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.

This article by Fowler et al was published in JAMA during October 2019 in volume 322 issue 13.
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.InterventionsPatients 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.
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Fluid resuscitation in patients with end-stage renal disease on hemodialysis presenting with severe sepsis or septic shock: A case control study

This research by Rajdev and colleagues was first published in October 2019 in the online edition of Journal of Critical Care.
Due to the potential risk of volume overload, physicians are hesitant to aggressively fluid-resuscitate septic patients with end-stage renal disease (ESRD) on hemodialysis (HD). Primary objective: To calculate the percentage of ESRD patients on HD (Case) who received ≥30 mL/Kg fluid resuscitation within the first 6 h compared to non-ESRD patients (Control) that presented with severe sepsis (SeS) or septic shock (SS). Secondary objectives: Effect of fluid resuscitation on intubation rate, need for urgent dialysis, hospital length of stay (LOS), intensive care unit (ICU) admission and LOS, need for vasopressors, and hospital mortality. Medical records of 715 patients with sepsis, SeS, SS, and ESRD were reviewed. We identified 104 Case and 111 Control patients. In the Case group, 23% of patients received ≥30 mL/Kg fluids compared to 60% in the Control group (p < 0.001). There was no significant difference in mortality, need for urgent dialysis, intubation rates, ICU LOS, or hospital LOS between the two groups. Subgroup analysis between ESRD patients who received ≥30 mL/Kg (N = 80) vs those who received <30 mL/Kg (N = 24) showed no significant difference in any of the secondary outcomes. Compliance with 30 mL/Kg fluids was low for all patients but significantly lower for ESRD patients. Aggressive fluid resuscitation appears to be safe in ESRD patients.
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Association of negative fluid balance during the de-escalation phase of sepsis management on mortality: A cohort study

This article by Dhondup and others was published online in the Journal of Critical Care during October 2019.
Purpose:  We aimed to evaluate the impact of negative fluid balance during the fluid de-escalation phase of sepsis management.
Material and methods:  This is a historical cohort study of adult intensive care units (ICU) patients with septic shock and severe sepsis in a quaternary medical center, from January 2007 through December 2009. We used regression modeling to assess the impact of negative volume balance on mortality after adjustments for age, comorbidities, and illness severity.
Results:  Among 633 enrolled patients, 387 patients reached negative fluid balance who in comparison with others had a lower 90-day mortality rate (36% vs. 44%; P = .048), despite higher severity of illness. Each 1-L negative daily fluid balance was associated with reduced ICU, hospital, 90-day and 1-year mortality (hazard ratio [HR] 0.39[95%CI, 0.28–0.57], 0.76[95%CI, 0.63–0.94], 0.69[95%CI, 0.59–0.81], 0.67 [0.58–0.78], respectively; P < .05). This protective effect of negative volume balance was maintained when cumulative ICU fluid balance was utilized.
Conclusions:  There is not only a significant association between outcomes of patients who were resuscitated for sepsis and achieving negative fluid balance, but also the amount of daily or cumulative negative fluid balance is associated with lower mortality of these patients. Prospective clinical trials are needed to validate this finding.
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Comparison of the sepsis-2 and sepsis-3 definitions in severely injured trauma patients

This research by Eriksson et al was published online in the Journal of Critical Care during August 2019.
Purpose:  To evaluate the performance of the new SOFA-based sepsis definition in trauma patients.
Materials and methods:  A single-centre, retrospective, observational study. Primary outcome was 30-day mortality including a censoring analysis for early deaths. The primary outcome was evaluated with logistic regression, receiver operating characteristics (ROC) curves and Kaplan-Meier survival analyses.
Results:  722 severely injured patients were included between 2007 and 2016. 315 patients fulfilled the sepsis-2 criteria and 148 fulfilled the sepsis-3 criteria during the first ten days in the ICU. The odds ratios for 30-day mortality were 0.7 (CI 0.4–1.2) for sepsis-2 and 1.5 (CI 0.8–2.6) for sepsis-3. When censoring patients dying at day 1, sepsis-3 became associated with 30-day mortality whereas sepsis-2 did not. This finding was persistent and enhanced through continuing day-by-day censoring of early deaths. The same pattern was seen for the ROC curves analyses, censoring of early deaths resulted in significant discriminatory properties for sepsis-3 but not for sepsis-2.
Conclusions:  The sepsis-3 definition identifies much fewer patients and is more strongly associated with adverse outcomes than the sepsis-2 definition. The sepsis-3 definition seems to be useful in the post trauma setting.
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Validation the performance of New York Sepsis Severity Score compared with Sepsis Severity Score in predicting hospital mortality among sepsis patients

