Hyperbaric Oxygen Therapy

by Ronald Lyman, DVM, DACVIM

INTRODUCTION

Hyperbaric oxygen therapy (HBOT) has gradually expanded from its traditional place in treatment of decompression illness ("the bends") to a variety of clinical applications globally. Basic science studies have demonstrated HBOT effects and mechanisms of action. Clinical studies on practical applications have been published. In My 2006 the 1st International Symposium for the Use of Hyperbaric Oxygenation in Neurosciences was held in Fort Lauderdale, Florida, with presentations from researchers and clinicians in the hyperbaric oxygenation field from around the world. This ACVIM Forum Proceedings manuscript and discussion will focus on hyperbaric oxygen therapy treatment methods, physiologic effects, therapeutic effects, clinical uses, and safety issues in small animal clinical neurology cases. Specific examples of small animal neurological patients treated with HBOT will be presented. The usefulness of this treatment modality in other veterinary clinical disciplines will be briefly noted.

HYPERBARIC OXYGEN THERAPY CHAMBERS AND ANCILLARY HARDWARE

Therapeutic chambers are available from both veterinary and human medical manufacturers and suppliers. Experienced professionals are available to assist in designing systems, obtaining and installing chambers, training hospital personnel regarding operation and safety issues, and servicing hyperbaric oxygen therapy equipment. Clinical chambers range in size from monoplace (single patient) design to chambers accommodating multiple patients and caregivers to operating suites, and "walk-in" equine chambers. All can be employed to treat small animal patients. Most chambers suitable for small animals require an oxygen supply system capable of large gas volumes delivered at a rapid flow rate. Liquid oxygen tanks and a medical grade oxygen pipeline of large diameter satisfy these requirements. A passive discharge pipeline directs the exhaust gases outside the hospital building. Some chambers have ports allowing (specific) IV lines and/or tubing for assisted ventilation to be connected to the patient during a HBOT session. Current oxygen costs to operate a monoplace chamber may range from approximately $8 to $30 per treatment session depending on chamber design, length of session, pressure employed, and oxygen supply system.

TREATMENT PROTOCOL (THE "DIVE")

The patient is prepared by examination and body temperature determination. Hyperbaric oxygen therapy is generally not given when the patient's body temperature is greater than 103 degrees Fahrenheit. Theoretically, excessive hyperthermia may increase oxygen uptake by tissues and enhance the chance of oxygen toxicity. The vast majority of patients are quiet and relaxed during HBOT. Some patients are given sedation. Acepromazine is the usual drug of choice. Occasionally, benzodiazepines or barbiturates are employed. Cotton bandages cover IV catheters. Metal collars are removed. A static inhibitor ground line is secured on a leg. Cotton towels are placed under the patient. The session begins with a gradual pressure increase to the designated treatment pressure over approximately 15 minutes. The desired treatment pressure may range from 1.5 to 3 atmospheres absolute (ATA) in a 100% oxygen environment. The treatment period "at pressure" may range from 45 minutes to 2 hours. Then, a gradual decompression over approximately 15 minutes is made, and the patient is removed from the chamber. Currently, most of our patients are treated at 2 ATA for 45 minutes "at pressure". In patients perceived to be at reduced threshold for seizures, we may employ the low range (1.5 ATA]) for the "at pressure" treatment period. The patients are rested at room atmospheric pressure for at least 4 hours between HBOT sessions to minimize the chances of CNS or pulmonary oxygen toxicity. We treat most patients with BID sessions, and continue HBOT acutely for at least one week, or until marked and progressive neurologic improvement occurs [for example, the tetraparetic, paraparetic, or monoparetic patient is using the affected limb(s) with improving strength and function over several days]. We have treated some patients with follow up sessions after initial discharge from the hospital.

PHYSIOLOGY OF HBOT

At normal atmospheric pressures (1 ATA) and while breathing room air, insignificant amounts of oxygen are dissolved and delivered to the tissues via the plasma. Mild increases are possible when oxygen is administered via mask, oxygen cage, intranasally, or intubation. The effects of HBOT are based upon the fact that oxygen delivered to the alveoli under increased atmospheric pressure results in large increases in the amount dissolved in plasma. This can increase the plasma arterial oxygen content from 0.32 ml vol % (ml 02/ dl whole blood) breathing room air at 1 ATA, to 4.44 vol % at 2 ATA breathing 100% oxygen, and up to 6.8 vol % at 3 ATA breathing 100% oxygen. This dramatic increase in dissolved oxygen (for example, breathing 100% oxygen at 3ATA) allows diffusion and delivery via the plasma up to 4 times further through the tissues than is possible while breathing room air at 1 ATA. This delivery is independent of the hemoglobin system. Tissue pO2 measurement devices have demonstrated that oxygen tension remains elevated at >10% of normal for up to 3 hours following a 1 hour HBOT session.1 Thus, cells and mitochondria in areas where nearby capillary blood flow has been compromised by traumatic, ischemic, or inflammatory processes may receive oxygen subsequent to HBOT which would otherwise be denied by the underlying pathological disease process. Hyperbaric oxygen at 2 ATA has been shown to reduce cerebral blood flow up to 25% (by effecting vasoconstriction), reduce nitric oxide production, yet concurrently increase (X 10) cerebral oxygen content. Intracranial pressure and cerebral edema are reduced following hyperbaric oxygen therapy. Three recent textbooks offer detailed discussions of the physiology of oxygenation, its relation to HBOT, and effects on the CNS and PNS234.

