Hyperbaric oxygen therapy in acute stroke: is it time for Justitia to open her eyes?

  • Milija D. MijajlovicEmail author
  • Vuk Aleksic
  • Nenad Milosevic
  • Natan M. Bornstein
Review Article


Hypoxia is a critical component of neuronal death in patients with stroke. Therefore increasing oxygenation of brain tissue seems to be a logical therapy against cerebral ischemia. Oxygen therapy exists in two modalities: normobaric hyperoxia therapy and hyperbaric oxygen therapy (HBO). HBO is a therapeutic procedure in which pure (100%) oxygen is administered at greater than atmospheric pressure in HBO therapy chambers. In this review article, we aimed to summarize the current knowledge regarding the therapeutic use of HBO in acute stroke patients. Literature review and electronic search were performed using PubMed, Medscape, and UpToDate with the keywords stroke, acute stroke, hyperbaric oxygen therapy, and hyperoxia. According to the reviewed literature, the use of HBO as routine stroke therapy cannot be justified in acute stage of stroke. More randomized, controlled studies are needed regarding safety and especially effectives of HBO in stroke patients. Also, standardized definition

of HBO should be proposed and used in all future studies.


Stroke Hyperoxia Normobaric hyperoxia therapy Hyperbaric oxygen therapy 


Compliance with ethical standards

Conflict of interest

Authors have no potential conflicts of interest do disclose.

Ethical approval

Not applicable.

