HYPERBARIC OXYGEN FOR TREATMENT OF
STROKE AND TRAUMATIC BRAIN INJURIES
July, 1998

Abstract

Fifty stable, chronic stroke and traumatic brain injury (TBI) patients (mean age 62, mean duration post stroke 29 months) were treated with a combination of hyperbaric oxygen, physical therapy and EEG biofeedback for two months. Surveys given to patients or their family members showed that 96.7% of the patients improved one or more of their lost or diminished functions. Pre- and post-treatment, physical therapy evaluations indicated that 100% of the patients experienced improvements in one or more functions. These results suggest hyperbaric oxygen therapy along with other modalities provide safe and efficient treatment of stroke or TBI related disabilities.

Introduction

Health institutes have shown different efforts to improve the quality of daily life for stroke patients. However, the general outcome is not a encouragement, especially for those of long term stroke or brain injury related disorders (TBI) patients. Although stroke is a leading cause of death and disability, its post management was often marked by feelings of hopelessness.

Hyperbaric oxygen therapy (HBO) uses oxygen under pressure and first clinical use of hyperbaric oxygen for treatment of stroke and TBI patients was reported in 1965. Since then many studies have demonstrated its safety and efficacy (1,2,16-20). It is expected that HBO will be a competitive therapy for this devastating neurological disorder.

The dominant theory of stroke and TBI for more than 100 years has been that the loss of function is largely related to the death of brain cells due to the interruption of blood flow and the resulting lack of oxygen to a part of the brain. This traditional concept of infarction is being challenged by a theory which has been slowly evolving over the past 25 years. This theory states that the death of brain cells occurs only when the flow of blood falls below a certain level (approximately 8-10 ml/100 gr./min., while at slightly higher levels of blood flow the tissue remains alive but not able to function. Thus in the acute stroke the affected central core of brain tissue dies while the more peripheral tissues may remain alive for many years after the initial insult, depending on the amount of blood the brain tissue receives (3,7).

Brain areas that are injured and are not receiving enough blood flow as a result of the stroke or trauma are now referred to as the "ischemic penumbra". This is the area that surrounds the central core of infracted (dead) tissue. These "rim" tissues do not receive enough oxygen to function but do receive enough to stay alive. These brain cells have been described as "sleeping beauties", "sleeping neurons" or "dormant" or "idling neurons". These neurons are nonfunctional but anatomically intact and can be revived. ( 3), (8-10).

It is widely recognized that damaged blood vessels are thought to produce the ischemic penumbra in stroke or TBI. In the acute phase of stroke or TBI, those damaged blood vessels lead to significant edema (swelling of the tissues as a result of the damage). This swelling may take up to 9 to 12 months to resolve, and the swelling compresses brain blood vessels, limits the flow of blood to the damaged tissues. As the swelling goes away, some of the blood vessels will regain their original diameters and normal blood flow will resume (9). It was widely documented that the water content of edematous tissue of the brain was decreased significantly by HBO. (12-14).

Another process is "neovascularization", also known as "angiogenesis". This is the process of forming new capillaries that extend from the surrounding healthy brain tissue into the areas of the ischemic penumbra. The outermost portions of the ischemic penumbra (those portions closest to normal brain tissue) are able to metabolize but at a reduced rate than normal tissues, however, they are receiving more blood and oxygen than the centrally located ischemic tissues. Adenosine, a metabolite of ATP, is released from ischemic "rim" tissues when cells metabolism and repair. Adenosine is a vasodilator that stimulates new capillaries to grow into the ischemic penumbra (neovascularization). Thus during the first year after a stroke or TBI, new blood vessels are stimulated to move into the ischemic penumbra to re-supply it with a new blood supply. (9)

Unfortunately, the ischemic penumbral tissues closer to the infarct area usually are not receiving enough oxygen or nutrients to generate adequate amounts of ATP - either from aerobic or anaerobic metabolism for neovascularization to occur. Due to the lack of ATP formation, adenosine is not produced and the formation of new capillaries does not occur. Thus the ischemic penumbra remains ischemic and static since the process of neovascularization is not able to be completed. This often results in a substantial amount of brain tissue that remains ischemic and non-functioning in the chronic stroke and TBI patients. This failure of natural healing processes is due ultimately to damaged blood vessels and their inability to provide oxygen and nutrients to those portions of the brain that are damaged.(11)

