Abrupt termination of vitamin C from ICU patients may increase mortality: secondary analysis of the LOVIT trial

Background
The LOVIT trial examined the effect of vitamin C on sepsis patients, and concluded that in adults with sepsis receiving vasopressor therapy in the ICU, those who received 4-day intravenous vitamin C had a higher risk of death or persistent organ dysfunction at 28 days than those who received placebo. The aim of this study was to determine whether the abrupt termination of vitamin C administration could explain the increased mortality in the vitamin C group.

Methods
We used Cox regression with two time periods to model the distribution of deaths over the first 11 days in the LOVIT trial.

Results
Compared with a uniform difference between vitamin C and placebo groups over the 11-day follow-up period, addition of a separate vitamin C effect starting from day 5 improved the fit of the Cox model (p = 0.026). There was no difference in mortality between the groups during the 4-day vitamin C administration with RR = 0.97 (95% CI: 0.65–1.44). During the week after the sudden termination of vitamin C, there were 57 deaths in the vitamin C group, but only 32 deaths in the placebo group, with RR = 1.9 (95% CI: 1.2–2.9; p = 0.004).

Conclusion
The increased mortality in the vitamin C group in the LOVIT trial is not explained by ongoing vitamin C administration, but by the abrupt termination of vitamin C. The LOVIT trial findings should not be interpreted as evidence against vitamin C therapy for critically ill patients.