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Diving In: Hyperbaric Oxygen Therapy in Veterinary Medicine

Lindsay Elam DVM, MPH, CVA

Dr. Elam completed her DVM concurrently with a master’s degree in public health in 2015 from the University of Florida (UF). She is trained in veterinary acupuncture and received her Certified Veterinary Acupuncturist certification from the Chi Institute in Reddick, Florida. She completed an integrative medicine internship at UF and has remained a clinical lecturer in the Integrative Medicine Department since 2016. She is board-eligible in canine sports medicine and rehabilitation. Her research interests include integrative interventions for spinal cord injury.

Diving In: Hyperbaric Oxygen Therapy in Veterinary Medicine
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Hyperbaric oxygen therapy (HBOT) is the therapeutic administration of oxygen administered at a pressure that exceeds that at sea level (1 atmosphere absolute [ATA]). The treatment pressure can vary but commonly ranges from 1 to 3 ATA to drive a significant increase in arterial oxygen tension and thereby induce a number of physiologic, cellular, and biochemical effects.1 This article provides a brief overview of the mechanism of action, veterinary applications and evidence, and general treatment mechanics associated with HBOT administration.

MECHANISM OF ACTION

In a healthy patient breathing “room air” at sea level (21% oxygen at 1 ATA), hemoglobin saturation is more than 97% and the plasma oxygen concentration is 0.3 mL/dL.2 The solubility of a gas is proportional to its pressure, as defined in Henry’s law of gas behavior; therefore, as the atmospheric pressure of oxygen rises, so does the plasma oxygen concentration. This concentration jumps fivefold with the administration of 100% oxygen alone without pressure changes, and tenfold when the oxygen is administered at 2 ATA. Increasing the pressure to 3 ATA results in a plasma oxygen concentration of 6 mL/dL, which is more than high enough to meet all resting cellular requirements without the need for hemoglobin-bound oxygen. This extraordinary circumstance proves particularly useful in human patients with exceptional blood loss when suitable blood is not available or transfusion is refused for religious reasons.3

Another benefit to increasing plasma oxygen concentration is that oxygen dissolved in the plasma can diffuse up to 4 times further into microcirculation than oxygen transported by red blood cells according to Fick’s law, which identifies an increased gas diffusion distance with increasing partial pressure differences.4 This is particularly crucial in damaged, edematous tissue in which the capillaries are pushed farther apart and are unable to deliver the oxygen necessary for cellular respiration and repair.

By facilitating tissue hyperoxia, HBOT exerts beneficial anti-inflammatory, immunomodulatory, antimicrobial, angiogenic, and barometric effects, which collectively contribute to its myriad clinical applications in veterinary medicine.

CLINICAL APPLICATIONS AND EVIDENCE

Indications for HBOT in human medicine are varied. The most widely accepted and covered by Medicare reimbursement are carbon monoxide toxicity, decompression sickness, and chronic refractory infections and wounds.5 Some veterinary indications for which evidence exists include the optimization of tissue repair, neurologic conditions, inflammatory and autoimmune disorders, and cancer.7

Tissue Repair

The postulated mechanism of HBOT in enhanced healing is largely related to improved oxygenation and perfusion, as well as increased phagocytosis of bacteria, antimicrobial activity, and angiogenesis.6,8-10 A number of experimental animal models and clinical studies have shown improvements in healing with HBOT in grafts and flaps, burns, necrotizing fasciitis, bone, cartilage, and muscle.11-17 In the author’s experience, complicated skin wounds—including those that result from envenomation or a fungal, oomycotic, or bacterial infection—are among the more commonly referred indications; in these cases, HBOT is used for attenuation of inflammation and potentiation of concurrent pharmacologic intervention.