Hyperbaric oxygen works to improve chronic stroke and TBI patients by regenerating, repairing and generating new blood vessels to the injured parts of the brain. In the ischemic penumbra, the blood vessels are often constricted to the point that red blood cells can not pass through them. This creates the situation where only plasma is able to pass slowly to part or most of the ischemic area. Since plasma has nutrients, the tissues of the ischemic penumbra are able to remain alive by using anaerobic glycolysis (metabolism without oxygen) also known as fermentation.. Anaerobic glycolysis only produces 2 moles of ATP per mole of glucose metabolized instead of the 36 moles of ATP formed when oxygen is present. Thus the tissues suffer from a chronic shortage of ATP and its subsequent metabolite- adenosine. Hyperbaric oxygen forces oxygen into the plasma to such a degree that as the plasma passes into the ischemic penumbra, the ischemic tissue begins to receive enough oxygen for aerobic glycolysis (metabolism that uses oxygen) to occur once more. This creates a surge of ATP production in the ischemic tissue which continues to be produced as long as the patient is within the hyperbaric oxygen chamber. When the patient is taken out of the chamber, blood and tissue levels of oxygen fall back to pre-treatment levels within 4 hours. As the tissue oxygen level falls, the newly generated ATP is used by the ischemic tissues and adenosine is released into the surrounding tissues in an effort by the tissues to continue to receive the oxygen that it just had been receiving. As a part of this survival mechanism, adenosine and other chemical mediators are released into the surrounding tissues stimulating angiogenesis. Done daily over time, the HBO stimulates new blood vessels to grow into the ischemic tissues returning them back to normal in terms of their oxygen supply. Recovery of function is associated with recovery of local perfusion and metabolism. (11)

Once the ischemic penumbral tissues are no longer suffering from a lack of oxygen, they are able to begin to repair their injured neurons, glial cells and extracellular matrix. These tissues now have to try to repair their own cell bodies, dendrites, axons and synapses but also have to grow out and extend to the many lost connections that occurred with the stroke.

Treatment of acute and chronic focal cerebral ischemia with hyperbaric oxygen has been reported both in animal and in humans. The results of the clinical research have suggested a promising role for the use of HBO. (2, 16-20). In this study, we showed that HBO is quite effucient when used as a part of combined therapy and patients did benefit from this therapy.

Method

A: Patients:

50 patients ( male 21 and female 29) voluntarily enrolled in this study. Patient's ages ranged from 31-89 years with a mean age of 61.8 years. The duration from onset of stroke to entry into our rehabilitation program varied from 1 month to 10 years. The average duration since stroke onset was 28 months. 3 of the patients suffered chronic stroke more than 8 years.

Table 1 : Patient's Pre-Treatment Condition

B. Treatment:

1. HBO Treatment: Patients received hyperbaric oxygen therapy (HBO) at a pressure of 1.5. to 2.0 atmospheres absolute (ATA) in a sealed single person chamber. Oxygen (100% medical grade) was inhaled through a plastic face mask.

The therapy was carried out for 90 minutes per day and 6 times per week in most patients. A few patients received HBO treatment twice a day. The average number of HBO treatments completed was 55.

Hyperbaric oxygen therapy feels much like going for a ride in a modern day jet - the chamber even looks like the cockpit of a jet fighter plane! As patients start their treatment they are sitting upright at a comfortable angle inside of this cockpit like chamber. Patients have an oxygen mask over their mouth and nose, the door is shut and they feel a slight movement of air as the chamber begins to be filled with more air. As the air enters the chamber you may notice a slight discomfort in one or both ears just like they have experienced while flying in the large commercial jets. Patients may choose to swallow, chew gum or hold their nose and blow outward to help equalize the pressure in their ears.

2. Physical Therapy Treatment: Physical therapy procedures included various physical activities and modalities as needed. The modalities used were electrical stimulation, hot or cold packs, ultrasound, short wave diathermy and paraffin bath therapy. Each patient's condition was evaluated to determine the appropriate modality, dosage, placement and methods of application.

Physical therapy techniques were provided and adjusted as the patient's condition warranted. These included strengthening, range of motion, endurance exercise, neurodevelopmental technique, joint mobilization, kinetic activities, myofascial release and detailed gait or orthotic training.

Initial evaluation assessed range of motion, strength grades, bed mobility, transfer status, balance, neurological findings, posture and ambulatory status. Periodic re-evaluations were performed to assess each patient's progress, and treatment plans were changed as needed. Upon discharge, a discharge evaluation was performed to assess progress and determine patient's long term therapy program.

The number of therapies varied from 13 to 85 treatments with a mean of 40. Patients came to physical therapy 5 times per week.

3. Bio-Feedback Treatment: Patients came to biofeedback therapy 5 times per week and received a minimum of 21 ( mean 35) one-half hour daily sessions of EEG biofeedback. Sessions consisted of inhibiting and rewarding various selected EEG frequencies through audio and visual displays to encourage flexibility in brain activity. Each session's threshold level were automatically calibrated by the instrument ( American Biotech Capscan 80) and a frequency spectral display summarized EEG amplitudes over 0 to 32 Hertz.

