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Hyperbaric Oxygen Therapy (HBOT) is a mode of medical treatment in which the patient is entirely enclosed in a pressure chamber and breathes 100% oxygen at a pressure greater than 1 atmosphere absolute (ATA). ATA is the units of pressure and 1 ATA is equal to 760 mm of mercury or pressure at sea level. Hyperbaric oxygen therapy involves breathing pure oxygen (100%) in a pressurized room or tube. In a hyperbaric oxygen therapy chamber, the air pressure may be increased up to three times higher than ATA. Under these conditions, the lungs can gather more oxygen than would be possible breathing pure oxygen at normal air pressure. The result is an increase of 10 to 15 times in plasma oxygen concentration. This increase translates to arterial oxygen values between 1500 and 2000 mmHg, which produces a four-fold increase in the diffusing distance of oxygen from functioning capillaries.
Over the past 50 years HBOT has been recommended and used in a wide variety of medical conditions. Animal studies and clinical trials have produced abundant scientific evidence of its efficacy and has now produced a set of indications for which HBOT is beneficial. This has led to a renaissance of HBOT, and hyperbaric facilities now form an important part of many hospitals all over the world. In 1996 there were more than 250 hyperbaric facilities in USA and there has been an annual increase in the number of hyperbaric centers and exponential increase in patients.
Breathing 100 percent oxygen under pressure causes the oxygen to diffuse into the blood plasma. This oxygen-rich plasma can travel past the restriction, diffusing up to three times further into the tissue. The pressurized environment helps to reduce swelling and discomfort, while providing the body with at least 10 times its normal supply of oxygen to help repair tissue damaged by original occlusion or subsequent hypoxic condition.
Additionally, by forcing more oxygen into the tissue, HBOT encourages the formation of new blood vessels. As these new blood vessels develop, the red blood cells start to flow, delivering even more oxygen to the affected area. This creates the optimal environment for the body’s natural healing.
Additionally, HBOT short term effects include an elevated leukocyte function and phagocytosis by improving the local microcirculation through the destruction of bacteria, all contributing to the anti-inflammatory effect. Late stage healing effects contribute to neovascularization (expansion of microvascular networks), through synthesis of growth factors and angiogenesis (local endothelial cells aid growth of new blood vessels). HBOT also stimulates synthesis of fibroblast collagen 7 production and osteogenesis.
Summary of HBOT Mechanisms of Action:
Reactive Vasoconstriction: Edema is reduced whilst normal tissue oxygen is maintained through the contraction of small vessels that are constricted.
Healing effect: improves and intensifies the growth of osteoclasts and osteoblasts, increases the synthesis of collagen and encourages angiogenesis in hypoxic tissues, thus increasing healing in chronic wounds osteoradionecrosis and burns.
Oxygen pressure increase: aids removal of toxic gases (carbon monoxide) because when high concentrations of oxygen are present in alveolar air carbon monoxide is displaced from hemoglobin faster than ambient air pressure. HBO causes vasoconstriction in normal tissues but with an overall increased delivery of oxygen due to the hyperoxygenation. This is the basis of use in reducing edema and tissue swelling. In cerebral edema this helps to reduce edema while maintaining hyperoxia. It also reduces the adherence of white cells to capillary walls and is useful in acute brain and spinal cord injury.
Hyperoxygenation accelerates neo-vascularization in hypoxic areas by augmentation of fibroblastic activity which further promotes capillary growth.
Antibacterial effect: - ensures oxygenation of antibacterial defenses. Hyperoxygenation causes immune stimulation by restoring WBC function, enhanced phagocytic capabilities and neutrophil mediated killing of bacteria. HBO therapy is bactericidal for certain anaerobic organisms and inhibits the growth of aerobic bacteria at pressures greater than 1.3 ATA.
The following are the most common and universally accepted conditions where HBO therapy should be given and may be combined with other bioregulatory therapies.
Non-healing ulcers, problem wounds, compromised skin grafts and flaps
Non-healing wounds / problem wounds (diabetic / venous etc.)
Crush injury, compartment syndrome, and acute traumatic ischemias
Gas gangrene / clostridial infections
Necrotizing soft tissue infections (subcutaneous tissue, muscle, fascia)
Exceptional blood loss (anemia)
Ocular ischemic pathology
Air or gas embolism
Carbon monoxide poisoning and smoke inhalation
Radiation tissue damage
The following are additional indications for HBOT that hold promise but have been less researched.