Neurologic Applications

The neuroprotective utilization of HBOT is gaining significant clinical and research attention. Based on the expanding favorable evidence in laboratory animals, human clinical trials are under way at Qinghai University in China and Medical University at Graz in Austria using HBOT as an adjunctive treatment for acute spinal cord injury. The suggested mechanisms of HBOT’s neuroprotective effects include reduction of oxidative stress, promotion of angiogenesis, modulation of inflammation, and reduction of edema in the central nervous system.18 Beyond spinal cord injury, HBOT has also been shown to be effective in the management of neuropathic pain, peripheral nerve regeneration, and traumatic and vascular brain injury, as well as some early research into delaying motor neuron disease onset.19-26

Modulation of Inflammation and Immune Function

HBOT’s ability to modulate neutrophil and macrophage function enables it to elicit positive effects for a number of internal medical conditions, particularly immune-mediated diseases and those characterized by inflammation. Besides ameliorating tissue hypoxia, which is a key trigger of ongoing inflammation, high oxygen concentrations interfere with polymorphonuclear leukocyte adhesion and stimulate the production of endogenous antioxidants. Emerging literature suggests that HBOT is useful in adjunctively managing allergic rhinitis, inflammatory bowel disease, pancreatitis, and inflammatory joint conditions such as rheumatoid and Lyme arthritis.27-31

Neoplasia

Given that HBOT promotes angiogenesis and increases tissue oxygen concentration, there is concern that treatment could promote tumor growth in a patient with known neoplastic disease. At present, neoplasia is considered an acceptable indication for HBOT in humans in China and Japan.32 A 2012 literature review concluded that the use of HBOT in malignancy is safe,33 and there are data supporting its potential tumor-inhibitory effects in certain cancer subtypes.34,35 More recent evidence suggests that adjunctive HBOT may enhance the cytostatic effect of certain chemotherapeutic agents and increase the effectiveness of radiation therapy.36

MECHANICS AND CONSIDERATIONS

Total treatment times, frequency, and pressure used vary in the literature and between practitioners. The author commonly employs a standard time of about 1.25 hours, including gradual pressurization and depressurization, at 2 ATA; however, specific treatment must be based on the patient’s condition.

The risks of HBOT in veterinary patients are minimal with appropriate precautions and operation.6,35 Patients should be prepared for the chamber by removing or covering materials that are inflammable or pose a risk of spark (e.g., exposed metal implants, synthetic bandages, petroleum-based drugs) and supervised for the entire session by a trained clinician or technician. Gradual pressure changes should be used and patients carefully screened for contraindicated pre-existing conditions (pulmonary bullae, pneumothorax) to minimize the risk of barotrauma.

Oxygen toxicity caused by increased reactive oxygen species manifests as a grand mal seizure and is addressed with monitoring and gradual decompression. The risk is pressure-dependent and low at 2 ATA (<0.4%; unpublished data based on more than 2200 treatment sessions at the author’s institution), and there are no reports of a subsequent epileptic predisposition. Patient hyperthermia can increase brain oxygen consumption;36 hypothetically, pretreatment sedation with medications that cause peripheral vasoconstriction may also have this effect. Based on clinical experience, the author avoids treating patients with a body temperature above 103.5°F as well as using α2-agonists for sedation in HBOT patients.

Given HBOT’s safety and wide variety of conditions that could benefit, the major hurdles in clinical veterinary practice are cost, accessibility, and the lack of veterinary clinical trials to guide its evidence-based use for a variety of conditions. Although the modality has seen increased use in the profession,37 only a few clinics, if any, offer it in each state and the average cost of a treatment session is $100 to $200. The Veterinary Hyperbaric Medicine Society (vhbot.org) and Hyperbaric Veterinary Medicine (hvmed.com) websites include U.S. location maps of veterinary chambers as a resource for owners and veterinarians seeking referral. Given the possible limitations, it is important to discuss the patient’s ongoing HBOT plan in addition to setting realistic goals at the outset.

CONCLUSION

Based on the favorable human and laboratory animal data, HBOT in veterinary medicine is continually expanding. Prospective veterinary clinical research will be key in identifying optimal treatment protocols and clinical implications, as well as further substantiating the modality’s utility as an adjunctive or primary treatment option.

