Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure: The CITRIS-ALI Randomized Clinical Trial.

Importance: Experimental data suggest that intravenous vitamin C may attenuate inflammation and vascular injury associated with sepsis and acute respiratory distress syndrome (ARDS). Objective: To determine the effect of intravenous vitamin C infusion on organ failure scores and biological markers of inflammation and vascular injury in patients with sepsis and ARDS. Design, Setting, and Participants: The CITRIS-ALI trial was a randomized, double-blind, placebo-controlled, multicenter trial conducted in 7 medical intensive care units in the United States, enrolling patients (N = 167) with sepsis and ARDS present for less than 24 hours. The study was conducted from September 2014 to November 2017, and final follow-up was January 2018. Interventions: Patients were randomly assigned to receive intravenous infusion of vitamin C (50 mg/kg in dextrose 5% in water, n = 84) or placebo (dextrose 5% in water only, n = 83) every 6 hours for 96 hours. Main Outcomes and Measures: The primary outcomes were change in organ failure as assessed by a modified Sequential Organ Failure Assessment score (range, 0-20, with higher scores indicating more dysfunction) from baseline to 96 hours, and plasma biomarkers of inflammation (C-reactive protein levels) and vascular injury (thrombomodulin levels) measured at 0, 48, 96, and 168 hours. Results: Among 167 randomized patients (mean [SD] age, 54.8 years [16.7]; 90 men [54%]), 103 (62%) completed the study to day 60. There were no significant differences between the vitamin C and placebo groups in the primary end points of change in mean modified Sequential Organ Failure Assessment score from baseline to 96 hours (from 9.8 to 6.8 in the vitamin C group [3 points] and from 10.3 to 6.8 in the placebo group [3.5 points]; difference, -0.10; 95% CI, -1.23 to 1.03; P = .86) or in C-reactive protein levels (54.1 vs 46.1 µg/mL; difference, 7.94 µg/mL; 95% CI, -8.2 to 24.11; P = .33) and thrombomodulin levels (14.5 vs 13.8 ng/mL; difference, 0.69 ng/mL; 95% CI, -2.8 to 4.2; P = .70) at 168 hours. Conclusions and Relevance: In this preliminary study of patients with sepsis and ARDS, a 96-hour infusion of vitamin C compared with placebo did not significantly improve organ dysfunction scores or alter markers of inflammation and vascular injury. Further research is needed to evaluate the potential role of vitamin C for other outcomes in sepsis and ARDS. Trial Registration: ClinicalTrials.gov Identifier: NCT02106975.

Identifying High-Attenuating and Low-Attenuating Muscle Using Computerized Tomography and Exploring Its Impact on Physical Function and Muscle Strength in Obese Critically Ill Patients.

BACKGROUND: Computed tomography (CT) methods to estimate sarcopenia in obesity do not differentiate high-attenuating from low-attenuating muscle. The primary purpose of this study was to determine agreement between a CT method using general workstation-derived total and high-attenuating psoas muscle cross-sectional area (CSA) and a commercially available segmentation software-derived value. Secondary purpose was to explore the relationship between quantity of high-attenuating muscle to physical functioning in a pilot cohort of obese medical intensive care unit (MICU) patients. METHODS: We conducted a prospective observational cross-sectional study. CT images of obese MICU patients were reconstructed to calculate total psoas muscle, low-attenuating muscle, and high-attenuating muscle within the third lumbar psoas CSA using a CT method and commercial software. We performed blinded outcome measures of CSA, physical function, and muscle strength in 28 patients. RESULTS: Concordance correlation coefficient for identifying total psoas muscle was 0.96 (95% confidence interval: 0.93-0.98, P-value < 0.0001) between CT method and commercial software. There was moderate correlation between modified Medical Research Council muscle strength scores and high-attenuating psoas muscle CSA (r = 0.47, P = 0.01) and lower extremity strength and high-attenuating psoas muscle CSA (r = 0.40, P = 0.04). CONCLUSION: There was strong agreement between our CT method and a commercial software method to identify total psoas muscle CSA in obesity. Greater total high-attenuating psoas CSA moderately correlated with muscle strength. Additional studies using more objective markers of muscle strength validating these findings are needed.

Effects of intra-resuscitation antiarrhythmic administration on rearrest occurrence and intra-resuscitation ECG characteristics in the ROC ALPS trial.

