The use of hyperbaric oxygen therapy in the treatment of thermal burns began in 1965 when Ikeda and Wada observed more rapid healing of second-degree burns in a group of coal miners who were being treated for carbon monoxide poisoning. They followed this serendipitous observation with a series of animal experiments that demonstrated a reduction of edema and improved healing. The Japanese experience stimulated interest in other countries, and there followed a series of reports of uncontrolled clinical experience with favorable results. In 1970 Gruber, working at a U.S. Army biophysics laboratory at the Edgewood Arsenal in Maryland, devised a series of experiments placing rats in a hyperbaric chamber breathing 100 percent oxygen at sea level and at 2 and 3 atmospheres (ATA) of oxygen, respectively. He demonstrated that the area subjacent to a third-degree burn was hypoxic when compared to normal skin and that the tissue oxygen tension could only be raised by oxygen administered at pressure. This important study suggested that HBOT could have a direct effect on the pathophysiology of the burn wound.
Subsequent studies demonstrated that hyperbaric oxygen therapy, when used as an adjunct in a comprehensive program of burn care, can significantly improve morbidity and mortality, reduce length of hospital stay, and lessen the need for surgery. It has been demonstrated to be safe in the hands of those thoroughly trained in rendering HBOT in the critical care setting and with appropriate monitoring precautions. Successful, cost-effective outcomes result from careful patient selection and screening.
Pathophysiology and Hyperbaric Effects
The burn wound is a complex and dynamic injury characterized by a central zone of coagulation surrounded by an area of stasis and bordered by an area of erythema. The zone of coagulation or complete capillary occlusion may progress by a factor of 10 during the first 48 hours after injury. Ischemic necrosis quickly follows. Hematologic changes, including platelet microthrombi and hemoconcentration, occur in the postcapillary venules. Edema forms rapidly in the area of the injury but also develops in distant, uninjured tissue. There are also changes occurring in the distal microvasculature where red cell aggregation, white cell adhesion to venular walls, and platelet thromboemboli occur. This progressive ischemic process, when set in motion, may extend damage dramatically during the early days after injury. The ongoing tissue damage seen in thermal injury arises from the failure of surrounding tissue to supply borderline cells with oxygen and nutrients necessary to sustain viability. The impediment of circulation below the injury leads to desiccation of the wound as fluid cannot be supplied via the thrombosed or obstructed capillaries. Topical agents and dressings may reduce but cannot prevent dessication of the burn wound and the inexorable progression to deeper layers.
Regeneration cannot take place until equilibrium is reached; hence, healing is retarded. Prolongation of the healing process may lead to excessive scarring. Hypertrophic scars are seen in about four percent of cases taking 10 days to heal, in 14 percent of cases taking 14 days or less, in 28 percent of cases taking 21 days, and up to 40 percent of cases taking longer than 21 days to heal. Therapy of burns, then, is directed towards minimizing edema, preserving marginally viable tissue, protecting the microvasculature, enhancing host defenses, and providing the essential substrate necessary to sustain viability.
Susceptibility to infection is greatly increased owing to the loss of the integumentary barrier to bacterial invasion, the ideal substrate present in the burn wound, and the compromised or obstructed microvasculature which prevents humoral and cellular elements from reaching the injured tissue. Additionally, the immune system is seriously affected, demonstrating decreased levels of immunoglobulins and serious perturbations of polymorphonuclear leukocyte (PMNL) function, including disorders of chemotaxis, phagocytosis, and diminished killing ability. These functions greatly increase morbidity and mortality; infection remains the leading cause of death from burns.
A significant body of animal data support the efficacy of HBOT in the treatment of thermal injury. Ikeda noted a reduction of edema in burned rabbits. Ketchum in 1967 reported an improvement in healing time and reduced infection in an animal model. He later demonstrated dramatic improvement in the microvasculature of burned rats treated with hyperbaric oxygen therapy. Working in Germany, in 1974 Hartwig reported very similar findings and additionally noted less inflammatory response in those animals that had been treated with hyperbaric oxygen. He suggested at that time that hyperbaric oxygen might be a useful adjunct to the technique of early debridement. Wells and Hilton, in a carefully designed and controlled experiment, reported a marked increase in extravasation of fluid in a series of dogs with 40 percent flame burns.