THERAPEUTIC EFFECTS AND CLINICAL USES

Complete Global Cerebral Ischemia
A 1992 paper5 described a controlled study from Japan where 20 dogs with complete global cerebral ischemia of 15 minutes duration were randomized and divided into two groups. One group received 1 hour sessions of HBOT at 3 ATA in 100% oxygen at 3, 24, and 29 hours after recirculation was established. The control group received room air at 1 ATA. Both groups received nursing support. The HBOT treated group's mean neurologic recovery score was >65/100 after 5 days, with neurologic recovery scores of > 95/100 reached in two dogs from the HBOT group (range: 0 = brain dead to 100 = normal). In contrast, in the group not receiving HBOT, the mean neurologic score remained < 60/100 throughout the 14 day follow up, and only 1 of 10 dogs from the non HBOT group recovered to a score of > 65/100. Seven members of the HBOT group survived to the 14 day follow up, whereas 3 members of the non hyperbaric oxygen therapy group survived through the 14 day study period.

Case example: A 1 year old M/I Shih-Tzu canine fell off a grooming table while the groomer was distracted, and was accidentally hung by the lead around the neck. CPR was successful. Acute cortical blindness followed. The patient was given IV methylprednisolone immediately following the resuscitation, and was referred for hyperbaric therapy the following day. Low dose oral prednisolone was continued. BID hyperbaric oxygen therapy (45 minute-sessions at 2 ATA) was given for 7 days. After the second HBOT treatment, vision began to return as evidenced by obstacle course performance. A two week follow up confirmed improving vision based on owner interview and obstacle course examination. Consultation by an ophthalmologist confirmed resolving cortical blindness. In human cases (near hanging, near drowning, neonatal asphyxia, stroke, cardiopulmonary arrest, etc.) SPECT brain blood flow imaging has been used to demonstrate abnormalities in cerebral perfusion and subsequent improvement following immediate and long term HBOT.

Head Trauma
Many studies have shown that hyperbaric oxygen therapy reduces elevations in intracranial pressure resulting from head trauma in animals and in human head trauma patients.4 Clinical trials have demonstrated improved survival rates and neurologic recovery scores in human head trauma patients.6 In addition, improved glucose utilization in rat brain tissue has been demonstrated to persist for up to 24 hours following the last HBOT.7 There is much contemporary focus and research on the role of matrix metalloproteinases (MMPs) in traumatic brain injury and inflammatory CNS and PNS diseases, including Multiple Sclerosis (MS) in humans. A change in the balance of certain types of these proteases is associated with cellular infiltrates, apoptosis, and gliosis in traumatic, inflammatory, and neoplastic CNS disease. A 2006 rat model study of traumatic brain injury demonstrated that subjects treated with HBOT had reduced expression of certain MMPs, milder neutrophilic inflammatory infiltrates, and decreased secondary cell death when compared to controls.8

Case example: A 3 month old F/I canine Yorkshire Terrier hit by a recliner chair. The patient presented obtunded and able to posture only when placed sternally. IV mannitol and ICU oxygen unit therapy were given and a neck brace placed overnight by the E/CC clinicians. BID hyperbaric oxygen therapy was begun the following morning (45 minute sessions at 2 ATA) and continued for 5 days. Marked neurologic improvement was obvious as the patient exited the chamber after the first session, and progressed rapidly until discharge.

Fibrocartilagenous Emboli
Some hyperbaric oxygen therapy studies performed on dogs date back several decades. A 1965 study demonstrated that spinal cord pO2 could be raised by HBOT as long as 72 hours after tissue hypoxia was created in a model of spinal cord injury in dogs.9 Canine cases of fibrocartilagenous emboli often show rapid improvement when promptly treated by HBOT. It is especially important for nursing care and physical therapy purposes to get these primarily large breed patients ambulatory as soon as possible.