Research involving human participants and/or animals

Not applicable

Informed consent

Not applicable


  1. 1.
    Jauch EC, Saver JL, Adams HP Jr, Bruno A, Connors JJ, Demaerschalk BM et al (2013) American Heart Association Stroke Council; Council on Cardiovascular Nursing; Council on Peripheral Vascular Disease; Council on Clinical Cardiology. Guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 44(3):870–947PubMedCrossRefPubMedCentralGoogle Scholar
  2. 2.
    GBD 2016 Lifetime Risk of Stroke Collaborators, FeiginVL NG, Cercy K, Johnson CO, Alam T, Parmar PG et al (2018) Global, regional, and country-specific lifetime risks of stroke, 1990 and 2016. N Engl J Med 379(25):2429–2437CrossRefGoogle Scholar
  3. 3.
    Liu W, Khatibi N, Sridharan A, Zhang JH (2011) Application of medical gases in the field of neurobiology. Med Gas Res 1(1):13PubMedPubMedCentralCrossRefGoogle Scholar
  4. 4.
    Hawkins BT, Egleton RD (2008) Pathophysiology of the blood-brain barrier: animal models and methods. Curr Top Dev Biol 80:277–309PubMedCrossRefPubMedCentralGoogle Scholar
  5. 5.
    Singhal AB, Lo EH, Dalkara T, Moskowitz MA (2005) Advances in stroke neuroprotection: hyperoxia and beyond. Neuroimaging Clin N Am 15(3):697–720 xii-xiiiPubMedCrossRefPubMedCentralGoogle Scholar
  6. 6.
    Chen F, Qi Z, Luo Y, Hinchliffe T, Ding G, Xia Y, Ji X (2014) Non-pharmaceutical therapies for stroke: mechanisms and clinical implications. ProgNeurobiol. 115:246–269Google Scholar
  7. 7.
    Shin HK, Dunn AK, Jones PB, Boas DA, Lo EH, Moskowitz MA, Ayata C (2007) Normobarichyperoxia improves cerebral blood flow and oxygenation, and inhibits peri-infarct depolarizations in experimental focal ischaemia. Brain. 130(Pt 6):1631–1642PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    Kheir JN, Scharp LA, Borden MA, Swanson EJ, Loxley A, Reese JH, Black KJ, Velazquez LA, Thomson LM, Walsh BK, Mullen KE, Graham DA, Lawlor MW, Brugnara C, Bell DC, McGowan FX Jr (2012) Oxygen gas-filled microparticles provide intravenous oxygen delivery. SciTransl Med 4(140):140ra88Google Scholar
  9. 9.
    Henninger N, Bratane BT, Bastan B, Bouley J, Fisher M (2009) Normobarichyperoxia and delayed tPA treatment in a rat embolic stroke model. J Cereb Blood Flow Metab 29(1):119–129PubMedCrossRefGoogle Scholar
  10. 10.
    Kim HY, Singhal AB, Le EH (2005) Normobarichyperoxia extends the reperfusion window in focal cerebral ischemia. Ann Neurol 57(4):571–575PubMedCrossRefGoogle Scholar
  11. 11.
    Wu O, Lu J, Mandeville JB, Murata Y, Egi Y, Dai G, Marota JJ, Diwan I, Dijkhuizen RM, KwongKK LEH, Singhal AB (2012) Dynamic functional cerebral blood volume responses to normobarichyperoxia in acute ischemic stroke. J Cereb Blood Flow Metab 32(9):1800–1809PubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    Singhal AB (2006) Oxygen therapy in stroke: past, present, and future. Int J Stroke 1(4):191–200PubMedCrossRefGoogle Scholar
  13. 13.
    Singhal AB, Benner T, Roccatagliata L, Koroshetz WJ, Schaefer PW, Lo EH, Buonanno FS, Gonzalez RG, Sorensen AG (2005) A pilot study of normobaric oxygen therapy in acute ischemic stroke. Stroke. 36(4):797–802PubMedCrossRefGoogle Scholar
  14. 14.
    Singhal AB, Ratai E, Benner T, Vangel M, Lee V, Koroshetz WJ, Schaefer PW, Sorensen AG, Gonzalez RG (2007) Magnetic resonance spectroscopy study of oxygen therapy in ischemic stroke. Stroke. 38(10):2851–2854PubMedCrossRefGoogle Scholar
  15. 15.
    Rønning OM, Guldvog B (1999) Should stroke victims routinely receive supplemental oxygen? A quasi-randomized controlled trial. Stroke. 30(10):2033–2037PubMedCrossRefGoogle Scholar
  16. 16.
    Chan YF, Katz M, Moskowitz A, Levine SR, Richardson LD, Tuhrim S et al (2014) Supplemental oxygen delivery to suspected stroke patients in pre hospital and emergency department settings. Med Gas Res. 4:16PubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    Al-Waili NS, Butler GJ, Beale J, Abdullah MS, Hamilton RW, Lee BY, Lucus P, Allen MW, Petrillo RL, Carrey Z, Finkelstein M (2005) Hyperbaric oxygen in the treatment of patients with cerebral stroke, brain trauma, and neurologic disease. Adv Ther. 22(6):659–678PubMedCrossRefGoogle Scholar
