Moderate hypothermia improves imbalances of thromboxane A2 and prostaglandin I2 production after traumatic brain injury in humans

Objective To examine the levels of thromboxane B2 (TXB2) and 6-keto prostaglandin F1α (6-keto PGF1α) production in arterial and internal jugular bulb sera in patients with traumatic brain injury (TBI). TBI is associated with arachidonate release and may be associated with an imbalance of vasoconstricting and vasodilating cyclooxygenase metabolites. Design A prospective, randomized study. Setting The intensive care unit of a medical university hospital. Interventions Twenty-six ventilated TBI patents (Glasgow Coma Scale score on admission, ≤8 points) were divided randomly into two groups: a hypothermic group (n = 15), in which the patients were cooled to 32 to 33°C after being giving vecuronium, midazolam, and buprenorphine; and a normothermic group (n = 11), in which the patients’ body temperature was controlled at 36 to 37°C by surface cooling using the same treatment as the hypothermic group. Body temperature control including normothermia was started 3 to 4 hrs after injury. The duration of hypothermia usually lasted for 3 to 4 days, after which the patients were rewarmed at a rate of approximately 1°C per day. Measurements and Main Results Blood sampling for TXB2 and 6-keto PGF1α was started shortly after admission in both groups. Arterial TXB2 levels on admission in both groups were elevated remarkably, but not 6-keto PGF1α, thereby causing an imbalance of the prostanoids after injury. In the normothermic group, TXB2 decreased transiently, but this prostanoid increased again 3 days after the injury. In the hypothermic group, such prostanoid differences disappeared shortly after therapy, and the condition was sustained for 10 days. Hypothermia attenuated differences in TXB2 levels between arterial and internal jugular bulb sera, which may reflect reduced cerebral prostanoid production. The Glasgow Outcome Scale score 6 months after the insult in the hypothermic group was significantly higher than that in the normothermic group (p = .04). Conclusion The current results from a limited number of patients suggest that moderate hypothermia may reduce prostanoid production after TBI, thereby attenuating an imbalance of thromboxane A2 and prostaglandin I2. However, it must be clarified whether the changes in the prostanoid after moderate hypothermia are a secondary effect of other mediator changes or whether they simply represent an epiphenomenon that is mechanistically unrelated to damage in TBI.