This article by Sathaporn and colleagues was first published on line in the Journal of Critical Care in late June 2019.
Purpose:  The aim of this study was to compare the performance of the New York Sepsis Severity Score (NYSSS) with the Sepsis Severity Score (SSS) and Acute Physiology and Chronic Health Evaluation and Simplified Acute Physiology Scores for predicting mortality in sepsis patients.
Method:  A retrospective analysis was conducted in the intensive care unit. The primary outcome was in-hospital mortality.
Results:  Overall 1680 sepsis patients were enrolled. The hospital mortality rate was 44.4%. The NYSSS underestimated actual mortality with standard mortality ratio (SMR) of 1.28 (95%CI 1.19–1.38). However, the SSS slightly overestimated the actual mortality with an SMR of 0.94 (0.88–1.01). The NYSSS had moderate discrimination with an AUC of 0.772 (0.750–0.794), in contrast to the SSS which had good discrimination with an AUC of 0.889 (0.873–0.904). The AUC of the SSS was statistically higher than that of the NYSSS. The AUCs of both the NYSSS and SSS were significantly lower than other standard severity scores. The calibrations for all severity scores were poor. The SSS had better overall performance than the NYSSS (Brier score 0.149 and 0.201, respectively).
Conclusion:  The SSS had better discrimination and overall performance than the NYSSS. However, both sepsis severity scores were poorly calibrated.
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Serum albumin as a risk factor for death in patients with prolonged sepsis: An observational study

This paper by Takegawa and colleagues was published on line in February 2019 in the Journal of Critical Care.
Purpose:  The aim of this study was to evaluate an association between nutritional biomarkers and prognosis in septic patients.
Methods:  We retrospectively searched the association between nutritional biomarkers including serum albumin (Alb), total protein (TP), total cholesterol (T-chol), and cholinesterase (ChE), and prognosis for septic patients treated in the ICU for >7 days. We used time-dependent Cox proportional hazard regression analysis to resolve the difference of the statistical weight of each day’s data for all 14 consecutive days among individual sepsis patients. The covariates were based on the minimum moving values determined from 1 day, 3 days, 7 days, and 14 days of serial data. The values of these covariates and ICU survival were considered as outcomes.
Results:  We included 136 septic patients. The decreases in the values of Alb, TP, T-chol, and ChE were significantly associated with the risk of death in the septic patients (p < .05). Especially, the daily changes of Alb were significantly associated with mortality during the ICU stay (p < .05).
Conclusions:  We found that the changes in serial data of the nutritional markers of Alb, TP, T-chol, and ChE reflected the higher risk of death in patients with prolonged sepsis.
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Acute kidney injury following contrast media administration in the septic patient: A retrospective propensity-matched analysis

This article by Hinson and others was published on line in February 2019 in the Journal of Critical Care.
Purpose:  To determine the risk for acute kidney injury (AKI) attributable to intravenous contrast media (CM) administration in septic patients.
Materials and methods:  This was a single-center retrospective propensity matched cohort analysis performed in the emergency department (ED) of an academic medical center. All visits for patients ≥18 years who met sepsis diagnostic criteria and had serum creatinine (SCr) measured both on arrival to the ED and again 48 to 72 h later were included. Of 4171 visits, 1464 patients underwent contrast-enhanced CT (CECT), 976 underwent unenhanced CT and 1731 underwent no CT at all.
Results:  The primary outcome was incidence of AKI. Logistic regression and between-groups odds ratios with and without propensity-score matching were used to test for an independent association between CM administration and AKI. Incidence of AKI was 7.2%, 9.4% and 9.7% in those who underwent CECT, unenhanced CT and no CT. CM administration was not associated with increased incidence of AKI.
Conclusions:  Sepsis is a medical emergency proven to benefit from early diagnosis and rapid initiation of treatment, which is often aided by CECT. Our findings argue against withholding CM for fear of precipitating AKI in potentially septic patients.
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