BACKGROUND: Intra-resuscitation antiarrhythmic drugs may improve resuscitation outcomes, in part by avoiding rearrest, a condition associated with poor out-of-hospital cardiac arrest (OHCA) outcomes. However, antiarrhythmics may also alter defibrillation threshold. The objective of this study was to investigate the relationship between rearrest and intra-resuscitation antiarrhythmic drugs in the context of the Resuscitation Outcomes Consortium (ROC) amiodarone, lidocaine, and placebo (ALPS) trial. HYPOTHESIS: Rearrest rates would be lower in cases treated with amiodarone or lidocaine, versus saline placebo, prior to first return of spontaneous circulation (ROSC). We also hypothesized antiarrhythmic effects would be quantifiable through analysis of the prehospital electrocardiogram. METHODS: We conducted a secondary analysis of the ROC ALPS trial. Cases that first achieved prehospital ROSC after randomized administration of study drug were included in the analysis. Rearrest, defined as loss of pulses following ROSC, was ascertained from emergency medical services records. Rearrest rate was calculated overall, as well as by ALPS treatment group. Multivariable logistic regression models were constructed to assess the association between treatment group and rearrest, as well as rearrest and both survival to hospital discharge and survival with neurologic function. Amplitude spectrum area, median slope, and centroid frequency of the ventricular fibrillation (VF) ECG were calculated and compared across treatment groups. RESULTS: A total of 1144 (40.4%) cases with study drug prior to first ROSC were included. Rearrest rate was 44.0% overall; 42.9% for placebo, 45.7% for lidocaine, and 43.0% for amiodarone. In multivariable logistic regression models, ALPS treatment group was not associated with rearrest, though rearrest was associated with poor survival and neurologic outcomes. AMSA and median slope measures of the first available VF were associated with rearrest case status, while median slope and centroid frequency were associated with ALPS treatment group. CONCLUSION: Rearrest rates did not differ between antiarrhythmic and placebo treatment groups. ECG waveform characteristics were correlated with treatment group and rearrest. Rearrest was inversely associated with survival and neurologic outcomes.

Compression-to-ventilation ratio and incidence of rearrest-A secondary analysis of the ROC CCC trial.

BACKGROUND: Previous work has demonstrated that when out-of-hospital cardiac arrest (OHCA) patients achieve return of spontaneous circulation (ROSC), but subsequently have another cardiac arrest prior to hospital arrival (rearrest), the probability of survival to hospital discharge is significantly decreased. Additionally, few modifiable factors for rearrest are known. We sought to examine the association between rearrest and compression-to-ventilation ratio during cardiopulmonary resuscitation (CPR) and to confirm the association between rearrest and outcomes. HYPOTHESIS: Rearrest incidence would be similar between cases treated with 30:2 or continuous chest compression (CCC) CPR, but inversely related to survival and good neurological outcome. METHODS: We conducted a secondary analysis of a large randomized-controlled trial of CCC versus 30:2 CPR for the treatment of OHCA between 2011 and 2015 among 8 sites of the Resuscitation OUTCOMES: Consortium (ROC). Patients were randomized through an emergency medical services (EMS) agency-level cluster randomization design to receive either 30:2 or CCC CPR. Case data were derived from prehospital patient care reports, digital defibrillator files, and hospital records. The primary analysis was an as-treated comparison of the proportion of patients with a rearrest for patients who received 30:2 versus those who received CCC. In addition, we assessed the association between rearrest and both survival to hospital discharge and favorable neurological outcome (Modified Rankin Score≤3) in patients with and without ROSC upon ED arrival using multivariable logistic regression adjusting for age, sex, initial rhythm and measures of CPR quality. RESULTS: There were 14,109 analyzable cases that were determined to have definitively received either CCC or 30:2 CPR. Of these, 4713 had prehospital ROSC and 2040 (43.2%) had at least one rearrest. Incidence of rearrest was not significantly different between patients receiving CCC and 30:2 (44.1% vs 41.8%; adjusted OR: 1.01; 95% CI: 0.88, 1.16). Rearrest was significantly associated with lower survival (23.3% vs 36.9%; adjusted OR: 0.46; 95%CI: 0.36-0.51) and worse neurological outcome (19.4% vs 30.2%; adjusted OR: 0.46; 95%CI: 0.38, 0.55). CONCLUSION: Rearrest occurrence was not significantly different between patients receiving CCC and 30:2, and was inversely associated with survival to hospital discharge and MRS.