The use of indomethacin in the treatment of plateau waves: effects on cerebral perfusion and oxygenation

Abstract

Plateau waves are sudden and steep increases in intracranial pressure (ICP) that can develop in patients with cerebral injuries, reduced pressure-volume compensatory reserve, and preserved autoregulation. They are caused by cerebral vasodilation in response to a reduction in cerebral perfusion and are associated with increased cerebral blood volume and reduced cerebral blood flow. The authors evaluated the hypothesis that administration of indomethacin, a potent cerebral arteriolar vasoconstrictor, could interrupt the vicious cycle that occurs during plateau waves, extinguishing these waves and, ultimately, restoring cerebral perfusion and oxygenation. Plateau waves developed in nine patients, seven with severe traumatic brain injury and two with intraparenchymal hemorrhage. One to four episodes of plateau waves per patient were treated with indomethacin (15-20 mg), which was delivered by an intravenous bolus injection. Each patient's mean arterial blood flow (MABP), ICP, cerebral perfusion pressure (CPP), and cerebral tissue PO2 were continuously monitored and the data obtained were stored in a personal computer. Each patient's jugular venous O2 saturation (SjvO2) and venoarterial difference in PCO2 were evaluated by intermittent blood sampling. During five episodes of plateau waves, middle cerebral artery flow velocities were evaluated by transcranial Doppler ultrasonography. Indomethacin extinguished all plateau waves. On average, the ICP decreased from an initial value of 58.9 +/- 11.6 mm Hg to 21.2 +/- 8.6 and 25.8 +/- 13.7 mm Hg after 5 and 10 minutes, respectively (p < 0.01). The MABP did not change significantly. As a consequence the CPP increased by 98 and 81% after 5 and 10 minutes, respectively (p < 0.01). Five and 10 minutes after indomethacin was administered, SjvO2 increased from an initial value of 50 +/- 10.5% to 62 +/- 7.6 and 59.9 +/- 9.3%, respectively (p < 0.01); the cerebral tissue PO2 increased from an initial value of 13.4 +/- 10.6 mm Hg to 23.6 +/- 9.58 and 21.9 +/- 9.2 mm Hg, respectively (p < 0.05); and the venous-arterial PCO2 decreased significantly. The mean and diastolic flow velocities increased significantly, whereas the pulsatility index decreased from 1.39 +/- 0.56 to 1.09 +/- 0.4 at 5 minutes and 1.06 +/- 0.36 at 10 minutes (p < 0.05). The findings confirm that plateau waves are caused by vasodilation and show that indomethacin, by constricting the cerebral arteries, is effective in extinguishing plateau waves, ultimately restoring cerebral perfusion and oxygenation.