References

1. Jain KK. Physical, physiological, and biochemical aspects of hyperbaric oxygenation. In: Jain KK, ed. Textbook of Hyperbaric Medicine. Basel, Switzerland: Springer; 2017:11-22.

2. Lambertsen CJ, Dough RH, Cooper DY, et al. Oxygen toxicity; effects in man of oxygen inhalation at 1 and 3.5 atmospheres upon blood gas transport, cerebral circulation and cerebral metabolism. J Appl Physiol 1953;5(9):471-486.

3. Hart G. HBO and exceptional blood loss anemia. In: Kindwall EP, Whalen HT, eds. Hyperbaric Medicine Practice. Flagstaff, AZ: Best Publishing Co; 1999:517-524.

4. Popel AS. Theory of oxygen transport to tissue. Crit Rev Biomed Eng 1989;17(3):257-321.

5. Gesell L. Hyperbaric Oxygen Therapy Indications: The Hyperbaric Oxygen Therapy Committee Report. Durham, NC: Undersea and Hyperbaric Medical Society; 2009.

6. Shmalberg J, Davies W, Lopez S, et al. Rectal temperature changes and oxygen toxicity in dogs treated in a monoplace chamber. Undersea Hyperb Med 2015;42:95-102.

7. Klemetti E, Rico-Vargas S, Mojon P. Short duration hyperbaric oxygen treatment effects blood flow in rats: pilot observations. Lab Anim 2005;39(1):116-121.

8. Zamboni WA, Browder LK, Martinez J. Hyperbaric oxygen and wound healing. Clin Plast Surg 2003;30(1):67-75.

9. Knighton DR, Halliday B, Hunt TK. Oxygen as an antibiotic: the effect of inspired oxygen on infection. Arch Surg 1984;119(2):199-204.

10. Marx RE, Ehler WJ, Tayapongsak P, Pierce LW. Relationship of oxygen dose to angiogenesis induction in irradiated tissue. Am J Surg 1990;160(5):519-524.

11. Holder TE, Schumacher J, Donnell RL, et al. Effects of hyperbaric oxygen on full-thickness meshed sheet skin grafts applied to fresh and granulating wounds in horses. Am J Vet Res 2008;69(1):144-147.

12. Richards L, Lineaweaver WC, Stile F, et al. Effect of hyperbaric oxygen therapy on the tubed pedicle flap survival in a rat model. Ann Plast Surg 2003;50(1):51-56.

13. Mazzi MF. The use of hyperbaric oxygen therapy in the treatment of necrotizing fasciitis in an elderly dog’s prepuce. PUBVET 2018;12:1-7.

14. Kerwin SC, Lewis DD, Elkins AD, et al. Effect of hyperbaric oxygen treatment on incorporation of an autogenous cancellous bone graft in a nonunion diaphyseal ulnar defect in cats. Am J Vet Res
2000;61(6):691-698.

15. Kawada S, Wada E, Matsuda R, Ishii N. Hyperbaric hyperoxia accelerates fracture healing in mice. PloS One 2013;8(8):e72603.

16. Başci O, Çimşit M, Zeren S, et al. Effect of adjuvant hyperbaric oxygen on healing of cartilage lesions treated with microfracture: an experimental study in rats. Undersea Hyperb Med 2018;45:411-419.

17. Oyaizu T, Enomoto M, Yamamoto N, et al. Hyperbaric oxygen reduces inflammation, oxygenates injured muscle, and regenerates skeletal muscle via macrophage and satellite cell activation. Sci Rep 2018;8:1288.

18. Patel NP, Huang JH. Hyperbaric oxygen therapy of spinal cord injury. Med Gas Res 2017;7(2):133-143.

19. Zhao BS, Song XR, Hu PY, et al. Hyperbaric oxygen treatment at various stages following chronic constriction injury produces different antinociceptive effects via regulation of P2X4R expression and apoptosis. PLoS One 2015;10:e0120122.

