Hyperbaric Oxygenation Accelerates the Healing Rate of Nonischemic Chronic Diabetic Foot Ulcers: A prospective randomized study

LAURENCE KESSLER PHD 2 PASCAL BILBAULT 1 FRANCOISE ORTEGA 2 CLAIRE GRASSO PHD 2 RAPHAEL PASSEMARD PHD 2 DOMINIQUE STEPHAN PHD 0 MICHEL PINGET PHD 2 FRANCIS SCHNEIDER PHD 1 0 Department of Cardiovascular Disease, University Hospital , Strasbourg, France. gie, Ho pitaux Universitaires 1, Place de l'H opital, 67091 Strausbourg Cedex , France 1 , transcutaneous oxygen tension. A table elsewhere in this issue shows conventional and Syste`me International (SI) units and conversion factors for many substances. 2003 by the American Diabetes Association 2 Department of Endocrinology and Diabetology, University Hospital , Strasbourg , France; the OBJECTIVE - To study the effect of systemic hyperbaric oxygenation (HBO) therapy on the healing course of nonischemic chronic diabetic foot ulcers. RESEARCH DESIGN AND METHODS - From 1999 to 2000, 28 patients (average age 60.2 9.7 years, diabetes duration 18.2 6.6 years), of whom 87% had type 2 diabetes, demonstrating chronic Wagner grades I-III foot ulcers without clinical symptoms of arteriopathy, were studied. They were randomized to undergo HBO because their ulcers did not improve over 3 months of full standard treatment. All the patients demonstrated signs of neuropathy. HBO was applied twice a day, 5 days a week for 2 weeks; each session lasted 90 min at 2.5 ATA (absolute temperature air). The main parameter studied was the size of the foot ulcer measured on tracing graphs with a computer. It was evaluated before HBO and at day 15 and 30 after the baseline. RESULTS - HBO was well tolerated in all but one patient (barotraumatic otitis). The transcutaneous oxygen pressure (TcPO2) measured on the dorsum of the feet of the patients was 45.6 18.1 mmHg (room air). During HBO, the TcPO2 measured around the ulcer increased significantly from 21.9 12.1 to 454.2 128.1 mmHg (P 0.001). At day 15 (i.e., after completion of HBO), the size of ulcers decreased significantly in the HBO group (41.8 25.5 vs. 21.7 16.9% in the control group [P 0.037]). Such a difference could no longer be observed at day 30 (48.1 30.3 vs. 41.7 27.3%). Four weeks later, complete healing was observed in two patients having undergone HBO and none in the control group. CONCLUSIONS - In addition to standard multidisciplinary management, HBO doubles the mean healing rate of nonischemic chronic foot ulcers in selected diabetic patients. The time dependence of the effect of HBO warrants further investigations. - L ble for 20% of the hospital admis- causes of lower-extremity injuries in the ower-extremity ulcers are responsi- (1). Foot ulcer represents one of the major sions of diabetic patients; the 220 million people suffering from diabeincidence of amputation is 6 per 1,000 tes worldwide, 2.5% of whom will de velop a foot ulcer each year (2). Moreover, duration of hospitalization attests to the high morbidity of this condition (3), which has been shown to require as long as 26 weeks for full recovery (4) despite a multidisciplinary approach (associating glycemia control, daily local care, foot offloading antibiotic therapy, and surgical revascularization). The diabetic foot is characterized by sensory, motor, and autonomic neuropathies leading to alteration of pressure distribution, foot deformities, and ulcerations. Metabolic control and infection treatments are of primary importance to control the evolution of the diabetic foot. Hyperbaric oxygenation (HBO) has previously been proposed as an adjunctive treatment for the diabetic foot because it improves in vitro the complex processes underlying healing (57). It has also been reported that HBO reduces the incidence of major amputation in diabetic patients with a gangrenous foot (8). The actual value of HBO on diabetic foot healing is, however, still a matter of discussion because conflicting data exist in the literature (9 13) on its true therapeutic effect. The difficulty in controlling the different parameters (metabolic, vascular, infectious, and foot off-loading) involved in the evolution of the diabetic foot and the lack of prospective randomized studies on the effect of HBO on this pathophysiological condition make it difficult to recognize HBO as an incontrovertible treatment. Recently, M echine et al. (14) have reported on the effect of HBO on the accele r a t i o n o f a n g i o g e n e s i s a n d o n a stimulation of neovascularization in an experimental model of wound healing in the rat. On the other hand, Wattel et al. (15) showed that the effectiveness of HBO on healing in nondiabetic patients was dependent on the peripheral arterial disesase. Consequently, the purpose of this study was to evaluate the effect of HBO on the healing of nonishemic chronic diabetic foot ulcer in a prospective controlled and randomized study on the basis of the experimental protocol proposed by Mechine et al. RESEARCH DESIGN AND METHODS Patients The protocol was approved by our local ethics committee, and written consent was obtained from each patient. From January 1999 to January 2000, 28 type 1 and type 2 diabetic patients consecutively admitted in our ward for chronic foot ulcers (Wagner grades I, II, and III) were prospectively included in this study. Their ulcers (depth 2 mm) were characterized by the absence of favorable evolution for at least 3 months despite the stabilization of glycemia, the absence of clinical local infection, and satisfactory off-loading measures. In 17 patients, the ulcers were located on the heels or soles and were mainly due to an initial hyperkeratosis area complicated with cutaneous fissures. When the ulcers were located on the toes, the initial provoking causes were a traumatism or blister resulting from ill-fitting shoes (n 11). In 13 cases the ulcers were associated with an aperture with chronic deep infection. The initial size of ulcers was 2.56 1.83 cm2. Clinical signs of arteriopathy were absent (the palpation of arterial pulses at lower extremities was normal). Doppler scans of lower limbs were normal and the transcutaneous oxygen tension (TcPO2) measured at the dorsum of the foot exhibiting the ulcer was 30 mmHg. Each patient was asked to keep weight off the affected foot. The patients had a stabilized nonproliferating retinopathy. During the study period, 64 diabetic patients were admitted to our unit for foot ulcers. Of them, 34 patients were excluded, 8 due to gangrenous ulcer with severe sepsis, 22 patients due to severe arteriopathy (TcPo2 30 mmHg), and 4 due exclusion criteria for HBO (emphysema, proliferating retinopathy, claustrophobia). Among the 30 selected patients, 2 patients refused to participate. The 28 patients selected were randomized to standard treatment or standard treatment plus HBO according to a randomization table. The HBO and control groups involved 15 and 13 diabetic patients, respectively. Study protocol On inclusion, physical examination was performed on patients, including palpation of the arterial p (...truncated)