Publications of the Week (July 1, 2022)

2022-07-01

Vitamin C infusions in ICU-treated patients with sepsis

Lamontagne F, Masse MH, Menard J, et al; LOVIT Investigators and the Canadian Critical Care Trials Group. Intravenous Vitamin C in Adults with Sepsis in the Intensive Care Unit. N Engl J Med. 2022 Jun 23;386(25):2387-2398. doi: 10.1056/NEJMoa2200644. Epub 2022 Jun 15. PMID: 35704292.

Background: In patients with sepsis a wide array of treatments has been investigated—ranging from various immune-modulating agents through antithrombotic drugs to commonly used drugs such as statins and beta-blockers—in an attempt to improve outcomes for a disease associated with a high morbidity and mortality. Vitamin C has been used in such patients based on the biological premise that its antioxidant properties may have an immunomodulatory effect. Vitamin C has also been used with glucocorticoids because of a putative synergistic anti-inflammatory effect. The LOVIT trial examined whether IV vitamin C improves outcomes in critically ill patients with sepsis.

Methods: This was a randomized, placebo-controlled trial involving adults who were in an intensive care unit (ICU) for ≤24 hours, had proven or suspected infection as the primary diagnosis, and were receiving vasopressor therapy. Patients were allocated to receive vitamin C, 50 mg/kg IV, or matching placebo every 6 hours for up to 96 hours. The primary outcome was a composite of death or persistent organ dysfunction (defined by the use of vasopressors, invasive mechanical ventilation, or new renal replacement therapy) on day 28.

Results: In the 872 patients randomized, death or persistent organ dysfunction occurred in 44.5% (191/429) of patients in the vitamin C group and in 38.5% (167/434) of patients in the placebo group (risk ratio [RR], 1.21; 95% CI, 1.04-1.40). Death occurred in 35.4% (152/429) and in 31.6% (137/434), respectively (RR, 1.17; 95% CI, 0.98-1.40), and persistent organ dysfunction occurred in 9.1% (39/429) of patients in the vitamin C group and 6.9% (30/434) in the placebo group (RR, 1.30; 95% CI, 0.83-2.05). The findings for other outcomes (organ dysfunction scores, biomarkers, 6-month survival, health-related quality of life, stage 3 acute kidney injury, and hypoglycemic episodes) were similar in both groups.

Conclusions: The authors concluded that in critically ill adults with sepsis who were receiving vasopressor therapy in the ICU, the use of IV vitamin C was associated with a higher risk of death or persistent organ dysfunction at 28 days than placebo.

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