20. Zhao B-S, Meng L-X, Ding Y-Y, Cao Y-Y. Hyperbaric oxygen treatment produces an antinociceptive response phase and inhibits astrocyte activation and inflammatory response in a rat model of neuropathic pain. J Mol Neurosci 2014;53(2):251-261.

21. Han G, Liu K, Li L, et al. Effects of hyperbaric oxygen therapy on neuropathic pain via mitophagy in microglia. Mol Pain 2017;13:1744806917710862.

22. Sanchez EC. Hyperbaric oxygenation in peripheral nerve repair and regeneration. Neurol Res 2007;29:184-198.

23. Eguiluz-Ordoñez R, Sánchez CE, Venegas A, et al. Effects of hyperbaric oxygen on peripheral nerves. Plast Reconstruct Surg 2006;118:350-357.

24. Huang L, Obenaus A. Hyperbaric oxygen therapy for traumatic brain injury. Med Gas Res 2011;1:21.

25. Xu Y, Ji R, Wei R, et al. The efficacy of hyperbaric oxygen therapy on middle cerebral artery occlusion in animal studies: a meta-analysis. PLoS One 2016;11:e0148324.

26. Dave KR, Prado R, Busto R, et al. Hyperbaric oxygen therapy protects against mitochondrial dysfunction and delays onset of motor neuron disease in wobbler mice. Neuroscience 2003;120(1):113-120.

27. Vuralkan E, Cobanoglu HB, Mirasoglu B, et al. May hyperbaric oxygen therapy play a role in the treatment of allergic rhinitis? A double-blind experimental study in rat model hyperbaric oxygen therapy on allergic rhinitis. J Otol Rhinol 2018;7:1-4.

28. Dulai PS, Gleeson MW, Taylor D, et al. Systematic review: the safety and efficacy of hyperbaric oxygen therapy for inflammatory bowel disease. Aliment Pharmacol Ther 2014;39:1266-1275.

29. Nikfarjam M, Cuthbertson CM, Malcontenti-Wilson C, et al. Hyperbaric oxygen therapy reduces severity and improves survival in severe acute pancreatitis. J Gastrointest Surg 2007;11(8):1008-1015.

30. Wilson HD, Toepfer VE, Senapati AK, et al. Hyperbaric oxygen treatment is comparable to acetylsalicylic acid treatment in an animal model of arthritis. J Pain 2007;8(12):924-930.

31. Fife W, Freeman D. Treatment of Lyme disease with hyperbaric oxygen therapy. Undersea and Hyperbaric Medical Society Annual Meeting. 1998.

32. Jain KK, Baydin SA. Textbook of Hyperbaric Medicine. Switzerland: Springer; 1996.

33. Moen I, Stuhr LEB. Hyperbaric oxygen therapy and cancer―a review. Target Oncol 2012;7(4):233-242.

34. Kawasoe Y, Yokouchi M, Ueno Y, et al. Hyperbaric oxygen as a chemotherapy adjuvant in the treatment of osteosarcoma. Oncol Rep 2009;22:1045-1050.

35. Peng ZR, Zhong WH, Liu J, Xiao P. Effect of the combination of hyperbaric oxygen and 5-fluorouracil on proliferation and metastasis of human nasopharyngeal carcinoma CNE-2Z cells. Undersea Hyperb Med 2010;37:141-150.

36. Stępień K, Ostrowski RP, Matyja E. Hyperbaric oxygen as an adjunctive therapy in treatment of malignancies, including brain tumours. Med Oncol 2016;33:101.

37. Birnie GL, Fry DR, Best MP. Safety and tolerability of hyperbaric oxygen therapy in cats and dogs. JAAHA 2018;54(4):188-194.

38. Heyboer M, Sharma D, Santiago W, McCullough N. Hyperbaric oxygen therapy: side effects defined and quantified. Adv Wound Care (New Rochelle) 2017;6(6):210-224.

