IV fluids provide the basis of resuscitation in an acute care setting. Many patients will only require relatively low volumes while in the emergency department, but there are also a number of common pathologies that require a large volume resuscitation. While the proper volume of fluid for these common pathologies has been well established, whether or not the choice of any specific fluid is beneficial is still a much debated topic in both emergency medicine and the broader medical field.
The Case for Normal Saline (and unbalanced fluids)
It’s cheap! It’s easy! It’s available! Maybe this is oversimplifying, but in all honesty, this is the whole argument. Numerous studies in the past, including the huge BaSICS and SPLIT trials, have indicated that there is no morbidity/mortality benefit to using balanced solutions such as lactated ringers or plasmalyte in comparison to normal saline, and even the ones that have indicated benefit tend to show marginal benefits and weak evidence. Essentially, the idea is: why bother using more hospital resources to achieve the same goal?
The Case for Balanced Solutions
The case for the use of balanced solutions is really also quite simple. While a number of studies have shown no benefit to these solutions over normal saline, there also exist a number of studies which seem to indicate that the opposite is true. The SMART study, for example, showed a statistically significant reduction in composite outcomes when balanced crystalloids were compared to saline. A recent meta-analysis, Balanced Crystalloids Versus Saline in Critically Ill Adults: A Systematic Review and Meta-analysis published in the Annals of Pharmacotherapy in 2019, also showed a mortality benefit at 28-30 days. The benefit was established using 13 eligible studies selected from 673 considered studies, and found a mortality benefit among ICU patients (95% CI 0.75-0.99). As mentioned in the case for normal saline, the evidence in this and other studies like it is typically graded as weak for all endpoints, and the confidence interval approaches (even if it doesn’t include) 1. However, the point here is that low, questionable benefit does not equal no benefit. It is also important to note that, while a significant mortality benefit has not been clearly established, mortality is not the only important endpoint. Many studies cite a significant decrease in the need for renal replacement therapy secondary to the use of balanced solutions. We as physicians should be doing absolutely everything we can to maximize each and every patient’s chance at making a reasonable long-term recovery.
The PLUS Trial
Patient Comparison Between Groups Following Randomization
The PLUS trial was a randomized, double-blinded, controlled clinical trial which took place in 53 ICUs in Australia and New Zealand between 2017 and 2020, with results published in the New England Journal of Medicine in March of 2022. The trial randomized selected patients into two groups – one receiving plasmalyte and one receiving normal saline, and followed patients to a primary endpoint of all-cause mortality at 90 days. Final analysis included 5037 adult non-pregnant patients requiring at least 3 days of ICU stay who required fluid resuscitation and were not deemed to be at significant risk of cerebral edema.
Table Displaying PLUS Trial Outcomes
Analysis of the data collected in the study showed no statistical difference between normal saline and Plasmalyte-148 in the primary or any of the secondary endpoints. Mortality at 90 days was seen in 530 patients in each group (21.8% in the plasmalyte group and 22.0% in the normal saline group), with a 95% CI of -3.60 to 3.30. Similarly, results for secondary outcomes including new renal replacement therapy, rise in creatinine, and serious adverse reactions to the therapy did not approach statistical significance, seemingly indicating that all important long-term outcomes were essentially equal.
From the perspective of a United States emergency physician, it is very easy to call into question the external validity of the study. While the study was seemingly conducted well, the study population (primarily Australians and New Zealanders) as well as the care locale (ICU) does not necessarily apply well to US emergency departments. Additionally, the study used Plasmalyte-148 as its balanced solution, as opposed to lactated ringer’s, which is more common in the US. While very little theoretical difference exists between the two solutions, a study comparing normal saline and lactated ringer’s would likely be more applicable in the United States.
Does it matter?
Authors Conclusions
The PLUS trial provides another useful data point regarding large volume fluid resuscitation in critically ill patients. The trial moves the proverbial needle back in the direction of no statistical benefit in using balanced solutions, strengthening the argument that cheaper, more readily available normal saline can be used just as effectively. However, it is important not to lose sight of the whole body of research when looking at one study, where the possible advantage of balanced solutions is still very much up for debate. As such, barring a large and consistent body of evidence pointing one direction or the other in the coming years, individual emergency providers likely should not change their personal approach to fluids based off of this trial alone.
Written By: Nicholas Wolff, MD
Peer Reviewed and Edited by: Stevely Koshy, DO
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