C. Treatment Evaluation:

The effects of treatment were evaluated by a patient's questionnaire and a licensed physical therapist's evaluation both given at the beginning of the program and again at the end.

In the patient questionnaire, 16 different functions ranging from motor ability and mental situations were analyzed. Patient's functions were self graded as followings:

- : negative change

0: no improvement at all.

Slight improvement: 1-10 % of the function improved.

Mild improvement: 10- 25% of the function improved.

Moderate improvement: 20-50% of the function improved.

Significant improvement: 50 -75% of the function improved.

Back to normal: 100% of the function improved.

In the physical therapist's evaluation, 33 different functions ranging from motor ability to cognitive functioning were analyzed. For statistical purposes we assigned the therapist's evaluation of each parameter as either being no improvement or improvement.

Range of movement: NA stands for "not available" because the patient's function was within normal limits before the treatment. " No improvement" means the increased range of movement is less than 10 degrees. "Improvement" stands for when the range of movement increased 10 degrees or more. No matter how much more than 10 degrees of increased range of motion occurred, all positive results were grouped simply as "improvement".

Extremities strength evaluation: Grading was on a 0-5 degree scale with 0 indicating no strength and 5 indicating normal as compared to the non-involved extremity. NA stands for "not available" because the patient's function of that extremity was normal before the treatment. No improvement means the increased strength is less than one degree, such as from 3- to 3+ was considered as no improvement. Improvement stands for the strength increased at least one degree, such as from 2 to 3. No matter how much more than one degree of improvement occurred in a particular patient, all of these patients with positive results were grouped simply as "improvement"

Other functions such as bed mobility, transfer ( supine to sit, sit to stand, bed to chair) balance ( sitting, standing, ambulatory) were graded as:

#1, independent;
#2, good;
#3, good with care;
#4, with minimal assistance;
#5, with maximal assistance;
#6, unable.

Improvement was defined to occur when the patient's functional evaluation score decreased by at least 1 (#6 being unable to perform the task and #1 being able to do the task independently) .

Results

A: Patient Questionnaire:

Patient questionnaires were collected prior to and after the series of treatments. Patients' general comments for this program are presented in Table 2.

Table 2:

Total Patient improvement in at least one of the functions is 96.7%. Only insignificant problems were encountered with the combination of therapies for treating chronic stroke patients. The summary of the patients' self evaluation is in table 3.

Table 3: Improvement level as evaluated by patients/caretakers.

B: Physical Therapist's Evaluation:

Physical therapist's evaluations were performed prior to and at the end of the program. 33 different functions including the range of motion, strength and balance function were analyzed. From the paired evaluations, all the patients showed one or more improvements among the 33 functions. The general findings from the physical therapist's evaluations are in table 4.

Table 4:

Patient % Functional Improvement Levels

10 % - Minimal Gains

08 % - Mild Gains

48 % - Moderate Gains

34 % - Excellent Gains

Total 100% Showed Improvement. No side effects or problems were encountered with the combination of therapies for treating chronic stroke patients. The result of paired analysis were shown in table 5 and 6.

Table 5: Physical Therapist's Evaluation of Extremities

Table 6: Physical Therapist's Evaluation.

Discussion:

The results from this study on this new procedure demonstrated that combined of HBO, physical therapy and EEG biofeedback benefit patients suffering from the effects of a chronic stroke. The improvements were similar among patients suffering from cerebral hemorrhage, and cerebral ischemia/thrombosis / embolism. Improvement also occurred in the 3 patients who had suffered from a stroke more than 8 years before beginning our combined therapy program.

Other improvements were also reported by the patients. For example, patients reported that their affected arm and leg felt chronically cold but changed to warm at some point during the therapy. Fingernails, which had stopped growing for several years, began to grow normally again. The chronic fatigue experienced by the patients prior to their therapy was generally relieved by the program.

The number of treatments required varies for each individual but experience told us that the best results occur when at least 60 daily treatments were done. If only 20 to 30 treatments were done, the patient would often experience "backsliding" and might lose some of the improvement they gained from the hyperbaric oxygen treatments. In addition, some patients would not even begin to improve until they have had more than thirty , forty or even more treatments. The reason for the "backsliding" that could occur with less than 30 treatments has not been studied scientifically but since it occurs at times of stress, it would seem to be due to the effects of excessive corticosteroids and catecholamines produced at these times. Stress hormones have anti-angiogenic properties and accelerate the production of free radicals and lipid peroxidation in blood vessels, all of which will have a detrimental effect on newly growing and fragile capillaries.

