Therapeutic Hypothermia Reduces Intracranial Pressure and Partial Brain Oxygen Tension in Patients with Severe Traumatic Brain Injury: Preliminary Data from the Eurotherm3235 Trial

Abstract

Traumatic brain injury (TBI) is a significant cause of disability and death and a huge economic burden throughout the world. Much of the morbidity associated with TBI is attributed to secondary brain injuries resulting in hypoxia and ischemia after the initial trauma. Intracranial hypertension and decreased partial brain oxygen tension (PbtO2) are targeted as potentially avoidable causes of morbidity. Therapeutic hypothermia (TH) may be an effective intervention to reduce intracranial pressure (ICP), but could also affect cerebral blood flow (CBF). This is a retrospective analysis of prospectively collected data from 17 patients admitted to the Western General Hospital, Edinburgh. Patients with an ICP >20 mmHg refractory to initial therapy were randomized to standard care or standard care and TH (intervention group) titrated between 32°C and 35°C to reduce ICP. ICP and PbtO2 were measured using the Licox system and core temperature was recorded through rectal thermometer. Data were analyzed at the hour before cooling, the first hour at target temperature, 2 consecutive hours at target temperature, and after 6 hours of hypothermia. There was a mean decrease in ICP of 4.3±1.6 mmHg (p<0.04) from 15.7 to 11.4 mmHg, from precooling to the first epoch of hypothermia in the intervention group (n=9) that was not seen in the control group (n=8). A decrease in ICP was maintained throughout all time periods. There was a mean decrease in PbtO2 of 7.8±3.1 mmHg (p<0.05) from 30.2 to 22.4 mmHg, from precooling to stable hypothermia, which was not seen in the control group. This research supports others in demonstrating a decrease in ICP with temperature, which could facilitate a reduction in the use of hyperosmolar agents or other stage II interventions. The decrease in PbtO2 is not below the suggested treatment threshold of 20 mmHg, but might indicate a decrease in CBF.

Therapeutic hypothermia to reduce intracranial pressure after traumatic brain injury: the Eurotherm3235 RCT

“…This would also be in keeping with the small but significant increase in the average daily lactate concentration and the greater prevalence of metabolic acidosis in the TH group. In a small, single-centre, retrospective analysis of the first 17 participants enrolled in the Eurotherm3235 Trial, Flynn et al 140 found that there was a significant decline in mean PbtO 2 from 30.2 mmHg to 22.4 mmHg in the TH group, from induction to stable hypothermia. In five out of the nine TH participants, PbtO 2 fell below the target value of 20 mmHg but was unaffected by cooling in the remainder of the TH group.…”

Therapeutic hypothermia versus normothermia in adult patients with traumatic brain injury: a meta-analysis

“…After removing duplicate records, animal studies, case reports, review articles, comments, or studies that were not randomized controlled trials, 22 studies remained for assessment. Three studies were preliminary reports of subsequent studies (Liu et al 2006 ; Flynn et al 2015 ; Marion et al 1993 ) and were excluded to avoid duplication. One study did not report the length of the follow-up period and incidence of complications, and was excluded (Yan and Tang 2001 ).…”

Therapeutic Hypothermia for Increased Intracranial Pressure after Decompressive Craniectomy: A Single Center Experience

“…The Eurotherm 3235 Trial8) was a large, randomized trial, and its results suggest that TH is beneficial for lowering ICP in patients with traumatic brain injury and ICP higher than 20 mmHg. This clinical trial is still ongoing.…”