Case examples: 1) An 8 year old M/N Labrador mix. Acutely monoparetic, then paraparetic. 2) An 8 year old F/S Boxer. Acutely monoparetic. Clinical diagnoses were based on neurologic examinations, CSF analyses, and myelograms within a few hours of emergency presentation. Both patients received one dose of parenteral corticosteroids, then low dose short term oral prednisolone. Both patients were given BID hyperbaric oxygen therapy (45 minute sessions at 2 ATA). The Lab received 14 HBOT treatments, the Boxer 10. It is interesting to note in this acute ischemic myelopathy that patients will often improve markedly as they exit the chamber session, then regress, presumably as p02 in the affected cord region drops off. Patients who exhibit this pattern normally improve for longer periods after each session, and eventually maintain their neurologic improvement.

Spinal Cord Trauma, Compressive Lesions, Intervertebral Disc Extrusions
In a 1972 canine model of spinal cord compression, spinal cord tissue p02 in the normal cord rose when the subjects were breathing 100% oxygen at 1 ATA. After compressive trauma, the cord p02 dropped to near zero on room air, and did not rise when the subjects were breathing 100% oxygen at 1 ATA. When hyperbaric oxygen therapy at 2 ATA was given with 100% oxygen, tissue p02 rose sharply even during the compressive period. Neurologic recovery of the HBOT treated group was improved compared to the control group.10

Case example: An 11 year old Bichon M/N. Acute upper motor neuron tetraparesis with severe neck pain and Normal CSF protein and cytology. Spinal stenosis at a C2-3 fusion site (no history of previous surgery or trauma) and a C3-4 disc extrusion were found on myelographic examination. Initial treatment was with hyperbaric oxygen therapy (ATA, 45 minutes) prior to the diagnostics. At this point the patient became strongly ambulatory. Diagnostics were performed, followed immediately by a limited continuous dorsal laminectomy. Low dose oral prednisolone and HBOT were given post operatively for 6 days. Progressive clinical improvement was rapid. A desirable effect in neurosurgical cases treated with post op HBOT is rapid surgical wound healing, with reduced swelling, inflammation, seroma, and sear formation. HBOT has become standard pre and post neurosurgical adjunctive therapy in our practice, for both spinal and brain surgical cases. We have used HBOT in conservative treatment of documented or presumed spinal cord compressive diseases.

Inflammatory CNS Diseases
We have discussed some of the mechanisms of hyperbaric oxygen therapy anti-inflammatory effects above. The reader should note that in the UK, there are 64 centers (spread out to cover the population density) which are dedicated solely to the treatment of MS in human patients. Over 1.7 million sessions have been completed in the last 24 years without serious incident.11 Patients generally manage their own long term treatment schedule, and typically find that their symptoms, especially frequency of micturition, are controlled only by regular HBOT sessions. Some schedule their holidays to be near a "Center". The reader is referred to a detailed chapter on rationale for HBOT in CNS inflammatory disease, including MS, in a recent HBOT textbook.2 A 2006 symposium presentation from a Russian HBOT research clinician described the use of combined HBOT and cyclosporine in the treatment of inflammatory CNS disease in humans.12

Case example: A 9 1/2 year old M/N mixed canine presented for persistent fever, sudden loss of coordination and slight personality change. Neurologic exam supported multifocal CNS lesions. CSF cisternal and lumbar puncture protein and cytology were normal. MRI revealed multiple small mixed size hyperintense T2-weighted lesions throughout the thalamus and rostral brainstem. Most remained hyperintense on T2-weighted FLAIR sequencing. Multiple serologies and PCR's, PARR [LSA] were submitted. A 1/164 positive serology for E equi was the only notable laboratory finding. BID treatments of hyperbaric oxygen therapy (45 minute sessions at 2 ATA over 7 days) were initiated along with cyclosporine, prednisolone, imidocarb, and doxycycline. Neurologic signs improved over a 7 day period, with the owner commenting on a marked improvement at home at the two week recheck exam. The immunosuppressive therapy is being tapered very slowly. We have not yet treated inflammatory CNS diseases with chronic HBOT therapy.

