The topic of normal saline vs. lactated ringers can spark fierce debate, but are we asking ourselves the wrong question?

An Age-Old Debate

Few topics in the world of resuscitation and critical care generate as much controversy as the discussion over which is the “superior” intravenous fluid: normal saline (NS) or lactated ringer’s (LR). I myself, a budding intensivist and self-professed LR acolyte, have often overzealously argued in favor of my fluid of choice.

The SMART trial in 2018 helped fuel the fire, showing a benefit of balanced solution (Plasma-Lyte or LR) over normal saline in critically ill patients with respect to a composite outcome of death from any cause, new renal-replacement therapy, or persistent renal dysfunction at 30 days.¹ However within the last year two new trials (PLUS and BASICS) have been published that throw water on the results of SMART. Both trials were overwhelmingly negative, revealing no difference between balanced crystalloids and NS in their primary outcomes.^2,3

Suboptimal Choices

While there may still be situations which call for one fluid in particular (BASICS showed a clear advantage of normal saline in TBI patients, and much literature points to LR as the fluid of choice in DKA management), I think a more fundamental issue lies beneath this debate and is rarely addressed. While LR is commonly lauded as more physiologic, I think we have to consider that even it is far from “ideal.”

There is in fact no ideal “physiologic” IV fluid available to us. Comparing both NS and LR to physiologic conditions reveals lackluster results: while NS certainly comes out the loser (composed of only supraphysiological concentrations of sodium and chloride), LR compared to serum plasma is actually hypotonic, hyponatremic and hypocalcemic, and contains no magnesium.⁴ 

Fluid “Resuscitation”: A Misnomer?

With this in mind, perhaps we should ask ourselves if perhaps all IV fluids have long been overrated, or at the very least over-utilized. While we reflexively reach for a bag of crystalloid when a patient presents with undifferentiated shock, a basic understanding of physiology would tell us that this would only be effective in cases of hypovolemic shock when a patient presents with a fluid deficit, whether that be from GI losses, insensible losses, or poor PO intake. While many critically ill patients will present with some degree of dehydration, more often than not they will require more than IV fluids to resolve the underlying cause of their shock.

While hypovolemic shock from dehydration is appropriately treated with IV fluids, giving crystalloid to patients with hypovolemic shock from hemorrhage can be absolutely detrimental. An important trial from 1993 showed that pre-hospital fluids administered to hypotensive patients with penetrating thoracic trauma increased mortality compared to no fluids given, with the group receiving fluids getting just 800 milliliters more than the control on average.⁵ This finding has since been confirmed in numerous studies, and the standard practice to limit crystalloid in favor of early administration of blood in hypotensive trauma patients.6 Diluting the little blood hemorrhaging patients have with salt water only worsens their ability to deliver oxygen to tissue and clot off the source of bleeding. 

Sepsis is the 10th leading cause of death, and fluid administration has long been a cornerstone of the management of septic patients. The landmark 2001 study by Emanuel Rivers on early goal directed therapy (EGDT) featured fluid resuscitation as a central feature of a bundle of interventions, and patients in the EGDT group received on average almost five liters of fluids in the first six hours of treatment.7 EGDT has since been “debunked” (although I think it is important to recognize the attention that the Rivers’s original trial brought toward improving the quality of sepsis care) in several studies.^8-10 What’s more, fluid overload has consistently been associated with increased mortality in critically ill patients with sepsis.^11-12 In light of these revelations, the Surviving Sepsis Campaign in 2021 changed its recommendation to give 30 ml/kg of fluids to sepsis patients with hypo-perfusion to a suggestion, acknowledging that the evidence for doing so is of low quality.¹³

Emerging literature shows benefit from starting vasopressors early in septic shock.^14-15 This makes physiologic sense. Septic shock is a form of distributive shock, not hypovolemic. No amount of fluid will resolve it without first clamping down the leaky blood vessels that result from the systemic inflammatory response triggered by the underlying infection.

Perhaps the most provocative evidence that calls into question the utility of IV fluids is found in the FEAST trial. Published in 2011 in the New England Journal of Medicine, the study compared a 20–40 mL/kg fluid bolus to no bolus in the treatment of critically ill children with signs of impaired perfusion in resource-limited settings in sub-Saharan Africa.¹⁶ Each group received antibiotics, maintenance IV fluids, and supportive care as needed. The primary outcome was mortality at 48 hours.

