Study Design Summary: Single center study of 15,802 ICU patients treated with either saline or balanced crystalloid, with a primary outcome of major adverse kidney event at 30 days or hospital discharge, whichever came first.
Notes: The intervention group (balanced crystalloid) vs saline group were very well balanced in their baseline characteristics. The primary outcome was a composite outcome called “major adverse kidney events” which included death, new RRT, or persistent renal dysfunction (defined as CR greater than or equal to 200% of patient’s baseline Cr) at 30 days or hospital discharge, which ever came first. The study needed 14,000 patients for a 90% power and it had well over this number at 15,802 patients total.
Just like in SALT-ED, fluid administration for patients was coordinated between ER and ICU (or ER and ward in the case of SALT-ED), and was assigned based on the month. Roughly 5% of patients in each group were given both saline and balanced crystalloid due to being in the ICU over the change in month.
The cumulative volume of fluids given to patients in the two groups over the first 7 days was relatively low at roughly around 2-2.5 liters. There was a measurable difference in chloride concentration between the two groups, higher in the saline group, as well as the bicarb concentration, higher in the balanced crystalloid group.
The composite primary outcome was statistically signifiant between the intervention and saline group with 14.3% vs 15.4% for p=0.04. Though none of the individual outcomes were significant on their own; death 10.3% vs 11.1% p=0.06, new RRT 2.5% vs 2.9% p=0.08, persistent renal dysfunction 6.4% vs 6.6% p=0.60. None of the secondary outcomes were statistically significant.
While the primary outcome is a composite outcome and none of the individual outcomes were significant on their own, it is an important outcome and likely more clinically significant than any of the individual outcomes. Lumping death with new RRT though is a bit of a stretch. The study had well over the number of patients needed to be appropriately powered, thus the statistical significance of the study is likely true. The authors note that their conclusion means that using balanced crystalloid instead of saline would result in preventing 1 out of every 94 patients from their primary outcome, which is respectable. They had preplanned subgroup analysis that were not shown in the paper’s tables but discussed, and they note that the difference between the groups were larger when more fluid was administered.
A sited relative contraindication to using balanced crystalloid was hyperkalemia and brain injury, and so clinicians could opt to not follow protocol for these patients. With that taken into account, potshot analysis showed that the difference between the intervention and saline groups were equal or favored balanced crystalloid in all subgroups of which ICU type the patient was in (MICU, SICU, burn ICU…), balanced fluids were better in patients with sepsis and patients without TBI but also better in the neurosurgical ICU. This NICU vs TBI contrast maybe due to the allowance for deviation from protocol for TBI patients. The intervention and saline group were equal for the primary outcome in all levels of kidney function, though favoring balanced crystalloid, except if patients had previous RRT then balanced crystalloid was favored.
According the First 10 in EM, the fragility index of this study is 0, meaning it is not clinically significant and the p value for the primary outcome is actually 0.06. Most other FOAM sites agreed with the authors’ conclusion.
Of note, no APACHE II scores are given.
Study Conclusion: Among critically ill adults, use of balanced crystalloid resulted in lower rate of major adverse kidney events than use of saline.
Fusion Beat Bottom Line Impression: Use of balanced crystalloid does result in less composite death, RRT and persistent renal dysfunction in critically ill patients as compared to saline.
A Fusion Beat 