Other Clinical Applications of HBOT
Other cases treated with hyperbaric oxygen therapy therapy, include acute tetraparesis secondary to Atlanto-axial [A/A] luxation, acute peripheral nerve injury, discospondylitis, and brain lesions pre and post operatively. Pancreatitis, Decubital ulcers, thermal burns, shearing wounds, poorly healing wounds, near drowning, smoke/ CO inhalation, and snakebite are a few of the other clinical applications for HBOT in veterinary medicine. Human medical practice is often limited by "approved indication lists" and diagnosis "codes". For example, in the U.S., there are currently about 14 indications approved by Medicare, and thus typically funded by third party payers. CO toxicity and decompression illness are the only indications commonly creating neurologic signs which are "approved" by Medicare. The U.K. has 13 "approved" indications, Japan 20, China 53, and Russia 85. In the latter three countries the "approved" lists contain several neurologic disease indications which translate as "severe spinal cord disorders", "acute and severe hypoxic brain disorders", "severe spinal cord injury", "Bell's palsy", "Multiple Sclerosis", "cranial traumas", "viral encephalitis", etc.

Safety Issues
HBOT should not be administered to patients with pneumothorax, certain older type pacemakers, within 48 hours of doxorubricin, or in a patient currently receiving cis-platinum or bleomycin. Acetazolamide or other carbonic anhydrase inhibitors should be tapered prior to hyperbaric oxygen therapy, as they inhibit oxygen induced vasoconstriction and increase blood flow to the brain, increasing the chance of oxygen toxicity. Transdermal patches should be temporarily removed. Conservative dosages of narcotic analgesics should be employed prior to HBOT, as increased CO2 tensions secondary to respiratory depression can cause cerebral vasodilatation and predispose to oxygen induced seizures. Insulin dosages should be tapered prior to HBOT therapy. Patients with hyperthyroidism also tend to have an increased chance for oxygen induced seizures. Vestibular signs may be aggravated due to barostimulation of the ear structures. This said, we have witnessed one mild motor seizure (the patient was an idiopathic epileptic canine) in over two thousand sessions at our hospital. The seizure ended as gradual decompression was initiated. The previously cited textbooks are a good source of detailed information on potential contraindications and specific interactions of HBOT with other therapeutic measures.2,3,4

The chamber contains 100 % oxygen under pressure. Measures should be taken to reduce the chance of fire. The chamber should be grounded. A static grounding limb strap should be considered. Cotton towels and bandages generate less static than synthetic fibers. No flammable materials or electronic devices should be placed in the chamber. No metal collars or skin staples should be used. No alcohol, Vaseline, or flammable based dressings should be used. A CO2 fire extinguisher should be close and functional. An emergency master oxygen shut-off valve should be known by all personnel. A textbook on hyperbaric safety is recommended.13

Conclusion
Over the past two years it has been very rewarding for the doctors and staff to observe the clinical improvement of many cases treated by hyperbaric oxygen therapy at our hospital. The addition of this treatment modality has resulted in an obvious enhancement of our ability to successfully treat many critically ill patients.

1Wells CH, et al. "Tissue gas measurements during hyperbaric oxygen exposure, in Smith[ed]. Proc 6th Int.Congress on Hyperbaric Med, Aberdeen Press, 1977, p118 2Jain KK, Textbook of Hyperbaric Medidne-4th ed. Cambridge, Ma. Hogrefe & Huber, 2004 3Bakker, DJ Cramer, FS [eds], Hypcrbaric Snrgery: Perioperatrve Care. Flagstaff, Az. Best, 2004 4Kindwall EP, Whelan HT [eds], Hyperbaric Medicine Practice-2nd ed. Revised. Flagstaff, Az. Best, 2004 5Takahashi M, et al. "Hyperbaric Oxygen Therapy accelerates neurologic recovery after 15 minute complete global cerebral ischemia in dogs". Critical Care Med. 1992;20[11]: p1588 6Holbach KH el al. "Improved reversibility of traumatic mid-brain syndrome with application of hyperbaric oxygen pressure" Acta Neurochir. 1974:30:p247 7Contreras FL et al. "The effect of hyperbaric oxygen on glucose utilization in freeze-traumatized rat brain" J Neurosurg. 1988:65:p615 8Vlodavsky, E et al. "Hyperbaric Therapy reduces neuroinflammation and expression of matrix metalltoproteinase-9 in the rat model of traumatic brain injury" Neuropathol Appl Neurobiol. 2006; 32:1:p40 9Maeda, N "Experimental studies on the effect of decompression procedures and hyperbaric oxygenation for the treatment of spinal cord injury" J Natl Med Assoc. 1965;16:p429 10Kelly DL et al. "Effects of hyperbaric oxygenation and tissue oxygen studies in experimental paraplegia'' Neurosurg. 1972:36:p425 11Neubauer RA, 1st International symposium for the use of Hyperbaric Oxygenation in the Neurosciences, 2006, p78 12Kazantseva NV, 1st Int Symposium for the use of Hyperbaric Oxygenation in the Neurosciences, 2006. p32 13Workman W. Hyperbaric Facility Safety: A Practical Guide. Flagstaff, Az. Best, 1999.