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Hyperchloremic metabolic acidosis

Hyperchloremic metabolic acidosis is defined as metabolic dysfunction characterized by acidemia (pH < 7.35), a normal anion gap, and an elevated serum chloride. In anesthesia practice, it is often the result of fluid resuscitation with normal saline (NS)

Normal saline reduces the strong ion difference, which creates a more acidic pH. This is in contrast to the alkalinizing effects of a balanced crystalloid, such as Lactated Ringers (LR) or PlasmaLyte-A. The lactate in LR and acetate and gluconate in PlasmaLyte are rapidly metabolized, increasing the strong ion difference and leading to a more alkaline body pH. Normal saline also contains a much higher concentration of chlorine than other commonly used intravenous fluids.

Several clinical trials (both randomized controlled and observational) have linked normal saline administration to hyperchloremic metabolic acidosis and inferior outcomes, though the effect on clinically-relevant outcomes remains controversial. In renal failure patients undergoing renal transplant, NS has been found to worsen hyperkalemia and metabolic acidosis. In a large, unblinded, cluster randomized, intention-to-treat study of critically ill patients, balanced crystalloids (LR and PlasmaLyte-A) were associated with decreased rates of composite all-cause mortality, renal replacement therapy, or persistent renal dysfunction when compared to NS. In non-critically ill patients, another non-blinded randomized control study of balanced crystalloid vs NS showed no differences in mortality, but when NS was used, patients were more likely to experience major adverse kidney events.


  1. Kellum JA. Saline-induced hyperchloremic metabolic acidosis. Critical care medicine 2002; 30: 259-61. PubMed Link
  2. Morgan TJ. The Stewart approach--one clinician's perspective. Clin Biochem Rev 2009; 30: 41-54. PubMed Link
  3. Rizoli S. PlasmaLyte. The Journal of trauma 2011; 70: S17-8. PubMed Link
  4. Li H, Sun S-r, Yap JQ, Chen J-h, Qian Q. 0.9% saline is neither normal nor physiological. Journal of Zhejiang University Science B 2016; 17: 181-7. PubMed Link
  5. Wan S, Roberts MA, Mount P. Normal saline versus lower‐chloride solutions for kidney transplantation. Cochrane Database of Systematic Reviews 2016. PubMed Link

Other References

  1. Prough DS, Bidani A. Hyperchloremic metabolic acidosis is a predictable consequence of intraoperative infusion of 0.9% saline. Anesthesiology: The Journal of the American Society of Anesthesiologists 1999; 90: 1247-9. Link
  2. Semler MW, Self WH, Wanderer JP, et al. Balanced Crystalloids versus Saline in Critically Ill Adults. New England Journal of Medicine 2018; 378: 829-39. Link