Ascorbic acid and microcirculation in cardiothoracic surgery: a pilot feasibility trial and matched cohort study

Ascorbic acid is an essential cofactor of catecholamine synthesis that increases capillary bed density and improves microcirculation perfusion. We hypothesized early ascorbic acid administration in cardiothoracic surgery would preserve the microcirculatory integrity and minimize postoperative vasoplegia.

This was a single-arm pilot feasibility study of adults undergoing septal myectomy combined with valve intervention or alone using cardiopulmonary bypass. Intravenous ascorbic acid 1,500 mg was administered before and immediately following cardiopulmonary bypass and every 6 h after for 12 doses. Three historical controls were identified and matched to each trial participant on age, gender, body mass index, preoperative ejection fraction, surgery performed, and time on cardiopulmonary bypass. The feasibility endpoint was a composite of successful and timely 1) ascorbic acid administration, 2) laboratory assessment, and 3) microcirculation measurements across the perioperative phases of care. Clinical endpoints included vasoplegia incidence, acute kidney injury, and lengths of stay compared to controls.

Fifteen patients were enrolled and compared to 45 historically matched controls. Participants' median baseline plasma ascorbic acid concentration was 0.5 (0.3, 0.9) mg/dL. Four (27%) patients had suboptimal concentrations. Eleven participants (75%) did not meet the feasibility composite endpoint due to the inability of microcirculation measurement. Incidence of vasoplegia and acute kidney injury, vasopressor duration, and lengths of stay were similar between participants and historical controls. No drug-related adverse events were noted.

Timely microcirculation measurements were challenging in the complex cardiothoracic surgery environment. Compared to historical controls, no meaningful differences in clinical endpoints were noted with ascorbic acid treatment. The utility of ascorbic acid on post-cardiopulmonary bypass vasoplegia remains unclear.

ClinicalTrials.gov (NCT03744702, registered on November 14, 2018).