[Hyperbaric oxygen therapy for necrotizing soft tissue infections: contra]. / Hyperbare Oxygenation bei nekrotisierenden Weichteilinfektionen: Kontra.

INTRODUCTION: Hyperbaric oxygen therapy (HBOT) is discussed as an adjuvant option to treat necrotizing soft tissue infections (NSTI). While the Federal Joint Committee decided in 2007 not to support HBOT for the indication necrotizing fasciitis and Fournier's gangrene, it was decided to accept HBOT for treatment of clostridial myonecrosis for the German health insurance. Thus, in Germany necrotizing fasciitis (NF) is not a confirmed indication for HBOT. Against this background the cons of the clinical benefits of HBOT should be formulated. METHODS: A literature search (MEDLINE/EMBASE/COCHRANE/manual search) using the keywords "necrotizing fasciitis", "Fournier's gangrene", "necrotizing cellulitis", "necrotizing soft tissue infections" as well as "hyperbaric medicine", "hyperbaric therapy" and "hyperbaric treatment" was carried out. An analysis of the spatial distribution of German hyperbaric oxygen chambers enabling intensive care (HOC-IC) was made. RESULTS: A total of 250 articles with n=2,556 NSTI patients (n=993 treated by HBOT) was found and 50% of the articles were case reports or series. There were only ten retrospective studies comparing the effects of HBOT with non-HBO treatment and none of them verified the benefit of HBOT in NF patients. In Germany only nine hyperbaric oxygen chambers (HOC-IC) enable intensive care. Currently, patient data are not included in scientific studies or multicenter studies, while studies assessing the benefit with higher evidence levels have been required for more than 15 years. CONCLUSIONS: The previously published human clinical studies do not confirm any therapeutic benefit of HBOT in NF patients. Any time delay in the start of surgical therapy by HBOT would not be acceptable. In Germany a comprehensive clinical care with HOC is not possible. On average the additional costs of HBO treatment for NF patients is approximately 8,000-25,000 /patient which is not generally reimbursed by health insurance companies. Initializing a register study to assess the benefit of HBOT in NF patients appears feasible and is urgently needed.

[Complicated skin and soft tissue infections]. / Komplizierte Haut- und Weichgewebsinfektionen.

Skin and soft tissue infections are common diseases. The spectrum ranges from slight furuncles to severe necrotizing soft tissue infections. Grampositive bacteria account for 70-80 % of cases as causative organisms. Diagnostics include rapid evaluation of locally limited or diffuse spreading extent of the disease. In complicated skin and soft tissue infections, surgical intervention with debridement and necronectomy is indicated. Necrotizing skin and soft tissue infections call for programmed redebridement. If systemic signs of inflammation are present (fever > 38 degrees C, leukocytosis, CRP elevation) or significant comorbidity exists, application of antibiotics is indicated. The prognosis in operatively treated patients is dependent on the time of surgical intervention.

Treatment outcome of nonclostridial gas gangrene at a Level 1 trauma center.

OBJECTIVE: To evaluate the results of treatment of nonclostridial gas gangrene at a Level 1 trauma center. DESIGN: Retrospective. SETTING: Level 1 trauma center. PATIENTS: Seven patients with nonclostridial gas gangrene were studied. The average age of all patients at the time of admission was 40.3 years (range 14 to 67 years). RESULTS: Three of seven patients had posttraumatic infection, and the remaining four were strongly associated with underlying diseases: diabetes mellitus in three and paraplegia as the result of a spinal cord injury in two. The time of symptom onset was clearly defined in four cases, and the average interval between symptom onset and transfer to our hospitals was six days (range 2 to 10 days). Surgical debridement was performed immediately on admission in six patients (86 percent). A triple antibiotic regimen consisting of penicillin, gentamicin, and clindamycin was used initially in all patients. In three patients, hyperbaric oxygen therapy was also used. The overall mortality rate was 42.9 percent (three of seven patients). In these patients, the interval from onset of symptom to transfer to our hospital was ten days in one patient, which was longer than average, and was not accurately known in the other two patients. CONCLUSION: Nonclostridial gas gangrene is extremely rare but life-threatening. The greatest pitfall for the emergency department physician is failure to suspect it clinically. Aggressive treatment, including surgical debridement and intravenous antibiotics with or without hyperbaric oxygen therapy, must be initiated immediately to minimize morbidity and mortality.

Management of clostridial gas gangrene and the role of hyperbaric oxygen.

