Pathophysiology and Hyperbaric Effects
Gas gangrene, or Clostridial myosistis and myonecrosis, is an invasive clostridial infection of muscle, characterized by toxemia, extensive edema, massive death of tissue, and a variable degree of gas production. Gas gangrene is either an endogenous infection, caused by contamination from a clostridial focus in the body, or an exogenous infection secondary to trauma. For the induction of gas gangrene, two conditions have to be fulfilled:
I. The presence of clostridial spores; and an area of lowered oxidation-reduction potential caused by circulatory failure in a local area, or
II. Extensive soft tissue damage and necrotic muscle tissue. This condition results in an area with a low oxygen tension where clostridial spores can develop into their vegetative form. Much of the disease process seen in gas gangrene is due to clostridial toxins. Nine clostridial exotoxins have been implicated in the local and systemic changes seen in gas gangrene: alpha, theta, kappa, my and pu toxin, fibrinolysin, neuraminidase, circulating factor, and bursting factor. The most prevalent is alpha-toxin, the oxygen-stable lecithincase-C, which is hemolytic, tissue necrotizing, and lethal. Alpha toxin can be fixed to susceptible skin cells in 20 to 30 minutes, is detoxified within two hours after its elaboration, and causes active immunity with production of a specific antitoxin. The infection, unfortunately, is so progressive, with continuous production of alpha-toxin that the patient dies before any effective immunity can develop. Local host defense mechanisms are eliminated when the toxin production is sufficiently high. Such an event results in fulminating tissue destruction, an increased volume of hypoxic tissue, and further clostridial growth.
The action of hyperbaric oxygen on Clostridia (and other anaerobes) is based on the formation of oxygen free radicals in the absence of free radical degrading enzymes, such as superoxide dismutases, catalases, and peroxidases. Van Unnink showed that an oxygen tension of 250 mm Hg is necessary to stop alpha-toxin production. Although it does not kill all Clostridia, it is bacteriostatic and bactericidal both in vivo and in vitro. The catalase effects of stimulating necrosis are inhibited by high oxygen concentrations. Demello, et al., demonstrated a reduction in the generation rate of heat-activated spores of Clostridia perfringens. Brummelkamp and Boerema were the first to report the successful use of hyperbaric oxygen therapy (HBOT) at 3 ATA in the management of gas gangrene.
Bakker DJ: The use of hyperbaric oxygen in the treatment of certain infectious diseases, especially gas gangrene and acute dermal gangrene. Drukkerij Veenman BV; 1984.
Bakker, DJ: Clostridial myonecrosis. In: Davis JC, Hunt TK, eds: Problem Wounds: The Role of Oxygen. New York, NY: Elsevier; 1988:13-172.
Balldin U, Hedstrum SA, Lundgren C, Thomson D: Cases of gas gangrene treated with hyperbaric oxygen. Nord Med 1968;79:589.
Bayliss GJ, Cass C: Hyperbaric oxygen used in the treatment of gas gangrene. Med J Aust 1967;2:991.
Bernhard WF, Filler RM: Hyperbaric oxygenation: current concepts. Am J Surg 1968;115:661.
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.
Brummelkamp WH: Considerations on hyperbaric oxygen therapy at three atmospheres absolute for clostridial infections type welchii. Ann NY Acad Sci 1965;117:688-699.
Darke SG, King AM, Slack WK: Gas gangrene and related infection: classification, clinical features and aetiology, management and mortality. A report of 88 cases. Br J Surg 1977;64:104.
Demello FJ, Hashimoto T, Hitchcock CR, Haglin JJ: The effects of hyperbaric oxygen on germination and toxin production of Clostridium perfringens spores. In: Wada J, Iwa JT, eds: Proceedings of the Fourth International Congress on Hyperbaric Medicine. Baltimore, MD: Williams & Wilkins Co.; 1970:276.
Demello FJ, Haglin JJ, Hitchcock CR: Comparative study of experimental Clostridium perfringens infection in dogs treated with antibiotics, surgery and hyperbaric oxygen. Surgery 1973;73:936-941.