Brain injury, spinal cord injury, closed head injury, sports injuries
Certain types of cancer
Post myocardial infarction.
When used according to standard protocols, with oxygen pressures not exceeding 3 atmospheres and treatment sessions limited to a maximum of 120 minutes, hyperbaric therapy is safe. However, some adverse effects may occur. Reversible myopia, a consequence of the direct toxic effect of oxygen on the lens, is the most common side effect.
The following are selected articles on HBOT with certain conditions.
The following are selected articles on HBOT with certain conditions.
Calvert, John W., Julian Cahill, and John H. Zhang. "Hyperbaric oxygen and cerebral physiology." Neurological research 29, no. 2 (2007): 132-141.
Harch, Paul G., and Teri Small. "Interview with Dr. Paul Harch: the application of hyperbaric oxygen therapy in chronic neurological conditions." Medical Veritas 2, no. 2 (2005): 637-646.
Sahni, T., P. Singh, and M. J. John. "Hyperbaric oxygen therapy: current trends and applications." Journal-Association of physicians of india 51 (2003): 280-288.
Sahni, Tarun, S. H
ukku, Madhur Jain, Arun Prasad, Rajendra Prasad, and Kuldeep Singh. "Recent advances in hyperbaric oxygen therapy." Med Update 14 (2004): 632-9.
Sahni, Tarun, and Madhur Jain. "Status of Hyperbaric Oxygen Therapy in neurological Illnesses-Review of International and Indian Experience." Neurosciences today 7 (2003): 28-36.
Tibbles, Patrick M., and John S. Edelsberg. "Hyperbaric-oxygen therapy." New England Journal of Medicine 334, no. 25 (1996): 1642-1648.
You, Yeon Ho, Heeduck Kim, Hyun Kim, Sangcheon Choi, and Giwoon Kim. "Clinical applications and contemporary trends of hyperbaric oxygen therapy in Korea." Journal of the Korean Medical Association 57, no. 7 (2014): 601-606.
Acute Thermal Burn Injury
Insufficient oxygen and nutrient supply leads to a rapid deterioration to a central area of coagulation found with severe burns. Initial therapy aims to preserve borderline tissue, reduce edema, improve local host defenses and promote wound closure. Hyper-oxygenation increases vasoconstriction of vessels and therefore decreases edema enhances the formation of collagen and angiogenesis. A number of studies support the use of HBOT in thermal burns.
Cianci, P. E., H. Lueders, H. Lee, R. Shapiro, J. Sexton, C. Williams, and B. Green. "Adjunctive hyperbaric oxygen reduces the need for surgery in 40-80% burns." (1988).
Radiotherapy is used in high doses to eliminate tumors often causing a degree of cellular impairment, leading to tissue hypoxia and cellular death. Osteoradionecrosis (ORN) is consistent with head and neck cancer patients receiving high doses of radiation. HBOT may be used to treat and halt the progression of ORN, increasing tissue oxygen tensions to sufficient levels to enable angiogenesis and improved leukocyte function. The evidence for the use of HBOT for delayed radiation injury is extensive.
Chuba, Paul J., Patricia Aronin, Kanta Bhambhani, Michael Eichenhorn, Lucia Zamarano, Paul Cianci, Michael Muhlbauer, Arthur T. Porter, and James Fontanesi. "Hyperbaric oxygen therapy for radiation‐induced brain injury in children." Cancer: Interdisciplinary International Journal of the American Cancer Society 80, no. 10 (1997): 2005-2012.
David, Lesley A., George KB Sàndor, A. Wayne Evans, and Dale H. Brown. "Hyperbaric oxygen therapy and mandibular osteoradionecrosis: a retrospective study and analysis of treatment outcomes." JOURNAL-CANADIAN DENTAL ASSOCIATION 67, no. 7 (2001): 384-385.
Kohshi, Kiyotaka, Hajime Imada, Satoshi Nomoto, Raizoh Yamaguchi, Haruhiko Abe, and Haruaki Yamamoto. "Successful treatment of radiation-induced brain necrosis by hyperbaric oxygen therapy." Journal of the neurological sciences 209, no. 1-2 (2003): 115-117.
