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Compromised Skin Grafts and Flaps

Compromised Skin Grafts and Flaps

Compromised Skin Grafts and Flaps

INTRODUCTION

Treatment Protocol Guidelines

The following hyperbaric medicine treatment protocol is based upon the recommendations of the Hyperbaric Oxygen Committee of the Undersea and Hyperbaric Medical Society. Clinical protocols and/or practice guidelines are systematically developed statements that help physicians, other practitioners, case managers and clients make decisions about appropriate health care for specific clinical circumstances.  

Protocols allow health providers to offer evidence-based, appropriate, standardized diagnostic treatment and care services to patients undergoing hyperbaric oxygen therapy (HBOT).  Evidenced-based medicine offers clinicians a way to achieve improved quality, improved patient satisfaction, and reduced costs. Utilization Review should be initiated when clinical decisions result in deviation from or modification of treatment protocols.  This includes any course of treatment at or above the recognized threshold limits. 

Medical Necessity

Medicare.gov defines “medically necessary” as “health-care services or supplies needed to prevent, diagnose, or treat an illness, injury, condition, disease, or its symptoms and that meet accepted standards of medicine.” 

This topic discusses Compromised Skin Flaps and Grafts, including reimplantation of digits or extremities.  This condition meets coverage indications per the National Coverage Determination (NCD) 20.29. [1] Continued HBOT without documented evidence of effectiveness does not meet the Medicare definition of medically necessary treatment. Thorough re-evaluation should be made at least every 30 days for documentation of response to therapy. 

TREATMENT PROTOCOL


 HBO request requirements checklist   | Sample Physician Order   |$ ICD-10 Crosswalk   |  Treatment Table   Urgent Indication 

Background Hyperbaric oxygen therapy is not indicated to improve viability of routine, uncompromised skin grafts or flaps. However, in cases where there is decreased perfusion or frank hypoxia in the absence of surgically treatable mechanical causes of flap compromise, HBO can help maximize the viability of the compromised tissue, thus reducing the need for re-grafting or repeat flap procedures. 

Mutilated limb injuries often lead to limb loss and severe functional impairment. When combined with meticulous microsurgical revascularization or replantation, early intervention with adjunctive HBOT can improve the survival of mutilated hands and preserve hand function as much as possible.[2] 

Goals of HBOT

    Maximize tissue viability, aiming at complete or at least partial salvage of compromised flaps and grafts by:

    • Increasing tissue oxygen concentrations in sub-optimally perfused areas to limit cellular death and further tissue damage
    • Stimulating secretion of collagen by fibroblasts and enhancing neovascularization
    • Increasing tissue perfusion by reducing capillary leakage, tissue swelling and edema 
    • Improve survival of replanted part
    • Limit effects of ischemia and ischemia-reperfusion injury by [2]: 
      • elevating tissue oxygenation
      • stimulating leukocyte function
      • decreasing peripheral edema
      • reducing TNF-alpha and other triggers of the inflammatory cascade
    • Provide tissue oxygenation to replanted part while vascularization is established 
    • Facilitate neovascularization in replanted digits

    Diagnosis

    Compromised soft tissue flaps and grafts without correctable mechanical causes that may be obstructing blood flow to flap and with questionable viability may present with findings that include obvious ischemia, discoloration, venous congestion, decreased temperature and inadequate transcutaneous oxygen response.[3][4]  

    Traumatic amputated limbs/ digits (e.g., from crush, degloving, cutting, or explosion injuries), and surgically treated with replantation 

    Hyperbaric

    Criteria 


    • Surgical referral with diagnosis and documentation of skin graft or flap compromise (e.g., random pattern ischemia, pain, coolness or a bluish/purple hue of the cutaneous portion of flap)
    • Absence of surgically correctable cause of decreased perfusion to flap or skin graft (e.g. skin flaps created by trauma with inadequate perfusion due to crush injury, large random flaps that do not follow the classic 3:1 length-to-width ratio, ischemia-reperfusion injuries, etc)
    • Initiation of first HBO session within 24 hours of the initial limb/ digit replantation/ revascularization. This is generally considered a hyperbaric emergency and due consideration for urgent (within one to a few hours) initial treatment in a hyperbaric chamber. 
    • Postoperative edema and congestion, in the absence of obvious surgically correctable causes of ischemia or congestion 
    • Postoperative concerns regarding viability of the replanted part. A reference to a verbal conversation with the surgeon is adequate documentation. 

