One of the growing debates in the critical care literature is the role of chloride-rich and chloride-poor crystalloid resuscitation fluids in critical care. This month, The Unit sponsors a point/counter-point on the use of saline as a resuscitation fluid in ED.
Michael C. Scott, MD
Michael E. Winters, MD, FACEP
University of Maryland School of Medicine
Since 1832, when Dr. Thomas Latta administered “two drachms of muriate and two scruples of carbonate, of soda, in sixty ounces of water” to a patient in hypovolemic shock from cholera, the administration of intravenous fluids has been the cornerstone of resuscitation of critically ill patients. Intravenous fluids are often given to critically ill patients to augment cardiac output and improve tissue perfusion and oxygenation. It is clear that the timing and dosing of their administration are critical to patient outcomes. In fact, indiscriminate and excessive volume administration (“salt water drowning”) is associated with increases in patient morbidity and mortality rates.1 Emerging evidence suggests that the specific type of intravenous fluid also could affect patient outcomes. The adage “There’s very little damage you can do with a few liters of normal saline” no longer holds water.
Quite simply, normal saline never has been, and never will be, a true physiologic solution. It contains 154 mEq/L of sodium and 154 mEq/L of chloride, with an osmolarity of 308 mOsm/L.2 With a strong ion difference of zero (Na2+ – Cl-), normal saline reliably produces, or worsens, metabolic acidosis. In addition, the chloride concentration of normal saline is approximately 40% higher than the chloride concentration of plasma. This supraphysiologic amount increases systemic inflammation and can cause renal vasoconstriction and decrease the glomerular filtration rate.3-7 In a prospective, open-label study of more than 1,500 patients at a single center in Australia, Yunos et al demonstrated a lower increase in creatinine and a lower rate of kidney injury by restricting the use of normal saline and other high-chloride-containing intravenous fluids. In a large, observational study of patients undergoing major abdominal surgery, Shaw et al demonstrated that those who received normal saline had a greater need for renal replacement therapy than did patients who received PlasmaLyte solution.8 In addition to its negative effects on the kidney, hyperchloremia can adversely affect the pulmonary, splanchnic, circulatory, and coagulation systems. Perhaps most importantly, hyperchloremia from fluid resuscitation could worsen patient outcome. In a recent retrospective review of more than 109,000 patients, Shaw et al demonstrated a lower in-hospital mortality rate among patients who received intravenous fluids with lower chloride loads.9
Balanced solutions such as Plasma-Lyte, lactated Ringer’s, and Hartmann’s solution have less of an adverse effect on acid‒base equilibrium than does normal saline. Through the addition of organic anions (eg, lactate, acetate, gluconate, citrate), balanced solutions contain significantly lower concentrations of chloride than does normal saline. Trials comparing balanced solutions with normal saline have demonstrated lower chloride concentrations, higher bicarbonate concentrations, and faster resolution of base deficit and correction of arterial pH.10-12 In fact, recent data suggest that balanced solutions might be superior to normal saline for fluid resuscitation. In a retrospective cohort from a large database, Raghunathan et al evaluated the association of balanced solutions versus higher chloride solutions on the in-hospital mortality rate among patients with sepsis.13 Almost 3,400 patients in this study received a balanced solution (most commonly lactated Ringer’s) as a component of their overall fluid volume. The in-hospital mortality rate was lower among patients who received a balanced solution than among those who received only saline. Based on a systematic review and network meta-analysis, Rochwerg et al reported that balanced solutions might be superior to saline for fluid resuscitation in sepsis.14
Admittedly, no large, randomized, double-blind study has compared normal saline with any of the balanced solutions. Furthermore, much of the literature on intravenous fluid administration and the harms of normal saline do not directly evaluate emergency department patients. Regardless, we know that interventions in the early stages of critical illness often have profound effects on patient morbidity and mortality. Critically ill patients deserve the same level and focus of care regardless of their location within the hospital. The signal from the literature regarding the negative physiologic and potential outcome effects of normal saline is becoming stronger. In short, there is nothing normal about normal saline. Stop using this fluid on a routine basis for volume resuscitation of critically ill patients in the emergency department.
The authors would like to acknowledge Linda Kesselring for editorial assistance.