Vitamin C may reduce the duration of mechanical ventilation in critically ill patients: a meta-regression analysis

Abstract

Background: Our recent meta-analysis indicated that vitamin C may shorten the length of ICU stay and the duration of mechanical ventilation. Here we analyze modification of the vitamin C effect on ventilation time, by the control group ventilation time (which we used as a proxy for severity of disease in the patients of each trial). Methods: We searched MEDLINE, Scopus, and the Cochrane Central Register of Controlled Trials and reference lists of relevant publications. We included controlled trials in which the administration of vitamin C was the only difference between the study groups. We did not limit our search to randomized trials and did not require placebo control. We included all doses and all durations of vitamin C administration. One author extracted study characteristics and outcomes from the trial reports and entered the data in a spreadsheet. Both authors checked the data entered against the original reports. We used meta-regression to examine whether the vitamin C effect on ventilation time depends on the duration of ventilation in the control group.Results: We identified nine potentially eligible trials, eight of which were included in the meta-analysis. We pooled the results of the eight trials, including 685 patients in total, and found that vitamin C shortened the length of mechanical ventilation on average by 14% (P = 0.00001). However, there was significant heterogeneity in the effect of vitamin C between the trials. Heterogeneity was fully explained by the ventilation time in the untreated control group. Vitamin C was most beneficial for patients with the longest ventilation, corresponding to the most severely ill patients. In five trials including 471 patients requiring ventilation for over 10 h, a dosage of 1-6 g/day of vitamin C shortened ventilation time on average by 25% (P < 0.0001). Conclusions: We found strong evidence that vitamin C shortens the duration of mechanical ventilation, but the magnitude of the effect seems to depend on the duration of ventilation in the untreated control group. The level of baseline illness severity should be considered in further research. Different doses should be compared directly in future trials.

High-dose vitamin C infusion for the treatment of critically ill COVID-19

“…In addition, this study was consistent with other studies that showed the protective role of vitamin C infusion in acute lung injury (ALI) and ARDS [20]. Moreover, the latest meta-analysis from eight vitamin C trials of a total of 685 patients indicated that vitamin C shortened the duration of mechanical ventilation in critically ill patients [26]. SARS-CoV-2 primarily affects the lung and causes pneumonia.…”

“…Thus, high-dose intravenous vitamin C (HDIVC) was added to the standard therapy of critically ill patients in recent studies, such as sepsis [18][19][20], ARDS [20,21], cardiac surgery [22], and burn [23]. The results showed that HDIVC was safe for critically ill patients and signi cantly reduced vasopressor support [24], limited organ injury [25], shortened the duration of mechanical ventilation [26] and ICU stay [27], and improved survival rates [18]. Additionally, vitamin C has direct nonspeci c antiviral activity in vitro [28], although it is unclear whether this confers any protection to humans with COVID-19.…”

Overview of the possible role of vitamin C in management of COVID-19

“…In fact, anti-oxidant treatment with vitamins C and E decreased duration of mechanical ventilation and shorten the length of ICU stay in critically ill surgical patients [ 82 ]. Meta-analysis showed that vitamin C as an adjuvant treatment shortened the duration of mechanical ventilation and ICU stay in non-surgical critically ill patients [ 83 , 84 ]. Although an individual study showed that treatment of septic patients requiring mechanical ventilation with IV vitamin C (6 g/day) did not improve mortality rate [ 85 ], a meta-analysis which enrolled 1210 patients from different clinical trials showed that treatment of critically ill patients with a dose ranging between 3 and 10 g/day of IV vitamin C decreased mortality rate [ 86 ].…”

Relevant Nutrition Therapy in COVID‐19 and the Constraints on Its Delivery by a Unique Disease Process

“…28,29 Using an animal model (chickens), 1 study showed that a vitamin A-deficient diet led to increased susceptibility to coronavirus (not SARS-CoV-2), 30 whereas a second trial showed that supplementation with vitamin C increased resistance to coronavirus. 31 Both a meta-analysis published in 2019 and a large prospective trial in septic ICU patients with ARDS reported no benefit from vitamin A supplementation in ICU patients. 32 In the nutrition management of patients with COVID-19, the trace minerals selenium and zinc have received the most attention.…”