Bench-to-bedside review: Chloride in critical illness

Department of Intensive Care, Austin Hospital, Heidelberg, Melbourne, VIC 33084, Australia.
Critical care (London, England) (Impact Factor: 4.48). 07/2010; 14(4):226. DOI: 10.1186/cc9052
Source: PubMed


Chloride is the principal anion in the extracellular fluid and is the second main contributor to plasma tonicity. Its concentration is frequently abnormal in intensive care unit patients, often as a consequence of fluid therapy. Yet chloride has received less attention than any other ion in the critical care literature. New insights into its physiological roles have emerged together with progress in understanding the structures and functions of chloride channels. In clinical practice, interest in a physicochemical approach to acid-base physiology has directed renewed attention to chloride as a major determinant of acid-base status. It has also indirectly helped to generate interest in other possible effects of disorders of chloraemia. The present review summarizes key aspects of chloride physiology, including its channels, as well as the clinical relevance of disorders of chloraemia. The paper also highlights current knowledge on the impact of different types of intravenous fluids on chloride concentration and the potential effects of such changes on organ physiology. Finally, the review examines the potential intensive care unit practice implications of a better understanding of chloride.

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    • "Transport of chloride across cell membranes is facilitated by both voltage-gated and non-voltage-gated chloride channels [3]. Hyperchloremic metabolic acidosis, myocardial dysfunction, renal tubular defects and cystic fibrosis are among the many pathological conditions associated with disruption of chloride homeostasis [1] [3] [4]. "
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    ABSTRACT: We recently reported that, in a concentration-dependent manner, chloride protects hepatic glutathione transferase zeta 1 from inactivation by dichloroacetate, an investigational drug used in treating various acquired and congenital metabolic diseases. Despite the importance of chloride ions in normal physiology, and decades of study of chloride transport across membranes, the literature lacks information on chloride concentrations in animal tissues other than blood. In this study we measured chloride concentrations in human liver samples from male and female donors aged 1 day to 84 years (n = 97). Because glutathione transferase zeta 1 is present in cytosol and, to a lesser extent, in mitochondria, we measured chloride in these fractions by high-performance liquid chromatography analysis following conversion of the free chloride to pentafluorobenzylchloride. We found that chloride concentration decreased with age in hepatic cytosol but increased in liver mitochondria. In addition, chloride concentrations in cytosol, (105.2 ± 62.4 mM; range: 24.7 - 365.7 mM) were strikingly higher than those in mitochondria (4.2 ± 3.8 mM; range 0.9 - 22.2 mM). These results suggest a possible explanation for clinical observations seen in patients treated with dichloroacetate, whereby children metabolize the drug more rapidly than adults following repeated doses, and also provide information that may influence our understanding of normal liver physiology. Copyright © 2015. Published by Elsevier Inc.
    Biochemical and Biophysical Research Communications 03/2015; 459(3). DOI:10.1016/j.bbrc.2015.02.128 · 2.30 Impact Factor
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    • "Since kw is directly proportional to the product of [OH−] and hydrogen ion concentration [H+], decreases in [OH−] lead to increases in [H+] causing acidosis. Infusing 0.9% saline provides relatively more chloride, compared to sodium, resulting in a reduction in the strong ion difference which in turn lowers the pH, causing hyperchloremic acidosis [44]. "
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    ABSTRACT: Sepsis results in widespread inflammatory responses altering homeostasis. Associated circulatory abnormalities (peripheral vasodilation, intravascular volume depletion, increased cellular metabolism, and myocardial depression) lead to an imbalance between oxygen delivery and demand, triggering end organ injury and failure. Fluid resuscitation is a key part of treatment, but there is little agreement on choice, amount, and end points for fluid resuscitation. Over the past few years, the safety of some fluid preparations has been questioned. Our paper highlights current concerns, reviews the science behind current practices, and aims to clarify some of the controversies surrounding fluid resuscitation in sepsis.
    BioMed Research International 08/2014; 2014:984082. DOI:10.1155/2014/984082 · 3.17 Impact Factor
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    • "Although enough evidence exists to support the rational use of perioperative restrictive hydration, the choice of the optimal crystalloid solution to use remains unclear, and intravenous chloride administration is ubiquitous [4]. Many of the fluids used for intravenous hydration contain supraphysiological concentrations of chloride, which can induce hyperchloremia and metabolic acidosis, resulting in renal vasoconstriction and decreased renal function [5]. The effect of chloride on the kidney is of concern because acute kidney injury has been associated with high mortality, and may require invasive renal replacement therapy [6,7]. "
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    ABSTRACT: Background The optimal crystalloid solution to use perioperatively in patients undergoing open radical cystectomy remains unclear. Many of the fluids used for intravenous hydration contain supraphysiologic concentrations of chloride, which can induce hyperchloremia and metabolic acidosis, resulting in renal vasoconstriction and decreased renal function. In addition, patients receiving less fluid and less sodium show faster recovery of gastrointestinal (GI) function after colonic surgery. Methods and design This is an investigator-initiated, single-center, randomized, controlled, parallel group trial with assessor-blinded outcome assessment, in the Department of Urology, University Hospital Bern, Switzerland. The study will involve 44 patients with bladder cancer scheduled for radical cystectomy and urinary diversion. The primary outcome is the duration between the end of surgery and the return of the GI function (first defecation). Secondary outcomes are fluid balance (body weight difference postoperatively versus preoperatively) and the incidence of kidney function disorders according to the Risk – Injury – Failure – Loss - End Stage Renal Disease (RIFLE classification). An equal number of patients are allocated to receive Ringerfundin® solution or a glucose/potassium-based balanced crystalloid solution as baseline infusion during the entire time that intravenous administration of fluid is necessary during the perioperative period. The randomized crystalloid solution is infused at a rate of 1 ml/kg/h until the bladder has been removed, followed by 3 ml/kg/h until the end of surgery. Postoperative hydration is identical in both groups and consists of 1,500 ml of the randomized crystalloid solution per 24 hours. Postoperative patient care is identical in both groups; patients are allowed to drink clear fluids immediately after surgery, and liquid diet is started on postoperative day 1, as well as active mobilization and the use of chewing gum. Body weight is measured daily in the morning. Time of first flatus and first defecation are recorded. Discussion This trial assesses the benefits and harms of two different balanced crystalloid solutions for perioperative fluid management in patients undergoing open radical cystectomy with urinary diversion, with regard to return of GI function and effects on postoperative renal function. Trial registration Current Controlled Trials ISRCTN32976792 (registered on November 21 2013).
    Trials 07/2014; 15(1):276. DOI:10.1186/1745-6215-15-276 · 1.73 Impact Factor
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