Supplementing Diabetic Wound Care With Hyperbaric Medicine

As the diabetes mellitus epidemic continues to grow, so does the number of diabetic wounds in the lower extremity. Researchers have estimated that the number of individuals with diabetes mellitus who eventually develop a lower extremity ulceration may be as high as 25 percent.1

   Heel ulcers are notoriously difficult to treat because of their late clinical presentation, which often involves large skin and soft tissue defects, extension to bone and insufficient local tissue for closure. Frequently, simpler treatment options have failed. In this presentation, the wounds have not responded to a trial of offloading or have healed with unstable scars and are now subject to recurrent ulceration due to being on a pressure bearing location.

   Our goal as foot and ankle surgeons is to guide therapy to heal these ulcerations and prevent major lower extremity amputations. The backbone to healing these ulcerations starts with good wound care that includes: offloading of the wound site; regular debridement of devitalized and hyperkeratotic tissue; and ensuring an adequate vascular stasis to healing. One also needs to ensure regular follow up by the patient with his or her primary care physician for glycemic control and medical management.

   However, even with dedicated care, researchers have estimated that the risk of an individual with diabetes mellitus having an outcome that leads to a major lower extremity amputation is nearly 10 percent.2 When wound healing is not progressing, the use of hyperbaric oxygen therapy (HBOT) could provide the key to healing.

   Henshaw first devised the concept of treating diseases with an increased ambient pressure in 1662. He created a sealed chamber called the “domicilium” to treat various ailments. However, his chamber was not based on scientific data but rather that it “seemed like a good idea.”3 Modern use of hyperbaric medicine began in 1955 through the work of Churchill-Davidson, who utilized high oxygen environments to enhance the effects of radiation therapy in cancer patients.4 In 1956, Boerema demonstrated that hyperbaric oxygen could be useful in patients undergoing cardiac surgery.5 Subsequently, other researchers reported success with HBOT, noting an inhibitory effect on anaerobic infections and benefits with the treatment of carbon monoxide poisoning.6,7

Understanding The Physiological Effects Of Hyberbaric Oxygen

When oxygen is in an environment of increased pressure, it behaves like a drug, having specific indications and side effects. Placing a patient in a hyperbaric chamber at 2.8 ATA O2 raises the oxygen tension 10 to 13 times above the normal levels, saturating the plasma and causing hemoglobin to remain fully oxygenated on the venous side. Even though high levels of oxygen cause vasoconstriction, the increased blood oxygen levels more than compensate for this. Furthermore, hypoxic tissue does not respond with vasoconstriction due to local mechanisms that lead to a redistribution effect, which further oxygenates this tissue.8

   Collagen synthesis by fibroblasts is triggered by the lactate produced by macrophages in the wound environment. Fibroblasts are unable to synthesize collagen in a hypoxic state as it is required in the steps that produce cross-linking.9 When oxygen levels are low, the collagen framework is unable to be produced, vessel growth into the wound is diminished and subsequent healing stalls. This leads to the formation of a chronic, non-healing wound.

   However, within 15 minutes of HBOT, endothelial cells begin to proliferate. After 120 minutes, fibroblasts begin to produce a response, which can last up to 72 hours post-exposure.10 There are also effects in red blood cells as hyperbaric oxygen increases their deformability and improves the ability of these cells to pass through narrow capillaries. Leukocytes use oxygen to create high-energy radicals and their rate of formation is directly proportional to the amount of oxygen available. Leukocytes can then lend these radicals to neutrophils for increased phagocytosis of bacteria, helping to clean the wound and prevent infection.11

Is The Patient A Viable Candidate For HBOT?

When assessing whether a diabetic foot ulceration meets criteria for HBOT, Medicare requires that the wound be staged as a Wagner III (a full thickness ulceration having bone and/or soft tissue infection present) ulcer, which has failed standard care for at least 30 days.12 Hyperbaric oxygen therapy is also indicated for the treatment of gas gangrene and progressive necrotizing infections as an adjunct to surgical debridement and antibiotic therapy. Hyperbaric oxygen therapy can also be indicated for use with the preservation of skin grafts and flaps if concerns of failure are present. Furthermore, if the graft or flap does fail, one can use HBOT to prepare the wound bed for the next graft or flap.

   The use of transcutaneous oxygen pressure (TcPO2) measurements offers a simple and noninvasive diagnostic technique to provide a reliable objective assessment of the local skin perfusion in room air. One can also use TcPO2 measurements to gauge the effect HBOT might have on local tissue by measuring changes in perfusion while supplementing the patient with 100% O2 via a mask or a nasal cannula.The results of this test show if the patient has the ability to heal a wound by way of tissue perfusion in room air and if one can achieve a benefit via supplementation with HBOT.13 It should be noted that in the presence of infection, there is a local decrease in tissue oxygen perfusion that does resolve once the infection is eradicated.14

What About Contraindications For HBOT?

