Christopher M. Palmer, MD
Brian M. Fuller, MD, MSCI
Washington University School of Medicine
It’s 2 AM during a busy ED shift on a Saturday night and you’ve identified a septic patient with pneumonia whose most recent blood pressure reading is 70/30 with a heart rate of 130. The nurse turns to you and asks, “Should I start a one liter normal saline bolus?” The answer in your mind has always been “yes” in this situation throughout your career, is there any reason to doubt that now?
While the debate rages on over crystalloid versus colloid, the new discussion over the past few years examining which crystalloid solution is best for resuscitation has drawn many people’s attention. Concerns related to normal saline leading to worse clinical outcomes such as acute kidney injury have led some to switch over to more balanced solutions like lactated Ringer’s or Plasma-Lyte for volume resuscitation. This practice pattern may not be cost effective or soundly evidence based.
Normal saline likely had its origin in the late 19th or early 20th century when it was being used to treat patients for cholera.1 Despite historical references reporting a more balanced composition of the “original” normal saline, the current version that is ubiquitous today as 0.9% saline has been used for over a century, saving countless lives as a resuscitation fluid. Normal saline does, however, provide a supraphysiologic chloride load and causes a non-gap metabolic acidosis utilizing the strong ion approach.2 There are several associations noted in the literature between normal saline and decreased renal perfusion leading to acute kidney injury (AKI), coagulopathy, immune dysfunction as well as other perceived negative consequences.. However, a direct causality has not been proven definitively.
Animal studies are among the most commonly cited head-to-head comparisons between normal saline and balanced solutions. In rat models of sepsis, infusing chloride-rich solutions suggests an increase in inflammatory cytokines and a decrease in renal blood flow.3-4 Zhou et al studied more clinically related variables in a rat model of sepsis looking at acute kidney injury and classifying it according to the RIFLE criteria.5 Plasma-Lyte compared to normal saline had less acute kidney injury and improved survival. Although thought-provoking, much of the literature supporting the use of balanced solutions involves animal models. Translating these outcomes into clinically relevant and definitive human trials has yet to be accomplished.
Human studies have been challenging to conduct in a randomized controlled fashion while eliminating crossover of different crystalloid solutions to properly study their effects. Most studies have been observational or retrospective and conducted in non-emergency department settings. Waters et al randomized patients undergoing abdominal aortic aneurysm repair to normal saline (n=33) or lactated Ringer’s (n=33) and found no differences in post-operative complications related to AKI, death, ICU length of stay, and time on the ventilator.6 There was a statistically significant difference in metabolic acidosis, which is not unexpected, and the normal saline group required more platelet transfusions. However, estimated blood loss and total packed red cells transfused were the same, which questions the clinical significance of this finding. A retrospective cohort study by Shaw et al examining patients treated with normal saline or Plasma-Lyte after undergoing major open abdominal surgery showed similar results.7 Despite using propensity matching due to significant differences in the cohorts (normal saline group being more sick, more emergent cases), there were no statistically significant differences between the groups in mortality, renal dysfunction, and other predefined endpoints. There were differences in infectious complications, bleeding, and electrolyte derangements, but this should be interpreted with caution given the nature of the study design.
One particular study that has received a lot of attention is the study by Yunos et al in JAMA from 2012.8 This was a prospective, open label before and after trial looking at AKI outcomes using a chloride-restrictive strategy in an ICU in Australia. They found a decreased incidence of AKI by RIFLE criteria as well as decreased need for renal replacement therapy (RRT) in the chloride-restrictive group. Despite these results, there are factors to consider with this trial. First, you cannot prove direct causality based on the trial design—one can only show association. Given that it was a bundled trial with fluids other than normal saline being restricted (including 4% albumin, and a gelatin solution) it is challenging to discern which change in fluid led to these results. Secondly, there is no data on the amount or which type of IV fluids the patients received prior to ICU arrival. If the quantity of IV fluids was not small this could certainly affect the results. Furthermore, even though the chloride-restrictive group required less RRT, long-term follow-up did not show any statistical differences in need for dialysis, and the trial was not designed to look for differences in mortality. In addition, before and after trials cannot take into account ICU practice changes and quality improvement that occur over time.
To say that normal saline should not be routinely used in the emergency department for volume resuscitation would be a significant change, and one that at least as of now requires further investigation before implementing. There are many instances in which normal saline should be the fluid of choice including in traumatic brain injury and for patients with metabolic alkalosis or hyponatremia. The debate parallels that of crystalloid versus colloid in terms of cost and truly relevant clinical outcomes, with the final answer still to be determined. In the emergency department, our true focus should be correcting life-threatening hypoperfusion, a much more significant acute problem than the chloride load received. Therefore, in the meantime, when the nurse asks me for a one liter bolus of normal saline for my patient in septic shock, I will respond, “Better make that two.”