In this episode, I’ll discuss whether the composition of the first few liters of resuscitation fluid is most important for patients with sepsis.
Despite the biological plausibility that using balanced crystalloid solutions for resuscitation in sepsis over normal saline should result in better outcomes due to less hyperchloremic acidosis, results from trials looking at this issue have been inconsistent.
However, a recent editorial published in Critical Care Medicine offers a potential explanation for why trial results using balanced crystalloids have not consistently demonstrated a clinical benefit. The editorial was written in response to a secondary analysis of the randomized controlled Crystalloid Liberal or Vasopressors Early Resuscitation in Sepsis (CLOVERS) trial.
The original CLOVERS trial examined a restrictive vs liberal fluid strategy in early treatment of sepsis. The restrictive fluid strategy prioritized vasopressors and lower intravenous fluid volumes and the liberal fluid strategy prioritized higher volumes of intravenous fluids before vasopressor use. the trial found no difference between groups but an interesting aspect of the design led researchers to perform the re-analysis: To meet the criteria for sepsis-induced hypotension refractory to initial treatment, patients were first given 1 to 3 liters of intravenous fluid before randomization.
The secondary analysis split patients into two groups based on what fluid they received prior to randomization – balanced crystalloids vs normal saline. The authors found that death before discharge home by day 90 occurred 12.2% of patients in the balanced crystalloid group and 15.9% in the normal saline group, resulting in a statistically significant adjusted hazard ratio of 0.71. Furthermore, patients receiving balanced crystalloids had significantly more hospital-free days at 28 days than those receiving normal saline.
The editorialist points out that the secondary analysis of the CLOVERS trial provides an important signal in favor of early use of balanced crystalloid solutions that matches what at least two other studies (1, 2) have found. They state:
This difference is potentially significant as it may provide insight into the importance of the initial fluid resuscitation choice regardless of subsequent fluid selection or strategies through the trial enrollment period. It suggests that targeting balanced solutions from the prehospital or early hospital setting may have an early mortality benefit that persists long-term, regardless of fluid choices later in care…At this point, the investigations comparing balanced and 0.9% NS solutions in early fluid resuscitation are consistent enough to indicate that the composition of these first few liters makes a clinical difference in many patients. As a result, balanced crystalloid solutions should continue to be considered early in patients with sepsis-induced hypotension.
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