Solutions And Major Adverse Renal Events Trial Research Articles

Saline versus Balanced Crystalloids for Adults with Aneurysmal Subarachnoid Hemorrhage: A Subgroup Analysis of the SMART Trial.

Whether the composition of intravenous crystalloid solutions affects outcomes in adults with aneurysmal subarachnoid hemorrhage (aSAH) remains unknown. Therefore, we determined whether the use of saline is associated with lower risk of disability and death in aSAH patients compared to balanced crystalloids. We conducted a post hoc subgroup analysis of the Isotonic Solutions and Major Adverse Renal Events Trial (SMART), a pragmatic, unblinded, cluster-randomized, multiple-crossover clinical trial that enrolled 15,802 adults between June 2015 and April 2017. We compared intravenous administration of saline to balanced crystalloids in consecutively enrolled aSAH patients aged 18 years or older whose ruptured aneurysm was procedurally secured at a single academic center in the United States. The primary outcome was the score on the modified Rankin scale (mRS, range, 0 [no symptoms] to 6 [death]) at 90 days obtained from a prospective institutional stroke registry. Secondary outcome included death by 90 days. Logistic or proportional odds regression models were used to test for between-group differences adjusted for age, hypertension, aSAH grade, and procedure type. Of the 79 aSAH patients procedurally treated during the SMART study period, 78 were enrolled (median age, 58 years; IQR, 49 to 64.5; 64% female), with 41 (53%) assigned to saline and 37 (47%) to balanced crystalloids. Plasma-Lyte was the primary balanced crystalloid used. Among 72 patients with 90-day mRS assessment, the adjusted common odds ratio, aOR, for mRS was 0.68 (95% CI, 0.28-1.63; P=0.39), with values less than 1.0 favoring saline. By 90 days, 2/39 patients (5%) in the saline group and 9/35 (26%) in the balanced-crystalloids group had died (aOR, 0.06; 95% CI, 0.00-0.50; P=0.02). Among procedurally treated aSAH patients, the risk of disability or death at 90 days did not significantly differ between saline and balanced crystalloids. Death occurred less frequently with saline than balanced crystalloids.

Balanced Crystalloid versus Saline in Adults with Traumatic Brain Injury: Secondary Analysis of a Clinical Trial.

Balanced crystalloids may improve outcomes compared with saline for some critically ill adults. Lower tonicity of balanced crystalloids could worsen cerebral edema in patients with intracranial pathology. The effect of balanced crystalloids versus saline on clinical outcomes in patients with traumatic brain injury (TBI) requires further study. We planned an a priori subgroup analysis of TBI patients enrolled in the pragmatic, cluster-randomized, multiple-crossover Isotonic Solutions and Major Adverse Renal Events Trial (SMART) (ClinicalTrials.gov: NCT02444988, NCT02547779). Primary outcome was 30-day in-hospital mortality. Secondary outcomes included hospital discharge disposition (home, facility, death). Regression models adjusted for pre-specified baseline covariates compared outcomes. TBI patients assigned to balanced crystalloids (n = 588) and saline (n = 569) had similar baseline characteristics including Injury Severity Score 19 (10); mean maximum head/neck Abbreviated Injury Score, 3.4 (1.0). Isotonic crystalloid volume administered between intensive care unit admission and first of hospital discharge or 30 days was 2037 (3470) mL and 1723 (2923) mL in the balanced crystalloids and saline groups, respectively (p = 0.18). During the study period, 94 (16%) and 82 (14%) patients (16%) died in the balanced crystalloid and saline groups, respectively (adjusted odds ratio [aOR], 1.03; 95% confidence interval [CI], 0.60 to 1.75; p = 0.913). Patients in the balanced crystalloid group were more likely to die or be discharged to another medical facility (aOR 1.38 [1.02-1.86]; p = 0.04). Overall, balanced crystalloids were associated with worse discharge disposition in critically injured patients with TBI compared with saline. The confidence intervals cannot exclude a clinically relevant increase in mortality when balanced crystalloids are used for patients with TBI.

