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

Object Oxygen delivered in supraphysiological amounts is currently under investigation as a therapy for severe traumatic brain injury (TBI). Hyperoxia can be delivered to the brain under normobaric as well as hyperbaric conditions. In this study the authors directly compare hyperbaric oxygen (HBO 2 ) and normobaric hyperoxia (NBH) treatment effects. Methods Sixty-nine patients who had sustained severe TBIs (mean Glasgow Coma Scale Score 5.8) were prospectively randomized to 1 of 3 groups within 24 hours of injury: 1) HBO 2 , 60 minutes of HBO 2 at 1.5 ATA; 2) NBH, 3 hours of 100% fraction of inspired oxygen at 1 ATA; and 3) control, standard care. Treatments occurred once every 24 hours for 3 consecutive days. Brain tissue PO 2 , microdialysis, and intracranial pressure were continuously monitored. Cerebral blood flow (CBF), arteriovenous differences in oxygen, cerebral metabolic rate of oxygen (CMRO 2 ), CSF lactate and F2-isoprostane concentrations, and bronchial alveolar lavage (BAL) fluid interleukin (IL)–8 and IL-6 assays were obtained pretreatment and 1 and 6 hours posttreatment. Mixed-effects linear modeling was used to statistically test differences among the treatment arms as well as changes from pretreatment to posttreatment. Results In comparison with values in the control group, the brain tissue PO 2 levels were significantly increased during treatment in both the HBO 2 (mean ± SEM, 223 ± 29 mm Hg) and NBH (86 ± 12 mm Hg) groups (p < 0.0001) and following HBO 2 until the next treatment session (p = 0.003). Hyperbaric O 2 significantly increased CBF and CMRO 2 for 6 hours (p ≤ 0.01). Cerebrospinal fluid lactate concentrations decreased posttreatment in both the HBO 2 and NBH groups (p < 0.05). The dialysate lactate levels in patients who had received HBO 2 decreased for 5 hours posttreatment (p = 0.017). Microdialysis lactate/pyruvate (L/P) ratios were significantly decreased posttreatment in both HBO 2 and NBH groups (p < 0.05). Cerebral blood flow, CMRO 2 , microdialysate lactate, and the L/P ratio had significantly greater improvement when a brain tissue PO 2 ≥ 200 mm Hg was achieved during treatment (p < 0.01). Intracranial pressure was significantly lower after HBO 2 until the next treatment session (p < 0.001) in comparison with levels in the control group. The treatment effect persisted over all 3 days. No increase was seen in the CSF F2-isoprostane levels, microdialysate glycerol, and BAL inflammatory markers, which were used to monitor potential O 2 toxicity. Conclusions Hyperbaric O 2 has a more robust posttreatment effect than NBH on oxidative cerebral metabolism related to its ability to produce a brain tissue PO 2 ≥ 200 mm Hg. However, it appears that O 2 treatment for severe TBI is not an all or nothing phenomenon but represents a graduated effect. No signs of pulmonary or cerebral O 2 toxicity were present.