Safety And Efficacy Of Hyperbaric Oxygen Therapy In .
Chronic Wound Care Management and ResearchDovepressopen access to scientific and medical researchReviewOpen Access Full Text ArticleSafety and efficacy of hyperbaric oxygen therapyin chronic wound management: current evidenceThis article was published in the following Dove Press journal:Chronic Wound Care Management and Research22 April 2015Number of times this article has been viewedPaul Eggleton 1Alexandra J Bishop 2Gary R Smerdon 2Institute of Biomedical & ClinicalScience, University of Exeter MedicalSchool, Exeter, 2DDRC Healthcare,Plymouth, UK1Abstract: The breathing of pure oxygen under pressure to treat tissue damage has been employedfor almost 45 years and has been investigated in prospective, retrospective, and randomizedcontrolled trials. The physiological effects of oxygen treatment on wound tissue are profound,and include activation of immune cells, changes in cytokine production, and modulation ofinflammatory and bactericidal mediators. Hyperbaric oxygen influences the biochemistry ofwhole cells, altering cell proliferation, angiogenesis, clotting, and tissue regeneration. Theprecise effects of hyperbaric oxygen on individual cell types and tissues are only beginningto be revealed in both animal and human studies. Many independent studies using hyperbaricoxygen adjunctively with standard wound care have observed improved healing, in particularfor diabetic foot ulcers, and can result in a significant reduction in major amputations. Sideeffects occur infrequently, but myopia, ear barotrauma, and rarely oxygen toxicity have beenreported. As antibiotics become less available, and clinician time and complex dressings becomemore expensive, use of hyperbaric oxygen as a means of treating a variety of wound types maybecome an increasingly appropriate option for treatment.Keywords: clinical trials, foot ulceration, non-healing wounds, oxygenIntroductionChronic wound ulcers can be categorized into four main groups, ie, venous, arterial, diabetic, and pressure/decubitus ulcers. All cause a significant financial andsocial burden worldwide.1,2 In 2009, approximately 6.5 million people requiredmedical intervention for chronic wounds in the USA alone at a cost of US 25 billion.3The prevalence of so many chronic wounds has led to the view that there is a lackof consistency in chronic wound care practice.4 Chronic wounds can be difficult toheal, with patients often following a path that interchanges between improvementand deterioration without healing for many years, despite the use of conventionaltreatments. Hyperbaric oxygen therapy (HBOT) has been used as an accompanimentcure for chronic wounds for many years, although treatment is not easily accessibleto many and often depends on geographic location, clinicians’ understanding of thetreatment, and evidence supporting its use.Correspondence: Paul EggletonInstitute of Biomedical & Clinical Science,University of Exeter Medical School, StLuke’s Campus, Heavitree Road, Exeter,Devon EX1 2LU, UKTel 44 1392 722940Email p.eggleton@exeter.ac.ukPathophysiology of chronic non-healing woundsMost wounds go through a normal healing process consisting of three stages, ie, anacute inflammatory phase, a proliferative phase, and a remodeling phase. To improvewound care practice further, physiological studies are required to assess the varioustreatment practices employed. This is also the case for use of HBOT. Chronic wounds81submit your manuscript www.dovepress.comChronic Wound Care Management and Research 2015:2 81–93Dovepress 2015 Eggleton et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0)License. The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any furtherpermission from Dove Medical Press Limited, provided the work is properly attributed. Permissions beyond the scope of the License are administered by Dove Medical Press Limited. Information onhow to request permission may be found at: doi.org/10.2147/CWCMR.S60319