39. Shmalberg J. Integrative rehabilitation: lasers and hyperbaric chambers. Canine Sports Med Symp 2014.

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Guiana</option><option value='French Polynesia' >French Polynesia</option><option value='French Southern Territories' >French Southern Territories</option><option value='Gabon' >Gabon</option><option value='Gambia' >Gambia</option><option value='Georgia' >Georgia</option><option value='Germany' >Germany</option><option value='Ghana' >Ghana</option><option value='Gibraltar' >Gibraltar</option><option value='Greece' >Greece</option><option value='Greenland' >Greenland</option><option value='Grenada' >Grenada</option><option value='Guadeloupe' >Guadeloupe</option><option value='Guam' >Guam</option><option value='Guatemala' >Guatemala</option><option value='Guernsey' >Guernsey</option><option value='Guinea' >Guinea</option><option value='Guinea-Bissau' >Guinea-Bissau</option><option value='Guyana' >Guyana</option><option value='Haiti' >Haiti</option><option value='Heard and McDonald Islands' >Heard and McDonald Islands</option><option value='Holy See' >Holy See</option><option value='Honduras' >Honduras</option><option value='Hong Kong' >Hong Kong</option><option value='Hungary' >Hungary</option><option value='Iceland' >Iceland</option><option value='India' >India</option><option value='Indonesia' >Indonesia</option><option value='Iran' >Iran</option><option value='Iraq' >Iraq</option><option value='Ireland' >Ireland</option><option value='Isle of Man' >Isle of Man</option><option value='Israel' >Israel</option><option value='Italy' >Italy</option><option value='Jamaica' >Jamaica</option><option value='Japan' >Japan</option><option value='Jersey' >Jersey</option><option value='Jordan' >Jordan</option><option value='Kazakhstan' >Kazakhstan</option><option value='Kenya' >Kenya</option><option value='Kiribati' >Kiribati</option><option value='Kuwait' >Kuwait</option><option value='Kyrgyzstan' >Kyrgyzstan</option><option value='Lao People&#039;s Democratic Republic' >Lao People&#039;s Democratic Republic</option><option value='Latvia' >Latvia</option><option value='Lebanon' >Lebanon</option><option value='Lesotho' >Lesotho</option><option value='Liberia' >Liberia</option><option value='Libya' >Libya</option><option value='Liechtenstein' >Liechtenstein</option><option value='Lithuania' >Lithuania</option><option value='Luxembourg' >Luxembourg</option><option value='Macau' >Macau</option><option value='Macedonia' >Macedonia</option><option value='Madagascar' >Madagascar</option><option value='Malawi' >Malawi</option><option value='Malaysia' >Malaysia</option><option value='Maldives' >Maldives</option><option value='Mali' >Mali</option><option value='Malta' >Malta</option><option value='Marshall Islands' >Marshall Islands</option><option value='Martinique' >Martinique</option><option value='Mauritania' >Mauritania</option><option value='Mauritius' >Mauritius</option><option value='Mayotte' >Mayotte</option><option value='Mexico' >Mexico</option><option value='Micronesia' >Micronesia</option><option value='Moldova' >Moldova</option><option value='Monaco' >Monaco</option><option value='Mongolia' >Mongolia</option><option value='Montenegro' >Montenegro</option><option value='Montserrat' >Montserrat</option><option value='Morocco' >Morocco</option><option value='Mozambique' >Mozambique</option><option value='Myanmar' >Myanmar</option><option value='Namibia' >Namibia</option><option value='Nauru' >Nauru</option><option value='Nepal' >Nepal</option><option value='Netherlands' >Netherlands</option><option value='New Caledonia' >New Caledonia</option><option value='New Zealand' >New Zealand</option><option value='Nicaragua' >Nicaragua</option><option value='Niger' >Niger</option><option value='Nigeria' >Nigeria</option><option value='Niue' >Niue</option><option value='Norfolk Island' >Norfolk Island</option><option value='North Korea' >North Korea</option><option value='Northern Mariana Islands' >Northern Mariana Islands</option><option value='Norway' >Norway</option><option