Comparison of Acetate-based, Lactate-based and Multiple Electrolyte Solution versus saline (MeSLAc trial) in Dengue shock – A multicenter randomized controlled trial

Septic shock and dengue shock syndrome are important cause of mortality and morbidity in children. Fluid resuscitation is a key intervention in the management of septic shock and dengue shock syndrome. The purpose of fluid resuscitation is to replenish the intravascular volume in order to improve microcirculation and tissue perfusion, and maintain normal cardiac index.

The WHO guideline issued in 2009 recommends prompt administration of crystalloids (saline or Ringers lactate) in patients with dengue shock followed by sequential tapering of the crystalloid regimen. Saline has been routinely used as bolus therapy in severe dengue in the first hour as it is inexpensive and readily available with an efficacy similar to colloids with respect to shock resolution and mortality.

Normal saline has its own set of undesired physicochemical actions. It is slightly hypertonic to plasma and is both hypernatremic as well as hyperchloremic relative to plasma. Emerging data strongly indicate the increased incidence of hyperchloremic metabolic acidosis and consequently, acute kidney injury associated with infusion of boluses of normal saline in critically ill adults and children in shock. 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, lactated Ringer’s, Ringer’s acetate) 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 children, in a recently concluded large multicentre trial by our group comparing balanced crystalloids and saline, there was significant reduction in the incidence of AKI (21% vs. 39%) and other metabolic derangements like hyperchloremia and metabolic acidosis with the use of balanced crystalloids. Even though the fluids were mainly used as bolus therapy and not maintenance, the protective effect on kidneys and metabolic parameters was observed with the use of BC.

Among the balanced crystalloids, Ringers Lactate is widely used in dengue for ongoing fluid therapy although there is no robust evidence to support its use. There are different BCs available in the market now apart from Ringers lactate such as Ringers acetate and Multiple electrolyte solution. There are few studies comparing various types of colloids with saline and Ringers lactate but none comparing the various crystalloids alone. Our rationale for conducting the present study is guided by lack of pediatric data comparing various crystalloids in dengue shock.  It needs to be seen which of these crystalloids have a better metabolic profile and are reno protective as compared to saline in dengue.