Results of a prospective randomized trial for treatment of severely brain-injured patients with hyperbaric oxygen

Abstract

The authors enrolled 168 patients with closed-head trauma into a prospective trial to evaluate the effect of hyperbaric oxygen in the treatment of brain injury. Patients were included if they had a total Glasgow Coma Scale (GCS) score of 9 or less for at least 6 hours. After the GCS score was established and consent obtained, the patient was randomly assigned, stratified by GCS score and age, to either a treatment or a control group. Hyperbaric oxygen was administered to the treatment group in a monoplace chamber every 8 hours for 1 hour at 1.5 atm absolute; this treatment course continued for 2 weeks or until the patient was either brain dead or awake. An average of 21 treatments per patient was given. Outcome was assessed by blinded independent examiners. The entire group of 168 patients was followed for 12 months, with two patients lost to follow-up study. The mortality rate was 17% for the 84 hyperbaric oxygen-treated patients and 32% for the 82 control patients (chi-squared test, 1 df, p = 0.037). Among the 80 patients with an initial GCS score of 4, 5, or 6, the mortality rate was 17% for the hyperbaric oxygen-treated group and 42% for the controls (chi-squared test, 1 df, p = 0.04). Analysis of the 87 patients with peak intracranial pressures (ICP) greater than 20 mm Hg revealed a 21% mortality rate for the hyperbaric oxygen-treated patients, as opposed to 48% for the control group (chi-squared test, 1 df, p = 0.02). Myringotomy to reduce pain during hyperbaric oxygen treatment helped to reduce ICP. Analysis of the outcome of survivors reveals that hyperbaric oxygen treatment did not increase the number of patients in the favorable outcome categories (good recovery and moderate disability). The possibility that a different hyperbaric oxygen treatment paradigm or the addition of other agents, such as a 21-aminosteroid, may improve quality of survival is being explored.

A prospective, randomized Phase II clinical trial to evaluate the effect of combined hyperbaric and normobaric hyperoxia on cerebral metabolism, intracranial pressure, oxygen toxicity, and clinical outcome in severe traumatic brain injury

“…As in previous clinical trials performed at our institution, 41,44,45 there were no signs of cerebral or pulmonary O 2 toxicity in the present trial. Brain tissue is especially vulnerable to lipid peroxidation because of its high rate of O 2 consumption and higher content of phospholipids.…”

“…These mechanisms have been demonstrated in both experimental and clinical investigations and include improved oxidative metabolism and mitochondrial function and reductions in intracranial hypertension, apoptosis, neuroinflammation, and free radical-mediated damage. 9,38,39,41,[44][45][46]50,52,[58][59][60][61]65 The results of the present randomized clinical trial help to support these findings.…”

“…Our institution has delivered 1984 HBO 2 treatments in 3 prospective clinical studies, and an emergency decompression has never been required. 41,44,45 If a proper treatment paradigm is maintained, our experience documents that HBO 2 treatment can be safely delivered to patients with severe TBI in monoplace as well as multiplace chambers.…”

“…This outcome is significantly better than our prior experience using HBO 2 as a single treatment or reports from the literature using NBH. 41,53 This improvement in clinical outcome may be due to the synergistic effect of combining HBO 2 and NBH treatments. There was significant improvement in markers of cerebral metabolism and oxygen toxicity as well as ICP during the NBH portion of the combined HBO 2 /NBH treatment.…”

Disorders of consciousness after acquired brain injury: the state of the science

“…Other treatments A wide range of other treatments, including structured sensory stimulation, 163 repetitive TMS, 164 hyperbaric oxygen, 165 and various dopaminergic and GABAergic medications, 166 have been administered to patients with DOCs, but the evidence is insufficient to formulate r ecommendations regarding their use in clinical practice.…”