Reply to Swenson: Balanced Crystalloid versus Saline Solution in Critically Ill Patients: Is Chloride the Villain?

From the Authors:

We appreciate the thoughtful letter from Dr. Swenson regarding our recent concise clinical review on balanced crystalloid solutions (1). Dr. Swenson notes that much of the recent research comparing balanced crystalloids with saline has examined clinical outcomes (2), leaving major questions about mechanism unanswered. Balanced crystalloids and saline differ in their concentrations of chloride, organic anions (e.g., lactate and acetate), potassium, and divalent cations (e.g., magnesium and calcium). Although saline-induced hyperchloremic metabolic acidosis has been the focus of most preclinical research comparing these solutions (3), which differences in composition cause the observed differences in clinical outcomes remains unknown.

We agree with Dr. Swenson’s interest in mechanism. We would be thrilled if ancillary studies to ongoing trials (4, 5), research in animal models, and future trials examining sodium bicarbonate in acute illness and comparing different formulations of balanced crystalloids could delineate the respective contributions of each cation and anion to organ function and clinical outcomes. Someday the evidence may allow a verdict on whether the chloride anion is individually guilty of worsening patient outcomes, a contributing accomplice, or an innocent bystander.

Mechanism aside, for the 30 million patients treated with intravenous fluid each year, we believe the weight of the current evidence favors balanced crystalloids over saline. Saline’s innocence can no longer be presumed. The burden of proof now lies with those who would defend saline’s safety.