Chloride Content of Fluids Used for Large-Volume Resuscitation Is Associated With Reduced Survival

Abstract

Objective We sought to investigate if the chloride content of fluids used in resuscitation was associated with short and long-term outcomes. Design We identified patients who received large volume fluid resuscitation (LVR), defined as greater than 60ml/kg over a 24 hour period. Chloride load was determined for each patient based on the chloride ion concentration of the fluids they received during LVR multiplied by the volume of fluids. We compared the development of hyperchloremic acidosis (HCA), AKI and survival among those with higher and lower chloride loads. Setting University Medical Center Patients Patients admitted to intensive care units (ICUs) from 2000–2008 Interventions None Main Results Among 4,710 patients receiving LVR HCA was documented in 523 (11%). Crude rates of HCA, AKI and hospital mortality all increased significantly as chloride load increased (p<0.001). However, chloride load was no longer associated with HCA or AKI after controlling for total fluids, age, and baseline severity. Conversely, each 100 mEq increase in chloride load was associated with a 5.5% increase in the hazard of death even after controlling for total fluid volume, age and severity (p=0.0015) over one year. Conclusions Chloride load is associated with significant adverse effects on survival out to one year even after controlling for total fluid load, age and baseline severity of illness. However the relationship between chloride load and development of HCA or AKI is less clear and further research is needed to elucidate the mechanisms underlying the adverse effects of chloride load on survival.

State of the art in fluid and volume therapy

“…At ISICEM 2016, Kellum presented results from a very large cohort of patients demonstrating that larger amounts of saline solution were associated with increased mortality compared to balanced solutions. These results were published as the current article was in press [34]. Contrary to widespread belief, the potassium content of balanced solutions does not cause hyperkalemia in renal insufficiency patients [35,36].…”

Balanced Crystalloids versus Saline in Critically Ill Adults

“…32 Studies involving healthy volunteers suggest saline may decrease renal perfusion through chloride-mediated renal vaso-constriction. 33 Observational studies involving critically ill adults have shown higher rates of acute kidney injury, 34 renal-replacement therapy, 5,10 and death 6,7,9,35 with saline than with balanced crystalloids, although results have been inconsistent. 36 Although underpowered for clinical outcomes, two recent pilot trials involving critically ill adults showed an absolute difference of 1 percentage point in mortality in favor of balanced crystalloids.…”

Another nail in the saline coffin

“…1 Numerous publications have documented an association between administration of hyperchloraemic crystalloids (mostly normal saline) and various adverse outcomes, including increased incidence of renal replacement therapy, 7,8 AKI, 9 kidney graft dysfunction, 7 and mortality. 8,10,11 The overall evidence clearly provides a harm signal associated with hyperchloraemic crystalloid solutions without a comparable benefit signal, and supports the use of balanced instead of hyperchloraemic crystalloid solutions in most acute care patients. 12 The low chloride load associated with the administration of small volumes of normal saline may be well handled by patients at low risk for AKI.…”