LACTATED RINGER'S VS SALINE AMONG CRITICALLY ILL ADULTS WITH CIRRHOSIS: A SECONDARY ANALYSIS OF THE ISOTONIC SOLUTIONS AND MAJOR ADVERSE RENAL EVENTS TRIAL

TOPIC: Critical Care TYPE: Original Investigations PURPOSE: The use of balanced crystalloids has been suggested to improve clinical outcomes among critically ill adults, compared to saline. However, some balanced crystalloids, such as lactated Ringer’s, include a significant concentration of lactate that could adversely impact patients with cirrhosis, who have an impaired ability to metabolize lactate. The purpose of this study was to determine, among critically ill patients with cirrhosis, the effect of lactated Ringer's, compared to saline, on plasma lactate levels, cirrhosis-related complications, and clinical outcomes. METHODS: We performed a secondary analysis of Isotonic Solutions and Major Adverse Renal Events Trial (SMART) using data from patients admitted to the medical intensive care unit with cirrhosis. A diagnosis of cirrhosis was determined using a screening algorithm that employed ICD-10 codes, followed by manual confirmation through chart review. SMART was a cluster-randomized, multiple-crossover trial that compared balanced crystalloids to saline for intravenous fluid administration among critically ill adults. The primary outcome of the SMART trial and this secondary analysis was major adverse kidney events (MAKE30), a composite of new renal replacement therapy, persistent renal dysfunction, or death. Secondary outcomes included plasma lactate levels and cirrhosis-related complications such as new ascites, variceal and nonvariceal bleeding, hepatorenal syndrome Type 1, hepatic encephalopathy, spontaneous bacterial peritonitis, or cerebral edema. Outcomes were compared using Pearson Chi-square test for categorical variables and Mann-Whitney U test for continuous variables. RESULTS: Of the 15,802 patients enrolled in SMART, 375 patients were admitted to the medical intensive care unit with a diagnosis of cirrhosis. Among the 169 patients with cirrhosis in the lactated Ringer’s group, 47 (28%) had a major adverse kidney event, compared to 78 (38%) of the 206 patients in the saline group (P = 0.04). In the lactated Ringer’s group, 31 patients (18%) developed a cirrhosis-related complication versus 46 (22%) in the saline group (P = 0.34). There was no significant difference in lactate levels between the two groups (P = 0.74). CONCLUSIONS: Among critically ill adults with cirrhosis in the medical intensive care unit, the use of lactated Ringer’s resulted in a lower rate of the composite outcome of death from any cause, new renal-replacement therapy, or persistent renal dysfunction than the use of saline. There was no significant difference in cirrhosis-related complications or lactate levels between the two groups. CLINICAL IMPLICATIONS: Lactated Ringer’s appears to be associated with improved clinical outcomes compared to saline and may be the crystalloid of choice for many critically ill adults with cirrhosis. DISCLOSURES: No relevant relationships by Jonathan Casey, source=Web Response No relevant relationships by Taylor Coston, source=Web Response No relevant relationships by Muhammad Hashim Hayat, source=Web Response No relevant relationships by Michael Koenig, source=Web Response No relevant relationships by Rishi Naik, source=Web Response No relevant relationships by Matthew Semler, source=Web Response No relevant relationships by Li Wang, source=Web Response

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

BackgroundRecent 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.MethodsFrom 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.ResultsThe 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).ConclusionsIn 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 registrationClinicalTrials.gov number: NCT02444988. Date registered: May 15, 2015.

Balanced crystalloids versus saline in critically ill adults with low plasma bicarbonate: A secondary analysis of a clinical trial.

We aimed to determine if balanced crystalloids compared with saline improve outcomes in critically ill adults admitted with low plasma bicarbonate. We performed a secondary analysis of the Isotonic Solutions and Major Adverse Renal Events Trial (SMART). We included patients who presented to the Emergency Department with a first measured plasma bicarbonate less than 20mmol/L. Among these patients, we compared the effect of balanced crystalloid versus saline on the primary outcome of major adverse kidney events within 30days (MAKE30), defined as a composite of death, new renal-replacement therapy, or persistent renal dysfunction (final inpatient creatinine ≥200% baseline). Secondary outcomes included 30day in-hospital mortality, receipt of new RRT, persistent renal dysfunction, incident AKI, and vasopressor-free days. Among the 2029 patients with an initial plasma bicarbonate concentration<20mmol/L, there was no difference in the incidence of MAKE30 between those assigned to balanced crystalloid versus saline (21.8% vs 21.3%; P=0.93). Secondary outcomes were similar between the balanced crystalloid and saline groups. Among critically ill adults presenting to the Emergency Department, initial plasma bicarbonate concentration does not appear to be a useful marker to guide the selection of balanced crystalloid versus saline.