BACKGROUND AND AIMS: Clostridial gas gangrene is one of the most dreaded infections in surgery. The aim of this study was to investigate the efficacy of surgery, antibiotic treatment, surgical intensive care and especially the role of hyperbaric oxygen in the management of clostridial gas gangrene. MATERIAL AND METHODS: 53 patients, 42 of them submitted from other hospitals in Finland. After the diagnosis had been made the patients underwent surgical debridement, broad spectrum antibiotic therapy and a series of hyperbaric oxygen (HBO) treatments at 2.5 ATA pressure. The necrotic tissue was excised and incisions were made in the affected areas. Amputations were performed when necessary. RESULTS: Twelve patients died (22.6%). Hyperbaric oxygen therapy decreased the systemic toxicity and prevented further extension of the infection thereby improving the overall outcome of the patients. CONCLUSION: Hyperbaric oxygen therapy of gas gangrene seems to be life-, limb- and tissue saving. Early diagnosis remains essential. Patient survival can be improved if the disease is recognized early and appropriate therapy applied promptly. Surgical and antibiotic therapy as well as HBO treatment combined with surgical intensive care must be started as soon as possible.

[The experimental validation of methods for the emergency immunoprophylaxis of gas gangrene]. / Eksperimental'noe obosnovanie metodov ékstrennoi immunoprofilaktiki gazovoi gangreny.

The effectiveness, both immunological (by an increase in the titers of antitoxins) and protective (by resistance to the inoculation of the absolute lethal dose of infective agents), of the regional (wound) revaccination with tetratoxoid (Clostridium perfringens, C. oedematiens, C. septicum, C. histolyticum) was demonstrated on the experimental model of wound infection (gas gangrene) of guinea pigs. The schedule of rapid immunization with tetratoxoid was developed, which made it possible to create good immunological preparedness (basic immunity) for subsequent revaccination in case of traumas within 6 days. The effectiveness of rapid immunization by the application of tetratoxoid on the wound was shown. This immunization ensured a considered increase in the titers of antitoxins within the first 6 days, which increased the protection of the animals from infection with each of the four causative agents of gas gangrene.

[Hyperbaric surgery and oxygen therapy in clostridial myonecrosis]. / Hyperbare Chirurgie und Sauerstofftherapie der clostridialen Myonekrose.

116 patients with verified clostridial myonecrosis were treated by means of a regimen of combined cyclic hyperbaric oxygenation at 3 ata and repeated necrectomy. With proximal localization of gas gangrene in the elbow or knee (n = 55) 34.5% of patients survived, whilst with peripheral localization at the limbs (n = 44) the survival rate was 88.6% amputation being avoided in 21 of these cases. Abdominal localization (n = 17) was associated with the lowest survival rate (23.5%). In spite of severe clostridial toxicity in 80.1% of patients at the time of admission, the overall mortality was 50.8%.

Evaluation of antimicrobials combined with hyperbaric oxygen in a mouse model of clostridial myonecrosis.

The efficacy of hyperbaric oxygen (HBO) alone and in combination with several antimicrobial agents was evaluated in a lethal model of gas gangrene in mice. Intraperitoneal administration of penicillin, imipenem, clindamycin, or metronidazole immediately followed inoculation of > 10(9) CFU of Clostridium perfringens type A in mice. Mice treated with hyperbaric oxygen were exposed twice a day to 100% oxygen at 303 kilopascals (kPa) pressure for 90 minutes. The total exposure time to HBO for surviving animals was 9 hours. Control (saline-injected) mice treated with HBO alone did not have an enhanced survival rate when compared with mice exposed to air at ambient pressure. Survival of infected mice treated with either clindamycin or metronidazole was significantly longer than that of groups treated with penicillin or imipenem (p < 0.05). Hyperbaric oxygen alone or in combination with the four antimicrobial agents evaluated did not statistically improve survival of mice infected with a lethal dose of C. perfringens.

The role of hyperbaric oxygenation in the treatment of clostridial myonecrosis.

Hyperbaric oxygenation as an adjunct in the treatment of clostridial myonecrosis (gas gangrene) has been used extensively in facilities with hyperbaric chambers. The United States Air Force has had extensive experience in the treatment of clostridial myonecrosis, treating 77 patients since 1965. This study reviews the experience in the treatment of this disease process in military multiplace hyperbaric chambers and provides an in-depth analysis of factors affecting patient survival. A comprehensive review of the literature on the treatment of clostridial myonecrosis with hyperbaric oxygenation is presented in this paper.

Hyperbaric oxygen in the treatment of gas gangrene and perineal necrotizing fasciitis. A clinical and experimental study.

