Vitamin C improves microvascular reactivity and peripheral tissue perfusion in septic shock patients

Jean-Rémi Lavillegrand, Lisa Raia, Tomas Urbina, Geoffroy Hariri, Paul Gabarre, Vincent Bonny, Naïke Bigé, Jean-Luc Baudel, Arnaud Bruneel, Thierry Dupre, Bertrand Guidet, Eric Maury, Hafid Ait-Oufella, Jean-Rémi Lavillegrand, Lisa Raia, Tomas Urbina, Geoffroy Hariri, Paul Gabarre, Vincent Bonny, Naïke Bigé, Jean-Luc Baudel, Arnaud Bruneel, Thierry Dupre, Bertrand Guidet, Eric Maury, Hafid Ait-Oufella

Abstract

Background: Vitamin C has potential protective effects through antioxidant and anti-inflammatory properties. However, the effect of vitamin C supplementation on microvascular function and peripheral tissue perfusion in human sepsis remains unknown. We aimed to determine vitamin C effect on microvascular endothelial dysfunction and peripheral tissue perfusion in septic shock patients.

Methods: Patients with septic shock were prospectively included after initial resuscitation. Bedside peripheral tissue perfusion and skin microvascular reactivity in response to acetylcholine iontophoresis in the forearm area were measured before and 1 h after intravenous vitamin C supplementation (40 mg/kg). Norepinephrine dose was not modified during the studied period.

Results: We included 30 patients with septic shock. SOFA score was 11 [8-14], SAPS II was 66 [54-79], and in-hospital mortality was 33%. Half of these patients had vitamin C deficiency at inclusion. Vitamin C supplementation strongly improved microvascular reactivity (AUC 2263 [430-4246] vs 5362 [1744-10585] UI, p = 0.0004). In addition, vitamin C supplementation improved mottling score (p = 0.06), finger-tip (p = 0.0003) and knee capillary refill time (3.7 [2.6-5.5] vs 2.9 [1.9-4.7] s, p < 0.0001), as well as and central-to-periphery temperature gradient (6.1 [4.9-7.4] vs 4.6 [3.4-7.0] °C, p < 0.0001). The beneficial effects of vitamin C were observed both in patients with or without vitamin C deficiency.

Conclusion: In septic shock patients being resuscitated, vitamin C supplementation improved peripheral tissue perfusion and microvascular reactivity whatever plasma levels of vitamin C. ClinicalTrials.gov Identifier: NCT04778605 registered 26 January 2021.

Keywords: Microvascular function; Mottling; Sepsis; Tissue perfusion; Vitamin C.

Conflict of interest statement

The authors declare that they have no competing interests.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
A Changes of forearm skin microcirculatory reactivity in response to acetylcholine challenge before and after vitamin C supplementation in patients with septic shock. B Example of skin microcirculatory blood flow change in response to acetylcholine iontophoresis before (blue) and after (orange) vitamin C injection. C Central-to-knee skin temperature gradient before and after vitamin C infusion. PU Perfusion units
Fig. 2
Fig. 2
A plasma levels of vitamin C in patients with and without deficiency in patients with septic shock. B Changes of microcirculatory reactivity before and after vitamin C supplementation in septic shock patients with and without vitamin C deficiency

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