Clinical Effects of Balanced Crystalloids vs Saline in Adults With Diabetic Ketoacidosis

Saline (0.9% sodium chloride), the fluid most commonly used to treat diabetic ketoacidosis (DKA), can cause hyperchloremic metabolic acidosis. Balanced crystalloids, an alternative class of fluids for volume expansion, do not cause acidosis and, therefore, may lead to faster resolution of DKA than saline. To compare the clinical effects of balanced crystalloids with the clinical effects of saline for the acute treatment of adults with DKA. This study was a subgroup analysis of adults with DKA in 2 previously reported companion trials-Saline Against Lactated Ringer's or Plasma-Lyte in the Emergency Department (SALT-ED) and the Isotonic Solutions and Major Adverse Renal Events Trial (SMART). These trials, conducted between January 2016 and March 2017 in an academic medical center in the US, were pragmatic, multiple-crossover, cluster, randomized clinical trials comparing balanced crystalloids vs saline in emergency department (ED) and intensive care unit (ICU) patients. This study included adults who presented to the ED with DKA, defined as a clinical diagnosis of DKA, plasma glucose greater than 250 mg/dL, plasma bicarbonate less than or equal to 18 mmol/L, and anion gap greater than 10 mmol/L. Data analysis was performed from January to April 2020. Balanced crystalloids (clinician's choice of Ringer lactate solution or Plasma-Lyte A solution) vs saline for fluid administration in the ED and ICU according to the same cluster-randomized multiple-crossover schedule. The primary outcome was time between ED presentation and DKA resolution, as defined by American Diabetes Association criteria. The secondary outcome was time between initiation and discontinuation of continuous insulin infusion. Among 172 adults included in this secondary analysis of cluster trials, 94 were assigned to balanced crystalloids and 78 to saline. The median (interquartile range [IQR]) age was 29 (24-45) years, and 90 (52.3%) were women. The median (IQR) volume of isotonic fluid administered in the ED and ICU was 4478 (3000-6372) mL. Cumulative incidence analysis revealed shorter time to DKA resolution in the balanced crystalloids group (median time to resolution: 13.0 hours; IQR: 9.5-18.8 hours) than the saline group (median: 16.9 hours; IQR: 11.9-34.5 hours) (adjusted hazard ratio [aHR] = 1.68; 95% CI, 1.18-2.38; P = .004). Cumulative incidence analysis also revealed shorter time to insulin infusion discontinuation in the balanced crystalloids group (median: 9.8 hours; IQR: 5.1-17.0 hours) than the saline group (median: 13.4 hours; IQR: 11.0-17.9 hours) (aHR = 1.45; 95% CI, 1.03-2.03; P = .03). In this secondary analysis of 2 cluster randomized clinical trials, compared with saline, treatment with balanced crystalloids resulted in more rapid resolution of DKA, suggesting that balanced crystalloids may be preferred over saline for acute management of adults with DKA. ClinicalTrials.gov Identifiers: NCT02614040; NCT02444988.

Effect of Early Balanced Crystalloids Before ICU Admission on Sepsis Outcomes

Studies suggest that using balanced crystalloids (lactated Ringer's solution or Plasma-Lyte A) rather than saline (0.9%sodium chloride) may improve outcomes for patients with sepsis in the ED and ICU. What is the relative impact on sepsis outcomes of fluid composition during early resuscitation in the ED vsafter ICU admission? We performed a secondary analysis of the Isotonic Solutions and Major Adverse Renal Events Trial (SMART) data set, examining medical ICU patients with a diagnosis of sepsis (n= 1,641). SMART was a cluster-crossover trial comparing balanced crystalloids vssaline among critically ill adults. During the first 7months of SMART, fluid choice was controlled only in the ICU ("ICU-only period"). In the final 15months, fluid choice was coordinated between the ED and ICU ("ED and ICU period"). We performed logistic regression modeling for 30-day in-hospital mortality with an interaction term between randomized group (balanced crystalloids vssaline) and study period (ICU-only period vsED and ICU period). Three hundred and sixty-seven patients with sepsis were enrolled during the ICU-only period and 1,274 were enrolled during the ED and ICU period. Thirty-day in-hospital mortality occurred in 47 of 142 patients (33.1%) in the balanced crystalloid group vs74 of 225 patients (32.9%) in the saline group during the ICU-only period (OR, 1.14; 95%CI, 0.70-1.88) and in 170 of 682 patients (24.9%) in the balanced crystalloid group vs181 of 592 patients (30.6%) in the saline group in the ED and ICU period (OR, 0.68; 95%CI, 0.52-0.89) (P value for interaction, .07), consistent with a beneficial effect of balanced crystalloid primarily in the ED and ICU period. Among patients with sepsis, the effect of balanced crystalloids vssaline on mortality was greater among patients for whom fluid choice was controlled starting in the ED compared with starting in the ICU.

