Indomethacin and cerebral autoregulation in severe head injured patients: a transcranial Doppler study.

Abstract

To assess the effect of indomethacin on cerebral autoregulation, systemic and cerebral haemodynamics, in severe head trauma patients. Prospective, controlled clinical trial, with repeated measurements. A 12-bed adult general intensive care unit in a third level referral university hospital. 16 severely head injured patients, 14 males, age range 17-60. Indomethacin was administrated as a load plus continuous infusion. Indomethacin reactivity was assessed as the estimated cerebral blood flow change elicited by the load. Dynamic and static cerebral autoregulation tests were performed before indomethacin administration, and during its infusion. Systemic and cerebral haemodynamic changes were assessed through continuous monitoring of mean arterial pressure, transcranial Doppler cerebral blood flow velocity, intracranial pressure, cerebral perfusion pressure, and jugular venous oxygen saturation. Indomethacin loading dose was immediately followed by a cerebral blood flow median decrease of 36 or 29% (p = ns) evaluated by two different methods, by an ICP decrease and by an AVDO(2) increase from 3.52 to 6.15 mL/dL (p = 0.002). Dynamic autoregulation increased from a median of 28 to 57% (p<0.05) during indomethacin infusion; static autoregulation also increased, from a median of 72 to 89% (p = ns). Indomethacin decreased intracranial pressure and cerebral blood flow, and increased cerebral perfusion pressure, while maintaining tissue properties of further extracting O(2). The increase in both autoregulatory values reveals an enhancement of cerebral microvasculature reactivity under indomethacin, during hypertensive and--especially--during hypotensive situations.