  18. 18.
    Plafki C, Peters P, Almeling M, Welslau W, Busch R (2000) Complications and side effects of hyperbaric oxygen therapy. Aviat Space Environ Med 71:119–124PubMedGoogle Scholar
  19. 19.
    Henshaw IN, Simpson A. Compressed air as a therapeutic agent in the treatment of consumption, asthma, chronic bronchitis and other diseases. 1857Google Scholar
  20. 20.
    Mader JT, Brown GL, Guckian JC, Wells CH, Reinarz JA (1980) A mechanism for the amelioration by hyperbaric oxygen of experimental staphylococcal osteomyelitis in rabbits. J Infect Dis 142(6):915–922PubMedCrossRefGoogle Scholar
  21. 21.
    Henry W (1803) Experiments on the quantity of gases absorbed by water, at different temperatures, and under different pressures. Phil Trans R Soc Lond 93:29–274CrossRefGoogle Scholar
  22. 22.
    Boerema I et al (1960) Life without blood. A study of the influence of high atmospheric pressure and hypothermia on dilution of the blood. J Cardiovasc Surg 1:133–146Google Scholar
  23. 23.
    Nylander G, Lewis D, Nordstrom H et al (1985) Reduction of postischemic edema with hyperbaric oxygen. Plast Reconstr Surg 76(4):596–603PubMedCrossRefGoogle Scholar
  24. 24.
    Sukoff MH, Ragatz RE (1982) Hyperbaric oxygenation for the treatment of acute cerebral edema. Neurosurgery. 10(1):29–38PubMedGoogle Scholar
  25. 25.
    Singhal AB, Dijkhuizen RM, Rosen BR, Lo EH (2002) Normobarichyperoxia reduces MRI diffusion abnormalities and infarct size in experimental stroke. Neurology. 58(6):945–952PubMedCrossRefGoogle Scholar
  26. 26.
    Nakajima S, Meyer JS, Amano T, Shaw T, Okabe T, Mortel KF (1983) Cerebral vasomotor responsiveness during 100% oxygen inhalation in cerebral ischemia. Arch Neurol 40(5):271–276PubMedCrossRefGoogle Scholar
  27. 27.
    Tal S, Hadanny A, Sasson E, Suzin G, Efrati S (2017) Hyperbaric oxygen therapy can induce angiogenesis and regeneration of nerve fibers in traumatic brain injury patients. Front Hum Neurosci 11:508PubMedPubMedCentralCrossRefGoogle Scholar
  28. 28.
    Thom SR (1990) Antagonism of carbon monoxide-mediated brain lipid peroxidation by hyperbaric oxygen. ToxicolApplPharmacol. 105(2):340–344Google Scholar
  29. 29.
    Ferretti G, Bacchetti T, Masciangelo S, Nanetti L, Mazzanti L, Silvestrini M, Bartolini M, Provinciali L (2008) Lipid peroxidation in stroke patients. ClinChem Lab Med 46(1):113–117Google Scholar
  30. 30.
    Hu Q, Manaenko A, Bian H, Guo Z, Huang JL, Guo ZN, Yang P, Tang J, Zhang JH (2017) Hyperbaric oxygen reduces infarction volume and hemorrhagic transformation through ATP/NAD(+)/sirt1 pathway in hyperglycemic middle cerebral artery occlusion rats. Stroke. 48(6):1655–1664PubMedPubMedCentralCrossRefGoogle Scholar
  31. 31.
    Chang CF, Niu KC, Hoffer BJ, Wang Y, Borlongan CV (2000) Hyperbaric oxygen therapy for treatment of postischemic stroke in adult rats. Exp Neurol 166(2):298–306PubMedCrossRefPubMedCentralGoogle Scholar
  32. 32.
    Zhai WW, Sun L, Yu ZQ, Chen G (2016) Hyperbaric oxygen therapy in experimental and clinical stroke. Med Gas Res. 6(2):111–118PubMedPubMedCentralCrossRefGoogle Scholar
  33. 33.
    Jain KK (2003) Hyperbaric oxygen in acute ischemic stroke. Stroke 34(9):e153 author reply e153–5PubMedCrossRefPubMedCentralGoogle Scholar
  34. 34.
    Godman CA, Chheda KP, Hightower LE, Perdrizet G, Shin DG, Giardina C (2010) Hyperbaric oxygen induces a cytoprotective and angiogenic response in human microvascular endothelial cells. Cell Stress Chaperones 15(4):431–442PubMedCrossRefPubMedCentralGoogle Scholar
  35. 35.
    Liska GM, Lippert T, Russo E, Nieves N, Borlongan CV (2018) A dual role for hyperbaric oxygen in stroke neuroprotection: preconditioning of the brain and stem cells. Cond Med 1(4):151–166PubMedPubMedCentralGoogle Scholar
  36. 36.
    Carson S, McDonagh M, Russman B, Helfand M (2005) Hyperbaric oxygen therapy for stroke: a systematic review of the evidence. Clin Rehabil. 19(8):819–833PubMedCrossRefPubMedCentralGoogle Scholar
  37. 37.
