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 hyperbaricconditions. In this study the authors directly compare hyperbaric oxygen (HBO2) 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) HBO2, 60 minutes of HBO2 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 every24 hours for 3 consecutive days. Brain tissue PO2, microdialysis, and intracranial pressure were continuously monitored. Cerebral blood flow (CBF), arteriovenous differences in oxygen, cerebral metabolic rate of oxygen (CMRO2),CSF lactate and F2-isoprostane concentrations, and bronchial alveolar lavage (BAL) fluid interleukin (IL)–8 andIL-6 assays were obtained pretreatment and 1 and 6 hours posttreatment. Mixed-effects linear modeling was used tostatistically 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 PO2 levels were significantly increasedduring treatment in both the HBO2 (mean ± SEM, 223 ± 29 mm Hg) and NBH (86 ± 12 mm Hg) groups (p < 0.0001)and following HBO2 until the next treatment session (p = 0.003). Hyperbaric O2 significantly increased CBF andCMRO2 for 6 hours (p ≤ 0.01). Cerebrospinal fluid lactate concentrations decreased posttreatment in both the HBO2and NBH groups (p < 0.05). The dialysate lactate levels in patients who had received HBO2 decreased for 5 hoursposttreatment (p = 0.017). Microdialysis lactate/pyruvate (L/P) ratios were significantly decreased posttreatment inboth HBO2 and NBH groups (p < 0.05). Cerebral blood flow, CMRO2, microdialysate lactate, and the L/P ratio hadsignificantly greater improvement when a brain tissue PO2 ≥ 200 mm Hg was achieved during treatment (p < 0.01).Intracranial pressure was significantly lower after HBO2 until the next treatment session (p < 0.001) in comparisonwith 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 potentialO2 toxicity.Conclusions. Hyperbaric O2 has a more robust posttreatment effect than NBH on oxidative cerebral metabolismrelated to its ability to produce a brain tissue PO2 ≥ 200 mm Hg. However, it appears that O2 treatment for severe TBIis not an all or nothing phenomenon but represents a graduated effect. No signs of pulmonary or cerebral O2 toxicitywere present. (DOI: 10.3171/2009.7.JNS09363)