The study was actually stopped early when the intervention group that received the IV fluid bolus showed an increased mortality of 45 percent. While it is important to recognize the limitations of this study (most of the children presented with malaria, which may predispose the patients to harm from a fluid bolus, and the study was conducted in hospitals without ICU-level capabilities) the results are nonetheless both thought-provoking and unsettling.

Water, Water, Everywhere…

Despite their limitations, IV fluids are here to stay, but the next time you consider another bolus to determine whether or not your patient is “fluid-responsive,” perhaps you should take a step back and ask yourself if they actually instead need blood, vasopressors, or another intervention in the next step of their care. When it comes to fluid “resuscitation,” it turns out that less is indeed more. 

Dr. Cunningham is a third-year emergency medicine resident at Maricopa Medical Center and soon-to-be critical care fellow at Stanford Medical Center in Standford, Calif.

References

1. Semler MW, Self WH, Wanderer JP, et al. Balanced Crystalloids versus Saline in Critically Ill Adults. N Engl J Med. 2018;378(9):829-839. doi:10.1056/NEJMoa1711584.
2. Finfer S, Micallef S, Hammond N, et al. Balanced Multielectrolyte Solution versus Saline in Critically Ill Adults. N Engl J Med. 2022;386(9):815-826. doi:10.1056/NEJMoa2114464.
3. Zampieri FG, Machado FR, Biondi RS, et al. Effect of Intravenous Fluid Treatment With a Balanced Solution vs 0.9% Saline Solution on Mortality in Critically Ill Patients: The BaSICS Randomized Clinical Trial [published online ahead of print, 2021 Aug 10]. JAMA. 2021;326(9):1-12. doi:10.1001/jama.2021.11684.
4. Myburgh JA, Mythen MG. Resuscitation fluids. N Engl J Med. 2013;369(13):1243-1251. doi:10.1056/NEJMra1208627.
5. Bickell WH, Wall MJ Jr, Pepe PE, et al. Immediate versus delayed fluid resuscitation for hypotensive patients with penetrating torso injuries. N Engl J Med. 1994;331(17):1105-1109. doi:10.1056/NEJM199410273311701.
6. Lier H, Fries D. Emergency Blood Transfusion for Trauma and Perioperative Resuscitation: Standard of Care. Transfus Med Hemother. 2021;48(6):366-376. Published 2021 Oct 29. doi:10.1159/000519696.
7. Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001;345(19):1368-1377. doi:10.1056/NEJMoa010307.
8. Peake SL, Delaney A, Bailey M, et al. Goal-directed resuscitation for patients with early septic shock. N Engl J Med 2014;371:1496-506. 10.1056/NEJMoa1404380.
9. Mouncey PR, Osborn TM, Power GS, et al. Trial of early, goal-directed resuscitation for septic shock. N Engl J Med 2015;372:1301-11. 10.1056/NEJMoa1500896.
10. ProCESS Investigators , Yealy DM, Kellum JA, et al. A Randomized Trial of Protocol-Based Care for Early Septic Shock. N Engl J Med 2014;370:1683-93. 10.1056/NEJMoa1401602.
11. Sadaka F, Juarez M, Naydenov S, O‘Brien J. Fluid resuscitation in septic shock: the effect of increasing fluid balance on mortality. J Intensive Care Med. 2014;29(4):213-217. doi:10.1177/0885066613478899.
12. Boyd JH, Forbes J, Nakada TA, Walley KR, Russell JA. Fluid resuscitation in septic shock: a positive fluid balance and elevated central venous pressure are associated with increased mortality. Crit Care Med. 2011;39(2):259-265. doi:10.1097/CCM.0b013e3181feeb15.
13. Evans L, Rhodes A, Alhazzani W, et al. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021. Intensive Care Med. 2021;47(11):1181-1247. doi:10.1007/s00134-021-06506-y.
14. Permpikul C, Tongyoo S, Viarasilpa T, Trainarongsakul T, Chakorn T, Udompanturak S. Early Use of Norepinephrine in Septic Shock Resuscitation (CENSER). A Randomized Trial. Am J Respir Crit Care Med. 2019;199(9):1097-1105. doi:10.1164/rccm.201806-1034OC.
15. Bai X, Yu W, Ji W, et al. Early versus delayed administration of norepinephrine in patients with septic shock. Crit Care. 2014;18(5):532. Published 2014 Oct 3. doi:10.1186/s13054-014-0532-y.
16. Ford SR, Visram A. Mortality after fluid bolus in African children with sepsis. N Engl J Med. 2011;365(14):1348-1353. doi:10.1056/NEJMc1108712.