The effect was clearly related to oxygen and not simply increased pressure. They also reported a reduction in hemoconcentration and improved cardiac output in treated dogs. Nylander, using a well-accepted animal model, showed that hyperbaric oxygen therapy reduced the generalized edema associated with burn injury.
Using an India ink technique in 1977, Korn and colleagues showed an early return of capillary patency in hyperbaric-treated animals. He also demonstrated survival of the dermal elements and more rapid epithelialization from these regenerative sites. He suggested the decreased desiccation of the wound he observed was a function of subjacent capillary integrity noted in the HBOT treated animals. Saunders and colleagues have recently done similar studies with similar results. They have also reported an improvement in collagen synthesis in HBOT treated animals. Perrins failed to show a beneficial effect in a small scald wound in a pig model treated with HBOT. In 1977, Niccole reported that HBOT offered no advantage over topical agents in controlling wound bacterial counts. He proposed that HBOT acted as a mild antiseptic. His data, however, supported the observation of improved healing of partial thickness injury noted by earlier investigators. Stewart and colleagues have shown preservation of adenosine triphosphate (ATP) in areas subjacent to partial thickness in burns in hyperbaric treated rats.
These studies may relate directly to the preservation of energy sources for the sodium pump. Failure of the sodium pump is felt to be a major factor in two processes: the ballooning of the endothelial cells that occurs after burn injury and the subsequent massive fluid losses. Both groups in Stewart’s study received identical treatment with topical antibiotic agents. In a very large 1973 controlled series, Bleser reported reduction of burn shock and a fourfold increased survival in 30 percent burned animals versus controls. Reduction of PMNL killing ability in hypoxic tissue has been well documented by Hohn, et al. Mader demonstrated the increased ability of PMNL killing in an O2 enriched animal model suggesting that this may be an additional benefit of HBOT. Thus, the overwhelming evidence in a large number of controlled animal studies suggests that hyperbaric oxygen produces numerous beneficial effects. These include reducing edema, preventing conversion of partial to full thickness injury, preserving the microcirculation, preserving adenosine triphosphate (ATP) (and perhaps secondarily the sodium pump), and improving survival. HBOT may eventually be proven to also enhance PMNL killing.
Beginning with the reports of Wada in 1965 and continuing with Ikeda, Lamy, and Tabor, reports of clinical series began to accumulate. In 1974 Hart reported a controlled, randomized series showing a reduction of fluid requirements, faster healing, and reduced mortality when his patients were compared to controls and to U.S. National Burn Information Exchange standards. Waisbren in 1982 reported a reduction in renal function, a decrease in circulating white blood cells, and an increase in positive blood cultures in a retrospective series of patients who had received HBOT. He stated he could demonstrate neither a salutary nor deleterious effect; however, his data showed a 75 percent decrease in the need for grafting in the hyperbaric-treated group. Grossman and colleagues have reported a very large clinical series showing improved healing, reduced hospital stay, and reduced mortality. Merola’s 1978 randomized study revealed faster healing of partial thickness burns in 37 patients treated with HBOT versus 37 untreated controls. Niu and his associates from the Naval Burn Center in Taiwan recently reported a very large clinical series showing a statistically significant reduction in mortality in 266 seriously burned patients who received adjunctive HBOT when compared to 609 control patients who did not receive HBOT. Hammarlund and colleagues have reported a reduction of edema and wound exudation in a carefully controlled series of human volunteers with ultraviolet irradiated blister wounds.
One hospital has shown a significant reduction in length of hospital stay in burns of up to 30 percent of the total body surface area (TBSA).
Comparison of Factors in HBOT and Non-HBOT Groups
In Patients With 18-39 Percent Total Body Surface Area Burns
|Total BodySurface Burn (%)|
|Full Thickness Injury|
|Cost ofBurn Care||$44,838||$55,650|
NS, Not Significant; *p<.012, significant (Mann-Whitney U test)
Reduced Surgical Requirements
Brookside group has additionally reported a reduction in the need for surgery, including grafting, in a series of patients with burns up to 80 percent of total body surface area (TBSA) when they were compared to non-HBOT treated controls.