    Evaluation

    • Comprehensive history
    • Physical examination
    • Complete Blood Count (CBC)
    • Erythrocyte Sedimentation rate (ESR)
    • C-reactive protein (CRP)
    • Chest x-ray
    • Electrocardiogram (ECG)
    • Transcutaneous oxygen (TCOM) assessment or doppler studies (If they can be performed without delaying initial therapy). While TcPO2 values are helpful, they should never be required as a barrier to treating these patients. 
    • Wound assessment documentation and immediate photography (if the wound/site is accessible without removing dressings)
    • Evaluation of tympanic membranes pre- and post-treatment as needed
    • Baseline and as needed visual acuity assessment for progressive myopia
    • Smoking/nicotine cessation
    • Nutritional assessment; dietary management;
    • Blood glucose control

    Treatment

    • Hyperbaric oxygen therapy at 2.0-2.5 ATA oxygen for 90 minutes. (Table 1 or Table 3)
    • Hyperbaric Oxygen therapy should be started as soon as signs of flap or graft compromise appear.
    • In an acutely failing flap, up to 3 treatments in the first 24 hours is recommended.
    • After the first 24 hours, twice daily treatments are recommended. This may continue until the hyperbaric physician and the surgeon agree that the flap is stable clinically or the flap shows signs of progress toward healing.
    • If the flap or graft begins to show evidence of advancing ischemia, the aggressive twice daily treatment protocol can be continued.
    • Should the compromised graft or flap fail, daily HBO treatments may be continued to prepare the compromised wound bed for a salvage graft or flap reconstruction. 
    • Consider TCOM at the flap site to monitor tissue oxygenation.
    • Flap or graft dressing change as indicated only by the surgeon

    Follow-Up

    • Transcutaneous oxygen assessment and doppler studies, if the flap is accessible and stable
    • Visual acuity assessment for progressive myopia
    • Photographic documentation of wound/replanted part

    Treatment Threshold

    6 – 20 treatments (concurrent peer review after 10 and 20 treatments, third party peer review after 25) 

    Coding

    Refer to the ICD-10 Guideline for the appropriate ICD-10 code

    Comments

    • It is important to recognize the underlying cause of the compromise of the flap or graft. Any correctable mechanical cause of decreased flap perfusion should be considered with surgical re-exploration. 
    • All flaps by definition have an inherent blood supply whereas grafts are avascular tissues that rely on the quality of the recipient bed for survival and revascularization. Because of this dependence, the diagnosis of compromised graft begins with assessment of the recipient wound bed. A graft (whether partial- or full-thickness) is not an urgent indication. In fact, HBOT should not be considered until the grafted tissue is declared non-viable and has failed advanced wound care therapy.
    • If diabetes mellitus is present, blood glucose should be checked within 1 hour prior to treatment and immediately post-HBOT.
    • Avoid petroleum based dressings and ointments whenever possible. If these are a necessary covered with 100% cotton during HBOT.
    • HBOT cannot salvage flaps with capillary thrombosis due to insufficient venous outflow. However, HBOT may help distinguish replanted flaps with insufficient venous outflow that need anastomosis revision (or leech therapy) in the early postoperative phase. These flaps are congested with "venous blood" and their color may change to bright pink during HBOT session, as a result of conversion of hemoglobin into oxyhemoglobin in the presence of sufficient dissolved oxygen.[5]
    • This indication may not be covered by the patient's health insurance plan. Confirmation of criteria to meet medical necessity and potential pre-authorization is recommended prior to starting HBOT.
    Primary Sources: Whelan and Kindwall [6]Weaver [7]

    DOCUMENTATION

    Hyperbaric oxygen therapy has been shown to be beneficial in the treatment of acutely compromised soft tissue flaps. In the acute case tissue is rendered hypoxic resulting from the surgical disruption of the transplanted tissue’s arterial blood supply. In many cases, this disruption is planned in conjunction with a free flap procedure. In some cases, the tissue may be further compromised through an ischemia-reperfusion injury or a “flow no reflow” phenomenon. In this acute scenario, hyperbaric oxygen provides a means for adequate oxygen delivery to tissue at risk and allows for continued oxidative metabolism thereby limiting the loss of transplanted tissue. HBOT has also been shown to attenuate the ischemia-reperfusion injury through preventing or limiting the ensuing inflammatory response. In the setting of a previously failed flap or graft, HBOT can be leveraged to help prepare the wound bed for subsequent surgical repair through enhanced angiogenesis and granulation tissue formation. Questionable viability may include obvious ischemia, discoloration, venous congestion, decreased temperature, and inadequate transcutaneous oxygen response. Below we explain in detail what needs to be documented and provide sample statements that can be adapted to suit your needs. See also:

