Objective:The purpose of this study was to compare the effects of two acute-care management strategies on the frequency of jugular venous desaturation and refractory intracranial hypertension and on long-term neurologic outcome in patients with severe head injury.Design:Randomized clinical trial.Setting:Level I trauma hospital.Patients:One hundred eighty-nine adults admitted in coma because of severe head injury.Interventions:Patients were assigned to either cerebral blood flow (CBF)-targeted or intracranial pressure (ICP)-targeted management protocols during randomly assigned time blocks. In the CBF-targeted protocol, cerebral perfusion pressure was kept at > 70 mm Hg and PaCO2was kept at approximately 35 torr (4.67 kPa). In the ICP-targeted protocol, cerebral perfusion pressure was kept at >50 mm Hg and hyperventilation to a PaCO2of 25-30 torr (3.33-4.00 kPa) was used to treat intracranial hypertension.Measurements and Main Results:The CBF-targeted protocol reduced the frequency of jugular desaturation from 50.6% to 30% (p= .006). Even when the frequency of jugular desaturation was adjusted for all confounding factors that were significant, the risk of cerebral ischemia was 2.4-fold greater with the ICP-targeted protocol. Despite the reduction in secondary ischemic insults, there was no difference in neurologic outcome. Failure to alter long-term neurologic outcome was probably attributable to two major factors. A low jugular venous oxygen saturation was treated in both groups, minimizing the injury that occurred in the ICP-targeted group. The beneficial effects of the CBF-targeted protocol may have been offset by a five-fold increase in the frequency of adult respiratory distress syndrome.Conclusions:Secondary ischemic insults caused by systemic factors after severe head injury can be prevented with a targeted management protocol. However, potential adverse effects of this management strategy may offset these beneficial effects.