Meta-analysis of high- versus low-chloride content in perioperative and critical care fluid resuscitation

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Abstract

Background

The objective of this systematic review and meta-analysis was to assess the relationship between the chloride content of intravenous resuscitation fluids and patient outcomes in the perioperative or intensive care setting.

Methods

Systematic searches were performed of PubMed/MEDLINE, Embase and Cochrane Library (CENTRAL) databases in accordance with PRISMA guidelines. Randomized clinical trials, controlled clinical trials and observational studies were included if they compared outcomes in acutely ill or surgical patients receiving either high-chloride (ion concentration greater than 111 mmol/l up to and including 154 mmol/l) or lower-chloride (concentration 111 mmol/l or less) crystalloids for resuscitation. Endpoints examined were mortality, measures of kidney function, serum chloride, hyperchloraemia/metabolic acidosis, blood transfusion volume, mechanical ventilation time, and length of hospital and intensive care unit stay. Risk ratios (RRs), mean differences (MDs) or standardized mean differences (SMDs) and confidence intervals were calculated using fixed-effect modelling.

Results

The search identified 21 studies involving 6253 patients. High-chloride fluids did not affect mortality but were associated with a significantly higher risk of acute kidney injury (RR 1·64, 95 per cent c.i. 1·27 to 2·13; P < 0·001) and hyperchloraemia/metabolic acidosis (RR 2·87, 1·95 to 4·21; P < 0·001). High-chloride fluids were also associated with greater serum chloride (MD 3·70 (95 per cent c.i. 3·36 to 4·04) mmol/l; P < 0·001), blood transfusion volume (SMD 0·35, 0·07 to 0·63; P = 0·014) and mechanical ventilation time (SMD 0·15, 0·08 to 0·23; P < 0·001). Sensitivity analyses excluding heavily weighted studies resulted in non-statistically significant effects for acute kidney injury and mechanical ventilation time.

Conclusion

A weak but significant association between higher chloride content fluids and unfavourable outcomes was found, but mortality was unaffected by chloride content.

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Most cited references 43

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Association between a chloride-liberal vs chloride-restrictive intravenous fluid administration strategy and kidney injury in critically ill adults.

Nor'azim Mohd Yunos, Rinaldo Bellomo, Colin Hegarty … (2012)

Administration of traditional chloride-liberal intravenous fluids may precipitate acute kidney injury (AKI). To assess the association of a chloride-restrictive (vs chloride-liberal) intravenous fluid strategy with AKI in critically ill patients. Prospective, open-label, sequential period pilot study of 760 patients admitted consecutively to the intensive care unit (ICU) during the control period (February 18 to August 17, 2008) compared with 773 patients admitted consecutively during the intervention period (February 18 to August 17, 2009) at a university-affiliated hospital in Melbourne, Australia. During the control period, patients received standard intravenous fluids. After a 6-month phase-out period (August 18, 2008, to February 17, 2009), any use of chloride-rich intravenous fluids (0.9% saline, 4% succinylated gelatin solution, or 4% albumin solution) was restricted to attending specialist approval only during the intervention period; patients instead received a lactated solution (Hartmann solution), a balanced solution (Plasma-Lyte 148), and chloride-poor 20% albumin. The primary outcomes included increase from baseline to peak creatinine level in the ICU and incidence of AKI according to the risk, injury, failure, loss, end-stage (RIFLE) classification. Secondary post hoc analysis outcomes included the need for renal replacement therapy (RRT), length of stay in ICU and hospital, and survival. RESULTS Chloride administration decreased by 144 504 mmol (from 694 to 496 mmol/patient) from the control period to the intervention period. Comparing the control period with the intervention period, the mean serum creatinine level increase while in the ICU was 22.6 μmol/L (95% CI, 17.5-27.7 μmol/L) vs 14.8 μmol/L (95% CI, 9.8-19.9 μmol/L) (P = .03), the incidence of injury and failure class of RIFLE-defined AKI was 14% (95% CI, 11%-16%; n = 105) vs 8.4% (95% CI, 6.4%-10%; n = 65) (P <.001), and the use of RRT was 10% (95% CI, 8.1%-12%; n = 78) vs 6.3% (95% CI, 4.6%-8.1%; n = 49) (P = .005). After adjustment for covariates, this association remained for incidence of injury and failure class of RIFLE-defined AKI (odds ratio, 0.52 [95% CI, 0.37-0.75]; P <.001) and use of RRT (odds ratio, 0.52 [95% CI, 0.33-0.81]; P = .004). There were no differences in hospital mortality, hospital or ICU length of stay, or need for RRT after hospital discharge. CONCLUSION The implementation of a chloride-restrictive strategy in a tertiary ICU was associated with a significant decrease in the incidence of AKI and use of RRT. Clinicaltrials.gov Identifier: NCT00885404.

