HYPERBARIC OXYGEN IN DIABETIC FOOT TREATMENT

Branko Novak, Zeljko Metelko, Nikica Car

Vuk Vrhovac Institute, University Clinic for Diabetes, Endocrinology and Metabolic Diseases,
Dugi dol 4a, 10000 Zagreb, Croatia

Editorial

Received: May 5, 1999

Key words: diabetes, diabetic foot, hyperbaric oxygen therapy

SUMMARY

Diabetic foot is a common problem in diabetic patients and contributes to morbidity and mortality in this population. About 15% of diabetic population are affected. The problems associated with foot ulcers (inflammation, amputation) result in a reduced quality of life, and significant morbidity and mortality in diabetic patients. The major contributing factors for diabetic foot development are diabetic neuropathy leading to foot deformities, elevated peak plantar pressure and callus formation; penetrating trauma; and ill-fitting shoes. Peripheral neuropathy has a central role, being present in over 80% of diabetic patients with foot lesions, but ischemia is also a frequent contributing factor. An interdisciplinary approach is mandatory in the treatment of diabetic foot, especially once neuropathic ulcers or inflammation have developed. Hyperbaric oxygen therapy has been used with the aim to improve diabetic foot oxygenation and accelerate healing. The role and place of hyperbaric oxygen in the management of diabetic foot are reviewed.

HYPERBARIC OXYGEN THERAPY

Hyperbaric oxygen (HBO; 100% oxygen under two- to three-fold atmospheric pressure) can produce arterial oxygen tension of 2000 mm Hg or more, and tissue oxygen tension of about 400 mm Hg. These oxygen pressures have a number of biochemical, physiologic and cellular effects, and have been used for therapeutic purpose in a number of pathologic states.
The main physiologic effect of HBO is the above mentioned rise in arterial oxygen tension which meets cellular requirements in a hypoxic tissue. Normalization of tissue oxygen tension improves the bactericidal ability of neutrophils (oxygen is essential for the generation of free radicals). Oxygen is also required for normal collagen synthesis, and thus for angiogenesis and healing as well. HBO is also known to help in crush injuries by inhibiting the adherence of neutrophils to the vessel wall (which is supposed to be the primary mechanism of reperfusion injury). In decompression sickness and gas embolism, the elevated atmospheric pressure increases the solubility of gases, while on the other hand inert nitrogen in air bubbles in blood vessels and tissues is replaced with oxygen, which is rapidly metabolized by the tissues.

Therapeutic uses of hyperbaric oxygen
There are four main indications for HBO therapy, where it is the primary and most efficient form of treatment:
  1. carbon monoxide poisoning - HBO delivers enough dissolved oxygen to the tissues, thus bypassing methemoglobin;
  2. air embolism - air bubbles dissolve under increased atmospheric pressure, and easily metabolized oxygen replaces inert nitrogen;
  3. decompression sickness - the mode of action is more or less the same as in air embolism; and
  4. severe blood loss in individuals who cannot or will not receive blood transfusion - again, dissolved oxygen in blood under hyperbaric conditions is sufficient for tissue supply until bone marrow is capable of an adequate red blood cell production.
There also are a number of states in which HBO is used as supportive therapy (with or without scientific proof of its efficacy). It has been demonstrated that HBO therapy is beneficial in clostridial myonecrosis, and in compromised flaps and grafts. HBO therapy is also used in osteoradionecrosis, thermal burns, macular edema, chronic refractory osteomyelitis, brain injuries, and problem wounds.

Contraindications for hyperbaric oxygen therapy
HBO therapy is contraindicated in any condition causing respiratory tract obstruction or air trapping (such as pneumothorax, asthma, upper respiratory tract infections, and emphysema). Other contraindications include viral infections (worsening of some viral infections after HBO therapy has been observed); high fever (this therapy lowers seizure threshold); use of some medications such as doxorubicin, cisplatin and disulphiram; optic neuritis; hereditary spherocytosis; middle ear surgery or disorders; history of seizures; and pregnancy (1).