In acute stroke situation, as much as 85% of the brain injury are charateristiced as " idling neurons". The newly approved "clot busting" drugs (tPA-tissue plasminogen activator) has been found to be effective in maintaining the viability of the ischemic penumbra if given within the first three hours of the onset of a blood clot type of stroke. Hyperbaric oxygen is being considered as a treatment in conjunction with tPA in the acute stroke setting since it will extend the period of time during which the tPA can be given. (4-6, 10)

When used according to standard protocols, with oxygen pressures not exceeding 3 atmospheres and treatment sessions limited to a maximum of 120 minute, hyperbaric oxygen is safe. ( 15) In this study, there was no side effect was reported.

There were three out of more than 500 patients who have had enough pain and discomfort in clearing their ears and were send to an ear specialist for a simple insertion of a small tube through the ear drum. In these cases, this cured the problem and the person was able to continue with the program without further pain and with no problems with their hearing.

Severe, advanced emphysema may be a contraindication if the person has large lung bullae (large air filled sacks within the lung). The bullae may trap the oxygen and rupture while the person is decompressing. The presence of large bullae can be checked by ordering a CT exam of the chest.

Patients who have had a seizure worry about having another episode while in the chamber. Doctor K.K. Jain (1) the MD neurosurgeon who wrote the "Textbook of Hyperbaric Medicine" states, "Seizures are extremely rare and no more than a chance occurrence during HBO sessions at pressures between 1.5 and 2 ATA (2 ATA gauge pressure= 14.7 psi=760 mmHg) even in patients with a history of epilepsy." Our experience is similar.

Claustrophobia is an often voiced fear but once the person begins to work with our technicians, he or she is generally able to overcome their fears without a problem.

Muscle, bone and peripheral nerve dysfunction and atrophy are also major factors that are present in many patients. This is due to inactivity, loss of weight bearing, hormonal deficiencies, mineral deficiencies and a variety of different disease states. These dysfunction's and atrophy require aggressive, daily rehabilitative efforts for a minimum of two months to produce significant, long term beneficial results.

From a practical point of view, the patient who is being considered for hyperbaric oxygen therapy can be tested to determine if he/she is a candidate. A 3-D SPECT scan (single photon computerized tomogram) for determining cerebral blood flow is available at most larger hospitals in the USA. If this test is done and shows focal diminished brain blood flow, the patient has a good chance for significant improvement with a course of hyperbaric oxygen treatments.

This protocol produces the best overall results when the therapy is given in combination with other treatments such as physical, occupational and biofeedback therapy et al. Patient comes to us at average 2 ½ years after their stroke or TBI. They usually have gone through all of the standard therapies and have not improved over the past year despite continuing physical therapy and an active exercise program. They or their family members recognize their lack of improvement and come to us as "the last hope". Due to the severity of their disabilities and their failure to improve with conventional therapies, most patients hope that the use of hyperbaric oxygen will produce gratifying results. However, even with 60 days of hyperbaric oxygen treatments, the results may not reach their expectations, especially if only hyperbaric oxygen is used. Most patient would like to maximize their chances of improving while they are attending our clinic. In view of their desires and the fact that the combination of hyperbaric oxygen and other therapies produces improved overall results, we recommend daily physical, occupational, speech, vision, biofeedback, nutritional, vitamin, hormonal and growth factor therapies as needed to help our patients reach their maximum recovery potential.

In addition to the use of the above mentioned therapies I have also found that many patients have other disease processes which must be treated to maximize their recovery. Many patients when entering our program suffer from chronic urinary tract or other infections, have autoimmune disorders such as vasculitis, suffer from diabetes and diabetic neuropathy, have osteoporosis of the paralyzed limb(s), have serious atherosclerosis or have hormonal deficiencies. All pathologic conditions and problems must be addressed and corrected to maximize the patient's healing.

Conclusion:

The chronic stroke and TBI patients, who are stable and have not improved their functioning abilities for months to years, can achieve benefits from the combined administration of HBO, physical therapy and bio-feedback. This therapy program has been demonstrated to have insignificant side effects.

References:

(1) Jain, K.K. : Textbook of Hyperbaric Medicine. 2nd ed. 1996. Hogrefe and Huber Publishers, Inc.

(2) Steenblock, D. "Review of Hyperbaric Oxygen for Stroke Rehabilitation." Explore! Volume 7, Number 5, 1996/97.

