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APhA Staff
Intravenous vitamin C in adults with sepsis shows mixed results
According to CDC, sepsis, the body’s extreme response to an infection in which the infection-fighting processes turn on the body, can be life threatening without early treatment with antibiotics and intravenous fluids. Sepsis causes organs to function poorly and abnormally, and critically ill patients with sepsis are known to have low plasma concentrations of vitamin C. Recent studies have suggested that high doses of vitamin C could mitigate tissue injury in seriously ill patients with sepsis.
A recent study published on June 23, 2022, in the New England Journal of Medicine described a phase 3, multicenter, randomized, controlled trial (termed the Lessening Organ Dysfunction with Vitamin C [LOVIT]trial) that tested the hypothesis that a high dose of vitamin C would reduce the risk of death or persistent organ dysfunction at 28 days in adults with sepsis who were receiving vasopressor therapy in the ICU. The global group of researchers led by François Lamontagne, MD, of the Université de Sherbrooke (Canada) and Neill K.J. Adhikari, MDCM, of the Sunnybrook Health Sciences Centre (Toronto) assigned adults who had been in the ICU for no longer than 24 hours, who had proven or suspected infection as the main diagnosis, and who were receiving a vasopressor to receive an infusion of either vitamin C (at a dose of 50 mg/kg of body weight) or a matched placebo administered every 6 hours for up to 96 hours.
The primary outcome of the trial 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.
A total of 872 patients were assigned to groups—435 to the vitamin C group and 437 to the control group. Death or persistent organ dysfunction occurred in 44.5% of patients in the vitamin C group and in 38.5% of the patients in the control group. At 28 days, death had occurred in 35.4% of patients in the vitamin C group and in 31.6% of patients in the placebo group and persistent organ dysfunction in 9.1% of patients in the vitamin C group and 6.9% of the patients in the control group.
Results for organ-dysfunction scores, biomarkers, 6-month survival, health-related quality of life, stage 3 acute kidney injury, and hypoglycemic episodes were similar for both groups, while in the vitamin C group, one patient had a severe hypoglycemic episode and another patient had a serious anaphylaxis event.
The authors indicated that the fact that the composite primary outcome (death or persistent organ dysfunction at trial day 28) occurred more frequently in patients who had received intravenous vitamin C than in those who had received placebo was unexpected and that they were unable to determine the cause of this result. They also indicated that the patients were representative of those with sepsis being treated in the ICU in many high-income countries, the trial population differs substantially from such patients in low- and middle-income countries, where the incidence of sepsis and the associated case fatality rate are highest.
In addition, the results of this trial results differ from those of two smaller randomized trials evaluating the same vitamin C regimen. The researchers postulate that these divergent findings could be the result of large effect estimates from smaller trials that may occur by chance or from differences in baseline characteristics, such as the presence of respiratory failure or receipt of vasopressors. They suggest that ongoing trials of the use of vitamin C in patients with SARS-CoV-2 infection may help to explain these differences. ■