Demello FJ, Hashimoto T, Hitchcock CR, Haglin JJ: The effect of hyperbaric oxygen on the germination and toxin production of Clostridium perfringens spores. In: Wada J, Iwas T, eds: Proceedings of the Fourth International Congress on Hyperbaric Medicine. Tokyo, Japan. Igaku Shoin Ltd., 1970:276.
Duff JH, Shibata HR, Vanschaik L, Usher R, Wigmore RA, MacLean LD: Hyperbaric oxygen: a review of treatment in eighty-three patients. Can Med Assn J 1967;97:510.
Encinas CM, Herrero MJ, Sanchez GU, Ortiz MF, Santidrian MJP, Quesada SA: Gas producing necrotizing infections. Role of hyperbaric oxygen. Med Clin 1988;90:316.
Fitzpatrick DT: Hyperbaric oxygen therapy. Mo Med 1994;91(11):684-689.
Gibson A, Davis FM: Hyperbaric oxygen therapy in the management of Clostridium perfringens infections. NZ Med J 1986;99:617.
Guidi ML, Proiette R, Carducci P, Magalini SI, Pelosi G: The combined use of hyperbaric oxygen, antibiotics and surgery in the treatment of gas gangrene. Resuscitation 1981;9:267.
Hart GB, Lam RC, Strauss MB: Gas gangrene. J Trauma 1983;23:991.
Hart GB, Lamb RC, Strauss MB: Gas gangrene I A collective review. II A 15-year experience with hyperbaric oxygen. J Trauma 1983;23:991-1000.
Hart GB, O’Reilly RR, Cave RH, Broussard ND: The treatment of clostridial myonecrosis with hyperbaric oxygen. J Trauma 1974;14:712.
Heimbach RD: Gas gangrene: Review and update. HBO Rev 1980;1 (1) 41-46 30.
Hill GB, Osterhout S: Experimental effects of hyperbaric oxygen on selected clostridial species, I in vitro studies and II in vivo studies in mice. J Infec Dis 1972;125:17-35.
Hill GB, Osterhout S: In vitro and in vivo experimental effects of hyperbaric oxygenClostridium perfringens. In: Brown IW, Cox BG, eds: Proceedings of the Third International Congress on Hyperbaric Medicine, Publ No. 1404. Washington, DC: National Academy of Sciences-National Research Council; 1966:538-543.
Hirn M: Hyperbaric oxygen in the treatment of gas gangrene and perineal necrotizing fasciitis. A clinical and experimental study. Eur J Surg Suppl 1993;(570):1-36.
Hirn M, Niinkoski J: Hyperbaric oxygen in the treatment of clostridial gas gangrene. Ann Chir Gynecol 1988;77:37.
Hitchcock CR, Demello EJ, Haglin JJ: Gangrene infection. New approaches to an old disease. Surg Clin N Am 1975;55(6):1043-1410.
Holland JA, Hill GB, Wofle WG, Osterhout S, Saltzman HA, Browns IV: Experimental and clinical experience with hyperbaric oxygen in the treatment of clostridial myonecrosis. Surgery 1975;77:75-85.
Jeffrey JS, Thomson S: Gas gangrene in Italy. A study of 33 cases treated with penicillin. Br J Surg 1944;32:159.
Kaye D: Effect of hyperbaric oxygen on Clostridia in vitro and in vivo. Pro Soc Exp Biol 1967;124:360-366.
Kelley HG, Pace WG: Treatment of anaerobic infections in mice with hyperpressure oxygen. Surg Forum 1963;14:46-47.
Kindwall EP: Gas gangrene: Acute medical emergency: the role of hyperbaric oxygen. Wis Med J 1970;69:261.
Kivisaari J, Niinikoski J: Use of silastic tube and capillary sampling technique in the measurement of tissue PO2 and PCO2. Am J Surg 1973;125:623-627.
Klopper PJ: Hyperbaric oxygen treatment after ligation of the hepatic artery in rabbits. In: Boerema I, Brummelkamp WH, Meijne NG, eds: Clinical Application of Hyperbaric Oxygen. Amsterdam, Holland: Elsevier; 1964:31-35.
