Background:
Hyperbaric oxygen (HBO) has been proven to enhance bone and soft tissue healing in ischemic tissue in vitro and in vivo studies. Although only a few reports have been proven using controlled studies, this treatment modality remains encouraging for chronic refractory osteomyelitis. In this retrospective study, we reported the clinical results of HBO therapy for chronic refractory osteomyelitis.
Methods:
From January through August 2000, 14 patients with chronic refractory osteomyelitis of the tibias treated with HBO were available for follow-up examination. According to the Cierny-Mader classification, all patients were classified as type III or IV osteomyelitis. Adequate debridement and parenteral antibiotic treatment in conjunction with HBO therapy at 2.5 atmospheres absolute for 120 minutes, and 5 days per week regimen was used in all patients. The patients were followed-up for an average of 15 months after completion of HBO therapy.
Results:
The most common infecting microorganism was Staphylococcus aureus. Mixed infections were usually found in patients with open fractures. The average number of operations before HBO therapy was 5.4 including soft tissue reconstruction in 11 patients. The average number of HBO treatments was 33.6 times. There were no HBO related complications. No recurrence of infection was noted in 11 patients, which resulted in a success rate of 79%.
Conclusions:
Hyperbaric oxygen therapy is effective and safe for chronic refractory osteomyelitis provided that patients had received appropriate medical and surgical management.
(Chang Gung Med J 2003;26:114-21)

Key words:
hyperbaric oxygen (HBO), chronic refractory osteomyelitis, atmosphere absolute (ATA).

METHODS

From January 2000 through August 2000, 85 patients with tibial osteomyelitis were treated at authors' hospital. Fourteen patients with chronic refractory osteomyelitis treated with HBO were available for follow-up examination (Table 1). There were 12 men and two women with an average age of 50 years (range, 25 to 79 years).
The initial evaluation included a complete medical history, laboratory data, culture, antibiotic therapy, and operative treatment. Image studies included x-ray, bone scans/ Gallium scans, and computerized tomograms as indicated. Chronic refractory osteomyelitis was defined as bone infections that persisted longer than 6 months, in the patients where aggressive, adequate surgical debridement and antibiotic therapy had failed.(11,12) All patients enrolled in this study had met the following 3 criteria: (1) infection for at least 6 months, (2) had received at least three surgical procedures to eradicate the infection, and (3) treatment with parenteral antibiotics.
Chronic osteomyelitis was classified using the Cierny-Mader classification system.(4) All patients had anatomic type III or IV osteomyelitis. Nine cases resulted from open fractures, and five from closed fractures. The duration of infection before HBO therapy averaged 14 months (range, 6 to 48 months). The average number of surgical procedures before HBO therapy was 5.4 (range, 3 to 10). The choice of antibiotics was determined according to the latest culture and sensitivity tests. The duration of parenteral antibiotic therapy after operation was usually 2 weeks; followed by an additional 2 to 4 weeks of oral antibiotics.
In addition to surgical debridement and parenteral antibiotics, all patients had received adjunctive HBO therapy in a diving chamber (Haux-Starmed 2000 Hyperbaric Chamber, Germany). The treatment regimen was designed according to the suggestions by the UHMS.(13) In the hyperbaric chamber, 100% oxygen was delivered using a mask system, with 2.5 atmospheres absolute (ATA), for 2 hours with an intermittent schedule of 25 minutes of 100% oxygen breathing and 5 minutes of air breathing, one session per day, 5 days per week. All patients were followed for a minimum of 1 year with an average follow-up of 15 months (range, 12 to 18 months). Success of treatment was defined as patients who had good wound healing with no discharge and no recurrence of infection during the follow-up period after HBO therapy.

RESULTS

The average number of treatments with HBO therapy was 33.6 times (range, 30 to 60 times). None of the patients exhibited signs of oxygen toxicity or barotrauma during HBO therapy. The wounds healed in 11 patients with a 79% success rate. The average number of surgical procedures was 5.4 (range, 3 to 10) before HBO therapy, and 1.6 (range, 0 to 3) during HBO therapy. Debridement and flap or skin graft was performed in 11 patients.
The most common microorganism was Staphylococcus aureus. Mixed infection was more common in patients with open fractures (Table 2). Three patients failed to heal despite combined surgical debridement, parenteral antibiotic therapy and HBO therapy. The patients who failed the treatment protocol had also undergone 30 sessions of HBO. One patient had tibial osteomyelitis following an open type IIIB fracture. The culture results showed microorganisms with mixed flora. Multiple surgical procedures including free flap reconstruction were performed to preserve the tibia. However, the infection persisted despite surgical debridement, parenteral antibiotics and HBO therapy. The patient finally received an above-knee amputation to eradicate the infection. The other two patients with tibial osteomyelitis had decreased wound drainage after 30 sessions of HBO. The infecting microorganism was Oxacillin-resistant Staphylococcus aureus. The discharge sinus persisted during the follow-up, but both patients refused further debridement, preferring to live with the osteomyelitis.
The remaining 11 patients had wound healing and no recurrence of osteomyelitis after HBO therapy (Fig. 1). The length of treatment averaged 48 days (range, 42 to 84 days). There was no recurrence at a follow-up period of 15 months after the completion of HBO therapy.

