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To conduct a systematic review and meta-analysis to evaluate the impact of IV vitamin C on outcomes in critically ill patients. DATA SOURCES: Systematic search of MEDLINE, EMBASE, CINAHL, and the Cochrane Register of Controlled Trials. STUDY SELECTION: Randomized controlled trials testing IV vitamin C in critically ill patients. DATA ABSTRACTION: Two independent reviewers abstracted patient characteristics, treatment details, and clinical outcomes.DATA SYNTHESIS: Fifteen studies involving 2,490 patients were identified. Compared with placebo, IV vitamin C administration is associated with a trend toward reduced overall mortality (relative risk, 0.87; 95% CI, 0.75-1.00; p = 0.06; test for heterogeneity I 2 = 6%). High-dose IV vitamin C was associated with a significant reduction in overall mortality (relative risk, 0.70; 95% CI, 0.52-0.96; p = 0.03), whereas low-dose IV vitamin C had no effect (relative risk, 0.94; 95% CI, 0.79-1.07; p = 0.46; test for subgroup differences, p = 0.14). IV vitamin C monotherapy was associated with a significant reduction in overall mortality (relative risk, 0.64; 95% CI, 0.49-0.83; p = 0.006), whereas there was no effect with IV vitamin C combined therapy. No trial reported an increase in adverse events related to IV vitamin C. CONCLUSIONS:IV vitamin C administration appears safe and may be associated with a trend toward reduction in overall mortality. High-dose IV vitamin C monotherapy may be associated with improved overall mortality, and further randomized controlled trials are warranted.

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Background: Uncertainty remains about the best route and timing of medical nutrition therapy in the acute phase of critical illness. Early combined enteral nutrition (EN) and parenteral nutrition (PN) may represent an attractive option to achieve recommended energy and protein goals in select patient groups. This meta-analysis aims to update and summarize the current evidence.Methods: This systematic review and meta-analysis includes randomized controlled trials (RCTs) targeting the effect of EN alone vs a combination of EN with PN in the acute phase of critical illness in adult patients. Assessed outcomes include mortality, intensive care unit (ICU) and hospital length of stay (LOS), ventilation days, infectious complications, physical recovery, and quality-of-life outcomes.Results: Twelve RCTs with 5543 patients were included. Treatment with a combination of EN with PN led to increased delivery of macronutrients. No statistically significant effect of a combination of EN with PN vs EN alone on any of the parameters was observed: mortality (risk ratio = 1.0; 95% CI, 0.79-1.28; P = .99), hospital LOS (mean difference, −1.44; CI, −5.59 to 2.71; P = .50), ICU LOS, and ventilation days. Trends toward improved physical outcomes were observed in two of four trials. Conclusion:A combination of EN with PN improved nutrition intake in the acute phase of critical illness in adults and was not inferior regarding the patients' outcomes. Large, adequately designed trials in select patient groups are needed to answer the question of whether this nutrition strategy has a clinically relevant treatment effect.

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Introduction Real-world evidence on the timing and efficacy of enteral nutrition (EN) practices in intensive care unit (ICU) patients with circulatory shock is limited. We hypothesized early EN (EEN), as compared to delayed EN (DEN), is associated with improved clinical outcomes in mechanically ventilated (MV) patients with circulatory shock. Methods We analyzed a dataset from an international, multicenter, pragmatic randomized clinical trial (RCT) evaluating protein dose in ICU patients. Data were collected from ICU admission, and EEN was defined as initiating < 48 h from ICU admission and DEN > 48 h. We identified MV patients in circulatory shock to evaluate the association between the timing of EN initiation and clinical outcomes. The regression analysis model controlled for age, mNUTRIC score, APACHE II score, sepsis, and Site. Results We included 626 patients, from 52 ICUs in 14 countries. Median age was 60 years [18–93], 55% had septic shock, 99% received norepinephrine alone, 91% received EN alone, and 50.3% were randomized to a usual protein dose. Forty-two percent of EEN patients had persistent organ dysfunction syndrome plus death at day 28, compared to 53% in the DEN group (p = 0.04). EEN was associated with more ICU-free days (9.3 ± 9.2 vs. 5.7 ± 7.9, p = 0.0002), more days alive and free of vasopressors (7.1 ± 3.1 vs. 6.3 ± 3.2, p = 0.007), and shorter duration of MV among survivors (9.8 ± 10.9 vs. 13.8 ± 14.5, p = 0.0002). This trend was no longer observed in the adjusted analysis. There were no differences in ICU/60-day mortality or feeding intolerance rates between groups. Conclusion In MV patients with circulatory shock, EEN, as compared to DEN, was associated with improved clinical outcomes, but no longer when adjusting for illness severity. RCTs comparing the efficacy of EEN to DEN in MV patients with circulatory shock are warranted.

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In critically ill surgical patients, early enteral caloric adequacy is associated with less inflammation and improved clinical outcomes.