Pentobarbital Coma With Therapeutic Hypothermia for Treatment of Refractory Intracranial Hypertension in Traumatic Brain Injury Patients: A Single Institution Experience

Abstract

Introduction Traumatic brain injury (TBI) results in primary and secondary brain injuries. Secondary brain injury can lead to cerebral edema resulting in increased intracranial pressure (ICP) secondary to the rigid encasement of the skull. Increased ICP leads to decreased cerebral perfusion pressure which leads to cerebral ischemia. Refractory intracranial hypertension (RICH) occurs when ICP remains elevated despite first-tier therapies such as head elevation, straightening of the neck, analgesia, sedation, paralytics, cerebrospinal fluid (CSF) drainage, mannitol and/or hypertonic saline administration. If unresponsive to these measures, second-tier therapies such as hypothermia, barbiturate infusion, and/or surgery are employed. Methods This was a retrospective review of patients admitted at Arrowhead Regional Medical Center from 2008 to 2019 for severe TBI who developed RICH requiring placement into a pentobarbital-induced coma with therapeutic hypothermia. Primary endpoints included mortality, good recovery which was designated at Glasgow outcome scale (GOS) of 4 or 5, and improvement in ICP (goal is <20 mmHg). Secondary endpoints included complications, length of intensive care unit (ICU) stay, length of hospital stay, length of pentobarbital coma, length of hypothermia, need for vasopressors, and decompressive surgery versus no decompressive surgery. Results Our study included 18 patients placed in pentobarbital coma with hypothermia for RICH. The overall mortality rate in our study was 50%; with 60% mortality in pentobarbital/hypothermia only group, and 46% mortality in surgery plus pentobarbital/hypothermia group. Maximum ICP prior to pentobarbital/hypothermia was significantly lower in patients who had a prior decompressive craniectomy than in patients who were placed into pentobarbital/hypothermia protocol first (28.3 vs 35.4, p<0.0238). ICP was significantly reduced at 4 hours, 8 hours, 12 hours, 24 hours, and 48 hours after pentobarbital and hypothermia treatment. Initial ICP and maximum ICP prior to pentobarbital/hypothermia was significantly correlated with mortality (p=0.022 and p=0.026). Patients with an ICP>25 mmHg prior to pentobarbital/hypothermia initiation had an increased risk of mortality (p=0.0455). There was no statistically significant difference in mean ICP after 24 hours after pentobarbital/hypothermia protocol in survivors vs non-survivors. Increased time to reach 33°C was associated with increased mortality (r=0.47, p=0.047); with a 10.5-fold increase in mortality for >7 hours (OR 10.5, p=0.039).

Effects of therapeutic hypothermia on the safety of children with severe traumatic brain injury: a systematic review and meta-analysis

“…As a result, the treatment of brain injuries among children is more complex and difficult than in adults. In most cases, the prognosis of the treatment of children is relatively poorer (21,22).…”

Physiological Impact of Hypothermia: The Good, the Bad, and the Ugly

“…An alternative to neurosurgical intervention to reduce intra-cerebral pressure has been the induction of a pentobarbital coma, which additionally reduces cerebral metabolism and oxygen consumption. Subsequently, a reduction of cerebral blood flow may take place, in addition to a decrease in neuro-excitotoxicity by reducing the release of glutamate and aspartate in brain tissue (4,12,13). Over the years, animal experiments have documented promising results by use of induced hypothermia to mitigate secondary brain injury by reducing cerebral metabolic demands, inflammation, excitotoxicity, lipid peroxidation, and cell death (44, 51, 64).…”

“…In children, the use of induced hypothermia has been shown to have worsening outcomes with an increase in mortality (75). In adults, data are conflicting and the use of therapeutic hypothermia is not currently recommended for prophylactic or routine use in traumatic brain injury (13).…”

Pentobarbital Coma Use in a Pregnant Patient With Refractory Intracranial Hypertension

“…Inducing a pentobarbital coma can slow brain metabolic pathways and reduce cerebral blood flow while increasing brain tissue oxygenation 1 . Although studies have investigated pentobarbital coma in both adults and children, its role in pregnant patients is currently unknown 6,7 …”

“…1 Although studies have investigated pentobarbital coma in both adults and children, its role in pregnant patients is currently unknown. 6,7 Here, we present a pregnant patient with dural arteriovenous fistula rupture who experienced persistent and refractory ICP elevations and, thus, required high-dose barbiturates to induce a pentobarbital coma. Identifying patient information is removed from the case presentation, and thus, consent was deemed unnecessary.…”