DISCUSSION

The basic principles of management for chronic osteomyelitis include adequate debridement and appropriate antibiotic therapy.(1,2,14,15) Soft tissue reconstruction or osteocutaneous transfer is necessary when there is soft tissue or bone defects. However, optimal surgical results are not always achieved, and this is one of the common causes of refractory infection. The recurrence rate in chronic refractory osteomyelitis is relatively high because the chronicity renders osteomyelitis resistant to conventional treatment.(16)
HBO therapy increases tissue oxygen tension and promotes bone and soft tissue healing in ischemic tissue which has been widely proven in vitro and in vivo studies.(7,10,17-19) The possible mechanisms of HBO in treating osteomyelitis are (1) HBO raises the tissue oxygen tension, (2) HBO enhances the leukocyte phagocytic mechanisms in bones and wounds with low oxygen tension,(5) (3) Optimal oxygen tension enhances osteogenesis or neovascularization to fill the dead space with vascular or bony tissue(17), and (4) HBO enhances osteoclastic activity to remove bony debris.(17) HBO also directly inhibits anaerobic organism growth in hypoxic tissue.
Normal oxygen tension in healthy bones is about 45 mmHg of oxygen under ambient conditions.(20) The infected bone and necrotic tissue produces an area of lower oxygen tension.(12) The level of oxygen tension under ambient conditions in chronic osteomyelitis is 23 mmHg or less.(20) The causes of low oxygen tension in chronic osteomyelitis include initial trauma, vascular compromise, dense fibrous scarring and undebrided infected bone. Intermittent oxygen tensions of 30 to 40 mmHg are necessary for neovascularization in an ischemic environment.(21) Also, elevating the oxygen tension above 30 to 40 mmHg further improves leukocyte killing.(22)
Although antibiotics help kill microorganisms in the soft tissue around the focus of infection and surgery removes the macroscopic portion of dead and infected bone, HBO improves host response by making the environment more favorable to leukocyte oxidative killing, neovascularization, and resorption of dead and infected bone. Small bone debris could be resorbed during HBO therapy, but persistent sequestrum should be surgically removed.(23) In addition, aminoglycoside transfer access to the bacterial wall is oxygen-dependent and is inhibited in conditions of a hypoxic environment. Therefore, HBO therapy enhances transport and augments the efficacy of the antibiotics.(24)
There were many reports of improvement for chronic osteomyelitis treated using HBO therapy. Davis reported a disease process arrested in 50% which remained so after 5 years of follow up in 98 patients treated with 2 ATA HBO.(25) In another report, Davis et al. found that 34 of 38 patients treated with 2ATA HBO plus wound debridement and antibiotics became free from clinical signs of osteomyelitis for 34 months.(7) Morrey et al. recommended that HBO be used as an adjunct to surgery and antibiotics. In their series of 40 patients treated with HBO, the cure rate at 2 years of follow-up was 85%.(11) In our series, 14 patients were treated with 2.5 ATA HBO. Eleven patients healed with a success rate of 79%. There was no recurrence at an average follow-up period of 15 months after the completion of HBO therapy.
All patients in our series were type III or IV osteomyelitis according to the Cierny-Mader classification system.(4) Three patients failed to respond to the treatment including one case with mixed infection, and two patients with Staphylococcus aureus infections. The first patient was a 64-year-old diabetic patient with multiple fractures. The second patient was a 27-year-old man who had large soft tissue defects combined with multiple flora infection. The third patient was a 63-year-old man who was an alcoholic and a heavy smoker. All of them were type IVB osteomyelitis. However, the number of patients who failed to heal after the treatment was too small to draw any conclusions concerning the poor results. The combination of infecting microorganism, duration and severity of infection, and underlying disease all contributed to the failure of the treatment.
Mader et al.(24) studied Staphylococcus aureus osteomyelitis using a rat tibial model to evaluate the effectiveness of HBO therapy. They found that HBO alone was as effective as Cephalothin in the treatment of experimental Staphylococcus aureus osteomyelitis. The best results were obtained in animals treated using a combination of HBO and Cephalothin. Therefore, they recommended that adjunctive HBO be used for stages 3B and 4B osteomyelitis and not indicated for all clinical types of osteomyelitis.
In two identical publications, Esterhai et al.(6,10) reported no benefits of HBO therapy in their patients with chronic refractory osteomyelitis. This is the only study in which no effects of HBO in chronic refractory osteomyelitis were reported.
The limitation of this study was the fact that it was uncontrolled and retrospective. The treatment course was more complicated in the patients as compared with treatment for a simple fracture. The treatment was individualized, and no strict principles were adhered to. The treatment results were unpredictable and the treatment course was long. Although HBO therapy has been proven to enhance bone and soft tissue healing in ischemic tissue, the healing of chronic osteomyelitis may not be attributed solely to the HBO therapy, especially when combined soft tissue reconstruction was done for the patient. However, local wound condition before HBO therapy may serve as a control parameter in comparison with conditions after HBO therapy. The clinical responses to HBO therapy were used as guidelines for further treatment.
In conclusion, 11 of 14 patients with chronic refractory osteomyelitis were successfully treated with HBO therapy. No complications were associated with the HBO therapy in this series. The results were encouraging at 15 months of follow-up. HBO therapy is effective and safe for chronic refractory osteomyelitis provided there are appropriate medical and surgical management.

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From the Department of Orthopedic Surgery, 1Department of Trauma Surgery, Chang Gung Memorial Hospital, Kaohsiung.
Received: Aug. 19, 2002
Accepted: Nov. 8, 2002
Address for reprints: Dr. Chin-En Chen, Department of Orthopedic Surgery, Chang Gung Memorial Hospital. 123, Ta-Pei Road, Niaosung 833, Kaohsiung, Taiwan, R.O.C.
Tel.: 886-7-7317123 ext. 8003
Fax: 886-7-7318762
E-mail: chinenmd@ms21.hinet.net