Time to First Culture Positivity Among Critically Ill Adults With Methicillin-Resistant Staphylococcus aureus Growth in Respiratory or Blood Cultures.

Background: For critically ill adults receiving empirical vancomycin, the duration of negative cultures after which vancomycin may be discontinued without risking subsequent growth of methicillin-resistant Staphylococcus aureus (MRSA) remains unknown. Objective: We hypothesized that if sputum cultures did not grow MRSA or blood cultures did not grow Gram-positive cocci on Gram stain by 48 hours, those cultures would not subsequently demonstrate MRSA. Methods: We conducted an ancillary analysis from patients enrolled in the Isotonic Solutions and Major Adverse Renal Events Trial (SMART). In this cohort of patients, we collected data on the time of either MRSA identification in culture or Gram-positive cocci identification on Gram stain and rate of vancomycin discontinuation. Results: Of the 15 802 patient admissions in the SMART study, 6553 (41.5%) received empirical intravenous vancomycin. Respiratory sputum cultures demonstrated MRSA during 178 patient admissions. Among respiratory cultures that would ultimately grow MRSA, 85% were positive within 48 hours, and 97% were positive within 72 hours. Cultures demonstrated MRSA bacteremia during 85 patient admissions. In 83 cases (97.6%) of MRSA bacteremia, Gram-positive cocci were identified within 48 hours after the culture was obtained. Conclusion and Relevance: This analysis of a large cohort of critically ill adults receiving empirical vancomycin found that Staphylococcus aureus was present in all but 15% of cases of MRSA-positive respiratory cultures after 48 hours, whereas Gram-positive cocci were identified within 48 hours during nearly all episodes of MRSA bacteremia. These findings may inform the timing of discontinuation of empirical vancomycin among critically ill adults.

Balanced crystalloids versus saline in the intensive care unit: study protocol for a cluster-randomized, multiple-crossover trial

BackgroundSaline, the intravenous fluid most commonly administered to critically ill adults, contains a high chloride content, which may be associated with acute kidney injury and death. Whether using balanced crystalloids rather than saline decreases the risk of acute kidney injury and death among critically ill adults remains unknown.MethodsThe Isotonic Solutions and Major Adverse Renal Events Trial (SMART) is a pragmatic, cluster-level allocation, cluster-level crossover trial being conducted between 1 June 2015 and 30 April 2017 in five intensive care units at Vanderbilt University Medical Center in Nashville, TN, USA. SMART compares saline (0.9% sodium chloride) with balanced crystalloids (clinician’s choice of lactated Ringer’s solution or Plasma-Lyte A®). Each intensive care unit is assigned to provide either saline or balanced crystalloids each month, with the assigned crystalloid alternating monthly over the course of the trial. All adults admitted to participating intensive care units during the study period are enrolled and followed until hospital discharge or 30 days after enrollment. The anticipated enrollment is approximately 14,000 patients. The primary outcome is Major Adverse Kidney Events within 30 days—the composite of in-hospital death, receipt of new renal replacement therapy, or persistent renal dysfunction (discharge creatinine ≥200% of baseline creatinine). Secondary clinical outcomes include in-hospital mortality, intensive care unit-free days, ventilator-free days, vasopressor-free days, and renal replacement therapy-free days. Secondary renal outcomes include new renal replacement therapy receipt, persistent renal dysfunction, and incidence of stage 2 or higher acute kidney injury.DiscussionThis ongoing pragmatic trial will provide the largest and most comprehensive comparison to date of clinical outcomes with saline versus balanced crystalloids among critically ill adults.Trial registrationFor logistical reasons, SMART was prospectively registered separately for the medical ICU (SMART-MED; ClinicalTrials.gov identifier: NCT02444988; registered on 11 May 2015; date of first patient enrollment: 1 June 2015) and the nonmedical ICUs (SMART-SURG; ClinicalTrials.gov identifier: NCT02547779; registered on 9 September 2015; date of first patient enrollment: 1 October 2015).