    •  HBO request requirements checklist

    History 

    An initial assessment including a history and physical that clearly substantiates the condition for which HBO is recommended. Items listed below should be included:

    • Prior medical, surgical procedures and/or HBO treatments 
    • Date flap or graft was performed, type of flap or graft and name of the surgeon
    • Clinical assessment of the flap or graft

    Sample documentation for an acutely failing flap is shown below:

    "Mrs. Jones was seen urgently, after-hours, at the request of Dr. Anglen (our breast plastic surgeon). Dr. Anglen had just performed a breast reconstruction with a latissimus dorsi free flap on the left side. By the time the patient reached recovery room, the flap was dusky and looked poorly perfused. The vascular assessment was undertaken with a Doppler probe and flow was positive at the arterial anastomosis. Some sutures were removed to help with venous congestion. Dr. Anglen is concerned about the overall viability of the free flap and has asked us to urgently consult for immediate HBOT in order to assist with viability and prevention of ischemia-reperfusion injuries."copy enabled

    Sample documentation for a failed flap/graft where HBOT will be used for "preparation of a flap/graft" is shown below (NOTE: This indication varies by insurer/intermediary, so be sure that you have carefully looked at the NCD/LCD before you proceed.)

    "Mr. Jones had a distant pedicle flap raised from his forearm 10 days ago. The forearm was attached to his forehead in order to cover for a MOHS surgical wide excision to skull. The goal of the surgery was to start the flap with the forearm attached, then come back and complete the procedure by releasing the forearm after half of it had a chance to vascularize on the recipient area. On examination by our plastic surgeon, the flap has failed entirely, leaving a 10 x 20 cm failed deficit. We have chosen to leave the eschar in place in order to protect the skull underneath. The indication for HBOT is a failed forearm to forehead pedicle flap with preparation for a myocutaneous free flap in the future. It is important to note that the surrounding tissue has never been radiated."

    (NOTE: To address the failed distant pedicle flap described in this scenario, we would suggest at least 15 - 20 HBOT treatments, followed by surgical debridement of remaining non-viable tissue, and a free flap to cover the forehead defect. If the free flap looks at all questionable postoperatively, we suggest another 10 - 15 post-operative treatments based on flap appearance and viability. If the free flap fails, other options to cover this area of skull are limited)

    Physical Exam

    • Documentation of Failing or Failed Flap (one of the following must be present)
      • Mottling/random pattern ischemia
      • Suture line dehiscence, areas of eschar 
      • Partial loss of flap
      • Threatened complete loss of flap
    • Documentation of optimization of nutritional status 
      • Albumin
      • Pre-Albumin
      • If abnormal, have a dietary/nutritionist consult to apply measures that address deficiencies. Document in a clinical note that this has been done.
    • Documentation of optimization of glucose control
      • HgbA1-C level; the results may be obtained from the primary care physician.
      • Documentation of measures taken to address poorly controlled blood glucose
      • While glucose control is important, there are no radomized controlled trials that link healing rate to HbA1c levels [8] 
    • Documentation of debridement by any means to remove devitalized tissue
      • In some cases, just document that there is no devitalized tissue present
      • Plan for debridement (as required)
    • Documentation of necessary treatment to resolve any infection that might be present.
      • In some cases, simply document that the wound/ulcer is free of infection. Sample: "The wound was examined. There was no erythema, no purulence, and no evidence of infection seen."
      • Measures taken to address treating any existing infection present.

    Impression

    • Compromised graft or flap Refer to ICD-10 Crosswalk

    Plan

    "A typical hyperbaric regimen for a patient with a compromised flap or graft consists of twice daily 2.0 to 2.4 ATA hyperbaric oxygen treatments with 90 to 120 minutes of oxygen breathing time. The flap or graft is monitored serially and the aggressive twice daily treatment schedule is continued for at least 48 hours, then daily hyperbaric oxygen treatments will follow until the flap or graft shows signs of progress toward healing. If the flap or graft begins to show evidence of advancing ischemia, the aggressive twice-daily treatment protocol can be extended or renewed.

