CO2 and indomethacin vasoreactivity in patients with head injury

The purpose of this study was to compare the effect of hyperventilation and indomethacin on cerebral circulation, metabolism and pressures in patients with acute severe head injury in order to see if indomethacin may act supplementary to hyperventilation. Fourteen severely head injured patients entered the study. Intracranial pressure(ICP), mean arterial blood pressure (MABP) and cerebral perfusion pressure(CPP) were monitored continuously. Within the first four days after the trauma the CO2 and indomethacin vasoreactivities were studied by measurements of cerebral blood flow (CBF) (Cerebrograph 10a, intravenous Xe-133 technique) and arterio-venous difference of oxygen (AVdO(2)). Ischaemia was evaluated from changes in CBF, saturation of oxygen in the jugular bulb (SvjO(2)), lactate and lactate/oxygen index (LOI). Data are presented as medians and ranges, results are significant unless otherwise indicated. Before intervention ICP was well controlled, (14.8 (9-24) mmHg) and basic CBF level was 39.1 (21.6-75.0) ml/100 g/min). The arterio-venous oxygen differences were generally decreased (AVdO(2) = 4.3 (1.8-8.1) ml/100 ml) indicating moderate luxury perfusion. Levels of CMRO(2) were decreased (1.54 (0.7-3.2) ml/100 g/min) as well. During hyperventilation (Delta PaCO2 = 0.88 (0.62-1.55) kPa) CBF decreased with 11.8 (-33.4-29.7) %/kPa and ICP decreased with 3.8 (0-10) mmHg. AVdO(2) increased 34.0 (4.0-139.2) %/kPa, MABP was unchanged, CMRO(2) and CPP increased (Delta CPP = 3.9 (-10-20) mmHg). AVD(lactate) and LOI were unchanged. No correlations between CBF responses to hypocapnia and outcomes were observed. An i.v. bolus dose of indomethacin (30 mg) decreased CBF 14.7 (-16.7-57.4) % and ICP decreased 4.3 (-1-17) mmHg. AVdO(2) increased 27.8 (-40.0-66.7) %, MABP(Delta MABP = 4.9 (-2-21) mmHg) and CPP (Delta CPP = 8.7 (3-29) mmHg) increased while CMRO(2) was unchanged. No changes in AVd (lactate) and LOI indicating cerebral ischaemia were found. Compared to hyperventilation (changes per 1 kPa, at PaCO2 level = 4.05 kPa) the changes in MABP, CPP and CBF were significantly greater after indomethacin, while the changes in AVdO(2), ICP, SvjO(2), and LOI were of the same order of magnitude. No correlation between relative reactivities to indomethacin and CO2, evaluated from changes in CBF and AVdO(2), or between some patients reacted to indomethacin but not to hyperventilation, and vice versa. These results suggest that indomethacin and hyperventilation might act independently, or in a complementary fashion in the treatment of patients with severe head injury.