DIABETIC FOOT

Diabetic foot is a common problem among diabetic patients. Some 15% of all diabetic patients in the USA are affected with foot ulcers (2). Problems associated with foot ulcers (inflammation, amputation) lead to significant morbidity and mortality in diabetic population. The major contributing factors for diabetic foot development are diabetic neuropathy leading to foot deformities, elevated peak plantar pressure and callus formation; penetrating trauma; and ill-fitting shoes (3). Peripheral neuropathy has a central role, being present in over 80% of diabetic patients with foot lesions. Neuropathy results in loss of protective sensation, leading to the loss of awareness of trauma, thus allowing the breakdown of the skin to occur (4). Most of the neuropathic ulcers develop on the sole, on the metatarsal heads. Claw toes and cavus foot result in increased vertical and horizontal forces under the metatarsal heads and heel, and callosities. The resulting mechanical stress is the major cause of diabetic foot ulcers. When walking, the subcutaneous tissue is exposed to high shear forces, because it is trapped between the thick, unpliable skin and bone (5).
Ischemia is also a frequent contributing factor. In diabetic patients, it often involves distal, tibial arteries, and is associated with poorer prognosis (4).
Once established, neuropathic foot ulcer can easily become infected. Local inflammation, purulent drainage and/or crepitations suggest the presence of infection. The severity of infection can vary from mild local inflammation to extensive and life-threatening infection. In mild cases, the most frequent cause of infection are gram positive cocci, whereas in limb-threatening, widespread infection a mixed bacterial flora is present. Osteomyelitis can also be present, but the diagnosis is not easy to make, because plain radiographs are neither sensitive nor specific, and diabetic osteoarthropathy can also easily be misinterpreted as osteomyelitis (4).
Diabetic foot ulcers should be inspected for the presence of infection and swabs for culture should be taken, if necessary. Necrotic and devitalized tissue should be debrided, and measures should be taken to relieve the affected foot of pressure. In the presence of vascular occlusion, the vascular status should be assessed and revascularization should be tried, if possible (4). In case of ischemia, treatment with HBO has been tried in several studies, hoping to improve the healing process. It was logical to suppose that HBO could improve the healing process of diabetic foot in the presence of ischemia. However, as oxygenation of the ischemic limb increases only for a short period of time, the overall benefits of such a treatment remained questionable.

HYPERBARIC OXYGEN IN DIABETIC FOOT MANAGEMENT

Oriani and Meazza studied the effect of HBO on diabetic gangrene in two groups of patients. Study group included 62 patients treated with both HBO and conventional measures, and control group had 18 patients treated with conventional measures alone. The groups were not randomized. The control group included patients who refused HBO therapy. The groups were matched according to diabetic complications (retinopathy, neuropathy, nephropathy, and peripheral vascular disease). Conventional therapy consisted of tight glycemic control and surgical procedures (curettage, callus and necrosis removal). The HBO group patients entered the hyperbaric chamber on 6 days a week until the beginning of granulation, then on 5 days a week until recovery. Out of 62 patients, 59 recovered after a mean of 72±29 sessions (three patients had amputations). In the conventionally treated group of patients, there were 6 amputations and 12 recoveries. The difference between the groups is statistically significant (6). Major objections to the study include: a relatively small number of patients; the patients were not randomized; the study was not blinded; and short follow-up. Baroni et al. studied a group of 28 patients (23 with gangrene and five with ulcers). The patients were divided into the HBO group (n=18, 15 with gangrene and three with ulcers) and control group (n=10, eight with gangrene and two with ulcers). The control group included patients who refused hyperbaric oxygenation for some reason. The level of glycemia and hemoglobin did not differ significantly between the groups either on admission or on discharge from the hospital. The groups were matched according to diabetic complications (retinopathy, nephropathy, autonomic neuropathy, and macroangiopathy). Both groups were treated with strict metabolic control and daily surgical wound debridement. In addition, the HBO group patients were treated with HBO for 90 min a day. In this group, the lesions healed in 16 patients, whereas amputation was required in two patients. In the control group, healing was recorded in one patient, unchanged condition in five, and amputation in four patients (7). The groups were also rather small and patients were not randomized. In the study of Faglia et al., there were 68 patients with diabetes and microangiopathy. They were randomized for HBO therapy. Study group consisted of 35, and control group of 33 patients. Major amputations were required in three (8.6%) and 11 (33.3%) patients from the the study and control group, respectively. The difference is statistically significant (8). This is the only randomized study in a larger (yet not very large) group of patients, however, the follow-up period was quite short again. Doctor et al. conducted a prospective study in 30 diabetic patients with chronic foot lesions. The patients were randomized into two groups matched by age, gender, type of diabetes, presence of neuropathy, and presence of peripheral pulses. All patients received three daily doses of insulin. The patients in the infection had ascended above the ankle underwent amputation. The patients received antibiotics for 3 days. One group received a complete course of HBO therapy (4 sessions at 3 atm for 45 min over 2 weeks). The number of minor (below ankle) amputations (4 vs. 2) and duration of hospital stay (40.6 vs. 47 days) did not differ significantly between the groups. The study group patients had significantly less major (above ankle) amputations than those from the control group (2 vs. 7). The number of positive wound cultures decreased from 19 to 3 in the study group, and from 16 to 12 in the control group (9). In this study, the number of patients was relatively small. It is not clear which patients received antibiotics (all, only those with amputation, or those with positive bacterial cultures?), and why only for 3 days. No data on the follow-up are provided. Zamboni et al. report on a prospective, non-randomized study in ten patients with diabetes and chronic foot wounds (one on the ankle and the rest involving the foot). Five patients who refused HBO therapy served as a control group. All patients were on insulin. The groups were matched according to age, sex, wound surface area, reference room air TcPO2 (II intercostal space), wound TcPO2 at room air, 100% oxygen by mask and HBO at 2 atm, and presence of osteomyelitis. There was no significant difference between the groups. Both groups were treated with standard surgical procedures (debridement of the wound and silver sulfadiazine dressings changed twice daily). The study group was additionally treated with HBO at 2 atm for 120 min on 5 days over 6 weeks. After the first 7 weeks of the study, there was a significant difference in the wound surface area between the groups. All patients were followed up for 4-6 months. In the control group, healing of the wound failed to occur even after that period in four out of five patients, whereas a stable callus over the wound developed in one patient. None of these patients required amputation. In the study group, spontaneous healing of the wound was recorded in four out of five patients, whereas surgical coverage with a skin flap had to be performed in one patient (10). This study also suffered from a small number of patients and lack of patient randomization, however, the follow-up period was quite long. Brakora and Sheffield developed a procedure for the assessment and treatment of diabetic foot lesions. They recommend hyperbaric oxygenation in the presence of tissue hypoxia, with TcPO2 between 10 and 40 mm Hg in the affected limb. Lower oxygen pressures suggest too deep hypoxia to benefit from HBO, whereas higher pressures indicate a sufficient oxygen supply where no benefit from HBO can be expected (11). Wattel et al. had 20 patients with chronic foot ulcers (11 diabetic patients and nine patients with peripheral arterial occlusion). This study confirmed the predictive value of TcPO2 during HBO therapy for treatment outcome (12).

