The importance of intracranial hematomas, raised intracranial pressure (ICP), and the early insults of systemic arterial hypoxemia and hypotension has previously been stressed.2,16–18 Adams1 has demonstrated a 90% prevalence of ischemic brain damage in fatal head injuries. This can be statistically linked to the presence of these brain insults during life. By the aggressive, prompt, and intensive management of head-injury patients, including rapid diagnosis and evacuation of intracranial hematomas, artificial ventilation, and continuous monitoring and control of ICP, we believe we have reduced the overall mortality rate in severely head-injured patients from 50% to 40% without a corresponding increase in morbidity.17 In this study we define two subgroups of patients in whom the mortality rate remains distressingly high. These are patients with intradural hematomas large enough to require surgical decompression and those with no mass lesion whose best motor response consists of flexor or extensor posturing. We describe a randomized controlled trial of prophylactic barbiturate therapy in these patients, in whom we have previously recorded a mortality rate of over 60% and a prevalence of intracranial hypertension of over 70%.
Use of barbiturates in patients with neurological disease is not new. As early as 1972, barbiturates were reported to protect against brain ischemia.3,7,8,19,25,27 Barbiturates have also been shown to lower elevated ICP.9,10,23,24 Their use was subsequently extended to include patients with other causes of intracranial hypertension, such as Reye's syndrome11 and hypoxia.14 Barbiturates, specifically pentobarbital, were employed by Marshall and others12,21,22 and recommended as part of the treatment of severe head injury. To date, however, no controlled study has shown a beneficial effect of prophylactic pentobarbital coma in patients with severe head injury.15
There are two possible approaches in trying to define the role of pentobarbital coma in head injury. The first is to assume that the benefit of pentobarbital lies primarily in its capacity to lower elevated ICP and keep it within the normal range.12,21,22 For such a study, pentobarbital is given only when ICP rises above a predetermined level, regardless of the severity of the injury. The second approach is to focus on the possible protective effects of barbiturates in improving outcome from severe head injury. In that case, barbiturates are started as soon as possible after the head injury, regardless of the ICP, and are continued for a prescribed period of time. We elected to pursue the second course in this particular study.
Michenfelder JD: The interdependency of cerebral functional and metabolic effects following massive doses of thiopental in the dog. Anesthesiology 41:231–2361974Michenfelder JD: The interdependency of cerebral functional and metabolic effects following massive doses of thiopental in the dog. Anesthesiology 41:
This work was supported by Grant NS 12587-09 from the National Institutes of Health.