DovepressEggleton et alare susceptible to infection, resulting in a prolonged inflammatory phase linked to tissue damage provoked by increasedfree radical production and proteolytic activity. Theseinflammatory mediators can lead to an imbalance in growthfactors, cytokines, and chemokines released into the tissue,triggering ischemia, edema, and inhibition of entry of nutrients into the wound.Role of oxygen in wound healingOxygen is important during normal wound healing, withhypoxic conditions triggering healing processes, and largeamounts of oxygen being consumed. The initial inflammatory phase of wound healing involves hemostasis to preventexcessive blood loss. This is instigated by activation of theclotting cascade by injured cells, and involves cleavage offibrinogen to fibrin by thrombin. The fibrin forms a stableclot and then the basic wound matrix, and traps activatedplatelets that release the contents of α-granules, includingthe various cytokines and growth factors responsible forinduction of the inflammatory phase.5 We have investigatedthe role of hyperbaric oxygen in human platelet activation.When platelets were exposed to hyperbaric oxygen (97.7%O2, balance CO2 at 2.2 absolute atmospheres [ATA]) weobserved a six fold increase in platelet aggregation andmore protein release, including chaperone 14-3-3-zeta andα-2-macroglobulin, both of which are involved in apoptosis.6 Within 6 hours of injury, numerous inflammatorygrowth factors are released, which aid the recruitment ofneutrophils and subsequently macrophages to the woundsite. Many of these processes require extra cell metabolismfor biosynthesis and transport of proteins, which requiresoxygen.During the proliferative phase, approximately 2 days intowound healing, macrophages continue to express growth factors, many of which stimulate angiogenesis and formation ofgranulation tissue comprising of endothelial cells, fibroblasts,and inflammatory cells. Then, during the migration and angiogenic step of the proliferation phase, these cells migrate intothe wound and continue to repair tissue. High levels of oxygenare required for this proliferation phase, especially when reepithelialization occurs surrounding the wound in conjunctionwith keratinocytes to seal the wound from the extracellularenvironment. We have investigated the effects of hyperbaricoxygen on inflammatory cell (neutrophil)–endothelial cellinteractions under hypoxic and chronic wound conditions,and found that hyperbaric oxygen reduces inflammatory cell–endothelial cell interaction, possibly reducing local inflammation during revascularization of wound tissue.7 The hypoxic82submit your manuscript www.dovepress.comDovepressconditions in the damaged vascularized wound area trigger inpart the production of transcription factors such as hypoxiainducible factor 1-α and vascular endothelial growth factorby endothelial cells and macrophages. As the macrophagesremove necrotic cellular debris, the phagocytic processestrigger production of reactive oxygen species, which requiressignificant amounts of oxygen. Finally, during the remodelingphase, oxygen is essential to aid in the removal of granulationtissue via the process of apoptosis. Oxygen is also requiredfor the synthesis of type I collagen and its organization intobundles, replacing the type III collagen that was originallylaid down in the granulation tissue, which ultimately enhanceswound tensile strength.Thus oxygen plays an important role in all cellular processes during wound healing, including cell metabolism,proliferation, and revascularization. Oxygen is also essentialfor increased antimicrobial activity, growth factor signaltransduction, and collagen synthesis. It is therefore of greatinterest to know how infusing wound tissues with oxygenunder pressure might be beneficial to the healing process. Thepartial pressure of oxygen (pO2) in normal subcutaneous tissue is in the range of 40–80 mmHg, but drops to ,20 mmHgunder chronic wound conditions (Figure 1). Despite thegrowing body of evidence indicating the usefulness of HBOTin wound healing, the mechanistic regulation of woundphysiology by HBOT is still in its infancy.Benefits of HBOTin chronic woundsVarious international HBOT associations, for example theUndersea and Hyperbaric Medical Society and the EuropeanCommittee for Hyperbaric Medicine, recommend the useof HBOT for a number of indications, including variousAir1 ATAO22.4 ATAO2EpidermisDermis2.5 mmSubcutaneoustissue40–80mmHg( 20)200–300mmHg( 100)250–500mmHg( 200)Partial pressure – pO 2 values(wound values)Figure 1 Partial pressure of oxygen in normal and wounded subcutaneous tissueupon exposure to air, oxygen, and hyperbaric oxygen.Abbreviations: ATA, absolute atmospheres; pO2, partial pressure of oxygen.Chronic Wound Care Management and Research 2015:2
