reduction and up to a 50% lower odds of dialysis compared to 0.9% Saline in observational and non-randomised interventional studies in adult sepsis. Nevertheless, because definitive conclusions have not been able to be drawn from existing observational and non-randomised studies, 0.9% Saline overwhelmingly remains the most commonly used fluid based on historical precedent (particularly in paediatrics).

In paediatrics, a recent propensity-matched analysis of 2,398 patients found a 2% lower mortality for children receiving Balanced Fluids versus 0.9% Saline.  Conversely, in a matched analysis of 4,234 children with septic shock from 382 hospitals in the Premier Healthcare Alliance, there was no superiority of Balanced Fluids over 0.9% Saline.  However, we noted that highly selective use of Balanced Fluids made it impossible to fully eliminate confounding factors and we concluded that these retrospective data are best used to support equipoise rather than declare 0.9% Saline and Balanced Fluids to be of equal benefit.  To definitively test the comparative effectiveness of 0.9% Saline versus Balanced Fluids, a well-powered randomised controlled trial (RCT) is necessary.