HBOT treated patients in this study experienced an average medical savings of $95,000 per case. In a series of patients with burns of up to 50 percent TBSA, averaging 28 percent total body surface area injury, similar results were obtained In a retrospective, blinded review by the same group, researchers examined resuscitative fluid requirements in a group of severely burned patients. A 25 percent reduction in resuscitative fluid administration and a statistically significant reduction in maximum weight gain and percent weight gain was noted in the HBOT treated group versus the controls. Maxwell and colleagues in 1991 reported a small controlled series showing a reduction of surgery, resuscitative weight gain, intensive care days, total hospitalization time, wound sepsis, and cost of hospitalization in the group treated with HBOT. Recent data demonstrate continuing improvement in outcome of large burns. The number of surgeries was reduced 85 percent (p<0.03).
Improved Inhalation Function
Considerable attention has been given to the use of HBOT in inhalation injury. There is currently a fear that it may cause worsening of pulmonary damage, particularly in those patients maintained on high levels of inspired O2. Grim and colleagues from the University of Chicago Burn Center reported no evidence of oxidative stress in HBOT treated burn patients, using exhaled products of lipid peroxidation as a marker. Ray and colleagues have analyzed serious burns being treated for concurrent inhalation injury, thermal injury, and adult respiratory distress syndrome. She noted no deleterious effect in those patients on continuously high-inspired oxygen. More rapid weaning from the ventilator was possible in the HBOT treated group (p<0.05). A significant savings in cost of care ($60,000) was achieved through the use of hyperbaric oxygen in this study (p<0.05). There is presently no evidence to controvert these data.
Over the past 20 years, the pendulum swung to an aggressive surgical management of the burn wound, i.e., tangential excision and early grafting of the deep second-degree, probable third-degree burns, especially to functionally important parts of the body. Hyperbaric oxygen, as adjunctive therapy, has offered the surgeon yet another modality of treatment for these deep second-degree burns to the hands and fingers, face and ears, and other areas where the surgical technique of excision and coverage is often imprecise. These wounds, not obvious third degree, are then best treated with topical antimicrobial agents, bedside debridement, and adjunctive HBOT, allowing the surgeon more time for healing to take place and to better define the extent and depth of injury. Adjunctive HBOT has drastically reduced the healing time in the major burn injury, especially if the wounds are deep second degree.
There is some theoretical benefit of hyperbaric oxygen therapy for obviously less well-defined third-degree burns. Fourth-degree burns, most commonly seen in high voltage electrical injuries, benefit from several processes, including reduced fascial compartmental pressures, reduced swelling of injured muscle due to preservation of aerobic glycolysis, and greatly reduced anaerobic infection.
Finally, reconstruction utilizing flaps and composite grafts, e.g., ear to nose grafts, has been greatly facilitated with HBOT. Often the decision to use HBOT has been made intraoperatively because a surgeon is concerned about a compromised cutaneous or musculocutaneous flap. The patient is, in many instances, prepared pre-operatively about the possibility of receiving this post-surgical adjunctive therapy.
Alexander JW, Meakins JL: A physiological basis for the development of opportunistic infections in man. Annals of Surgery 1972;176:273.
Alexander JW, Wilson D: Neutrophil dysfunction and sepsis in burn injury. Surg Gynec Obstet 1970;130:431.
Arturson G:Pathophysiology of the burn wound. Ann Chir Gynaecol 1980;69:178.
Arturson G: The pathophysiology of severe thermal injury. J Burn Care Rehab 1985;6(2) 129.
Bleser F, Benichoux R: Experimental surgery: the treatment of severe burns with hyperbaric oxygen. J Chir (Paris) 1973;106:281.
Boykin JV, Eriksson E, Pittman RN: In vivo microcirculation of a scald burn and the progression of post burn dermal ischemia. Plast Reconstr Surg 1980;66:191.
Brown IW, Cox BG: Proceedings of the Third International Congress on Hyperbaric Medicine, Publ No. 1404. Washington, DC: National Academy of Sciences-National Research Council; 1966:611.
Cianci P, Lueders H, Lee H, et al.: Adjunctive hyperbaric oxygen reduces the need for surgery in 40-80 percent burns. J. Hyperbar Med 1988;3:97.
