The Impact of Normal Saline or Balanced Crystalloid on Plasma Chloride Concentration and Acute Kidney Injury in Patients With Predicted Severe Acute Pancreatitis: Protocol of a Phase II, Multicenter, Stepped-Wedge, Cluster-Randomized, Controlled Trial

Introduction/aim: The supraphysiologic chloride concentration of normal saline may contribute to acute kidney injury (AKI). Balanced crystalloids can decrease chloride concentration and AKI in critically ill patients. We aim to test the hypothesis that, in patients with predicted severe acute pancreatitis (pSAP), compared with saline, fluid therapy with balanced crystalloids will decrease plasma chloride concentration.Methods/Design: This is a multicenter, stepped-wedge, cluster-randomized, controlled trial. All eligible patients presenting to the 11 participating sites across China during the study period will be recruited. All sites will use saline for the first month and sequentially change to balanced crystalloids at the pre-determined and randomly allocated time point. The primary endpoint is the plasma chloride concentration on day 3 of enrollment. Secondary endpoints will include major adverse kidney events on hospital discharge or day 30 (MAKE 30) and free and alive days to day 30 for intensive care admission, invasive ventilation, vasopressors, and renal replacement therapy. Additional endpoints include daily serum chloride and sequential organ failure assessment (SOFA) score over the first seven days of enrollment.Discussion: This study will provide data to define the impact of normal saline vs. balanced crystalloids on plasma chloride concentration and clinical outcomes in pSAP patients. It will also provide the necessary data to power future large-scale randomized trials relating to fluid therapy.Ethics and Dissemination: This study was approved by the ethics committee of Jinling Hospital, Nanjing University (2020NZKY-015-01) and all the participating sites. The results of this trial will be disseminated in peer-reviewed journals and at scientific conferences.Trial registration: The trial has been registered at the Chinese Clinical Trials Registry (ChiCTR2100044432).

Effect of balanced crystalloids versus saline on urinary biomarkers of acute kidney injury in critically ill adults

Background Recent trials have suggested use of balanced crystalloids may decrease the incidence of major adverse kidney events compared to saline in critically ill adults. The effect of crystalloid composition on biomarkers of early acute kidney injury remains unknown. Methods From February 15 to July 15, 2016, we conducted an ancillary study to the Isotonic Solutions and Major Adverse Renal Events Trial (SMART) comparing the effect of balanced crystalloids versus saline on urinary levels of neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) among 261 consecutively-enrolled critically ill adults admitted from the emergency department to the medical ICU. After informed consent, we collected urine 36 ± 12 h after hospital admission and measured NGAL and KIM-1 levels using commercially available ELISAs. Levels of NGAL and KIM-1 at 36 ± 12 h were compared between patients assigned to balanced crystalloids versus saline using a Mann-Whitney U test. Results The 131 patients (50.2%) assigned to the balanced crystalloid group and the 130 patients (49.8%) assigned to the saline group were similar at baseline. Urinary NGAL levels were significantly lower in the balanced crystalloid group (median, 39.4 ng/mg [IQR 9.9 to 133.2]) compared with the saline group (median, 64.4 ng/mg [IQR 27.6 to 339.9]) (P < 0.001). Urinary KIM-1 levels did not significantly differ between the balanced crystalloid group (median, 2.7 ng/mg [IQR 1.5 to 4.9]) and the saline group (median, 2.4 ng/mg [IQR 1.3 to 5.0]) (P = 0.36). Conclusions In this ancillary analysis of a clinical trial comparing balanced crystalloids to saline among critically ill adults, balanced crystalloids were associated with lower urinary concentrations of NGAL and similar urinary concentrations of KIM-1, compared with saline. These results suggest only a modest reduction in early biomarkers of acute kidney injury with use of balanced crystalloids compared with saline. Trial registration ClinicalTrials.gov number: NCT02444988. Date registered: May 15, 2015.

State of the evidence for emergency medical services care of adult patients with sepsis: an analysis of research from the Prehospital Evidence-based Practice

Introduction The Prehospital Evidence-Based Practice (PEP) program is an online, freely accessible, continuously updated emergency medical services evidence repository. This PEP summary describes the research evidence for the identification and management of adult patients with sepsis or septic shock. Methods A systematic search of the literature on sepsis or septic shock was conducted. Studies were scored by trained appraisers on a three-point level of evidence scale (based on study design and quality) and a three-point direction of evidence scale (supportive, neutral or opposing findings based on the studies’ primary outcome for each intervention). Results One hundred forty-three studies (80 existing and 63 new) were included for 16 interventions listed in PEP for adult patients with sepsis. The evidence matrix rank for supported interventions (n=16) were supportive-high quality (n=2, 12.5%) for crystalloid infusion and vasopressors, supportive-moderate quality (n=8, 50%) for identification tools, pre-notification, point-of-care lactate, titrated oxygen, temperature monitoring and balanced crystalloids. The benefit of pre-hospital antibiotics, colloids, Trendelenburg position and early goal-directed therapy remain inconclusive with a neutral direction of evidence. There is moderate level evidence opposing the use of high flow oxygen. Conclusion Several standard treatments are well supported by the evidence including fluid resuscitation, using balanced crystalloids, vasopressors and titrating oxygen. Tools for identifying and guiding treatment are also supported (eg. pre-notification, temperature monitoring and lactate). The evidence for antibiotic use is inconclusive. This PEP state of the evidence analysis can be used to guide selection of appropriate pre-hospital therapies during the development of pre-hospital protocols or clinical practice guidelines.