(3) Neubauer, R.R., et al. "Hyperbaric Oxygen and Imaging Techniques in Diagnosis and Therapy of Stroke. Does the Ischemic Penumbra alter the outcome in Stroke?" International Symposium: Neuropsychomotor, Neuropharmacological, Psychosocial and Ethical Aspects, Oct. 7-11,1992 Siracusa, Italy. Pp 1-9.

(4) Gottlieb SF, Koehler GL, Rhodes, LVG, "An Oxygen- and pressure-sensitive enzyme: NaK adenosinetriphosphatase. In: CJ Lambertson (ed), "Underwater Physiology V, Proceedings of the 5th Symposium on Underwater Physiology," FASEB,Bethseda,1976 pp:431-442.

(5) Gottlieb SF, Schnitt PL. "Effects of increased pCO2 on activity of N-K-ATPase during purification from beef brain cortex:existence of new controlling mechanism?" Undersea Biomed Res 8:28-29,1981

(6) Schmitt, PL, Gottlieb SF. "Enhancement of cortical Na-K-ATPase by increased Oxygen tensions: Evidence of a new controlling mechanism." Brain Res. 242:271-278,1982

(7) Limberg M, VanRoyen EA, Hijdra A, et al. "99mm TC-HMPAO washout in prognosis of stroke." Lancet 1 (8642):839, April 15,1989

(8) Neubauer, R. et al . " Enhancing idling neurons." (Letter) Lancet, March 3, 1990, p542

(9) Neubauer, R.et al. " Stroke Treatment." (Letter)The Lancet, June 29,1991 p 1601

(10) Toole, James. American Heart Association. International Meeting on the Cerebral Circulation and Stroke. Anaheim, CA 1997.

(11) Meye, JS., Obara,K. "Diasschisis." Neurol Res. ( England) 15 (6) p362-6, Dec. 1993

(12) Akashi, K., Takakura, K., Lin, C.Y., Kitamura, K., Takagi, T., "Hyperbaric oxygen therapy; Clinical and basic studies." Neurologia Medico Chirur., 10: 294, 1968.

(13) Watanabe, M., Kanaya, H., Fuchizawa, K.,Onodera, H., and Suzuki, H., "Experimental study on compressed air therapy on cerebral edema." Jap. J. Hyperbaric Medicine 5: 23, 1970

(14) Micheal H. Sukoff, and Robert E. Ragatz. "Hyperbaric oxygenation for the Treatment of Acute Cerebral Edema." Neurosurgery 10:29-38, 1982

(15) Patrick M. Tibbles, John S. Edelsberc. "Hyperbaric Therapy." The New England Journal of Medicine 334 (25) 1642, 1996

(16) Akimov, G.A., et al. " Assessment of the effiency of hyperbaric oxygen therapy in early forms of cerebrovascular disorders" Neurosci Behav Phys. 15: 13-16, 1985

(17) Holbach, K.H., et al. "Reversibility of the chronic post-stroke state." Stroke , 7 (3) 296-300, 1976

(18) Holbach, K.H., et al. "Differentiation between reversible and ireversible post-stroke changes in brain tissue: Its relevance for cerebraovascular surgery." Surg. Neurol, 7: 325-331, 1977

(19) Marroni, A., et al. "Hyperbaric oxygen therapy at 1.5 or 2.0 ATA as an adjunct to the rehabilitation of stabilized stroke patients. A controlled study." Nineth International Congress on Hyperbaric Medicine, Sydney, Australia: March 1-4, 1987, pp. 161-167

(20) Li, W., "Cerebral thrombosis treated by hyperbaric oxygenation." Nineth International Congress on Hyperbaric Medicine, Sydney, Australia, March 1-4, 1987:pp 153-154

Shiokawa, O. et al. "Hyperbaric oxygen therapy in experimentally induced acute cerebral ischemia." UNDERSEA BIOMED RES, 1986, 13(3): 337-44. (animal study). Effects of hyperbaric oxygen (HBO) on acute cerebral ischemia were studied in spontaneously hypertensive rats, which had the carotid artery bilaterally ligated. The animals were exposed to HBO (2 ata) for 30 minutes at 1 or 3 hours after carotid ligation. The animals treated at 3 hours after ligation survived longer (6.5 hours) than did nontreated ones (4.3 hours). The cerebral lactate increased much less in the treated animals. Cerebral ATP levels tended to decrease less in the experimental group than the control group. The present results indicate that HBO administered at 3 hours after brain ischemia prevents further increase in cerebral lactate and produces a slight but significant increase in survival time.