Lamy M, LeJeune G, Noel FX, Carlier P: Gas gangrene: importance of early diagnosis hyperbaric oxygen therapy. Rev Med Liege 1977;32:589.
McLeod JW: Variations in the periods of exposure to air and oxygen necessary to kill anaerobic bacteria. Acta Pathol Microbiol Scan 1930;3(Suppl):255.
MacLennan JD: the histotoxic clostridial infections of man. Bacteriol Rev 1962;26:177-276.
Maudsley RH: Post-operative gas gangrene managed by hyperbaric oxygen. J Bone Jt Surg Br 1975;57:251.
Nier H, Kremer K: Der Gasbrand-weiterhin ein diagnostisches und therapeutisches problem. Zentrabl Chir 1984;109;402-417.
Nier H, Sailer R, Palomba P: Hyperbaric oxygen treatment in gas gangrene. Dtsch Med Wochenschr 1978;103:1958.
Nora PF, Mousavipour M, Laufman H: Mechanisms of action of high pressure oxygen in Clostridium perfringens exotoxin toxicity. In: Brown IW, Cox BG, eds: Hyperbaric Medicine, Publ. No. 1404. Washington, DC: National Academy of Sciences, National Research Council; 1966,:544-51.
Nora PF, Mousavipour M, Mittlepunkt A, Rosenburg M, Laufman H: Brain as target organ in Clostridium perfringens cytotoxin. Arch Surg 1966;92:243-246.
Pailler JL, Labeau F: La gangrene gazeuse: Une affection militaire? Acta Chir Belg 1986;86:63-71.
Peirce EC II: Gas gangrene. A critique of therapy. Surg Rounds 1984;7:17-25.
Roding B, Groenveld PHA, Boerema I: Ten years of experience in the treatment of gas gangrene with hyperbaric oxygen. Surg Gynecol Obstet 1972;134:579.
Sailer R, Junemann A, Ghazwinian R: Therapy of gas gangrene. Comparison of results of standard and hyperbaric oxygen therapy. Med Kin 1974;69:1620.
Schoemaker G: Oxygen tension measurements under hyperbaric conditions. In: Boerema, Brummelkamp WH, Meijne NG, eds. Clinical Application of Hyperbaric Oxygen. Amsterdam, Holland: Elsevier; 1964:330-335.
Schott H: Die gasbrand infection hefte unfalheik. Prinzipien der Behandlung, Ergbrisse 1979;138:179-186.
Sheffield PJ: Tissue oxygen measurement. In: Davis JC, Hunt TK, eds: Problem Wounds: Role of Oxygen. New York: Elsevier; 1988:17-51.
Shibuya H, Terashi H: Gas gangrene following sacral pressure sores. J Dermatol 1994;21(7)518-523.
Slack WK, Hanson GC, Chew HE: Hyperbaric oxygen in the treatment of gas gangrene clostridial infection. A report of 40 patients treated in a single-person hyperbaric oxygen chamber. Br J Surg 1969;56:505.
Stephens MB: Gas gangrene: potential for hyperbaric oxygen therapy. Postgrad Med 1996;99(4):217-220.
Tabrah FL, Tanner R: Baromedicine today–rational uses of hyperbaric oxygen therapy. Hawaii Med J 1994;53(4):112-115.
Tooley AH, Watt J: Hyperbaric oxygen therapy: review of the present position and experience in the management of naval patients. JR Nav Med Serv 1968;54:101.
Unsworth IP, Sharp PA: Gas Gangrene. An 11-year review of 73 cases managed with hyperbaric oxygen. Med J Aust 1984;140:256.
Van Unnik AJM: Inhibition of toxin production in Clostridium perfringens in vitro by hyperbaric oxygen. Antonie Leewenhoek Microbiol 1965;31:181-186.
Van Zijl JJW: Discussion. In: Brown IW, Cox BG, eds: Proceedings of the Third International Conference on Hyperbaric Medicine. Washington, DC: National Academy of Sciences-National Research Council; 1966:552-54.
Weinstein L, Barza, MA: Medical intelligence. Current concepts: Gas gangrene. NEJM 1973;289:1129-1131.
Willis AT: Clostridia of wound infection. London, England: Butterworth; 1969:490.