Ohguri, Takayuki, Hajime Imada, Kiyotaka Kohshi, Shingo Kakeda, Norihiro Ohnari, Tomoaki Morioka, Keita Nakano, Nobuhide Konda, and Yukunori Korogi. "Effect of prophylactic hyperbaric oxygen treatment for radiation-induced brain injury after stereotactic radiosurgery of brain metastases." International Journal of Radiation Oncology* Biology* Physics 67, no. 1 (2007): 248-255.
Sahni, Tarun, Madhur Jain, S. Hukku, and G. K. Jadhav. "Role of hyperbaric oxygen therapy in oncology and radiation induced tissue damage." Apollo Medicine 1, no. 2 (2004): 186-189.
Kranke, Peter, Michael H. Bennett, Marrissa Martyn‐St James, Alexander Schnabel, Sebastian E. Debus, and Stephanie Weibel. "Hyperbaric oxygen therapy for chronic wounds." Cochrane Database of Systematic Reviews 6 (2015).
Roeckl‐Wiedmann, I., M. Bennett, and P. Kranke. "Systematic review of hyperbaric oxygen in the management of chronic wounds." British journal of surgery 92, no. 1 (2005): 24-32.
Wang, Chenchen, Steven Schwaitzberg, Elise Berliner, Deborah A. Zarin, and Joseph Lau. "Hyperbaric oxygen for treating wounds: a systematic review of the literature." Archives of Surgery 138, no. 3 (2003): 272-279.
Wang, Chenchen, and Joseph Lau. "Hyperbaric oxygen therapy in treatment of hypoxic wounds." Technology Assessment. Agency for Healthcare Research and Quality (AHRQ) (2001).
Leg and Foot Ulcers
HBOT is frequently used for the treatment of problem wounds including insufficiency ulcers and diabetic foot ulcers.
Abidia, A., G. Laden, G. Kuhan, B. F. Johnson, A. R. Wilkinson, P. M. Renwick, E. A. Masson, and P. T. McCollum. "The role of hyperbaric oxygen therapy in ischaemic diabetic lower extremity ulcers: a double-blind randomised-controlled trial." European journal of vascular and endovascular surgery 25, no. 6 (2003): 513-518.
Barnes, Robert C. "Point: hyperbaric oxygen is beneficial for diabetic foot wounds." Clinical infectious diseases 43, no. 2 (2006): 188-192.
Doctor, N., S. Pandya, and A. Supe. "Hyperbaric oxygen therapy in diabetic foot." Journal of postgraduate medicine 38, no. 3 (1992): 112.
Duzgun, Arife Polat, Hakan Ziya Satır, Omer Ozozan, Barıs Saylam, Bahadır Kulah, and Faruk Coskun. "Effect of hyperbaric oxygen therapy on healing of diabetic foot ulcers." The Journal of foot and ankle surgery 47, no. 6 (2008): 515-519.
Löndahl, Magnus, Per Katzman, Anders Nilsson, and Christer Hammarlund. "Hyperbaric oxygen therapy facilitates healing of chronic foot ulcers in patients with diabetes." Diabetes care 33, no. 5 (2010): 998-1003.
Niinikoski, Juha. "Hyperbaric oxygen therapy of diabetic foot ulcers, transcutaneous oxymetry in clinical decision making." Wound repair and regeneration 11, no. 6 (2003): 458-461.
Stoekenbroek, R. M., T. B. Santema, D. A. Legemate, D. T. Ubbink, A. Van Den Brink, and M. J. W. Koelemay. "Hyperbaric oxygen for the treatment of diabetic foot ulcers: a systematic review." European journal of vascular and endovascular surgery 47, no. 6 (2014): 647-655.
Faglia, Ezio, Favales Favales, Aldeghi Aldeghi, Patrizia Calia, Antonella Quarantiello, Giorgio Oriani, Michael Michael, Pietro Campagnoli, and Alberto Morabito. "Adjunctive systemic hyperbaric oxygen therapy in treatment of severe prevalently ischemic diabetic foot ulcer: a randomized study." Diabetes care 19, no. 12 (1996): 1338-1343.
Buchman, Alan L., Caroline Fife, Carlos Torres, Latisha Smith, and Jaime Aristizibal. "Hyperbaric oxygen therapy for severe ulcerative colitis." Journal of clinical gastroenterology 33, no. 4 (2001): 337-339.