Veltkamp, R. et al. "Hyperbaric oxygen decreases infarct size and behavioral deficit after transient focal cerebral ischemia in rats." BRAIN RES, 2000, 853(1): 68-73.(animal study)
Cerebral hypoxia is a major component of immediate and secondary cell damage caused by ischemia. Hyperbaric oxygen (HBO) is a potent means to increase the amount of oxygen dissolved in blood plasma. The authors sought to determine whether treatment with HBO initiated early after focal cerebral ischemia-onset protects the brain when experimental conditions such as brain temperature are controlled. Male Wistar rats underwent reversible filament occlusion of the right middle cerebral artery for 75 minutes. Animals were awakened after filament introduction and assessed for presence of forelimb paresis. Rats then underwent a 60 minute course of either 100% O2 at 1.0 atmosphere absolute (ata: control group), HBO 1.5 ata, or HBO 2.5 ata in a customized HBO chamber allowing physiological monitoring and pericranial temperature control. Rats treated with HBO 2.5 ata had better mean standard deviation behavioral scores than the control group or HBO 1.5 ata-treated animals. Similarly, total infarct volumes were smaller in animals receiving HBO at 2.5 ata compared to the control and 1.5 ata groups. Cortial infarction occurred less frequently in HBO 2.5 ata-treated than in control animals (44% vs 71%). The authors conclude that HBO can improve outcome after temporary focal ischemia when treatment is started early after ischemia-onset but HBO dose appears important. Potential mechanisms include enhanced oxygen supply to marginally perfused cells.

Vila, J.F. et al. "Hyperbaric oxygenation in subcortical frontal syndrome due to small artery disorders with leukoaraiosis." REV NEUROL, 1999, 28(7): 655-60.
Frontal leukoaraiosis is a common finding in patients with subcortical small-vessel disease and currently its pathogenesis is attributed to ischemic-hypoxic mechanisms. It associates to a vascular subcortical frontal syndrome for which an effective treatment does not exist. In this study, the authors present four subjects from a prospective patient-blind controlled pilot trial to study efficacy and safety of hyeprbaric oxygen therapy vs. hyperbaric air in vascular subcortical frontal syndrome with frontal leukoaraiosis. All of them had moderate to severe gait disorders, urinary dysfunction, cognitive impairment, and dependence in the daily living activities. Patients were assessed with validated scales and tests one week before and after being administered ten daily sessions of HBO at 2.5 atmospheres absolute for 45 minutes with a multiplace chamber. Serious adverse effects did not occur. After treatment a noticeable gait, urinary and cognitive improvement was observed in all subjects, increasing their independence. They remained clinically improved during four to five months, after which the previous deficits reappeared. Then, three patients received ten daily sessions of air at 1.1 atmospheres absolute for 45 minutes (controls) and the other a new HBO regimen, which improved as the first time. From the controls, there were no changes in two, while the other improved only cognitively. The authors conclude that these patients show that HBO is effective and safe in reversing, at least partially, although at great length, chronic neurological deficits associated to vascular frontal leukoaraiosis.

"A registry for carbon monoxide poisoning in New York City. Hyperbaric Center Advisory Committee Emergency Medical Service, City of New York." J TOXICOL CLIN TOXICOL, 1988, 26(7): 419-41. In 1983 the North American Hyperbaric Center (affiliated with Bronx Municipal Hospital Center) was designated to provide Hyperbaric oxygen (HBO) for carbon monoxide patients meeting Emergency Medical System criteria: (1) Unconscious or CNS derangement, any carboxyhemoglobin level; (2) Carboxyhemoglobin level of 25% or more; (3) Pregnant, any carboxyhemoglobin level. Through 1984, 39 carbon monoxide patients received HBO; in 1985, 81 were treated including 8 pregnant and 16 pediatric cases. Carbon monoxide sources were fire (43), heater (21) and engine (17). Forty-two of 59 acute patients were initially in a coma; 16 required CPR. Time to Hbo averaged 4.5 hours. HBO typically was 46 minutes at 3 ata, presented few problems, and gave rapid clinical improvement. Thirteen of 19 patients comatose before HBO were responsive after HBO. EMS efforts to make HBO available for carbon monoxide was a success.

Edema

Brown, J.A. et al. "Hyperbaric oxygen in the treatment of elevated intracranial pressure after head injury." PEDIATR NEUROSCI, 1988, 14(6): 286-90. This study is the first to evaluate the effect of hyperbaric oxygen on elevated intracranial pressure after severe head injury during documented controlled ventilation, hypocapnea, and minute-by-minute ICP data collection. The authors studied the effect of HBO at 2 atmospheres absolute with 100% O2, on intracranial pressure in 2 patients, aged 5 and 21 years. Each patient had diffuse cerebral swelling after blunt trauma and after a gun shot wound, respectively. Both required controlled hyperventilation, osmotic diuretics and intracranial pressure monitoring. During pressurization the mean ICP dropped from 13 to 8 Torr, then returning to 12 Torr after HBO therapy. The authors conclude that HBO may lower ICP in head-injured patients with diffuse cerebral swelling during the first 15 minutes, or the pressurization phase of therapy. Lasting effects of treatment were not seen with 4 treatments. The effect of HBO deserves further careful study in those patients with severe enough injury to require intracranial pressure monitoring.