Hyperbaric oxygen therapy is not without risks and proper patient selection is important. If patients are taking the chemotherapeutic drug doxorubicin, HBOT is contraindicated as the drug can become cardiac toxic and lead to death.

   The use of Sulfamylon® (UDL Laboratories) cream on a wound is also contraindicated when a patient undergoes HBOT as this leads to local CO2 buildup and vasodilatation, which is further compounded by central vasoconstriction caused by HBOT. One should utilize a different topical wound agent or remove the ointment from the wound before starting a HBOT treatment.

   Untreated pneumothorax is also a contraindication. It is of benefit to screen patients with a chest radiograph to rule this out before starting HBOT. Other conditions that present a risk with HBOT include: seizure disorders, emphysema with CO2 retention, uncontrolled high fevers, a history of spontaneous pneumothorax, chronic sinusitis and upper respiratory tract infections, viral infections, a history of optic neuritis, previous otosclerosis surgery and congenital spherocytosis.8 However, authors have noted that one can take possible precautions if one of these conditions is present in order to allow HBOT to proceed.8

Case Study: When A Patient With Diabetes Has An Involved Infection With Gas Gangrene

A 66-year-old male with type 2 diabetes mellitus had an involved infection with the presence of subcutaneous gas gangrene in the lateral foot. The patient subsequently had a wide margin excisional debridement and partial fifth ray resection. The resulting foot had an exposed bone of the fourth metatarsal shaft and the fifth metatarsal base as well as concerns of further tissue loss occurring due to local ischemia.

   The patient immediately began treatments in the HBOT chamber due to his gas gangrene infection. The TcPO2 results showed a reading of 21 mmHg in the presence of room air with a significant improvement to 46 mmHg when the patient was breathing 100% O2 via a nasal cannula. Shortly after the initial debridement, the patient returned to the operating room for conversion to a transmetatarsal amputation of the foot due to the presence of exposed bone and advancing distal ischemia and necrosis of the foot.

   The patient’s foot responded well after one month of treatment and healed completely after the completion of the 60 HBOT treatments.

   Dr. Johnson is the Director of the Chronic Wound Clinic at the Hennepin County Medical Center in Minneapolis.

References
1. Singh N, Armstrong DG, Lipsky BA. Preventing foot ulcers in patients with diabetes. JAMA. 2005; 293(2):217-28.
2. Eggers PW, Gohdes D, Pugh J. Nontraumatic lower extremity amputations in the Medicare end-stage renal disease population. Kidney Int. 1999; 56(4):1524-1533.
3. Henshaw IN, Simpson A. Compressed air as a therapeutic agent in the treatment of consumption, asthma, chronic bronchitis, and other diseases. Sutherland and Knox, Edinburgh, 1857.
4. Churchill-Davidson I, Sanger C, Thomlinson RH. High pressure oxygen and radiotherapy. Lancet. 1955; 268(6874):1091-1095.
5. Boerema I, Kroll JA, Meijne NG, Lokin E, Kroon B, Huiskes JW. High atmospheric pressure as an aid to cardiac surgery. Arch Chir Neerl. 1956; 8(3):193-211.
6. Brummelkamp WH, Hogendijk J, Boerema I. Treatment of anaerobic Infections (Clostridial myositis) by drenching the tissues with oxygen under high atmospheric pressure. Surgery. 1961; 49:299-302.
7. Smith G, Sharp GR. Treatment of coal gas poisoning with oxygen at two atmospheres pressure. Lancet. 1962; 1(7234):816-819.
8. Kindwall EP, Whelan HT. Hyperbaric Medicine Practice. 3rd Edition. Best Publishing Co. Flagstaff, AZ. 2008.
9. Hunt TK. The physiology of wound healing. Ann Emerg Med. 1988; 17(12):1265-1273.
10. Tompach PC, Lew D, Stoll JL. Cell response to hyperbaric oxygen treatment. Int J Oral Maxillofac Surg. 1997; 26(2):82-86.
11. Badway JA, Karnovsky ML. Active oxygen species and the functions of phagocytic leucocytes. Ann Rev Biochem. 1980; 49:695-726.
12. Centers for Medicare and Medical Services: National Coverage Determination for Hyperbaric Oxygen Therapy (20.29) Published number 100-3. Section 3 20.29. Version 3. 6/19/2006.
13. Pinzur MS, Sage R, Stuck R, Ketner L, Osterman H. Transcutaneous oxygen as a predictor of wound healing in amputation of the foot and ankle. Foot Ankle. 1992; 13(5):271-272.
14. Pinzur MS, Sage R, Stuck R, Osterman H. Transcutaneous tension in the dysvascular foot with infection. Foot Ankle. 1993; 14(5):254-256.

   For further reading, see “A Guide To Hyperbaric Oxygen Therapy For Diabetic Foot Wounds” in the December 2007 issue of Podiatry Today.