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Efficacy of red blood cell transfusion in the critically ill: a systematic review of the literature.

Paul E Marik, Howard Corwin (2008)

Red blood cell (RBC) transfusions are common in intensive care unit, trauma, and surgical patients. However, the hematocrit that should be maintained in any particular patient because the risks of further transfusion of RBC outweigh the benefits remains unclear. A systematic review of the literature to determine the association between red blood cell transfusion, and morbidity and mortality in high-risk hospitalized patients. MEDLINE, Embase, Cochrane Register of Controlled Trials, and citation review of relevant primary and review articles. Cohort studies that assessed the independent effect of RBC transfusion on patient outcomes. From 571 articles screened, 45 met inclusion criteria and were included for data extraction. Forty-five studies including 272,596 were identified (the outcomes from one study were reported in four separate publications). The outcome measures were mortality, infections, multiorgan dysfunction syndrome, and acute respiratory distress syndrome. The overall risks vs. benefits of RBC transfusion on patient outcome in each study was classified as (i) risks outweigh benefits, (ii) neutral risk, and (iii) benefits outweigh risks. The odds ratio and 95% confidence interval for each outcome measure was recorded if available. The pooled odds ratios were determined using meta-analytic techniques. Forty-five observational studies with a median of 687 patients/study (range, 63-78,974) were analyzed. In 42 of the 45 studies the risks of RBC transfusion outweighed the benefits; the risk was neutral in two studies with the benefits outweighing the risks in a subgroup of a single study (elderly patients with an acute myocardial infarction and a hematocrit <30%). Seventeen of 18 studies, demonstrated that RBC transfusions were an independent predictor of death; the pooled odds ratio (12 studies) was 1.7 (95% confidence interval, 1.4-1.9). Twenty-two studies examined the association between RBC transfusion and nosocomial infection; in all these studies blood transfusion was an independent risk factor for infection. The pooled odds ratio (nine studies) for developing an infectious complication was 1.8 (95% confidence interval, 1.5-2.2). RBC transfusions similarly increased the risk of developing multi-organ dysfunction syndrome (three studies) and acute respiratory distress syndrome (six studies). The pooled odds ratio for developing acute respiratory distress syndrome was 2.5 (95% confidence interval, 1.6-3.3). Despite the inherent limitations in the analysis of cohort studies, our analysis suggests that in adult, intensive care unit, trauma, and surgical patients, RBC transfusions are associated with increased morbidity and mortality and therefore, current transfusion practices may require reevaluation. The risks and benefits of RBC transfusion should be assessed in every patient before transfusion.

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Resuscitation Fluids

John A Myburgh, Michael G Mythen (2013)

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Author and article information

Journal

Journal ID (nlm-ta): Br J Surg

Journal ID (iso-abbrev): Br J Surg

Journal ID (publisher-id): bjs

Title: The British Journal of Surgery

Publisher: John Wiley & Sons, Ltd (Chichester, UK )

ISSN (Print): 0007-1323

ISSN (Electronic): 1365-2168

Publication date (Print): January 2015

Publication date (Electronic): 30 October 2014

Volume: 102

Issue: 1

Pages: 24-36

Affiliations

[1 ]Department of Anesthesiology, Duke University Medical Center North Carolina, USA

[2 ]Anesthesiology Service, Durham VA Medical Center, Durham North Carolina, USA

[3 ]Boston Strategic Partners, Boston Massachusetts, USA

[4 ]Baxter Healthcare Corporation, Deerfield Illinois, USA

[5 ]Department of Anesthesiology, Vanderbilt University Medical Center, Nashville Tennessee, USA

Author notes

Correspondence to: Professor A. D. Shaw, Division of Cardiothoracic Anesthesiology, Vanderbilt University Medical Center, Nashville, Tennessee 37232–8274, USA (e-mail: andrew.shaw@ 123456vanderbilt.edu )

Article

DOI: 10.1002/bjs.9651

PMC ID: 4282059

PubMed ID: 25357011

SO-VID: 7aa56bf2-722a-4d86-ae0e-5d6ee24d5909

License:

This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

History

Date accepted : 14 August 2014

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Meta-analysis of high- versus low-chloride content in perioperative and critical care fluid resuscitation

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Most cited references 43

Association between a chloride-liberal vs chloride-restrictive intravenous fluid administration strategy and kidney injury in critically ill adults.

Efficacy of red blood cell transfusion in the critically ill: a systematic review of the literature.

Resuscitation Fluids

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Cited by 103

Most referenced authors 1,708