Between 1971 and 1987, 32 patients with clostridial gas gangrene were treated in the Department of Surgery, University of Turku. A presumptive diagnosis of gas gangrene was made on the basis of the clinical appearance of the patient and a predominance of Gram positive rods on stain. Between 1973 and 1989, 11 patients with perineal necrotizing fasciitis (Fournier's gangrene) were treated. The diagnosis was based on fulminating progression of perineal gangrene and on the presence of multiple pathogenic organisms in the primary Gram stain or culture. All patients in both series underwent surgical debridement, antibiotic therapy, and intensive care. In addition, the patients were exposed to pure oxygen at 2.5 atmospheres absolute pressure (ATA) for 120 minutes. Three such treatments were given during the first 24 hours after admission after which the treatment was repeated twice daily. Seventeen patients with clostridial gas gangrene had diffusely spreading myonecrosis; 6 died. Fifteen patients developed clostridial cellulitis with toxicity; 3 died. Thus, the overall mortality in gas gangrene was 28%. All the 9 patients who died had been transferred from other hospitals in Finland and were moribund on arrival. The infection in 8 of these patients developed postoperatively. None of the patients with a posttraumatic infection died. Each of the patients with Fournier's gangrene had had nonspecific symptoms before the gangrene became evident. The infection originated from the anorectal area in 5 patients, 1 patient had sustained a scrotal trauma and in 5 patients the underlying condition was unknown. One patient died 2 days after admission. Six patients required a colostomy. To evaluate the therapeutic value of hyperbaric oxygen (HBO) treatment, two experimental models of clostridial gas gangrene, mono- and multimicrobial, were developed in rats. In the monomicrobial infection model, 10(7) colony forming units (cfu) of Clostridium perfringens were injected intramuscularly into the left hind limb of the rat. The mortality of untreated rats was 100%. The mortality of the rats treated with surgery alone was 38% compared to 13% when surgery was used in combination with HBO (p < 0.01; chi 2 test). In the group treated with HBO and surgery, 94% of the survivors healed completely and were able to walk normally, whereas the corresponding figure in the rats treated with surgery alone was 20% (p < 0.001; chi 2-test). In the multimicrobial gas gangrene model the infection was induced by an intramuscular injection of a mixture containing approximately 10(7) cfu of each of the following bacteria: Clostridium perfringens, Bacteroides fragilis, Escherichia coli and Streptococcus faecalis.(ABSTRACT TRUNCATED AT 400 WORDS)

[Treatment of gas gangrene. Results of a retro- and prospective analysis of a traumatologic patient sample over 20 years]. / Behandlung des Gasödems. Ergebnisse einer retro- und prospektiven Analyse des unfallchirurgischen Krankenguts aus 20 Jahren.

From 1970 to 1977 and from 1978 to 1990, the treatment and outcome in 136 patients with gas gangrene were investigated. The prognosis was better in patients with gas gangrene after trauma than in patients with gas gangrene resulting from vascular insufficiency or malignant tumours. In the first group the lethality of gas gangrene was 28.6%, in the second group, 7.1%. This difference is significant (P < 0.05). In 40.5% the infected extremities were saved. Patients with injuries without fractures did not lose limbs because of gas gangrene or die of it. When an operation was performed before or after the first session of oxygenation at high pressure (OHP) lethality was lower (20%) and the rate of saved limbs higher (80%) than with later operation (lethality, 50%; saved limbs, 45.5%). All patients who could not be treated by OHP, or only once or twice, died. From 1970 to 1977 patients who were treated surgically and received OHP for 5 days survived, and since 1978 this has applied to patients treated for 4 days. In general, the lives of patients with gas gangrene are no longer in danger by the 5th day of therapy. The use of checklists for diagnosis and therapy has been practised since 1978, and this is assumed to be one factor in the better outcome.

[Is penicillin G the drug of choice in gas gangrene? Results of a prospective documentation of clinical, microbiological and animal experiment data]. / Ist Penicillin-G das Mittel der Wahl beim Gasödem? Ergebnisse aus prospektiver Dokumentation klinischer, mikrobiologischer und tierexperimenteller Daten.

Between 1978 and 1990 98 patients with gas gangrene were treated in the departments of general surgery and traumatology of the University of Kiel. The microbiological results of tissue samples and results of animal infectious experiments were correlated to the clinical outcome. It could be shown, that gas gangrene due to C.perfringens alone had a higher mortality than gas gangrene due to polymicrobial infection. In trauma patients, however, the rate of amputations was lower in cases of clostridial monoinfections (25%), than in patients with mixed infections (48%). The results of animal experiments with guinea pigs which were infected by patients' infectious material showed a correlation to the clinical outcome. This correlation could not bee shown using isolated and cultured clostridia. Therefore and because of the quantity of mixed infections it is necessary to use broad spectrum antibiotics for treatment in cases of gas gangrene and for perioperative antibiotic prophylaxis. Penicillin-G alone can not more be recommended for this purpose.

