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

Abstract

BackgroundThe 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.MethodsSystematic 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.ResultsThe 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.ConclusionA weak but significant association between higher chloride content fluids and unfavourable outcomes was found, but mortality was unaffected by chloride content.

Acute kidney injury in the perioperative period and in intensive care units (excluding renal replacement therapies)

“…However, there is currently no real randomized controlled trial that confirms these data and results concerning mortality remain uncertain [82,85]. A recent meta-analysis including more than 6000 patients concluded that the use of crystalloids rich in chloride increases the risk of AKI and blood transfusion, without affecting mortality rates as compared with balanced solutions [86]. Finally, considering these data, we consider non-balanced solutions as potentially deleterious, especially for kidneys, and suggest minimizing their use, especially for large-volume resuscitation [87].…”

Balanced Crystalloids versus Saline in the Intensive Care Unit. The SALT Randomized Trial

“…The most commonly used crystalloid solution globally is 0.9% sodium chloride (saline) (2), with more than 200 million liters administered each year in the United States alone (1). However, the high chloride content of saline has been hypothesized to contribute to the development of acute kidney injury (AKI) in at-risk patients (3,4). Alternatives to saline include crystalloids with electrolyte compositions that more closely approximate that of plasma (balanced crystalloids), such as lactated Ringer's solution or Plasma-Lyte A.…”

“…Alternatives to saline include crystalloids with electrolyte compositions that more closely approximate that of plasma (balanced crystalloids), such as lactated Ringer's solution or Plasma-Lyte A. Emerging data suggest that the use of balanced crystalloids in critically ill adults may decrease rates of AKI (3,4), renal replacement therapy (RRT) (3,5), and death (6,7).…”

The good receipt for the kidneys: salty…but not too much

“…Toxicity, in general, is dose dependent and the consequences of the exposure depend on the susceptibility of the patients, as for all the other substances present in nature, water included (18). Serum chloride concentrations were not reported in the study by Young and colleagues (6). Therefore, it could be argued that the negative (mainly renal) effects of chloride loading might be more pronounced, and therefore easier to be demonstrated, in sicker patients, with more limited renal functional reserve, who receive larger chloride amounts with replacement fluids.…”

“…With this background, safety concerns arose about the use of saline in critically ill patients and other nonrandomized studies and meta-analyses seemed to confirm that high chloride content of saline may contribute to the development of acute kidney injury (AKI), increase the need for RRT, and even rise the mortality rate (6,7). In light of these effects on renal function, balanced solutions with lower, more physiologic chloride concentration, have been suggested (1,4 .…”