A major loss of red blood cells causing limited oxygen carriage as a result of hemolysis or hemorrhage results in tissue hypoxia leading to ischemia. In these situations, and where transfusions are not possible, e.g. rare blood group or religious beliefs, HBOT may be used to increase levels of oxygen dissolved in plasma, compensating for reduced hemoglobin levels.
Greensmith, J. Eric. "Hyperbaric oxygen reverses organ dysfunction in severe anemia." Anesthesiology: The Journal of the American Society of Anesthesiologists 93, no. 4 (2000): 1149-1152.
Holland, N. Julian, Jonathan M. Bernstein, and John W. Hamilton. "Hyperbaric oxygen therapy for Bell's palsy." Cochrane Database of Systematic Reviews 2 (2012). (Abstract)
Racic, G., P. J. Denoble, N. Sprem, L. Bojic, and B. Bota. "Hyperbaric oxygen as a therapy of Bell's palsy." Undersea & hyperbaric medicine: journal of the Undersea and Hyperbaric Medical Society, Inc 24, no. 1 (1997): 35-38. (Abstract)
Toros, Sema Zer, Çiğdem Tepe Karaca, Pembegül Güneş, Çağatay Oysu, Çiğdem Kalaycık Ertugay, Barış Naiboğlu, Emin Elbüken, and Erol Egeli. "Hyperbaric oxygen versus steroid in facial nerve injury: an experimental animal study." American journal of otolaryngology 34, no. 5 (2013): 530-536. (Abstract)
Perrins, D. J., and P. B. James. "Hyperbaric oxygen therapy and multiple sclerosis." (2002).
Improved diagnosis and therapy in conditions including subdural empyema, cerebral abscess have decreased the mortality rate related to them. HBOT may be used in circumstances where patients have failed to respond to standard care. HBOT can modify the immune response and reduce cerebral edema.
Bartek, Jiri, Asgeir S. Jakola, Simon Skyrman, Petter Förander, Peter Alpkvist, Gaston Schechtmann, Martin Glimåker, Agneta Larsson, Folke Lind, and Tiit Mathiesen. "Hyperbaric oxygen therapy in spontaneous brain abscess patients: a population-based comparative cohort study." Acta neurochirurgica 158, no. 7 (2016): 1259-1267.
Kutlay, Murat, Ahmet Colak, Şenol Yıldız, Nusret Demircan, and Osman Niyazi Akın. "Stereotactic aspiration and antibiotic treatment combined with hyperbaric oxygen therapy in the management of bacterial brain abscesses." Neurosurgery 57, no. 6 (2005): 1140-1146. (abstract)
Lampl, L. A., G. Frey, T. Dietze, and M. Trauschel. "Hyperbaric oxygen in intracranial abscesses." (1989).
Stroke and Cerebral Ischemia
The rationale of use of hyperbaric oxygen in neurological indications is based on the finding in SPECT studies that around the central area of neuronal death is the penumbra: peri-infarct zone. This zone has hibernating/idling or sleeping neurons. Also, what appears as gliosis (dead neurons) on CT scans may be viable tissue for years following the insult. HBO delivers high oxygen to these “sleeping cells” and reactivates them. HBO increases oxygen supply to the ischemic neurons, reduces edema and reverses the reduced flexibility of erythrocytes. This is the basis of its use by some centers in acute stroke, post-traumatic brain injuries and cerebral palsy.
Bennett, M. H., J. Wasiak, and C. French. "Oxigenoterapia hiperbárica para el accidente cerebrovascular isquémico agudo."
Lim, J., W. K. Lim, T. T. Yeo, Y. Y. Sitoh, and E. Low. "Management of Haemorrhagic Stroke with Hyperbaric Oxygen Therapy–." Singapore Med J 42, no. 5 (2001): 220-223.
Nighoghossian, N., P. Trouillas, P. Adeleine, and F. Salord. "Hyperbaric oxygen in the treatment of acute ischemic stroke: a double-blind pilot study." Stroke 26, no. 8 (1995): 1369-1372.
Schäbitz, Wolf-Ruediger, Holger Schade, Sabine Heiland, Rainer Kollmar, Jürgen Bardutzky, Nils Henninger, Harald Müller et al. "Neuroprotection by hyperbaric oxygenation after experimental focal cerebral ischemia monitored by MRI." Stroke 35, no. 5 (2004): 1175-1179.