    Having no absolute contraindication to hyperbaric oxygen therapy the patient will be offered treatment at 2.0 ATA for 90 minutes. Ten treatments will initially be provided on a BID basis. Thereafter, a re-evaluation of the patient’s clinical progress will be in order to determine if additional treatments may be required."copy enabled

    Risk and Benefit of Hyperbaric Oxygen Therapy

    Please refer to topic "Documentation HBO: Risks and Benefits"

    Indication for Hyperbaric Oxygen Therapy (HBOT)

    "Hyperbaric oxygen therapy is not needed for routine, uncompromised skin grafts or flaps. However, in cases where there is decreased perfusion or frank hypoxia, hyperbaric oxygen can help maximize the viability of the compromised tissue thus reducing the need for re-grafting or repeat flap procedures. There are multiple clinical studies showing the benefit of hyperbaric oxygen for failed or failing flaps and skin grafts. Types of grafts and flaps studied include free skin grafts, pedicle flaps, random flaps, irradiated wounds and flaps, composite grafts and axial pattern flaps. Although the types of flaps and grafts are different, the common denominator to flap necrosis is tissue hypoxia. 

    Hyperbaric oxygen can be beneficial in managing failing flaps and skin grafts by several mechanisms: 1) Increasing tissue oxygen concentrations over 1000%, thus preventing cellular death, 2) stimulating fibroblasts and macrophages to secrete collagen and enhance neovascularization, 3) reducing edema formation by reducing capillary leakage and tissue swelling, thus increasing tissue perfusion, and 4) maintaining the bacterial killing ability of leukocytes after phagocytosis."copy enabled

    Sample Order

    •  Sample Physician Order

    CLINICAL EVIDENCE AND RECOMMENDATIONS  

    • 2CFor patients with compromised skin flaps or grafts, we suggest HBOT to salvage and increase survival rates of skin flap or graft (Grade 2C)
      • Rationale: Currently, low certainty evidence supports the use of HBOT to salvage compromised flaps and grafts (evidence level C), with evidence primarily drawn from animal, observational studies and many case series. [3][9][10][11][12][13]There have been no randomized controlled trials (RCTs) that addressed the use of HBOT to salvage compromised flaps and grafts to date. Only 1 RCT [14] studied HBOT on the survival of skin grafts, however all patients with skin grafts (not only compromised skin grafts) were included, and the RCT was considered at high risk of bias due to lack of patient blinding, incomplete outcome data, and selective reporting [15].
      • In practice, HBOT has been shown to be beneficial in the treatment of acutely compromised soft tissue flaps. In the acute setting, the tissue is rendered hypoxic resulting from the surgical disruption of the transplanted tissue’s arterial flow. In some cases,  tissue may be further compromised through an ischemia-reperfusion injury or a “flow no reflow” phenomenon. In this acute scenario, hyperbaric oxygen provides a means for adequate oxygen delivery to tissue at risk and allows for continued oxidative metabolism thereby limiting the loss of transplanted tissue. HBOT has also been shown to attenuate the ischemia-reperfusion injury through preventing or limiting the ensuing inflammatory response. [4] Mechanisms of action by which HBOT is beneficial for compromised flaps are listed below:
        • Reversal of tissue hypoxia
        • Reducing localized edema surrounding the flap
        • Reduction of hypoxic insult
        • Provides immediate support of marginally perfused/oxygenated portions of the flap
        • Enhancement of fibroblast and collagen synthesis
        • Creation of neovascularity
        • Possibly closes arteriovenous shunts
        • Favorable effects on micro-circulation by reducing TNF-alpha and Matrix Metalloproteases. HBOT improves Nitric Oxide and oxidative pathways.
      • To be maximally effective, HBOT should be started as soon as signs of flap or graft compromise appear. [4] Mechanical causes of flap compromise that can be treated surgically should be addressed prior to initiation of HBOT. In the setting of a previously failed flap or graft, HBOT can be leveraged to help prepare the wound for subsequent surgical repair through enhanced angiogenesis and granulation tissue formation. The criteria for selecting the proper patients who are likely to benefit from adjunctive HBOT for graft or flap compromise are crucial for a successful outcome. Identification of the underlying cause for graft or flap compromise can assist in determining the proper clinical management and use of HBOT. [4] Questionable viability may include obvious ischemia, discoloration, venous congestion, decreased temperature and inadequate transcutaneous oxygen response. [3][4]  
      • Use of resources: Failed flaps are extremely expensive and result in significant morbidity and distress to both the patient and the surgeon. Adjunctive HBOT can reduce these financial, physical and psychological costs by salvaging skin grafts, pedicle flaps, random flaps, composite grafts, as well as free flaps and thus eliminating or minimizing the need for secondary surgeries and alternate donor sites. [4] 
      • Medicare Coverage: Medicare covers HBOT when it is utilized for graft or flap salvage in cases where hypoxia or decreased perfusion has compromised the viability of an existing skin graft or flap. Medicare coverage does not apply to the initial preparation of the body site for a graft. [1] See  HBO Request Requirements Checklist, and section on 'Coverage and Reimbursement' below.

