Gaylan L. Rockswold

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 (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 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 (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 < or = 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 > or = 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 > or = 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.

Civilian gunshot wounds to the brain: prognosis and management.

The extent of treatment for the victims of gunshot wounds to the brain remains quite controversial, particularly when these patients present with extensive neurological dysfunction. We propose guidelines regarding the degree and aggressiveness of therapy. The factors that seem to have a significant impact on the patients final outcome are the neurological examination at the time of admission, the radiological findings, and the motivation for the shooting. Thus, the authors propose a nonsurgical line of therapy for comatose patients with unilateral or bilateral cerebral gunshot wounds where bone or metal fragments are visualized away from the bullet path on computed tomography scan, particularly when these individuals are suicide victims.

Inhibition of microglial cell RANTES production by IL-10 and TGF-beta.

Using human fetal microglial cell cultures, we found that the gram‐negative bacterial cell wall component lipopolysaccharide (LPS) stimulated RANTES (regulated upon activation of normal T cell expressed and secreted) production through the protein kinase C signaling pathway and that activation of transcription nuclear factor (NF)‐κB was required for this effect. Similarly, the proinflammatory cytokines interleukin (IL)‐1β and tumor necrosis factor‐α dose‐dependently stimulated microglial cell RANTES production via NF‐κB activation. Anti‐inflammatory cytokines, IL‐10, and transforming growth factor (TGF)‐β sequentially inhibited LPS‐ and cytokine‐induced microglial cell NF‐κB activation, RANTES mRNA expression, and protein release. Proinflammatory cytokines but not LPS also stimulated RANTES production by human astrocytes. These findings demonstrate that human microglia synthesize RANTES in response to proinflammatory stimuli, and that the anti‐inflammatory cytokines IL‐10 and TGF‐β down‐regulate the production of this β‐chemokine. These results may have important therapeutic implications for inflammatory diseases of the brain. J. Leukoc. Biol. 65: 815–821; 1999.

Barbiturate therapy in uncontrolled intracranial hypertension

From July 1978 to September 1981, 27 patients from a group of 210 patients with severe head injuries developed uncontrolled intracranial hypertension despite intensive medical and surgical management. These 27 patients were considered appropriate candidates for barbiturate therapy. Abnormal posturing or flaccidity was present in 70% of the patients, and 41% had bilaterally fixed pupils. Twenty-five of 27 patients had mass lesions requiring operation. Of the 15 patients who responded to barbiturate therapy with normalization of intracranial pressure for 24 hours, 5 died (33% mortality). Nine of the 12 patients who did not respond to the barbiturate therapy died (75% mortality). The total mortality in this group of 27 patients was 52%. Of the survivors, 69% had a recovery classified as good recovery/moderate disability, and 31% were in a severe disability/vegetative state. The morbidity and mortality in these patients is high, but comparisons with previous studies show that this is a selected group of severe head injuries with a high percentage of poor prognostic indicators. Our experience suggests that barbiturates can be effective in lowering intracranial pressure in patients with otherwise unresponsive intracranial hypertension, and, by doing so, may decrease the mortality in a group of patients considered untreatable by the usual therapeutic modalities.

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

OBJECT Preclinical and clinical investigations indicate that the positive effect of hyperbaric oxygen (HBO2) for severe traumatic brain injury (TBI) occurs after rather than during treatment. The brain appears better able to use baseline O2 levels following HBO2 treatments. In this study, the authors evaluate the combination of HBO2 and normobaric hyperoxia (NBH) as a single treatment. METHODS Forty-two patients who sustained severe TBI (mean Glasgow Coma Scale [GCS] score 5.7) were prospectively randomized within 24 hours of injury to either: 1) combined HBO2/NBH (60 minutes of HBO2 at 1.5 atmospheres absolute [ATA] followed by NBH, 3 hours of 100% fraction of inspired oxygen [FiO2] at 1.0 ATA) or 2) control, standard care. Treatments occurred once every 24 hours for 3 consecutive days. Intracranial pressure, surrogate markers for cerebral metabolism, and O2 toxicity were monitored. Clinical outcome was assessed at 6 months using the sliding dichotomized Glasgow Outcome Scale (GOS) score. Mixed-effects linear modeling was used to statistically test differences between the treatment and control groups. Functional outcome and mortality rates were compared using chi-square tests. RESULTS There were no significant differences in demographic characteristics between the 2 groups. In comparison with values in the control group, brain tissue partial pressure of O2 (PO2) levels were significantly increased during and following combined HBO2/NBH treatments in both the noninjured and pericontusional brain (p < 0.0001). Microdialysate lactate/pyruvate ratios were significantly decreased in the noninjured brain in the combined HBO2/NBH group as compared with controls (p < 0.0078). The combined HBO2/NBH groups intracranial pressure values were significantly lower than those of the control group during treatment, and the improvement continued until the next treatment session (p < 0.0006). The combined HBO2/NBH groups levels of microdialysate glycerol were significantly lower than those of the control group in both noninjured and pericontusional brain (p < 0.001). The combined HBO2/NBH groups level of CSF F2-isoprostane was decreased at 6 hours after treatment as compared with that of controls, but the difference did not quite reach statistical significance (p = 0.0692). There was an absolute 26% reduction in mortality for the combined HBO2/NBH group (p = 0.048) and an absolute 36% improvement in favorable outcome using the sliding dichotomized GOS (p = 0.024) as compared with the control group. CONCLUSIONS In this Phase II clinical trial, in comparison with standard care (control treatment) combined HBO2/NBH treatments significantly improved markers of oxidative metabolism in relatively uninjured brain as well as pericontusional tissue, reduced intracranial hypertension, and demonstrated improvement in markers of cerebral toxicity. There was significant reduction in mortality and improved favorable outcome as measured by GOS. The combination of HBO2 and NBH therapy appears to have potential therapeutic efficacy as compared with the 2 treatments in isolation. CLINICAL TRIAL REGISTRATION NO.: NCT00170352 (ClinicalTrials.gov).