Camporessi, Enrico et al. "Hyperbaric Medicine: An integral part of trauma care." CRITICAL CARE CLINICS, 1990; 6(1): 203-219. The author states that "hyperbaric medicine plays an integral role in comprehensive trauma care, from resuscitation to definitive therapy and subsequent recovery." Among his list of traumatic conditions include crush injury, exceptional blood loss, head injury and spinal cord injury.

Coe, John et al. "The Effect of hyperbaric oxygenation upon recovery of maze performance after experimental concussion." THE JOURNAL OF TRAUMA, 1971, 11(5): 436-439. (animal study). Thirty rats were divided into 3 groups, were tested for errors in 10 consecutive maze runs and then subjected to either (a) nonlethal concussion, un-treated group, (b) concussion followed by 98% oxygen and 2% carbon dioxide at 3 atmospheres absolute for 1 hr, and (c) to the same hyperbaric oxygenation without concussion (control). The maze-running performance of the rats with concussion treated with hyperbaric oxygen recovered faster and equaled that of the control group by the fifth day after the concussion. The untreated group of animals showed a greater lag in performance persisting throughout the observation period.

Contreras, F.L. et al. "The effect of hyperbaric oxygen on glucose utilization in a freeze-traumatized rat brain." J NEUROSURG, 1998, 68(1): 137-41. (animal study). Local cerebral glucose utilization was measured with the autoradiographic 2-deoxyglucose technique in rats injured by a focal parietal cortical freeze lesion then treated with hyperbaric oxygen. The cold lesion depressed glucose utilization in the contralateral as well as in the ipsilateral hemisphere. Treatment of lesioned animals with HBO at 2 atm for 90 minutes on each of 4 consecutive days tended to increase the overall cerebral glucose utilization measured 5 days after injury when compared to animals exposed to normobaric air. This improvement reached statistical significance in five of the 21 structure studied: the auditory cortex, medial genicuate body, superior olivary nucleus, and lateral geniculate body ipsilateral to the lesion, and the mammallary body. The data indicate that changes in lesioned rats exposed to HBO are not restricted to the period of time that the animals are in the hyperbaric chamber but are persistent.

Kawamura, S. et al. "Effects of Hyperbaric Oyxgenation in Patients with Subarachnoid Hemorrhage." JOURNAL OF HYPERBARIC MEDICINE, 1988; 3(4): 243-256. Changes of N1-amplitude in somatosensory evoked potential (SEPs) were studied to evaluate the effects of hyperbaric oxygenation (HBO) in 26 subarachnoid hemorrhage patients. During HBO, significantly improved SEPs were seen in 57% of 21 records from 2 to 14 days after the onset of subarachnoid hemorrhage, in 34% of 35 records in cases where there was no or only mild brain swelling, and in 38% of 26 records in cases where there were free-to-mild neurologic symptoms. In cases of moderate swelling, and mild to severe neurologic deficits, significant improvement was recognized less frequently.

Mao, B. et al. "Clinical analysis of diffuse axonal injury." HUA HIS I KO TA HSUEH HSUEH PAO, 1996, 27(4): 422-5. Sixty cases of diffuse axonal injury were analysed in this paper. All cases were caused by traffic accident; the mortality was 53.12%. Clinical manifestations were post-traumatic immediate and continuous coma with severe dysfunction of the brain stem. Pathological findings included the diffuse axonal injury of cortical white matter, corpus callosum, brain stem, and focal hemorrhage and infarction. The early use of hyperbaric oxygen combined with neuro-growth factor as an effective therapy is recommended.

Neubauer, R.A. et al. "Hyperbaric oxygen for treatment of closed head injury." SOUTHERN MEDICAL JOURNAL, 1994, 87(9): 933-6. Traumatic and vascular brain injuries consist of acute episodes followed by development of chronic components of varying magnitude and duration whose potentials for recovery differ. The authors discuss a case of closed head injury in which interventional hyperbaric oxygen (HBO) with single photon emission computed tomography were used as aids in determining the presence of recoverable neurons, to follow therapeutic progress, and to determine the end point of therapy. This case also shows the successful use of intensive HBO as a therapeutic modality.