    CODING

    ICD-10 Coding

    COVERAGE AND REIMBURSEMENT

    • Medicare Coverage Criteria: HBOT is utilized for graft or flap salvage in cases where hypoxia or decreased perfusion has compromised the viability of an existing skin graft or flap. Medicare coverage does not apply to the initial preparation of the body site for a graft. HBOT is not necessary for normal, uncompromised skin grafts or flaps, for primary management of wounds, or dehiscence of surgical wounds not related to a flap surgery. Clinicians should review and document the medical necessity for the use of HBOT for more than 20-25 treatments, regardless of the condition of the patient. The documentation present in the clinical record must provide an accurate description and diagnosis of the medical condition supporting that the continued use of HBOT is reasonable and medically necessary.[1]  See HBO Request Requirements Checklist

    APPENDIX

    Summary of Evidence

    We reviewed the clinical guidelines, systematic reviews, meta-analyses and clinical trials summarized below. Applying the GRADE framework to the combined body of evidence, we found that:

    • Low certainty evidence supports the use of HBOT to salvage compromised flaps and grafts (evidence level C), drawn from animal studies, observational studies and many case series. There have been no randomized controlled trials (RCTs) that addressed the use of HBOT to salvage compromised flaps and grafts to date. Only 1 RCT studied HBOT on the survival of skin grafts, however all patients with skin grafts (not only compromised skin grafts) were included, and the RCT was considered at high risk of bias due to lack of inadequate patient blinding, incomplete outcome data, and selective reporting [15] 

    - Systematic reviews and meta-analyses

    • No systematic reviews or meta-analyses on HBO as an adjunctive therapy to treat compromised flaps and grafts were found

    - Clinical guidelines

    • The 2014 Undersea and Hyperbaric Medicine Society (UHMS) [4] and the 2017 European Committee for Hyperbaric Medicine (ECHM) [16] guidelines support the use of HBO for the salvage of compromised skin flaps and grafts. The UHMS issued a Class 1b based on an RCT that included 48 patients who underwent skin grafting and received HBO treatment to increase the survival rate. Authors state that all patients with skin graft were included, and not only the ones with compromised graft take. (Perrins, 1967)
    Intervention UHMS ECHM
    HBO for the salvage of compromised skin flaps and grafts AHA Class 1b Grade 2C

    -  Randomized controlled trials (RCTs): 

    • No RCTs on HBOT as an adjunctive therapy to treat compromised flaps and grafts were found. There were other RCTs on use of HBOT to increase survival rate of flaps and grafts.[14]

    - Observational studies and case series: 

    •  Many observational studies and case series reported improved survival rates when using HBOT for the salvage of compromised skin flaps and grafts.[17][18][19][9][10][11][12][13]

    REVISION UPDATES

    DateDescription
    4/22/19Added section on Coverage and Reimbursement. Added additional documentation statements in the section on Documentation
    Official reprint from WoundReference® woundreference.com ©2018 Wound Reference, Inc. All Rights Reserved
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    NOTE: This is a controlled document. This document is not a substitute for proper training, experience, and exercising of professional judgment. While every effort has been made to ensure the accuracy of the contents, neither the authors nor the Wound Reference, Inc. give any guarantee as to the accuracy of the information contained in them nor accept any liability, with respect to loss, damage, injury or expense arising from any such errors or omissions in the contents of the work.

