Blood mitochondrial enzymatic assay as a predictor of long-term outcome in severe traumatic brain injury

Abstract

Recent studies have observed the central role of mitochondrial dysfunction in severe traumatic brain injury (sTBI). One hundred and seven sTBI patients (18–65years old, presenting within 8hours of injury) were randomised for a placebo controlled phase II trial of progesterone with or without hypothermia. We serially analysed blood mitochondrial enzymes (Complex I [C1], Complex IV [C4] and pyruvate dehydrogenase complex [PDH]) using a dipstick assay at admission and 7days later for 37 patients, irrespective of assigned group. Favorable Glasgow Outcome Scale (GOS) at 1year was associated with admission C1 levels above 0.19μg, admission C4 levels above 0.19μg and day 7 C1 levels above 0.17μg, all per 25μl of blood. Unfavorable GOS at 1year was associated with admission serum PDH levels above 0.23μg/25μl of blood. Survivors at 1year had significantly higher admission serum C1 levels above 0.19μg/25μl and day 7 C1 levels above 0.17μg/25μl. To our knowledge this is the first clinical trial associating blood mitochondrial enzymes with long-term outcome in sTBI. Serial monitoring and optimisation of blood C1, C4 and PDH levels could aid in prognostication and potentially guide in using mitochondrial targeted therapies. Blood mitochondrial enzymatic assay might suggest global reduction–oxidation status.