    Anderson DC, Bottini AG, Jagiella WM, Westphal B, Ford S, Rockswold GL, Loewenson RB (1991) A pilot study of hyperbaric oxygen in the treatment of human stroke. Stroke. 22(9):1137–1142PubMedCrossRefPubMedCentralGoogle Scholar
  38. 38.
    Reitan JA, Kien ND, Thorup S, Corkill G (1990) Hyperbaric oxygen increases survival following carotid ligation in gerbils. Stroke 21:119–123PubMedCrossRefPubMedCentralGoogle Scholar
  39. 39.
    Burt JT, Kapp JP, Smith RR (1987) Hyperbaric oxygen and cerebral infarction in the gerbil. Surg Neuml 28:265–268Google Scholar
  40. 40.
    Weinstein PR, Anderson GG, Telles DA (1987) Results of hyperbaric oxygen therapy during temporary middle cerebral artery occlusion in unanesthetized cats. Neurosurgery 20:518–524PubMedCrossRefGoogle Scholar
  41. 41.
    Corkill G, Van Housen K, Hein L, Reitan J (1985) Videodensitometric estimation of the protective effect of hyperbaric oxygen in the ischemic gerbil brain. Surg Neural 24:206–210CrossRefGoogle Scholar
  42. 42.
    Weinstein PR, Hameroff SR, Johnson PC, Anderson GG (1986) Effect of hyperbaric oxygen therapy or dimethyl sulfoxide on cerebral ischemia in unanesthetized gerbils. Neurosurgery 18:528–532PubMedCrossRefGoogle Scholar
  43. 43.
    Ruiz E, Brunette DD, Robinson EP, Tomlinson MJ, Lange J, Wieland MJ, Sherman R (1986) Cerebral resuscitation after cardiac arrest using hetastarch hemodilution, hyperbaric oxygenation and magnesium ion. Resuscitation 14:213–222PubMedCrossRefGoogle Scholar
  44. 44.
    Shiokawa O, Fujishima M, Yanai T, Ibayashi I, Ueda K, Yagi H (1986) Hyperbaric oxygen therapy in experimentally induced acute cerebral ischemia. Undersea Biomed Res 13:337–344PubMedGoogle Scholar
  45. 45.
    Kapp JP, Phillips M, Markov A, Smith RR (1982) Hyperbaric oxygen after circulatory arrest: Modification of postischetnic encephalopathy. Neurosurgery ll:496–499Google Scholar
  46. 46.
    Patterson RH, McSherry CK, Schwartz MS (1968) Hyperbaric oxygen, hypothermia, and cerebral ischemia in the dog. J Surg Res 8:279–285PubMedCrossRefGoogle Scholar
  47. 47.
    Moor GF, Fuson RL, Margolis G, Brown IW, Smith WW (1966) Protective effect of hyperbaric oxygenation on the central nervous system during circulatory arrest. In: Brown IW, Cox BG (eds) Proceedings of the third international conference on hyperbaric medicine. National Academy of Sciences, Washington, DC, pp 367–371Google Scholar
  48. 48.
    McSherry CK, Patterson RH, Lanphier EH (1966) Effect of hyperbaric oxygen and hypothermia on cerebral ischemia. In: Brown IW, Cox BG (eds) Proceedings of the third international conference on hyperbaric medicine. National Academy of Sciences, Washington, DC, pp 374–380Google Scholar
  49. 49.
    Thomas AN, Hall AD, Blaisdell FW, Connolly JE (1966) Survival after prolonged induced circulatory arrest, hyperbaric oxygenation, and hypothermia. In: Fw B, Cox BG (eds) Proceedings of the third international conference on hyperbaric medicine. National Academy of Sciences, Washington, DC, pp 382–390Google Scholar
  50. 50.
    Whalen RE, Heyman A, Saltzman H (1966) The protective effect of hyperbaric oxygenation in cerebral anoxia. Arch Neurol 14:15–20PubMedCrossRefGoogle Scholar
  51. 51.
    FusonRL MGF, Smith WW, Brown IW (1965) Hyperbaric oxygenation in experimental cerebral ischemia. Surg Forum 16:416–418Google Scholar
  52. 52.
    Jacobson I, Lawson DD (1963) The effect of hyperbaric oxygen on experimental cerebral infarction in the dog: With preliminary correlations of cerebral blood flow at 2 atmospheres of oxygen. J Neurosurg 20:849–859PubMedCrossRefGoogle Scholar
  53. 53.
    Smith G, Lawson DD, Renfrew S, Ledingham IM, Sharp GR (1961) Preservation of cerebral cortical activity by breathing oxygen at two atmospheres of pressure during cerebral ischemia. Surg Gynecol Obstet 113:13–16Google Scholar
  54. 54.
    Rusyniak DE, Kirk MA, May JD et al (2003) Hyperbaric oxygen therapy in acute ischaemic stroke: results of the hyperbaric oxygen in acute ischaemic stroke trial pilot study. Stroke 34:571–574PubMedCrossRefGoogle Scholar
  55. 55.
