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 PARTICIPANTSThe 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 MEASURESThe 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 RELEVANCEIn 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.

Background Acute kidney injury (AKI) is the most frequent extra-pulmonary organ failure in acute respiratory distress syndrome (ARDS). The objective of this study was to assess the factors associated with the development and severity of AKI in patients with ARDS. Methods This is a retrospective cohort study of ARDS patients without acute or chronic kidney disease prior to the onset of ARDS over a 7-year period (2010–2017). AKI and severity of AKI were defined according to the Kidney Disease Improving Global Outcomes 2012 guidelines. Results Of the 634 ARDS patients, 357 patients met study criteria. A total of 244 (68.3%) patients developed AKI after ARDS onset: 60 (24.6%) had stage I AKI, 66 (27%) had stage II AKI, and 118 (48.4%) had stage III AKI. The median time of AKI onset for stage I AKI was 2 days (interquartile range, 1.5–5.5) while stage II and III AKI was 4 days. On multivariable analysis, factors associated with development of AKI were age [subdistribution hazard ratio (SHR) 1.01, 95% confidence interval (CI) 1.00–1.02], SOFA score (SHR 1.16, 95%CI 1.12–1.21), a history of diabetes mellitus (DM) (SHR 1.42, 95%CI 1.07–1.89), and arterial pH on day 1 of ARDS (SHR per 0.1 units decrease was 1.18, 95%CI 1.05–1.32). In severity of AKI, stage I AKI was associated with age (SHR 1.03, 95%CI 1.01–1.05) and serum bicarbonate on day 1 of ARDS (SHR 1.07, 95%CI 1.02–1.13). Stage II AKI was associated with age (SHR 1.03, 95%CI 1.01–1.05), serum bicarbonate on day 1 (SHR 1.12, 95%CI 1.06–1.18), SOFA score (SHR 1.19, 95%CI 1.10–1.30), history of heart failure (SHR 3.71, 95%CI 1.63–8.46), and peak airway pressure (SHR 1.04, 95%CI 1.00–1.07). Stage III AKI was associated with a higher BMI (SHR 1.02, 95%CI 1.00–1.03), a history of DM (SHR 1.79, 95%CI 1.18–2.72), SOFA score (SHR 1.29, 95%CI 1.22–1.36), and arterial pH on day 1 (SHR per 0.1 units decrease was 1.25, 95%CI 1.05–1.49). Conclusions Age, a higher severity of illness, a history of diabetes, and acidosis were associated with development of AKI in ARDS patients. Severity of AKI was further associated with BMI, history of heart failure, and peak airway pressure. Electronic supplementary material The online version of this article (10.1186/s13613-019-0552-5) contains supplementary material, which is available to authorized users.

Background: Acute kidney injury (AKI) is the most common extra-pulmonary organ failure in acute respiratory distress syndrome (ARDS). Renal recovery after AKI is determined by several factors. The objective of this study was to determine the predictors of renal non-recovery in ARDS patients. Methods: A single center retrospective cohort study of patients with AKI after onset of ARDS. Patients with preexisting chronic kidney disease or intensive care unit stay < 24 h were excluded. AKI staging was defined according to the Kidney Disease Improving Global Outcomes (KDIGO) 2012 guidelines. Renal non-recovery was defined as death, dialysis dependence, serum creatinine ≥1.5 times the baseline, or urine output < 0.5 mL/kg/h more than 6 h. Results: Of the 244 patients that met study criteria, 60 (24.6%) had stage I AKI, 66 (27%) had stage II AKI, and 118 (48.4%) had stage III AKI. Of those, 148 (60.7%) patients had renal non-recovery. On multivariable analysis, factors associated with renal non-recovery were a higher stage of AKI (odds ratio [OR] stage II 5.71, 95% confidence interval [CI] 2.17-14.98; OR stage III 45.85, 95% CI 16.27-129.2), delay in the onset of AKI (OR 1.12, 95% CI 1.03-1.21), history of malignancy (OR 4.02, 95% CI 1.59-10.15), septic shock (OR 3.2, 95% CI 1.52-6.76), and a higher tidal volume on day 1-3 of ARDS (OR 1.41, 95% CI 1.05-1.90). Subgroup analysis of survival at day 28 of ARDS also found that higher severity of AKI (OR stage II 8.17, 95% CI 0.84-79.91; OR stage III 111.67, 95% CI 12.69-982.91), delayed onset of AKI (OR 1.12, 95% CI 1.02-1.23), and active malignancy (OR 6.55, 95% CI 1.34-32.04) were significant predictors of renal non-recovery. Conclusions: A higher stage of AKI, delayed onset of AKI, a history of malignancy, septic shock, and a higher tidal volume on day 1-3 of ARDS predicted renal non-recovery in ARDS patients. Among survivors, a higher stage of AKI, delayed onset of AKI, and a history of malignancy were associated with renal non-recovery.

