How Much Fluid to Administer

The next question, however, having made the choice of fluid, remains precisely how much to give. This is the question addressed by the Conservative Versus Liberal Approach to Fluid Therapy of Septic Shock in Intensive Care (CLASSIC) trial.³ In this trial, patients admitted to the ICU were randomized to standard care or a conservative strategy in which 250- or 500-mL fluid boluses were permitted only for objective evidence of ongoing and worsening severe hypoperfusion. The difference in fluid administered in the ICU despite these restrictions, however, was only about 1.5 liters over the first five days. Ultimately, the authors could not identify any specific advantage of one treatment strategy versus another.

Tucked within these data, however, were some interesting secondary analyses with potential relevance to the emergency physician. On average, patients had already received three liters of fluid prior to enrollment in the trial. However, approximately one-third of their cohort had received less than 30 mL/kg of fluid upon enrollment, while the remainder had received greater than that amount. In patients having received the lowest fluid resuscitation per body weight there was a 5.3 percent mortality advantage to allowing the standard liberal strategy in the ICU, while those aggressively resuscitated prior to enrollment displayed a 2.1 percent advantage to a restrictive strategy. Neither of these advantages were statistically significant, and might have been affected by multiple potential confounding biases, but it does fit with a reassuring narrative: the fluid resuscitation commonplace in the emergency department may indeed be the necessary first step. Further data relevant specifically to early fluid administration is likely to be available from the Crystalloid Liberal or Vasopressors Early Resuscitation in Sepsis (CLOVERS) trial, which has seen early termination of enrollment in May 2022.

It isn‘t all bad news for 0.9 percent saline, however, as the evidence works in its favor in the Resuscitation with Blood Products in Patients with Trauma-Related Haemorrhagic Shock Receiving Prehospital Care (RePHILL) trial.⁴ This is a randomized controlled trial in which trauma patients with hypotension thought to be related to traumatic hemorrhage received either prehospital blood and plasma or 0.9 percent sodium chloride. The total volume of fluids to be administered in the trial protocol was either two units of packed red blood cells combined with two units of lyophilized plasma or one liter of sodium chloride.

In this physician-led prehospital service in the United Kingdom, the authors were able to enroll 432 patients prior to the onset of the SARS-CoV-2 (COVID-19) global pandemic. The enrolled population was primarily young and male, and the majority of patients were included as a result of severe injuries sustained in motor vehicle collisions. The primary outcome was a composite of mortality and inability to clear lactate within two hours of randomization, but the more likely relevant patient-oriented outcome is mortality alone. In this quite severely injured cohort with prehospital hypotension, overall mortality was 43 percent in those receiving blood products and 45 percent in those receiving saline.