    REFERENCES

    1. CMS. National Coverage Determination (NCD) for Hyperbaric Oxygen Therapy (20.29) . 2017;.
    2. Chiang IH, Tzeng YS, Chang SC et al. Is hyperbaric oxygen therapy indispensable for saving mutilated hand injuries? International wound journal. 2017;volume 14(6):929-936.
    3. Francis A, Baynosa RC et al. Hyperbaric Oxygen Therapy for the Compromised Graft or Flap. Advances in wound care. 2017;volume 6(1):23-32.
    4. Undersea and Hyperbaric Medical Society Hyperbaric Oxygen Committee,, et al. Hyperbaric Oxygen Therapy Indications . 2014;.
    5. Kiyoshige Y. Effect of hyperbaric oxygen therapy as a monitoring technique for digital replantation survival. Journal of reconstructive microsurgery. 1999;volume 15(5):327-30.
    6. Harry T. Whelan, Eric Kindwall et al. Hyperbaric Medicine Practice 4th Edition Best Publishing Company. 2017;volume fourth():.
    7. Richard C. Baynosa MD, William A Zamboni, MD, FACS et al. Undersea and Hyperbaric Medical Society, Hyperbaric Oxygen Indications, 13th edition: Compromised Grafts and Flaps . 2014;.
    8. Moffat AD, Worth ER, Weaver LK et al. Glycosylated hemoglobin and hyperbaric oxygen coverage denials. Undersea & hyperbaric medicine : journal of the Undersea and Hyperbaric Medical Society, In.... 2015;volume 42(3):197-204.
    9. Fredman R, Wise I, Friedman T, Heller L, Karni T et al. Skin-sparing mastectomy flap ischemia salvage using urgent hyperbaric chamber oxygen therapy: a case report. Undersea & hyperbaric medicine : journal of the Undersea and Hyperbaric Medical Society, In.... 2014;volume 41(2):145-7.
    10. Larson JV, Steensma EA, Flikkema RM, Norman EM et al. The application of hyperbaric oxygen therapy in the management of compromised flaps. Undersea & hyperbaric medicine : journal of the Undersea and Hyperbaric Medical Society, In.... 2013;volume 40(6):499-504.
    11. Roje Z, Roje Z, Eterović D, Druzijanić N, Petrićević A, Roje T, Capkun V et al. Influence of adjuvant hyperbaric oxygen therapy on short-term complications during surgical reconstruction of upper and lower extremity war injuries: retrospective cohort study. Croatian medical journal. 2008;volume 49(2):224-32.
    12. Friedman HI, Stonerock C, Brill A et al. Composite earlobe grafts to reconstruct the lateral nasal ala and sill. Annals of plastic surgery. 2003;volume 50(3):275-81; discussion 281.
    13. Saber AA, Yahya KZ, Rao A, Castellano M, Cioroiu M, Grossi R, Tornambe RM et al. A new approach in the management of chronic nonhealing leg ulcers. Journal of investigative surgery : the official journal of the Academy of Surgical Research. 2005;volume 18(6):321-3.
    14. Perrins DJ. Influence of hyperbaric oxygen on the survival of split skin grafts. Lancet (London, England). 1967;volume 1(7495):868-71.
    15. Eskes A, Vermeulen H, Lucas C, Ubbink DT et al. Hyperbaric oxygen therapy for treating acute surgical and traumatic wounds. The Cochrane database of systematic reviews. 2013;.
    16. Mathieu, Daniel; Marroni, Alessandro; Kot, Jacek et al. Tenth European Consensus Conference on Hyperbaric Medicine: recommendations for accepted and non-accepted clinical indications and practice of hyperbaric oxygen treatment. Diving and hyperbaric medicine. 2017;volume 47(1):24-32.
    17. Mathieu D, Neviere R, Pellerin P, Patenotre P, Wattel F et al. Pedicle musculocutaneous flap transplantation: prediction of final outcome by transcutaneous oxygen measurements in hyperbaric oxygen. Plastic and reconstructive surgery. 1993;volume 91(2):329-34.
    18. Assaad NN, Chong R, Tat LT, Bennett MH, Coroneo MT et al. Use of adjuvant hyperbaric oxygen therapy to support limbal conjunctival graft in the management of recurrent pterygium. Cornea. 2011;volume 30(1):7-10.
    19. Gould LJ, May T et al. The Science of Hyperbaric Oxygen for Flaps and Grafts. Surgical technology international. 2016;volume 28():65-72.
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