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Chloride-Liberal vs Chloride-Restrictive Fluid Strategies in the ICU

Greg Martin, MD

Apr 02, 2013

Association Between a Chloride-Liberal vs Chloride-Restrictive Intravenous Fluid Administration Strategy and Kidney Injury in Critically Ill Adults
Yunos NM, Bellomo R, Hegarty C, Story D, Ho L, Bailey M JAMA. 2012;308:1566-1572
Summary

Normal saline has 40% higher chloride than human plasma despite being roughly isotonic. Chloride has known effects on renal function (renal vasoconstriction and decrease in glomerular filtration) and acid-base balance ("bicarbonate dilutional acidosis" or "hyperchloremic metabolic acidosis").[1] Given the relative high frequency of acute kidney injury (AKI) in critically ill patients, it is conceivable that fluid administration may contribute to AKI development. The authors of this study sought to determine if a chloriderestrictive intravenous fluid strategy in critically ill patients would be associated with a decreased incidence and severity of AKI compared with a chloride-liberal intravenous strategy. This study was a prospective before/after design conducted during two 6-month periods with an intervening 6-month wash-out period. During the initial period, routine care included the administration of chloride-rich, normal saline solution. During the follow-up period, chloride-rich solutions were restricted and instead balanced solutions were available on the formulary (a lactated Hartmann solution and a balanced Plasma-Lyte solution). There were 760 patients in the first period and 773 patients in the later period. Chloride administration decreased from 694 to 496 mmol/patient on average, and the mean serum creatinine level change while in the intensive care unit (ICU) was less (+22.6 mol/L vs +14.8 mol/L, P = .03). The incidence of injury and failure class of RIFLE (risk, injury, failure, loss, end-stage kidney disease)-defined AKI was 14% vs 8.4% (P < .001) and the use of renal replacement therapy (RRT) was 10% vs 6.3% (P = .005). After adjustment for covariates, the association between chloride and both AKI and the need for RRT remained the same (both with an odds ratio of 0.52). There were no differences in hospital mortality, hospital or ICU length of stay, or need for RRT after hospital discharge. The authors concluded that the implementation of a chloride-restrictive strategy in the ICU was associated with a significant decrease in the incidence of AKI and use of RRT.

Viewpoint
Concern about chloride has existed for many years and has become particularly of interest as we have discerned more of its effects on renal physiology and clinical outcomes. Recently, studies have shown that chloride-rich fluids are associated with a prolonged time to first micturition and a decrease in urine output after major surgery.[2,3] In addition, a double-blind, randomized, controlled trial demonstrated that 2 L of normal saline given to normal human volunteers decreased renal cortical perfusion compared with a more balanced solution.[4] Because this study was conducted in a time-series intervention, it is impossible to know with confidence that chloride was the cause of the adverse consequences seen during the period in which chloride-rich fluids were used. It is certainly possible that other simultaneous changes in patients or management strategies could have contributed.
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However, the consistency and concordance of the data raise the likelihood of a real cause-effect relationship. If so, it would suggest at least a need to overhaul the way we use intravenous fluids to treat critically ill patients and possibly a need to return to the laboratory to develop more appropriate intravenous solutions. At the very least, this study reinforces that fluids, despite being prescribed almost daily in every hospitalized patient and generally ignored for their potential to cause problems, require much more thoughtful consideration about what, how, when, and how much they should be used in critically ill patients. Abstract
References

1. Yunos NM, Kim IB, Bellomo R, et al. The biochemical effects of restricting chloride-rich fluids in intensive care. Crit Care Med. 2011;39:2419-2424. 2. Williams EL, Hildebrand KL, McCormick SA, Bedel MJ. The effect of intravenous lactated Ringers solution versus 0.9% sodium chloride solution on serum osmolality in human volunteers. Anesth Analg. 1999;88:9991003. 3. Wilkes NJ, Woolf R, Mutch M, et al. The effects of balanced versus saline-based hetastarch and crystalloid solutions on acid-base and electrolyte status and gastric mucosal perfusion in elderly surgical patients. Anesth Analg. 2001;93:811-816. 4. Chowdhury AH, Cox EF, Francis ST, Lobo DN. A randomized, controlled, double-blind crossover study on the effects of 2-L infusions of 0.9% saline and Plasma-Lyte148 on renal blood flow velocity and renal cortical tissue perfusion in healthy volunteers. Ann Surg. 2012;256:18-24. Medscape Critical Care 2013 WebMD, LLC

Cite this article: Greg Martin. Chloride-Liberal vs Chloride-Restrictive Fluid Strategies in the ICU. Medscape. Apr 02, 2013.

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