CONCLUSION

Methodologically, most of the above mentioned studies were quite improperly performed. The number of patients included was too small to allow reliable results to obtain and any definite conclusion to make. Beside this, the patients were not randomized. However, long-term follow-up appears to be the most important issue. Diabetic patients are chronic patients. All contributing factors that play a role in the development of diabetic foot persist after the initial success of hyperbaric oxygen therapy. The treatment with hyperbaric oxygen should only be considered as a adjunct measure in an aggressive multidisciplinary therapeutic approach, and can probably be used in a limited number of patients. Only patients with a fairly preserved vascular status can benefit from hyperbaric oxygen therapy. Prevention of diabetic foot development, including appropriate education and glycemic control, remains the main point in our efforts to save patients from amputations. There is a need of a properly conducted, prospective, randomized and blind study in a large number of patients, and with a several year follow-up, in order to assess the real place of hyperbaric oxygen therapy in diabetic foot management.

REFERENCES

  1. Tibbles PM, Edelsberg JS. Medical progress: hyperbaric oxygen therapy. N Engl J Med 1996;334:1642-1648.
  2. Parente ST, Mohr PE, Franco SJ. Cost and management of diabetic foot ulcers in American elderly. Diabetes 1998;47(S1):A400.
  3. Lavery LA, Peters EJG, Armstrong DG. Pathways to diabetic foot ulceration. Diabetes 1998;47(S1):A19.
  4. Caputo GM, Cavanagh PR, Ulbrecht JS, Gibbons GW, Karchmer AW. Current concepts: assessment and management of food disease in patients with diabetes. N Engl J Med 1994;331:854-860.
  5. Laing P. Diabetic foot ulcers. Am J Surg 1994;167:31S-36S.
  6. Oriani G, Meazza D. Hyperbaric oxygen therapy in diabetic gangrene. J Hyperb Med 1990;5:171-175.
  7. Baroni G, Porro T, Faglia E, et al. Hyperbaric oxygen in diabetic gangrene treatment. Diabetes Care 1987;10:81-86.
  8. Faglia E, Favales F, Aldeghi A, et al. Adjunctive systemic hyperbaric oxygen therapy in treatment of severe prevalently ischemic diabetic foot ulcer. A randomized study. Diabetes Care 1997;19:1338-1343.
  9. Doctor N, Pandya S, Supe A. Hyperbaric oxygen therapy in diabetic foot. J Postgrad Med 1992;38:112-114.
  10. Zamboni WA, Wong HP, Stephenson LL, Pfeifer MA. Evaluation of hyperbaric oxygen for diabetic wounds: a prospective study. Undersea Hyperb Med 1997;24:175-179.
  11. Brakora MJ, Sheffield PJ. Hyperbaric oxygen therapy for diabetic wounds. Clin Podiatr Med Surg 1995;12:105-117.
  12. Wattel F, Mathieu D, Coget JM, Billard V. Hyperbaric oxygen therapy in chronic vascular wound management. Angiology 1990;41:59-65.


 HOME PAGE