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J Trauma Acute Care Surg. 2018 Jul;85(1S Suppl 2):S57-S67. doi: 10.1097/TA.0000000000001844.

Interventional vitamin C: A strategy for attenuation of coagulopathy and inflammation in a swine multiple injuries model.

Author information

1
From the Department of Anesthesiology (P.S.R., B.D.S.), Department of Internal Medicine (B.J.F., J.M., C.S., P.M., M.E., E.F., A.A.F., R.N.), Department of Pharmacotherapy and Outcomes Science (E.J.M., D.F.B.), Virginia Commonwealth University, Richmond, Virginia; Department of Anesthesiology (P.S.R., B.D.S.), University of Florida, Gainesville, Florida; and Naval Medical Center Portsmouth (R.N.), Portsmouth, Virginia.

Abstract

BACKGROUND:

Coagulopathy and inflammation induced by hemorrhagic shock and traumatic injury are associated with increased mortality and morbidity. Vitamin C (VitC) is an antioxidant with potential protective effects on the proinflammatory and procoagulant pathways. We hypothesized that high-dose VitC administered as a supplement to fluid resuscitation would attenuate inflammation, coagulation dysfunction, and end-organ tissue damage in a swine model of multiple injuries and hemorrhage.

METHODS:

Male Sinclair swine (n = 24; mean body weight, 27 kg) were anesthetized, intubated, mechanically ventilated, and instrumented for physiologic monitoring. Following stabilization, swine were subjected to shock/traumatic injury (hypothermia, liver ischemia and reperfusion, comminuted femur fracture, hemorrhagic hypotension), resuscitated with 500 mL of hydroxyethyl starch, and randomized to receive either intravenous normal saline (NS), low-dose VitC (50 mg/kg; LO), or high-dose VitC (200 mg/kg; HI). Hemodynamics, blood chemistry, hematology, and coagulation function (ROTEM) were monitored to 4 hours postresuscitation. Histological and molecular analyses were obtained for liver, kidney, and lung.

RESULTS:

Compared with VitC animals, NS swine showed significant histological end-organ damage, elevated acute lung injury scores, and increased mRNA expression of tissue proinflammatory mediators (IL-1β, IL-8, TNFα), plasminogen activation inhibitor-1 and tissue factor. There were no statistically significant differences between treatment groups on mean arterial pressure or univariate measures of coagulation function; however, NS showed impaired multivariate clotting function at 4 hours.

CONCLUSION:

Although correction of coagulation dysfunction was modest, intravenous high-dose VitC may mitigate the proinflammatory/procoagulant response that contributes to multiple organ failure following acute severe multiple injuries.

LEVEL OF EVIDENCE:

Prospective randomized controlled blinded trial study, Preclinical (animal-based).

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