DovepressHyperbaric oxygen therapy for chronic woundsTable 1 Approved clinical indications for hyperbaric oxygentherapyClinical conditionDefinitionGas embolismCarbon monoxidepoisoningGas gangreneCrush injuryDecompression sicknessEntry of gas bubbles into arteries or veinsHypoxic stress by elevatedcarboxyhemoglobinToxemia, edema, and necrotic tissueTrauma to multiple tissuesSupersaturation of tissue with inert gascausing organ damageHypoxia, persistent infection, and cellularfailureLoss of red blood cell massBrain abscess normally deep-seated, withinfection and immune cell involvementTissue necrosis due to infection, cellulitis,and fasciitis with impaired immunityInfection of boneCellular toxicity caused by radiotherapyAreas compromised by hypoxia ordecreased blood perfusionCompromised tissue unable to supplyoxygen and nutrients to surrounding tissueLoss of oxygen concentration in thecochleaArterial inefficienciesSevere anemiaIntracranial abscessNecrotizing soft tissueinfectionOsteomyelitisDelayed radiation injuryCompromised graftsand flapsAcute thermal burnsIdiopathic suddenhearing losstypes of chronic wounds and other clinical conditions(Table 1). During HBOT, patients are placed in a multiplaceor monoplace chamber where they are required to breath100% oxygen intermittently, at a pressure greater than sealevel (ie, .1 ATA). The duration and frequency of treatmentwith HBOT and the ATA employed is often open for debate,but the pressurization used is normally 1.4 ATA or higher. Theunits used to measure pO2 in healthy and wound tissue areoften quoted in mmHg, kilopascals, or bar pressure (Table 2)before and after HBOT.Patients with chronic wounds selected for HBOT usuallyhave a history of nonresponsiveness to conventional treatments, including antibiotics and topical dressings, and faileddebridement. Patient selection for HBOT can be assistedby noninvasive transcutaneous oxygen pressure (TcpO 2)Table 2 Units used to monitor partial pressure of oxygen andsome commonly cited values for subcutaneous healthy andwound tissuesConditionBar (kgf/cm2)mmHg (Torr)kPaNormoxiapO2 in chronic woundspO2 in healthy tissueHBOpO2 in chronic woundspO2 in healthy 3–10.66240,26.6633.33–66.66Abbreviations: HBO, hyperbaric oxygen; pO2, partial pressure of oxygen.Chronic Wound Care Management and Research 2015:2monitoring. This technique has recently been recommendedfor long-term monitoring of the efficacy of HBOT andin other clinical settings.8 One of the major functions ofHBOT is to supply wound tissue with sufficient oxygen toencourage metabolism in the wound environment, especiallywhen the vascular supply is impaired. Fife et al determinedthe predictive value of TcpO2 in envisaging the likelihoodof benefit of HBOT in a large cohort (n 1,114) of diabeticpatients with a variety of lower extremity wounds9 gradedon the Wagner scale.10 Based on this and other studies,current protocols recommend that patients with woundpO2 ,40 mmHg (hypoxic) while breathing air at 1 ATAthat increases to about 100 mmHg while breathing oxygenat 1 ATA are suitable candidates for HBOT. Whenever possible, the patients are tested at pressure inside a hyperbaricoxygen chamber, and if their wound pO2 values increaseto .200 mmHg, 74% of patients are predicted to respondwell to HBOT.Patients with problem non-healing wounds attendingthe DDRC Healthcare facility (http://www.ddrc.org/) inPlymouth, UK, are treated using the protocol outlined inRoyal Navy Treatment Table 66 (Figure 2). The patientsenter the chamber and are pressurized during a 10-minutedescent to 2.4 ATA. The patient remains at this pressurefor 90 minutes, before being decompressed back to 1 ATAover a 10-minute period. Patients breathe oxygen duringthree 30-minute cycles, and to minimize the risk of oxygen toxicity, patients have 5-minute “air breaks” after 30and 65 minutes, during which they remain under pressurebut breathe air instead of 100% oxygen (Figure 2). Theprocedure itself is relatively safe, and our experience oftreating patients over two decades has demonstrated theRoyal Navy treatment table 6610ATADepth (m) O2o2Air Air2.4553035540305 207075 90Time (minutes)(cumulative time)1410100For chronic woundsRepeat HBOT procedure once daily for 40–60 daysFigure 2 HBOT protocol for treatment of chronic wounds.Abbreviations: ATA, absolute atmospheres; HBOT, hyperbaric oxygen therapy.submit your manuscript www.dovepress.comDovepress83
