Fluid Resuscitation: Isotonic Saline vs Balanced Fluids


For years, it has been known that fluid resuscitation with isotonic saline causes metabolic derangements.1 A greater understanding of the physiochemical (Stewart) approach to acid-base has demonstrated that hyperchloremia drives the metabolic acidosis associated with large-volume resuscitation with isotonic saline. Dr. Scott Weingart popularized this concept among emergency physicians and resuscitationists in an amazing series of podcasts, and an excellent summary can be found on the Life in the Fast Lane blog. Increasing the serum chloride (by infusing isotonic saline) decreases the strong ion difference (SID; the difference between the cations and anions that dissociate completely in solution) and results in the release of protons to maintain electrical neutrality, thus lowering the pH.2

Current Research

Laboratory and animal studies have demonstrated the adverse effects of saline-induced hyperchloremic metabolic acidosis on blood pressure in sepsis, renal function, and hemostasis.1 While the saline-induced hyperchloremic metabolic acidosis has troubled (especially surgical) intensivists for some time, untoward patient-centered effects had not definitively been demonstrated until recently.1,2

Two relatively recent studies demonstrated increased morbidity and renal dysfunction among patients treated with isotonic saline as compared with balanced solutions (e.g.,Lactated Ringer’s or PlasmaLyte).3,4 The most notable of these found a decreased incidence of acute kidney injury and renal replacement therapy among ICU patients in Australia treated with a chloride-restrictive (i.e. less isotonic saline) fluid strategy.3

In the current study, researchers retrospectively looked at over 50,000 patients with ICD-code identified sepsis who were admitted to the ICU and on vasopressors. Because only a small subset of these patients were treated with balanced fluids (and this subset differed substantially from the larger group – in some ways, sicker; in other ways, less ill), they performed a propensity analysis comparing the approximately 3300 patients treated with balanced fluids with 3300 matched patients treated with isotonic saline. In this analysis, they found lower overall mortality (19 versus 22%) among the patients treated with balanced solution (in this study, predominantly Lactated Ringer’s). In addition, they observed progressively lower mortality among patients who received a greater proportion of balanced fluid, suggesting a dose response. Interestingly, there were no differences in acute kidney injury. Clearly, this study has some limitations given its retrospective nature, the use of ICD codes to define cases of sepsis, and differences between groups (mitigated somewhat by the propensity analysis).

Nonetheless, given the mounting data, emergency physicians and resuscitationists should consider the importance of choosing the right fluid for the right patient, like we would for any other medication. It’s also important to note that Lactated Ringer’s costs approximately twice as much as isotonic per liter bag (approximately $4 vs $2), but another recent study found that restricting the use of isotonic saline actually led to decreased overall fluid cost among ICU patients.6

Further Reading


  1. Yunos et al. “Bench-to-bedside review: Chloride in critical illness.” Critical Care. 2010 Crit Care. 2010; 14(4): 226.
  2. Kaplan et al. “Clinical Review: Acid-base abnormalities in the intensive care unit.” Critical Care. 2005; 9(2):198-203.
  3. Yunos et al. “Association between a chloride-liberal vs chloride-restrictive intravenous fluid administration strategy and kidney injury in critically ill adults.” JAMA. 2012 Oct 17; 308(15):1566-72.
  4. Shaw et al. “Major complications and mortality, and resource utilization, after open abdominal surgery: 0.9% saline versus PlasmaLyte”. Ann Surg. 2012; 255:821-825.
  5. Raghunathan et al. “Association between the choice of IV crystalloid and in-hospital mortality among critically ill adults with sepsis.” Critical Care Medicine. 2014. E-pub ahead of print.
  6. Yunos et al. “The biochemical effects of restricting chloride-rich fluids in intensive care” Critical Care Medicine. 2011; 39(11):2419-24.
Edited by Adaira Landry, MD

3 thoughts on “Fluid Resuscitation: Isotonic Saline vs Balanced Fluids”

  1. While I have some concerns about the retrospective nature of this particular study, the weight of evidence is slowly trending towards balanced fluids. This study probably isn’t practice changing on its own merits, it is yet another chink in the armor of “normal” saline. I encourage my residents to use LR in almost every situation (except elevated ICP issues and a few others).

  2. Great post, Nick. Clearly, there needs to be more study in how best to resuscitate in regards to fluids. I’ve definitely taken to using more LR (plasmalyte not available in my shop) in resuscitation. Some combination of normal saline, LR and bicarbonate solution may be best. We just don’t know. It seems reasonable, based on what we know, to use more LR.

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