Nida, TY et al. "Effect of hypoxia or hyperbaric oxygen on cerebral edema following moderate fluid percussion or cortical impact injury in rats." J NEUROTRAUMA, 1995, 12(1): 77-85. (animal study). This study was designed to evaluate the production of cerebral edema following moderate fluid percussion and cortical impact injury in rodents. To determine the effects of asecondary systemic insult, hypoxia (13% oxygen for 30 minutes) was added to some experimental groups immediately after head injury. To determine the effects of hyperbaric oxygen (HBO) on injured cortical tissue, additional animal groups were exposed to HBO (1.5 atm, for 60 minutes) beginning 4 hours after head trauma. HBO reduced the water content of the trauma site in animals that had received fluid percussion but not in animals receiving cortical impact injury. The authors conclude that both fluid percussion and cortical impact appear to produce focal cerebral edema at the site of trauma. Hypoxia does not worsen the edema. HBO appears to reduce edema produced by fluid percussion but the number of treatments and the ata were not enough to reduce the effects from cortical injury.

Okamura, A. et al. "Hyperbaric oxygen therapy in the Hokkaido University Hospital." MASUI, 1994, 43(6): 947-50. The authors surveyed hyperbaric oxygen therapy during the past seven years in the Hokkaido University Hospital. The mean number of patients was 27 per year. The average number of the therapy was 328 per year. There were neither complications nor accidents attributable to the hyperbaric oxygen therapy. Three representative diseased states: hypoxic brain damage, sudden deafness and occlusion of retinal arteries showed remarkable recovery by this therapeutic modality.

Blood Loss

Iakoviev, V.N. et al. "Bioenergetic processes in the cerebral cortex and diensephalon during hyperbaric oxygenation therapy of acute blood loss." BIULL EKSP BIOL MED, 1983, 95(5): 48-50. It has been demonstrated in experiments on 134 cats that during acute blood loss (24 ml/kg), hyperbaric oxygen therapy (3039 hPa, 60 minutes) stimulates cytochrome oxidase, eliminates compensatory activation of mitochondrial creatine kinase and maintains the hyperactivity of cytoplasmic creatine kinase in the diencephalons, stabilizes the elevated AMP content at the level of blood loss compensation state, prevents the fall in p02 and in the ATP level as well as that in the energy charge and creatine phosphate content in the sensomotor cortex and subcortex, that is typical for the decompensation stage. Besides, hyperbaric oxygen therapy also averts the development of the terminal state that supervenes in the majority of untreated animals.

Coma

Dean, B.S. et al. "Coma reversal with cerebral dysfunction recovery after repetitive hyperbaric oxygen therapy for severe carbon monoxide poisoning." AM J EMERG MED, 1993, 11(6): 616-8. An unresponsive 33 year old woman was found in a closed garage, inside her automobile with the ignition on. Her husband found her 6 hours later. 100% normobaric oxygen was administered in the prehospital and emergency department settings. The patient had an initial carboxyhemoglobin saturation of 46.7%, a Glasgow coma score of 3, and was transferred for HBO therapy. The electroencephalogram pattern suggested bilateral cerebral dysfunction consistent with a toxic metabolic or hypoxic encephalopathy. The patient underwent HBO therapy at 2.4 ATA for 90 minutes twice a day for 3 consecutive days. ON day 7, the patient began to awaken, was weaned from ventilatory support. Neurological examination demonstrated mild residual left upper extremity weakness and a normal gait. There was no evidence of significant neurological sequelae at 1 month follow-up.

Durmaz, E. et al. "Carbon monoxide poisoning and hyperbaric oxygen therapy." BR J NURSE, 1999, 8(16): 1067-72. This article describes the treatment of carbon monoxide poisoning with hyperbaric oxygen therapy (HBO). Carbon monoxide poisoning is the commonest cause of fatal poisoning in the United Kingdom. Despite this, HBO is an underused treatment modality. Current criteria for hyperbaric treatment include any patient with neurological deficit and any episode of depressed consciousness, cardiovascular disturbance, patients initially treated with surface oxygen and who developed recurrent symptomatology and minor symptoms unresponsive to oxygen. During a 5-year period 82 patients have been treated from a wide geographical area. Of these patients 57% suffered carbon monoxide poisoning as a result of self-poisoning. Other causes of poisoning were: house fire, faulty gas appliances, industrial furnaces; and petrol generators. Of the 82 patients treated, 13 required mechanical ventilation and full haemodynamic monitoring, while the remainder were able to walk in and a few patients received intravenous sedation. In recent years the trend has been to re-treat patients more than once in the first 24 hours to increase efficacy and hopefully decrease the serious sequelae that can occur following carbon monoxide poisoning.