Hyperbaric oxygen in the treatment of clostridial gas gangrene.

Thirty-two cases with clostridial gas gangrene were treated during the years 1971-87 in the Department of Surgery, Turku University Central Hospital. The presumptive diagnosis was made on the basis of the clinical appearance of the patient and presence of gram-positive bacilli on a smear. Each patient underwent surgical debridement, antibiotic therapy and hyperbaric oxygen treatment. Seventeen cases had diffuse spreading myonecrosis, 11 of whom survived. Fifteen patients developed clostridial cellulitis with toxicity, 12 survived. Thus the over-all mortality was 28.1%. All those patients who died had been transferred from other hospitals of the country and were already moribund on arrival. Twenty-two infections developed postoperatively, in 6 cases trauma was the antedecent cause and 4 were spontaneous infections. None of the patients with a posttraumatic infection died. The most common underlying disorders included arteriosclerosis, diabetes mellitus, malignancy and Buerger's disease. The addition of hyperbaric oxygenation to the treatment of gas gangrene--although strictly adjunctive to surgery, antibiotics and supportive therapy--has dramatically changed the surgical approach to treatment. Early diagnosis remains essential. Patient survival can be achieved if the disease is recognized early and appropriate therapy applied promptly.

[Effect of immunomodulators on resistance to gas gangrene. The enhanced resistance of white mice to perfringens toxin type A as affected by prodigiozan]. / Izuchenie vliianiia immunomoduliatorov na ustoichivost' organizma k agzovoi gangrene. Povyshenie ustoichivosti belykh myshei k toksinu perfringens tipa A pod vliianiem prodigiozana.

Experiments on 575 noninbred white mice have revealed that the nonspecific resistance of the animals to type A C. perfringens toxin can be enhanced by the administration of Prodigiosan, a commercial immunostimulating agent. Prodigiosan, introduced in 3-4 injections (the last one made 24 hours before intoxication) has been found to enhance the resistance of the animals to the subcutaneous injection of type A C. perfringens toxin by 40-60% and to its intraperitoneal injection by 60-97%.

[Postoperative gas gangrene. Apropos of 22 cases]. / Gangrènes gazeuses post-opératoires. A propos de 22 cas.

The authors report twenty two cases of post-operative gas gangrene. In the series studied mortality was 40.9 p. 100, independent of age and sex. Rapidly progressive forms were the most severe. The delay before effective treatment was prescribed influenced prognosis. In clinical terms, shock and associated renal insufficiency were grave, as well as a picture of respiratory distress which led, in certain cases, to contra-indication of one of the therapeutic possibilities, i.e. that of hyperbaric oxygen. Responsible organisms could be isolated in nineteen cases from local samples. There was a marked predominance (15 cases) of clostridium perfringens. Contamination with aerobic flora was common. Examination to assess favourizing circumstances led essentially to a conclusion of the role of microbial contamination, ischemia, broad spectrum antibiotics, absence of appropriate antibiotics and underlying immuno-depression. Treatment was based in the majority of cases on the triple combination of antibiotics, surgery and hyperbaric oxygen, as well as the correction of any general systemic disorders. Mortality was markedly reduced (31 p. 100) in patients receiving complete and early treatment. The gravity and recrudescence of disorders due to anaerobic organisms lead the authors to review current therapeutic possibilities. Appropriate treatment should be prescribed in all situations where an infection due to anaerobic organisms is feared, and should cover the risk of clostridial infection (penicillin 200,000 mu/kg/24 h) as well as the risk of bacteroides (metronidazole 25 mg/kg/24 h). Curative treatment should be prescribed, even in the absence of bacteriological proof, on the basis of presumptive clinical evidence, this being a true emergency which should not be delayed under any circumstances.

Gas-producing clostridial and nonclostridial infections.

Clostridial infections have always been treated promptly and aggressively on the basis of history and Gram's strain. We believe that nonclostridial infections with similar fulminating, septic courses also should receive as prompt and radical treatment and perhaps more so, as hyperbaric oxygen therapy is of far less benefit in a nonclostridial infection. It is particularly important to treat the high risk, obese, patient with diabetes and an infection of the perineum or groin promptly and aggressively if the current, high morality is to be decreased.