For ICU patients, the choice of normal saline versus buffered crystalloid IV fluid does not appear to impact the incidence of AKI when administered in low volumes.

Given concerns that the supraphysiologic chloride concentration of normal saline may induce renal vasoconstriction and thus contribute to AKI, this question was studied in SPLIT,¹ a prospective, blinded, double cross-over cluster randomized controlled trial conducted among 2278 ICU patients at four academic centers in New Zealand. Patients were randomized to normal saline versus a proprietary buffered crystalloid solution (Plasma-Lyte) during their ICU stay. Individuals receiving or likely to receive renal replacement therapy (RRT) within 6 hours of admission were excluded. The primary outcome was the development of
renal injury as defined by RIFLE (Risk, Injury, Failure, Loss, End-Stage Renal Disease) criteria: ≥2-fold increase in serum creatinine from baseline. Secondary outcomes included AKI by Kidney Disease: Improved Global Outcomes (KDIGO) criteria, RRT use, hospital mortality, and utilization measures (e.g., length-of-hospital, ICU stay).

The volume of fluid administered was comparable across groups (median 2000 mL for both groups; P = .63), with the majority of fluid administered in the first day of the ICU stay. No differences were observed in the development of AKI (9.6% in the buffered crystalloid group vs. 9.2% in the normal saline group, RR 1.04, 95% CI 0.80-1.36; P = .77), RRT use (3.3% in the buffered crystalloid group vs. 3.4%, in the normal saline group, RR 0.96, 95% CI 0.62-1.50; P = .91), or hospital mortality (7.6% in the buffered crystalloid group vs. 8.6%, in the normal saline group, RR 0.88, 95% CI, 0.67-1.17; P = .40). There were also no differences in ICU or hospital stays. Study caveats include large proportions of patients admitted to the ICU after cardiac surgery and confidence intervals too wide to definitively exclude meaningful clinical effects, which may not have been detected, given low volumes of administered fluids.

The association between type of fluid and renal dysfunction was further evaluated in the SMART trial,² a prospective cluster randomized trial of 15,000 ICU patients who were randomized to buffered crystalloid versus normal saline for initial resuscitation. The primary outcome was major adverse kidney events at 30 days (defined as the incidence of death, new RRT, or persistent elevation of creatinine over twice the baseline). Secondary outcomes included stage 2 or greater AKI (defined via KDIGO criteria).

The primary outcome occurred less frequently in patients receiving balanced crystalloid in the overall cohort (14.3% vs. 15.4%; P = .04), with differences driven by higher mortality among patients receiving normal saline, as well as in a prespecified subgroup of patients admitted with sepsis (33.8% vs. 38.9%; P = .01). Occurrence of stage 2 or greater AKI did not differ by type of fluid (10.7% vs. 11.5%; P = .09). As in SPLIT, the generalizability of findings from SMART is hindered by relatively low volume of administered fluids.

Nonetheless, consistent with the lack of clear impact of fluid type on AKI demonstrated by these studies, the 2016 Surviving Sepsis Campaign guidelines do not establish a preference between buffered crystalloid and normal saline during initial resuscitation.

Compared to other commonly used broad-spectrum antibiotic regimens, the combination of vancomycin and piperacillin/tazobactam is associated with the greatest risk of nephrotoxicity.

This question was addressed by a 2017 meta-analysis³ that incorporated 15 published studies and 17 abstracts encompassing 24,799 patients who received one of the following regimens: vancomycin alone, piperacillin/tazobactam alone, vancomycin plus piperacillin/tazobactam, or vancomycin plus cefepime or a carbapenem. The primary outcome was AKI (defined by each individual study but most commonly based on AKIN, RIFLE, or KDIGO guidelines).