UMEM Educational Pearls

Balanced crystalloids:  So Hot Right Now

Brief Read:

The use of balanced crystalloids has been the subject of several RCTs with conflicting results. However, recent post-hoc and meta-analyses of these same trials suggest that balanced crystalloids may be the best choice initially. See nice summary at: https://www.atsjournals.org/doi/full/10.1164/rccm.202203-0611ED.

 

Long Read:

While I had thought about summarizing the recently published data on EPR from the CRITICAL trial in Japan, JournalFeed today covered the recent post-hoc analysis of the BaSICS trial originally seen on CC Pearls back in August 31, 2021 by Dr. Sjelocha. This subject is as important as it is confusing. There are large and relatively well done RCTs that point in opposite and sometimes strange directions. However, as the authors of the SMART trial summarized, even an NNT of 94 in this population could be a huge number of patients!

The use of balanced crystalloids (e.g. Plasmalyte) has been the subject of several previous RCTs (SMART and SALT-ED) with conflicting results. Recently the PLUS RCT and BaSICS trials seemed to push the literature towards to concluding there was no difference, but there are caveats for both trials now in the literature:

• While the PLUS RCT found no difference, a concurrently published meta-analysis seemed to conclude the opposite (https://doi.org/10.1056/EVIDoa2100010).
• Further confusing the issue, apost-hoc analysis of the similarly negative BaSICS RCTcame out in March 2022 suggesting that overall there was a benefit for patients who received balanced crystalloid when they hit the door, but that those who arrived with sepsis and were unplanned admissions benefited most!
  • The authors note that their original analysis is likely affected by the fact that 68% of the original BaSICS study population had already received balanced fluid, saline, or both before randomization.

This paper makes a nice point which I think is important for us in the ED: the evidence is suggesting a commonality in many critical care concepts, which is that decisions made in early resuscitation may have an outsized impact on patient outcomes. However, this will not be the last we hear on this subject, but for the time being, I agree with Dr. Lacy that “It might not matter as much what fluids you choose when patients are on their third, fourth, or fifth liter of fluid – but especially for the sickest patients, it sure seems like the initial resuscitation fluid makes a difference.”

 

BaSICS post hoc: https://www.atsjournals.org/doi/full/10.1164/rccm.202111-2484OC (See JournalFeed post from today and the accompanying editorial)

• 68% (10,520) of enrolled patients had balanced crystalloids (3,202), saline (2,096), or both (1,862) prior to enrollment
• “There was a high probability that balanced solution use was associated with lower 90-day mortality in patients who exclusively received balanced solutions before study enrollment.”

BASICS: https://jamanetwork.com/journals/jama/fullarticle/2783039 (summary stolen from Dr. Sjeklocha’s  August 31, 2022 CC Pearl)

• No difference in 90 days mortality (P-Lyte 26.4% v NS 27.2, aHR p=0.47), AKI or RRT out to 7-days, or in duration of MV, ICU LOS or hospital LOS
• Signal for possible harm in TBI population with balanced crystalloids compared to normal saline

PLUS: https://www.nejm.org/doi/10.1056/NEJMoa2114464

• 5,037 critically ill patients
• No statistically significant difference in the primary outcome of death within 90 days of randomization in the BMES group compared to the saline group (21.8% vs 22.0%, 95% CI -3.6 to 3.3; P=0.90).
• Subgroup analyses were conducted based on illness severity before randomization, presence of sepsis, kidney injury, age, sex, and ICU admission after surgery, and did not show a significant difference between the two groups.

SMART: https://www.nejm.org/doi/full/10.1056/nejmoa1711584

• 7942 patients in the balanced-crystalloids group,
• Balanced: 1139 (14.3%) versus Saline: 1211 of 7860 patients (15.4%) had a major adverse kidney event in the saline group (marginal odds ratio, 0.91; 95% confidence interval [CI], 0.84 to 0.99; conditional odds ratio, 0.90; 95% CI, 0.82 to 0.99; P=0.04).
• “Our results suggest that the use of balanced crystalloids rather than saline might prevent 1 patient among every 94 patients admitted to an ICU from the need for new renal-replacement therapy, from persistent renal dysfunction, or from death.”

SALT-ED: https://www.nejm.org/doi/full/10.1056/nejmoa1711586

• 13,347 patients
• The number of hospital-free days did not differ between the balanced-crystalloids and saline groups (median, 25 days in each group; adj. OR, 0.98; 95% CI, 0.92 to 1.04; P=0.41).
• Balanced crystalloids resulted in a lower incidence of major adverse kidney events within 30 days than saline (4.7% vs. 5.6%; adjusted odds ratio, 0.82; 95% CI, 0.70 to 0.95; P=0.01).

https://journalfeed.org/article-a-day/2022/back-to-basics-first-fluid-choice-matters-a-reanalysis-of-the-basics-rct/