value='Oman' >Oman</option><option value='Pakistan' >Pakistan</option><option value='Palau' >Palau</option><option value='Palestine, State of' >Palestine, State of</option><option value='Panama' >Panama</option><option value='Papua New Guinea' >Papua New Guinea</option><option value='Paraguay' >Paraguay</option><option value='Peru' >Peru</option><option value='Philippines' >Philippines</option><option value='Pitcairn' >Pitcairn</option><option value='Poland' >Poland</option><option value='Portugal' >Portugal</option><option value='Puerto Rico' >Puerto Rico</option><option value='Qatar' >Qatar</option><option value='Réunion' >Réunion</option><option value='Romania' >Romania</option><option value='Russia' >Russia</option><option value='Rwanda' >Rwanda</option><option value='Saint Barthélemy' >Saint Barthélemy</option><option value='Saint Helena' >Saint Helena</option><option value='Saint Kitts and Nevis' >Saint Kitts and Nevis</option><option value='Saint Lucia' >Saint Lucia</option><option value='Saint Martin' >Saint Martin</option><option value='Saint Pierre and Miquelon' >Saint Pierre and Miquelon</option><option value='Saint Vincent and the Grenadines' >Saint Vincent and the Grenadines</option><option value='Samoa' >Samoa</option><option value='San Marino' >San Marino</option><option value='Sao Tome and Principe' >Sao Tome and Principe</option><option value='Saudi Arabia' >Saudi Arabia</option><option value='Senegal' >Senegal</option><option value='Serbia' >Serbia</option><option value='Seychelles' >Seychelles</option><option value='Sierra Leone' >Sierra Leone</option><option value='Singapore' >Singapore</option><option value='Sint Maarten' >Sint Maarten</option><option value='Slovakia' >Slovakia</option><option value='Slovenia' >Slovenia</option><option value='Solomon Islands' >Solomon Islands</option><option value='Somalia' >Somalia</option><option value='South Africa' >South Africa</option><option value='South Georgia' >South Georgia</option><option value='South Korea' >South Korea</option><option value='South Sudan' >South Sudan</option><option value='Spain' >Spain</option><option value='Sri Lanka' >Sri Lanka</option><option value='Sudan' >Sudan</option><option value='Suriname' >Suriname</option><option value='Svalbard and Jan Mayen Islands' >Svalbard and Jan Mayen Islands</option><option value='Sweden' >Sweden</option><option value='Switzerland' >Switzerland</option><option value='Syria' >Syria</option><option value='Taiwan' >Taiwan</option><option value='Tajikistan' >Tajikistan</option><option value='Tanzania' >Tanzania</option><option value='Thailand' >Thailand</option><option value='Timor-Leste' >Timor-Leste</option><option value='Togo' >Togo</option><option value='Tokelau' >Tokelau</option><option value='Tonga' >Tonga</option><option value='Trinidad and Tobago' >Trinidad and Tobago</option><option value='Tunisia' >Tunisia</option><option value='Turkey' >Turkey</option><option value='Turkmenistan' >Turkmenistan</option><option value='Turks and Caicos Islands' >Turks and Caicos Islands</option><option value='Tuvalu' >Tuvalu</option><option value='Uganda' >Uganda</option><option value='Ukraine' >Ukraine</option><option value='United Arab Emirates' >United Arab Emirates</option><option value='United Kingdom' >United Kingdom</option><option value='United States' >United States</option><option value='Uruguay' >Uruguay</option><option value='US Minor Outlying Islands' >US Minor Outlying Islands</option><option value='Uzbekistan' >Uzbekistan</option><option value='Vanuatu' >Vanuatu</option><option value='Venezuela' >Venezuela</option><option value='Vietnam' >Vietnam</option><option value='Virgin Islands, British' >Virgin Islands, British</option><option value='Virgin Islands, U.S.' >Virgin Islands, U.S.</option><option value='Wallis and Futuna' >Wallis and Futuna</option><option value='Western Sahara' >Western Sahara</option><option value='Yemen' >Yemen</option><option value='Zambia' >Zambia</option><option value='Zimbabwe' 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