Hypertonic saline and its effect on intracranial pressure, cerebral perfusion pressure, and brain tissue oxygen.

OBJECTIVEHypertonic saline is emerging as a potentially effective single osmotic agent for control of acute elevations in intracranial pressure (ICP) caused by severe traumatic brain injury. This study examines its effect on ICP, cerebral perfusion pressure (CPP), and brain tissue oxygen tension (PbtO2). METHODSTwenty-five consecutive patients with severe traumatic brain injury who were treated with 23.4% NaCl for elevated ICP were evaluated. Bolt catheter probes were placed in the noninjured hemisphere, and hourly ICP, mean arterial pressure, CPP, and PbtO2 values were recorded. Thirty milliliters of 23.4% NaCl was infused over 15 minutes for intracranial hypertension, defined as ICP greater than 20 mm Hg. Twenty-one male patients and 4 female patients aged 16 to 64 years were included. The mean presenting Glasgow Coma Scale score was 5.7. RESULTSMean pretreatment values included an ICP level of 25.9 mm Hg and a PbtO2 value of 32 mm Hg. The posttreatment ICP level was decreased by a mean of 8.3 mm Hg (P < 0.0001), and there was an improvement in PbtO2 of 3.1 mm Hg (P < 0.01). ICP of more than 31 mm Hg decreased by 14.2 mm Hg. Pretreatment CPP values of less than 70 mm Hg increased by a mean of 6 mm Hg (P < 0.0001). No complications occurred from this treatment, with the exception of electrolyte and chemistry abnormalities. At 6 months postinjury, the mortality rate was 28%, with 48% of patients achieving a favorable outcome by the dichotomized Glasgow Outcome Scale. CONCLUSIONHypertonic saline as a single osmotic agent decreased ICP while improving CPP and PbtO2 in patients with severe traumatic brain injury. Patients with higher baseline ICP and lower CPP levels responded to hypertonic saline more significantly.

Hyperbaric oxygen in traumatic brain injury.

Abstract Objectives: This critical literature review examines historical and current investigations on the efficacy and mechanisms of hyperbaric oxygen (HBO) treatment in traumatic brain injury (TBI). Potential safety risks and oxygen toxicity, as well as HBOs future potential, are also discussed. Methods: Directed literature review. Results: Historically, cerebral vasoconstriction and increased oxygen availability were seen as the primary mechanisms of HBO in TBI. HBO now appears to be improving cerebral aerobic metabolism at a cellular level, namely, by enhancing damaged mitochondrial recovery. HBO given at the ideal treatment paradigm, 1.5 ATA for 60 minutes, does not appear to produce oxygen toxicity and is relatively safe. Discussion: The use of HBO in TBI remains controversial. Growing evidence, however, shows that HBO may be a potential treatment for patients with severe brain injury. Further investigations, including a multicenter prospective randomized clinical trial, will be required to definitively define the role of HBO in severe TBI.

Neurologic recovery following rapid spinal realignment for complete cervical spinal cord injury.

A case of impressive neurologic recovery after a complete cervical spinal cord injury is presented. The importance of prehospital recognition and immobilization and prompt management of cervical spine injuries is emphasized. Full reduction of the fracture-dislocation of C3 on C4 was accomplished 90 minutes postinjury.

Radiation-induced meningiomas in pediatric patients

Radiation-induced meningiomas rarely have latency periods short enough from the time of irradiation to the clinical presentation of the tumor to present in the pediatric patient. Three cases of radiation-induced intracranial meningiomas in pediatric patients are presented. The first involved a meningioma of the right frontal region in a 10-year-old boy 6 years after the resection and irradiation of a 4th ventricular medulloblastoma. Review of our pediatric tumor cases produced a second case of a left temporal fossa meningioma presenting in a 15-year-old boy with a history of irradiation for retinoblastoma at age 3 years and a third case of a right frontoparietal meningioma in a 15-year-old girl after irradiation for acute lymphoblastic leukemia. Only three cases of meningiomas presenting in the pediatric age group after radiation therapy to the head were detected in our review of the literature.

Neurology of Micturition

The understanding, diagnosis and management of neurologic dysfunction of the bladder have undergone considerable changes during the last 2 decades. These changes were the result of animal experimentation into physiology and pharmacology and the accelerated use of biomedical engineering technology. The implementation of these advances will require physician re-education in the neurology of micturition.