Zhang, John H., Aneesh B. Singhal, and James F. Toole. "Oxygen therapy in ischemic stroke." Stroke 34, no. 9 (2003): e152-e153.
Bennett, Michael H., Barbara Trytko, and Benjamin Jonker. "Hyperbaric oxygen therapy for the adjunctive treatment of traumatic brain injury." Cochrane Database of Systematic Reviews 12 (2012).
Harch, Paul G., Susan R. Andrews, Edward F. Fogarty, Juliette Lucarini, and Keith W. Van Meter. "Case control study: hyperbaric oxygen treatment of mild traumatic brain injury persistent post-concussion syndrome and post-traumatic stress disorder." Medical gas research 7, no. 3 (2017): 156.
Harch, Paul G., Christopher Kriedt, Keith W. Van Meter, and Robert James Sutherland. "Hyperbaric oxygen therapy improves spatial learning and memory in a rat model of chronic traumatic brain injury." Brain research 1174 (2007): 120-129.
Harch, Paul G. "Hyperbaric oxygen in chronic traumatic brain injury: oxygen, pressure, and gene therapy." Medical gas research 5, no. 1 (2015): 9.
Kraitsy, Klaus, Muammer Uecal, Stefan Grossauer, Lukas Bruckmann, Florentina Pfleger, Stefan Ropele, Franz Fazekas et al. "Repetitive long-term hyperbaric oxygen treatment (HBOT) administered after experimental traumatic brain injury in rats induces significant remyelination and a recovery of sensorimotor function." PloS one 9, no. 5 (2014).
Lin, Jia-Wei, Jo-Ting Tsai, Liang-Ming Lee, Chien-Min Lin, Ching-Chang Hung, Kuo-Sheng Hung, Wei-Yu Chen et al. "Effect of hyperbaric oxygen on patients with traumatic brain injury." In Reconstructive Neurosurgery, pp. 145-149. Springer, Vienna, 2008.
Rockswold, Sarah B., Gaylan L. Rockswold, and Archie Defillo. "Hyperbaric oxygen in traumatic brain injury." Neurological research 29, no. 2 (2007): 162-172.
Tal, Sigal, Amir Hadanny, Nadav Berkovitz, Efrat Sasson, Eshel Ben-Jacob, and Shai Efrati. "Hyperbaric oxygen may induce angiogenesis in patients suffering from prolonged post-concussion syndrome due to traumatic brain injury." Restorative neurology and neuroscience 33, no. 6 (2015): 943-951.
Zhang, Yongming, Yanyan Yang, Hong Tang, Wenjiang Sun, Xiaoxing Xiong, Daniel Smerin, and Jiachuan Liu. "Hyperbaric oxygen therapy ameliorates local brain metabolism, brain edema and inflammatory response in a blast-induced traumatic brain injury model in rabbits." Neurochemical research 39, no. 5 (2014): 950-960. (Abstract)
Zhou, Hai-xiao, Zhi-gang Liu, Xiao-jiao Liu, and Qian-xue Chen. "Umbilical cord-derived mesenchymal stem cell transplantation combined with hyperbaric oxygen treatment for repair of traumatic brain injury." Neural regeneration research 11, no. 1 (2016): 107.
Marois, Pierre, and Michel Vanasse. "Hyperbaric oxygen therapy and cerebral palsy." Developmental medicine and child neurology 45, no. 9 (2003): 646-647.
Sethi, Amit, and Arun Mukherjee. "To see the efficacy of hyperbaric oxygen therapy in gross motor abilities of cerebral palsy children of 2–5 years, given initially as an adjunct to occupational therapy." The Indian Journal of Occupational Therapy 25, no. 1 (2003): 7-11.
Idiopathic sudden sensorineural hearing loss (ISSHL) is a hearing impairment with sensorineural hearing loss greater than 30 dB in three sequential frequencies occurring over three. The use of HBOT has been proposed because it has been suggested that hearing loss may be the result of hypoxia or other inflammatory processes leading to ischemic changes effecting the cochlea apparatus function (Mazurek et al, 2006). In the event of reduced oxygenation to structures within the cochlea, the oxygen concentration would be restored using HBOT (Pezzoli et al, 2015).