Cianci P, Lueders H, Lee H: Hyperbaric oxygen and burn fluid requirements: observations in 16 patients with 40-80 percent TBSA burns. Undersea Biomed Research Suppl. 1988;15:14.
Cianci P, Lueders HW, Lee H, et al.: Adjunctive hyperbaric oxygen therapy reduces length of hospitalization in thermal burns. J Burn Care Rehabil 1989;10:432.
Cianci P, Williams C, Lueders H. et al.: Adjunctive hyperbaric oxygen in the treatment of thermal burns: an economic analysis. J Burn Care Rehabil 1990;11:140.
Cianci P, Sato R: Adjunctive hyperbaric oxygen therapy in the treatment of thermal burns: a review. Burns 1994;20(1)5-14.
Cianci P, Sato R, Green B: Adjunctive hyperbaric oxygen reduces length of hospital stay, surgery, and the cost of care in severe burns. Undersea Biomed Research Suppl 1991;18:108.
Deitch E, Wheelahan T, Rose M, et al.: Hypertrophic burn scars: analysis of variables. J Trauma 1993;23:S895.
Germonpre P, Reper P: Hyperbaric oxygen therapy and piracetam decrease the early extension of deep partial-thickness burns. Burns 1996;22(6):468-73.
Grim P S, Nahum A, Gottlieb L, et al.: Lack of measurable oxidative stress during HBOT therapy in burn patients. Undersea Biomed Res Suppl 1989;(16)22.
Grogan JB: Altered neutrophil phagocytic function in burn patients. J Trauma 1976;16:734. Grossman AR: Hyperbaric oxygen in the treatment of burns. Annals of Plastic Surgery 1978;1:163. Grossman AR, Grossman AJ: Update on hyperbaric oxygen and treatment of burns. Hyperbaric Oxygen Review 1982;3:51. Gruber RAP, Brinkley B, Amato JJ, et al.: Hyperbaric oxygen and pedicle flaps, skin grafts, burns. Plast Reconstr Surg 1970;45:24. Hammarlund C, Svedman C, Svedman P: Hyperbaric oxygen treatment of healthy volunteers with UV-irradiated blister wounds. Burns 1991;17:296. Hart GB, O’Reilly RR, Broussard ND, et al.: Treatment of burns with hyperbaric oxygen. Surg Gynecol Obstet 1974;139:693. Hartwig VJ and Kirste G: Experimentele untersuchungen uber die revaskularisierung von verbrennungswunden unter hyperbarer sauerstofftherapie. Zbl Chir 1974;99:1112 Heggers JP, Robson, MC, Zachary LS: Thromboxane inhibitor for the prevention of progressive dermal ischemia due to the thermal injury. J Burn Care Rehabil 1980;6:466. Hohn DC, MacKay RD, Halliday B, et al.: Effect of oxygen tension on the microbicidal function of leukocytes in wounds and in vitro. Surg Forum 1976;27:18. Ikeda K, Ajiki H, Nagao H: Experimental and clinical use of hyperbaric oxygen in burns. In: Wada J, Iwa T, eds: Proceedings of the Fourth International Congress on Hyperbaric Medicine. Tokyo: Igaku Shoin Ltd.; 1970:370.Ikeda K, Ajiki H, Kamiyama T, et al.: Clinical application of oxygen hyperbaric treatment. Geka (Japan) 1967;29:1279. Iwa T: Discussion. In: Brown JW, 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. Kaiser VW, Schnaidt U, von der Leith H: Auswirkungen hyperbaren sauerstoffes auf die fresche brandwunde. Handchir Mikrochir Plast Chir 1989;21:158. Ketchum SA, Zubrin JR, Thomas AN, et al.: Effect of hyperbaric oxygen on small first, second and third degree burns. Surg Forum 1967;18:65. Ketchum SA, Thomas AN, Hall AD: Angiographic studies of the effect of hyperbaric oxygen on burn wound revascularization. In: Wada J and Iwa T, eds: Proceedings of the Fourth International Congress on Hyperbaric Medicine. Tokyo, Japan: Igaku Shoin Ltd.; 1980:388.Korn HN, Wheeler ES, Miller TA: Effect of hyperbaric oxygen on second degree burn wound healing. Arch Surg 1977;112:732. Lamy ML, Hanquet MM: Application opportunity for OHP in a general hospital–a two year experience with a monoplace hyperbaric oxygen chamber. In: Wada J and Iwa T, eds: Proceedings of the Fourth International Congress on Hyperbaric Medicine. Tokyo: Igaku Shoin, Ltd.; 1970:517. Mader JT, Brown GL, Guckian JC, et al.: A mechanism for the amelioration of hyperbaric oxygen of experimental staphylococcal osteomyelitis in rabbits. J Infect Dis 1980;42:915. Maxwell G, Meites H, Silverstein P: Cost effectiveness of hyperbaric oxygen therapy in burn care. Paper presented at: 1991 Winter Symposium on Baromedicine; Aspen, CO. Merola L, Piscitelli F: Considerations on the use of HBOT in the treatment of burns. Ann Med Nav 1978;83:515. Niccole MW, Thornton JW, Danet RT, et al.: Hyperbaric oxygen in burn management: a controlled study. Surgery 1977;82:727. Niezgoda JA, Cianci P: The effect of hyperbaric oxygen therapy on a burn wound model in human volunteers. Plast Reconstr Surg 1997;99(6):1620-25. Niu AKC, Yang C, Lee HC, et al.: Burns treated with adjunctive hyperbaric oxygen therapy: a comparative study in humans. J Hyperbar Med 1987;2:75. Nylander G, Nordstrom H, Eriksson E: Effects of hyperbaric oxygen on edema formation after a scald burn. Burns 1984;10:193. Ogle CK, Alexander JW, Nagy E, et al.: A long-term study and correlation of lymphocyte and neutrophil function in the patient with burns. J Burn Care Rehab 1990;112:105.
Perrins DJD: Failed attempt to limit tissue destruction in scalds of pig’s skin with hyperbaric oxygen. In: Wada J, Iwa T, eds:Proceedings of the Fourth International Congress on Hyperbaric Medicine. Tokyo, Japan: Igaku Shoin Ltd., 1970:381.
Ray CS, Green G, Cianci P: Hyperbaric oxygen therapy in burn patients: cost effective adjuvant therapy. Undersea Biomed Res Suppl 1991;18:77.
Ross JC, Cianci PE: Barotitis media resulting from hyperbaric oxygen therapy. a retrospective study of 395 consecutive cases. Undersea Biomed Res Suppl 1990;17:02.
Saunders J, Fritz E, Ko F, et al.: The effects of hyperbaric oxygen on dermal ischemia following thermal injury. In: Proceedings of the American Burn Association. New Orleans, LA; 1989:58.
Stewart RJ, Yamaguchi KT, Cianci PE, et al.: Effects of hyperbaric oxygen on adenosine triphosphate in thermally injured skin. Surg Forum 1988;39:87.
Stewart RJ, Yamaguchi KT, Cianci PE, et al.: Burn wound levels of ATP after exposure to elevated levels of oxygen. In: Proceedings of the American Burn Association. New Orleans, LA, 1989:67.
Tabor CG: Hyperbaric oxygenation in the treatment of burns of less than forty percent. Korean J Int Med, 1967.
Wada J, Ikeda T, Kamata K, et al.: Oxygen hyperbaric treatment for carbon monoxide poisoning and severe burn in coal mine (hokutanyubari) gas explosion. Igakunoaymi (Japan) 1965;5:53.
Wada J, Ikeda K, Kagaya H, et al.: Oxygen hyperbaric treatment and severe burn. Jap Med J 1966;13:2203.
Waisbren BA, Schultz D, Collentine G, et al.: Hyperbaric oxygen in severe burns. Burns 1982;8:176.
Wells CH, Hilton JG: Effects of hyperbaric oxygen on post-burn plasma extravasation. In: Davis JC, Hunt TK, eds: Hyperbaric Oxygen Therapy. Bethesda, MD: Undersea Medical Society; 1977:259.
Wiseman DH, Grossman AR: Hyperbaric oxygen in the treatment of burns. Crit Care Clin 1985;2:129.