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

Clinical article

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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 (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 every 24 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 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 PO2 levels were significantly increased during 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 and CMRO2 for 6 hours (p ≤ 0.01). Cerebrospinal fluid lactate concentrations decreased posttreatment in both the HBO2 and NBH groups (p < 0.05). The dialysate lactate levels in patients who had received HBO2 decreased for 5 hours posttreatment (p = 0.017). Microdialysis lactate/pyruvate (L/P) ratios were significantly decreased posttreatment in both HBO2 and NBH groups (p < 0.05). Cerebral blood flow, CMRO2, microdialysate lactate, and the L/P ratio had significantly 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 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 O2 toxicity.

Conclusions

Hyperbaric O2 has a more robust posttreatment effect than NBH on oxidative cerebral metabolism related to its ability to produce a brain tissue PO2 ≥ 200 mm Hg. However, it appears that O2 treatment for severe TBI is not an all or nothing phenomenon but represents a graduated effect. No signs of pulmonary or cerebral O2 toxicity were present.

Abbreviations used in this paper:AVDO2 = arteriovenous differences in oxygen; BAL = bronchial alveolar lavage; CBF = cerebral blood flow; CMRO2 = cerebral metabolic rate of oxygen; FiO2 = fraction of inspired oxygen; GCS = Glasgow Coma Scale; HBO2 = hyperbaric oxygen; ICP = intracranial pressure; ICU = intensive care unit; IL = interleukin; L/P = lactate/pyruvate; NBH = normobaric hyperoxia; OEF = oxygen extraction fraction; PEEP = positive end expiration pressure; P/F = PaO2/FiO2; PvO2 = partial pressure of venous oxygen; ROS = reactive oxygen species; TBI = traumatic brain injury; TIL = therapeutic intensity level; UPTD = unit pulmonary toxicity dose.

Article Information

Address correspondence to: Gaylan L. Rockswold, M.D., Ph.D., Department of Surgery, Hennepin County Medical Center, 701 Park Avenue, Minneapolis, Minnesota 55415. email: gaylan.rockswold@hcmed.org.

Please include this information when citing this paper: published online October 23, 2009; DOI: 10.3171/2009.7.JNS09363.

© AANS, except where prohibited by US copyright law.

Headings

Figures

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    Graph showing CMRO2 with post-/pretreatment ratio means. A value > 1 indicates the posttreatment value is > the pretreatment value, and a value < 1 indicates the posttreatment value is < the pretreatment value. The graph also depicts the overall comparison of change among the treatment arms. There was an improvement of 32% from pre- to posttreatment in the HBO2 group as compared with the control group (standard care). There was no change in the NBH group as compared with the control group. As a significant time*group interaction was not found in the statistical model, only the global pre- to posttreatment ratio means are shown. *p = 0.01, compared with the standard treatment (control) group. n = number of patients.

  • View in gallery

    Graph showing brain tissue PO2 with post-/pretreatment ratio means. A value > 1 indicates the posttreatment value is > the pretreatment value, and a value < 1 indicates the posttreatment value is < the pretreatment value. The graph also depicts the overall comparison of change among the treatment arms. In the HBO2 group compared with the control group, there was an increase of ~ 280% in brain tissue PO2 from pretreatment to 30 minutes posttreatment. The HBO2 group's brain tissue PO2 then remained higher than that in the control group by ~ 50% throughout the posttreatment period. In comparison with the control group, the NBH group had a 180% increase in brain tissue PO2 at 30 minutes posttreatment, but the brain tissue PO2 decreased to baseline levels within 1 hour after each treatment was completed. Because a significant time*group interaction was found in the statistical model, the ratio means are shown for the first 6 hours posttreatment. *p < 0.05 and **p < 0.0001, compared with the control group. post = posttreatment.

  • View in gallery

    Graph showing microdialysate L/P ratio in “uninjured” brain with posttreatment/pretreatment ratio means. A value > 1 indicates the posttreatment value is > the pretreatment value, and a value < 1 indicates the posttreatment value is < the pretreatment value. This figure also depicts the overall comparison of change between the treatment arms. Posttreatment microdialysate L/P ratios were decreased by 10% for patients in the HBO2 group and by 3% for those in the NBH group, in comparison with control group levels. As a significant time*group interaction was not found in the statistical model, only the global pre- to posttreatment ratio means are shown. *p = 0.0037 and **p < 0.0001 in comparison with the control group.

  • View in gallery

    Graph showing the mean pre- to posttreatment difference in ICP resulting from the statistical model. The difference in pre- to posttreatment values was used for ICP instead of the ratio of pretreatment values to posttreatment values because of 0 values. This figure also depicts the overall comparison of change between the treatment arms. The HBO group's difference in ICP from pre- to posttreatment was significantly lower than the control group. The NBH group's difference in ICP from pre- to posttreatment did not differ significantly from the control group following treatment sessions. As a significant time*group interaction was not found in the statistical model, only overall pre- to posttreatment mean differences are shown. *p = 0.0010 in comparison with the control group.

  • View in gallery

    Graph showing ventricular CSF F2-isoprostane with post-/ pretreatment ratio means. A value > 1 indicates the posttreatment value is > the pretreatment value, and a value < 1 indicates the posttreatment value is < the pretreatment value. This graph also depicts the overall comparison of change among the treatment arms. The levels of CSF F2-isoprostane did not change over time for either the HBO2 or NBH group in comparison with the control group. As a significant time*group interaction was not found in the statistical model, only overall pre- to posttreatment ratio means are shown.

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