Abstract
BackgroundFluid resuscitation is frequently required for cardiac surgical patients admitted to the intensive care unit. The ideal fluid of choice in regard to efficacy and safety remains uncertain. Compared with crystalloid fluid, colloid fluid may result in less positive fluid balance. However, some synthetic colloids are associated with increased risk of acute kidney injury (AKI). This study compared the effects of succinylated gelatin (4%) (GEL) with compound sodium lactate (CSL) on urinary AKI biomarkers in patients after cardiac surgery.MethodsCardiac surgical patients who required an intravenous fluid bolus of at least 500 mL postoperatively were randomly allocated to receive GEL or CSL as the resuscitation fluid of choice for the subsequent 24 h. Primary outcomes were serial urinary neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C concentrations measured at baseline, 1 h, 5 h and 24 h after enrolment, with higher concentrations indicating greater kidney injury. Secondary biomarker outcomes included urinary clusterin, α1-microglobulin and F2-isoprostanes concentrations. Differences in change of biomarker concentration between the two groups over time were compared with mixed-effects regression models. Statistical significance was set at P < 0.05.ResultsForty cardiac surgical patients (n = 20 per group) with similar baseline characteristics were included. There was no significant difference in the median volume of fluid boluses administered over 24 h between the GEL (1250 mL, Q1–Q3 500–1750) and CSL group (1000 mL, Q1–Q3 500–1375) (P = 0.42). There was a significantly greater increase in urinary cystatin C (P < 0.001), clusterin (P < 0.001), α1-microglobulin (P < 0.001) and F2-isoprostanes (P = 0.020) concentrations over time in the GEL group, compared to the CSL group. Change in urinary NGAL concentration (P = 0.68) over time was not significantly different between the groups. The results were not modified by adjustment for either urinary osmolality or EuroSCORE II predicted risk of mortality.ConclusionsThis preliminary randomised controlled trial showed that use of succinylated gelatin (4%) for fluid resuscitation after cardiac surgery was associated with increased biomarker concentrations of renal tubular injury and dysfunction, compared to crystalloid fluid. These results generate concern that use of intravenous gelatin fluid may contribute to clinically relevant postoperative AKI.Trial registration ANZCTR.org.au, ACTRN12617001461381. Registered on 16th October, 2017, http://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=373619&isReview=true.
Highlights
Fluid resuscitation is frequently required for cardiac surgical patients admitted to the intensive care unit
Optimising cardiac preload with intravenous fluid boluses is frequently required in cardiac surgical patients admitted to the intensive care unit (ICU)
Animal models have shown that gelatin fluid causes renal tubular epithelial vacuolation, or vesiculation, and an increase in biomarkers of acute kidney injury (AKI) including neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C [12,13,14]
Summary
Trial design and participants The GELATIne Fluid and Acute Kidney Injury in Critical Illness (GELATI) Trial was an investigator-initiated, single-centre, randomised, open-label, parallel-arm designed clinical trial. After postoperative admission to the ICU, consented patients were screened again by a study investigator, in conjunction with the ICU clinician Eligible patients were those for whom the treating ICU clinician intended to administer an intravenous fluid bolus of 500 mL or more within 60 min, and in whom they believed there was equipoise in using either GEL or CSL. Extrapolating the means and standard deviations from the data provided in this study (AKI: 240 ± 76 ng/mL; no AKI: 140 ± 38 ng/mL), a sample size of 5 in each arm would give 80% power (α = 0.05) to detect a twofold difference in NGAL. A Bonferroni-corrected P value significance cut-off of < 0.01 for each linear mixed-effects model was further applied in order to reduce Type I error created by multiple biomarker analyses. Analyses were performed using Stata 14 (College Station, TX, USA) and SAS (SAS Institute, Cary, NC, USA) with significance set at two-sided P < 0.05, except for Bonferroni correction where stated
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