ImportanceSepsis is associated with long-term cognitive impairment and worse psychological and functional outcomes. Potential mechanisms include intracerebral oxidative stress and inflammation, yet little is known about the effects of early antioxidant and anti-inflammatory therapy on cognitive, psychological, and functional outcomes in sepsis survivors.ObjectiveTo describe observed differences in long-term cognitive, psychological, and functional outcomes of vitamin C, thiamine, and hydrocortisone between the intervention and control groups in the Vitamin C, Thiamine, and Steroids in Sepsis (VICTAS) randomized clinical trial.Design, Setting, and ParticipantsThis prespecified secondary analysis reports the 6-month outcomes of the multicenter, double-blind, placebo-controlled VICTAS randomized clinical trial, which was conducted between August 2018 and July 2019. Adult patients with sepsis-induced respiratory and/or cardiovascular dysfunction who survived to discharge or day 30 were recruited from 43 intensive care units in the US. Participants were randomized 1:1 to either the intervention or control group. Cognitive, psychological, and functional outcomes at 6 months after randomization were assessed via telephone through January 2020. Data analyses were conducted between February 2021 and December 2022.InterventionsThe intervention group received intravenous vitamin C (1.5 g), thiamine hydrochloride (100 mg), and hydrocortisone sodium succinate (50 mg) every 6 hours for 96 hours or until death or intensive care unit discharge. The control group received matching placebo.Main Outcomes and MeasuresCognitive performance, risk of posttraumatic stress disorder and depression, and functional status were assessed using a battery of standardized instruments that were administered during a 1-hour telephone call 6 months after randomization.ResultsAfter exclusions, withdrawals, and deaths, the final sample included 213 participants (median [IQR] age, 57 [47-67] years; 112 males [52.6%]) who underwent long-term outcomes assessment and had been randomized to either the intervention group (n = 108) or control group (n = 105). The intervention group had lower immediate memory scores (adjusted OR [aOR], 0.49; 95% CI, 0.26-0.89), higher odds of posttraumatic stress disorder (aOR, 3.51; 95% CI, 1.18-10.40), and lower odds of receiving mental health care (aOR, 0.38; 95% CI, 0.16-0.89). No other statistically significant differences in cognitive, psychological, and functional outcomes were found between the 2 groups.Conclusions and RelevanceIn survivors of sepsis, treatment with vitamin C, thiamine, and hydrocortisone did not improve or had worse cognitive, psychological, and functional outcomes at 6 months compared with patients who received placebo. These findings challenge the hypothesis that antioxidant and anti-inflammatory therapy during critical illness mitigates the development of long-term cognitive, psychological, and functional impairment in sepsis survivors.Trial RegistrationClinicalTrials.gov Identifier: NCT03509350

BACKGROUND: Treatments of ARDS that improve patient outcomes include use of lung-protective ventilation, prone ventilation, and conservative fluid management. Implementation of ARDS protocols via educational programs might improve adherence and outcomes. The objective of this study was to investigate the effects of an ARDS protocol implementation on outcomes and adherence with ARDS guidelines. METHODS: This was a single-center, interventional, comparative study before and after protocol implementation. Staff education for the ARDS protocol was implemented between June 2014 and May 2015. A retrospective cohort analysis was conducted during between January 2012 and May 2014 (pre-protocol) and between June 2015 and June 2017 (post-protocol). A total of 450 subjects with ARDS were included. After propensity score matching, 432 subjects were analyzed. Of those, 330 subjects were treated after protocol implementation. RESULTS: The median (interquartile range [IQR]) plateau pressure and tidal volume over the first 3 d decreased significantly after protocol implementation (30.5 [IQR 24.2-33] vs 25.5 [IQR 21.7-30], P 5 .01 and 7.65 vs 7.4 mL/kg predicted body weight, P 5 .032, respectively). The percentage of subjects with unsafe tidal volume (> 10 mL/kg predicted body weight) decreased (14.4% vs 5.8%, P 5 .02). The percentage of subjects with safe plateau pressure (^30 cm H 2 O) increased (47.4% vs 76.5%, P < .001). PEEP deviation from the ARDSNet PEEP/F IO 2 table was significantly lower after the implementation. Mortality at 28 and 90 days improved after implementation (53.9% vs 41.8% and 61.8% vs 48.2%, respectively). Adjusted odds ratios for 28-d and 90-d mortality were 0.47 (95% CI 0.28-0.78) and 0.45 (95% CI 0.27-0.76), respectively. CONCLUSIONS: ARDS protocol implementation was associated with improved survival and rate of adherence.