    Nighoghossian N, Trouillas P, Adeleine P, Salord F (1995) Hyperbaric oxygen in the treatment of acute ischaemic stroke: a double-blind pilot study. Stroke 26:1369–1372PubMedCrossRefGoogle Scholar
  56. 56.
    Sarno JE, Rusk HA, Diller L, Sarno MT (1972) The effect of hyperbaric oxygen on the mental and verbal ability of stroke patients. Stroke 3:10–15PubMedCrossRefGoogle Scholar
  57. 57.
    Efrati S, Fishlev G, Bechor Y, Volkov O, Bergan J, Kliakhandler K, Kamiager I, Gal N, Friedman M, Ben-Jacob E, Golan H (2013) Hyperbaric oxygen induces late neuroplasticity in post stroke patients--randomized, prospective trial. PLoS One 8(1):e53716PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    Shirachi DY, Hoggard ML, Jonhson KE (2003) The effect of hyperbaric oxygen therapy on a 3 year post-stroke aphasic patient. Proc XIVth Int Congr Hyperbaric Med 14:153–156Google Scholar
  59. 59.
    Bennett MH, Weibel S, Wasiak J, Schnabel A, French C, Kranke P (2014) Hyperbaric oxygen therapy for acute ischaemic stroke. Cochrane Database Syst Rev 11:CD004954Google Scholar
  60. 60.
    Mathieu D, Marroni A, Kot J (2017) Tenth European Consensus Conference on Hyperbaric Medicine: recommendations for accepted and non-accepted clinical indications and practice of hyperbaric oxygen treatment. Diving Hyperb Med 47(1):24–32PubMedPubMedCentralGoogle Scholar
  61. 61.
    Micarelli A, Jacobsson H, Larsson SA, Jonsson C, Pagani M (2013) Neurobiological insight into hyperbaric hyperoxia. Acta Physiol (Oxf) 209(1):69–76CrossRefGoogle Scholar
  62. 62.
    McCormick JG, Houle TT, Saltzman HA, Whaley RC, Roy RC (2011) Treatment of acute stroke with hyperbaric oxygen: time window for efficacy. Undersea Hyperb Med 38(5):321–334PubMedGoogle Scholar
  63. 63.
    Yan D, Shan J, Ze Y, Xiao-Yan Z, Xiao-Hua H (2015) The effects of combined hyperbaric oxygen therapy on patients with post-stroke depression. J Phys Ther Sci 27(5):1295–1297PubMedPubMedCentralCrossRefGoogle Scholar
  64. 64.
    Calvert JW, Zhou C, Zhang JH (2004) Transient exposure of rat pups to hyperoxia at normobaric and hyperbaric pressures does not cause retinopathy of prematurity. Exp Neurol 189(1):150–161PubMedCrossRefGoogle Scholar
  65. 65.
    Chavko M, Xing G, Keyser DO (2001) Increased sensitivity to seizures in repeated exposures to hyperbaric oxygen: role of NOS activation. Brain Res 900:227–233PubMedCrossRefGoogle Scholar
  66. 66.
    Matchett GA, Martin RD, Zhang JH (2009) Hyperbaric oxygen therapy and cerebral ischemia: neuroprotective mechanisms. Neurol Res 31:114–121PubMedCrossRefGoogle Scholar
  67. 67.
    Hillard JR (1990) Severe claustrophobia in a patient requiring hyperbaric oxygen treatment. Psychosomatics. 31(1):107–108PubMedCrossRefGoogle Scholar
  68. 68.
    Campbell BC, Meretoja A, Donnan GA, Davis SM (2015) Twenty-year history of the evolution of stroke thrombolysis with intravenous alteplase to reduce long-term disability. Stroke. 46(8):2341–2346PubMedCrossRefGoogle Scholar
  69. 69.
    National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group (1995) Tissue plasminogen activator for acute ischemic stroke. N Engl J Med 333(24):1581–1587CrossRefGoogle Scholar
  70. 70.
    Smith WS, Furlan AJ (2016) Brief history of endovascular acute ischemic stroke treatment. Stroke. 47(2):e23–e26PubMedCrossRefPubMedCentralGoogle Scholar
  71. 71.
    Singer OC, Sitzer M, du Mesnil de Rochemont R, Neumann-Haefelin T (2004) Practical limitations of acute stroke MRI due to patient-related problems. Neurology. 62(10):1848–1849PubMedCrossRefPubMedCentralGoogle Scholar

Copyright information

© Fondazione Società Italiana di Neurologia 2020

Authors and Affiliations

  1. 1.Neurology Clinic, Clinical Center of SerbiaFaculty of Medicine University of BelgradeBelgradeSerbia
  2. 2.Department of NeurosurgeryClinical Hospital Center ZemunBelgradeSerbia
  3. 3.Faculty of MedicineUniversity of Pristina - Kosovska MitrovicaKosovska MitrovicaSerbia
  4. 4.Department of Neurology, Tel-Aviv Sourasky Medical CenterTel-Aviv UniversityTel-AvivIsrael
  5. 5.ShaareZedek Medical CenterJerusalemIsrael

Personalised recommendations