DovepressEggleton et almost common side effects to be mild barotrauma andmyopia.Effects of hyperbaric oxygenon wound healing in humansThe wound environment is a complex and dynamic one, andthe overall objective of HBOT is to increase the diffusiongradient of oxygen in subcutaneous tissue by about 10–20fold to allow hyperoxygenation of ischemic tissue, reducethe levels of inflammatory cytokines, and stimulate theproduction of growth factors. In addition, HBOT enhancesantibacterial activity, including production of oxygen freeradicals, whilst reducing nonspecific activation of inflammatory cells. Further functions of HBOT are to promotetransmigration of stem cells to infected wound tissue, alterleukocyte-endothelial cell adhesion, and promote collagenformation. There are numerous animal and clinical studiessupporting these functions, and are described below.Clinical evidence supports the concept that HBOTpromotes the vascularization of wounds. A subset of bonemarrow-derived stem/progenitor cells called endothelialprogenitor cells have the ability to transmigrate to wounds,where they rapidly differentiate into mature endothelial cellsand assist in vascular repair. In a study of eight diabeticpatients treated with hyperbaric oxygen for a single 2-hourperiod at a pressure of 2.0 ATA on 6 consecutive days forup to 20 treatments, a significant but temporary increasein both stem/progenitor cells and endothelial progenitorcells was observed in the patients’ blood after one, ten, and20 treatments with HBOT.11 In the same study, biopsies ofwound tissue revealed a marked elevation in the presence ofCD133 stem/progenitor cells, indicating that HBOT stimulates vasculogenic stem cell mobilization. With evidence ofincreased vascularization in wounds post-HBOT, the possibility of increased infiltration of proinflammatory cells such asneutrophils is of concern. However, it has been shown thatHBOT inhibits adhesion of leukocytes to injured endothelium by inhibiting integrin expression.12 Our own studieshave determined that changes in endothelial cell adhesionmolecules are altered by a single HBOT treatment via nitricoxide-mediated mechanisms.7 In addition, we have shownthat a single dose of HBOT enhances generation of reactiveoxygen species and phagocytosis by neutrophils. Althoughthis could lead to nonspecific inflammation at the site ofa wound, it may also help prevent microbial colonization.HBOT also elicits enhanced apoptosis of phagocytes, thusoffsetting the accumulation of potentially necrotic celldebris.13 Patients with type 2 diabetes are known to have84submit your manuscript www.dovepress.comDovepressimpaired wound healing of ulcers, and HBOT consisting ofthree 25-minute periods of 100% oxygen at a pressure of2.4 ATA, interspersed with 5-minute periods of breathingair, for 6 days/week over 5–6 weeks has been shown to progressively reduce wound areas in diabetic patients (n 18) byenhancing production and secretion of type I and III procollagens by fibroblast, which can be detected in plasma andhelp increase the tensile strength of wounds.14From the evidence presented above, HBOT appears tobe useful in promoting wound healing in a variety of waysthat can affect the physiology of the wound even after thetreatment has ceased. Limited HBOT research has been conducted using animal models, and has revealed a number ofphysiological pathways of wound healing affected by HBOT.However additional research is required, especially humantrials or the use of human tissues, in order to advance ourknowledge of the usefulness and safety of this treatment.Safety and efficacy of HBOTAs presented in Table 1, the Undersea and Hyperbaric Medical Society currently identifies 14 disease states (indications)for HBOT, of which “enhancement of healing in selectedproblem wounds” falls within the clinical condition termed“arterial insufficiencies”. Two types of chambers (monoplaceand multiplace) are commonly used to administer HBOT topatients (Figure 3A and B). Monoplace chambers permitonly single occupancy and in modern chambers the patientis moved in and out of the chamber on a sliding stretcher.The chamber walls are made of clear acrylic, providing highvisibility and helping to reduce claustrophobia. Monoplacechambers are normally compressed with 100% oxygen,with the patients simply breathing the atmosphere withinthe chamber. Air breaks, if required, are administered by thepatient