İnci, Ender, Ferhat Erişir, Mehmet Ada, O. Oztürk, Ender Güçlü, F. Oktem, and Murat Toprak. "Hyperbaric oxygen treatment in sudden hearing loss after unsuccessful medical treatment." Kulak burun bogaz ihtisas dergisi: KBB= Journal of ear, nose, and throat 9, no. 5 (2002): 337-341. (Abstract)
Krajčovičová, Zdenka, Rastislav Zigo, and Vladimír Meluš. "Possibilities of hyperbaric oxygen therapy usage in comprehensive treatment of selected hearing diseases and disorders." University review 9, no. 2-3 (2015): 45-53.
Al-Waili, Noori S., Glenn J. Butler, Jorge Beale, Roger W. Hamilton, Bok Y. Lee, and Paul Lucas. "Hyperbaric oxygen and malignancies: a potential role in radiotherapy, chemotherapy, tumor surgery and phototherapy." Medical science monitor 11, no. 9 (2005): RA279-RA289.
Granowitz, Eric V., Noriko Tonomura, Rita M. Benson, Deborah M. Katz, Vimla Band, Grace P. Makari-Judson, and Barbara A. Osborne. "Hyperbaric oxygen inhibits benign and malignant human mammary epithelial cell proliferation." Anticancer research 25, no. 6B (2005): 3833-3842.
Kohshi, K., Y. Kinoshita, H. Imada, N. Kunugita, H. Abe, H. Terashima, N. Tokui, and S. Uemura. "Effects of radiotherapy after hyperbaric oxygenation on malignant gliomas." British journal of cancer 80, no. 1 (1999): 236-241.
Moen, Ingrid, and Linda EB Stuhr. "Hyperbaric oxygen therapy and cancer—a review." Targeted oncology 7, no. 4 (2012): 233-242.
Moen, Ingrid, Karl J. Tronstad, Odd Kolmannskog, Gerd S. Salvesen, Rolf K. Reed, and Linda EB Stuhr. "Hyperoxia increases the uptake of 5-fluorouracil in mammary tumors independently of changes in interstitial fluid pressure and tumor stroma." BMC cancer 9, no. 1 (2009): 446.
Petre, Paul M., Frank A. Baciewicz Jr, Stefan Tigan, and J. Richard Spears. "Hyperbaric oxygen as a chemotherapy adjuvant in the treatment of metastatic lung tumors in a rat model." The Journal of thoracic and cardiovascular surgery 125, no. 1 (2003): 85-95.
Raa, Anette, Christine Stansberg, Vidar M. Steen, Rolf Bjerkvig, Rolf K. Reed, and Linda EB Stuhr. "Hyperoxia retards growth and induces apoptosis and loss of glands and blood vessels in DMBA-induced rat mammary tumors." BMC cancer 7, no. 1 (2007): 23.
Sletta, Kristine Yttersian, Maria K. Tveitarås, Ning Lu, Agnete ST Engelsen, Rolf K. Reed, Annette Garmann-Johnsen, and Linda Stuhr. "Oxygen-dependent regulation of tumor growth and metastasis in human breast cancer xenografts." PloS one 12, no. 8 (2017).
Stępień, Katarzyna, Robert P. Ostrowski, and Ewa Matyja. "Hyperbaric oxygen as an adjunctive therapy in treatment of malignancies, including brain tumours." Medical Oncology 33, no. 9 (2016): 101.
Stuhr, Linda Elin Birkhaug, A. Raa, A. M. Øyan, K. H. Kalland, P. O. Sakariassen, K. Petersen, R. Bjerkvig, and R. K. Reed. "Hyperoxia retards growth and induces apoptosis, changes in vascular density and gene expression in transplanted gliomas in nude rats." Journal of neuro-oncology 85, no. 2 (2007): 191-202.
Wenwu, Liu, Sun Xuejun, Tao Hengyi, and Liu Kan. "Hyperbaric oxygen and cancer: more complex than we expected." (2013): 79-81.
Acute Carbon Monoxide Poisoning
Weaver, Lindell K., Ramona O. Hopkins, Karen J. Chan, Susan Churchill, C. Gregory Elliott, Terry P. Clemmer, James F. Orme Jr, Frank O. Thomas, and Alan H. Morris. "Hyperbaric oxygen for acute carbon monoxide poisoning." New England Journal of Medicine 347, no. 14 (2002): 1057-1067.