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

Crystalloids are the standard resuscitative fluid for septic shock. NS and LR 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, NS is used in 80 to 95 percent of cases of pediatric septic shock, despite data supporting that LR resuscitation may have superior efficacy and safety.

NS contains a supra-physiologic concentration of chloride (1.5 times that of plasma) and a strong ion difference (SID) of zero, but is isotonic compared to extracellular fluid. Balanced solutions 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 NS has been associated with acute kidney injury (AKI), acidemia, hyperkalemia, vascular permeability, inflammation, coagulopathy, fluid overload, and death.

Buffered crystalloids, including LR, have demonstrated a 1 to 4 percent absolute mortality reduction and up to 50 percent lower odds of dialysis compared to NS in observational and non-randomized interventional studies in adult sepsis. Nevertheless, because definitive conclusions have not been able to be drawn from existing observational and non-randomized studies, NS overwhelmingly remains the most commonly used fluid based on historical precedent (particularly in pediatrics).

In pediatrics, a recent propensity-matched analysis of 2,398 patients in the PHIS database found a 2 percent lower mortality for children receiving LR versus NS.

Conversely, in a matched analysis of 4,234 children with septic shock from 382 hospitals in the Premier Healthcare Alliance, the authors could not demonstrate superiority of LR or NS. However, they noted that highly selective use of LR made it impossible to fully eliminate confounding factors, and they concluded that these retrospective data are best used to support equipoise rather than declare NS and LR to be of equal benefit. To definitively test the comparative effectiveness of NS versus LR, a well-powered randomized controlled trial (RCT) is necessary.

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