holding an air-delivering built-in breathing systemmask to the face. Multiplace chambers can accommodatemultiple patients (ten patients are not uncommon), andpatients can enter the chamber on foot if appropriate. Thewalls of the multiplace chamber are of steel construction.The chamber is compressed with air and the patient breathes100% oxygen under pressure administered by means of abuilt-in breathing system mask or a hood. HBOT describesthe systemic delivery of hyperbaric oxygen and should notbe confused with normobaric (ambient pressure) oxygendelivery or topical oxygen therapy. The pressures used todeliver hyperbaric oxygen do not exceed 3 ATA (equivalent toa depth of 20 m in seawater) and the duration of treatment forelective therapies does not generally exceed 2 hours. Withinthese parameters, HBOT is considered a safe treatmentChronic Wound Care Management and Research 2015:2
DovepressHyperbaric oxygen therapy for chronic woundsAMultiplace chamberCBefore HBO treatmentBMonoplace chamberDPost 34 HBO treatmentsFigure 3 Patient HBO chambers and effect of HBO on components of wound healing. (A and B) Multiplace and monoplace chambers used to treat chronic wounds.(C) Typical type 2 diabetic foot sepsis leading to third digit amputation secondary to osteomyelitis. (D) Effect of a complete course of 36 sessions of HBO therapy over a2-month period.Abbreviation: HBO, hyperbaric oxygen.modality, but does carry some risks due to hyperoxia andincreased pressure. Absolute contraindications to HBOTare limited to untreated pneumothorax and treatment withcertain chemotherapeutic drugs (doxorubicin, cisplatin, andbleomycin). Relative contraindications include upper respiratory tract infections, chronic obstructive pulmonary disease,history of thoracic or ear surgery, hyperthermia, pregnancy,and claustrophobia.The most common side effect of hyperoxia is a progressive myopia in patients undergoing prolonged periods ofdaily hyperbaric oxygen.15 The exact mechanism for thischange in sight remains obscure but appears to be of lenticula
Safety and efficacy of hyperbaric oxygen therapy in chronic wound management: current evidence Paul eggleton1 Alexandra J Bishop2 Gary R Smerdon2 1institute of Biomedical & Clinical Science, University of exeter Medical School, exeter,2DDRC Healthcare, Plymouth, UK Correspondence: Paul eggleton institute of Biomedical & Clinical Science,
Hyperbaric Oxygen Therapy Improves Outcome of Hypoxic-Ischemic Encephalopathy (NCT02894866) –Ongoing Chinese multicenter, randomized trial –The aim of study is to evaluate the safety and efficacy of hyperbaric oxygen in term infants with HIE –The hyperbaric oxygen treatment will be administered for 60 min in a baby hyperbaric oxygen .
4.6.5 Decompression illness after hyperbaric treatment 4.6.6 Altitude changes after therapeutic hyperbaric exposure 4.6.7 Oxygen toxicity 4.6.8 Thermal stress 4.6.9 Fire safety 4.6.1 O Electrical safety 4.6.11 Manual handling 4.7 Hyperbaric Facility Systems Procedures 4.8 Patient Reception, Treatment and Disposition
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1. Knowledge deficit related to hyperbaric oxygen therapy and treatment procedures 2. Potential for anxiety related to hyperbaric oxygen treatments or other medical procedures 3. Potential for injury within the hyperbaric facility related to transferring patient in/out of chamber 4. Potential for injury related to fire within the hyperbaric chamber
local anaesthetic in the subarachnoid space [ ]. Scienti c evidence regarding the di erences of spinal block character-istics of hyperbaric prilocaine and hyperbaric bupivacaine is lacking. is study compared % hyperbaric prilocaine mg fentanyl gto. %hyperbaricbupivacaine . mg fentanyl g for day-case spinal anaesthesia. e outcome
Hyperbaric CRA Welding Qualification Trials 10 Objective Determine if hyperbaric welding is a feasible option for repair of CRA clad and lined pipelines Subsea7 Scope "Complete hyperbaric welding trials to qualify a Proposed Welding Procedure Specification (pWPS) using 100% manual Gas Tungsten Arc Welding process"
19 patients, we evaluated the safety and efficacy of hyperbaric oxygen for COVID-19 patients with respiratory distress. Methods: This was a single-center clinical trial of COVID-19 patients at NYU Winthrop Hospital from March 31 to April 28, 2020. Cases received hyperbaric oxygen therapy at 2.0 atmospheres
