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Differing Opinions on Hyperbaric Oxygen Therapy
2 Perrins DJD, Davis JC. Enhancement of healing in soft tissue
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wounds. In: Davis JC, Hunt TK, eds. Hyperbaric oxygen therapy. Bethesda, MD: Undersea Medical Society 1978; 229-48 Ketchum FA, Thomas AN, Hall AD. Angiographic studies of the effects of hyperbaric oxygen on burn wound revascularization. In: Wada J, Iwa 1: eds. Proceedings of the Fourth International Congress on Hyperbaric Medicine. Baltimore, MD: The Williams and Wilkins Co, 1970; 383-94 Manson PN, Im MJ, Myers RAM, Hoopes JE. Improved capillaries by hyperbaric oxygen in skin flaps. Surg Forum 1980; 31:564-66 McFarlane RM, Wermuth RE. The use of hyperbaric oxygen to prevent necrosis in experimental pedicle flaps and composite skin grafts. Plast Reconstr Surg 1966; 37:422-30 Champion WM, McSherry CK, Goulian D. Effects ofhyperbaric oxygen on survival of pedicled skin flaps. J Surg Res 1967; 7:58386 Arturson GG, Khanna NN. The effects of hyperbaric oxygen, dimethyl sulfoxide and complamin on survival of experimental skin flaps. Scand J Plast Reconstr Surg 1970; 4:8-10 Jurell G, Kaijser L. The influence of varying pressure and duration of treatment with hyperbaric oxygen on the survival of skin flaps: an experimental study; Scand J Plast Reconstr Surg 1973; 7:25-28 Nemiroff PM, Merwin GE, Brant 1: Cassisi NJ. Effects of hyperbaric oxygen and irradiation on experimental skin flaps in rats. Otolaryngol Head Neck Surg 1985; 93:485-91 Nemiroff PM, Lungu AL. The influence of hyperbaric oxygen and irradiation on vascularity in skin flaps: a controlled study; Surg Forum 1987; 38:565-67 Hunt TK, Zerderfeldt BH, Goldstick TK. Oxygen and healing. Am J Surg 1969; 118:521-26 Hunt TK, Pai MP. The effect of varying ambient oxygen tensions on wound metabolism and collagen synthesis. Surg Gynecol Obstet 1972; 135:561-67 Niinikoski JD, Hunt TK. Oxygen tension in human wounds. J Surg Res 1972; 12:77-82 Mader J1: Brown GL, Guckian JC, Wells CH, Reinarz JA. A mechanism for the amelioration by hyperbaric oxygen of experimental staphlococcal osteomyelitis in rabbits. J Infect Dis 1980; 142:915-22 Marx RE, Ames JR. The use of hyperbaric oxygen therapy in bony reconstruction of the irradiated and tissue deficient patient. J Oral Maxillofac Surg 1982; 40:412-20 Marx RE. Osteoradionecrosis of the jaws: review and update. HBO Rev 1984; 5:78-126
To the Editor: Dr. Nemiroff makes several fundamental errors in his letter. He implicitly proposes the following syllogism: 1) An adequate oxygen supply is required for wound healing. (This premise is reasonable and supported by the relevant literature.) 2) Hyperbaric oxygen increases Pa02' (This premise is obviously correct for the period during which HBO is used.) 3) Hyperbaric oxygen increases tissue P0 2 (This premise is not obviously valid. For example, ifHBO produces arteriolar vasoconstriction or increases capillary flow resistance, the net impact on oxygen supply would be unpredictable. It is also not predictable that the hypothesized increases in tissue P0 2 for one or several hours per day would impact favorably on wound healing. In fact, one authority states, "the best environment for wound healing therefore appears to be one in which the partial pressure of oxygen -is low at the wound surface, thereby stimulating angiogenesis, and high at the subsurface, increasing the secretion of macrophagederived growth factor and fibroblasts." 4) Therefore, HBO improves wound healing in patients with slow wound healing. Whether the first three premises are correct, the fourth premise does not follow The only valid way to determine whether or not premise 4 is correct would be to perform a prospective, randomized, controlled clinical trial. None of the 16 references supplied by the correspondent provide such data. I don't believe that it is too
demanding a requirement that a faculty member at a modern medical school understand such an elementary concept. An example from a similar problem involves the treatment of chronic refractory osteomyelitis. Any number of papers can be cited to support a beneficial effect of HBO in that disorder. However, when a prospective controlled (not randomized or double blind) clinical trial was performed, the results were as follows." "Hyperbaric oxygen therapy had no effect on length of hospitalization, rapidity of wound repair, initial clinical outcome, or recurrence of infection noted to date." Even if HBO worked in refractory osteomyelitis, this would not mean it would work in wound healing. Conversely though it is not effective in osteomyelitis, this does not mean that it might not be effective in wound healing. There is no way of knowing without an appropriate clinical trial. It will now be of interest to note the rate at which HBO proponents give up HBO therapy for chronic osteomyelitis. You might also be interested in the comments of one of the discussors of this paper: "In conclusion, I think we can say that the primary indication for hyperbaric oxygen treatment remains a marketing gimmick by the hospital and also by physicians. This study I think, shows that hyperbaric oxygen does not work in osteomyelitis and until we have a better study that proves otherwise we should not use it." The final statement seems to me to be applicable to all of the communciations we have received. It is uncomfortable for me to see Ms. Gabb singled out as the focus of wrath. All she did was to look at HBO with unbiased and fresh eyes. Perhaps the entire field of HBO could benefit from her example. I estimate that HBO is used to treat some 30 or 40, or more, disorders (as of 1985). I trust that it will not be necessary to counter the claims made by HBO proponents for each of these conditions, most not supported by adequate validation. These claims conform to a stereotypic pattern. Finally I know of no "hidden agenda" on my part. I would have thought that my "agenda" was quite obvious. It is to analyze the appropriateness of the data base used to rationalize the use of HBO, to bring the analysis to the attention of the chest community; and to stimulate the performance of adequate clinical trials by the HBO community; Nor are my conclusions hidden in Aesopian language. I find that, for most indications, there is no acceptable data base which supports its use. If and when such data are made available, I would be eager to expose the data to the widest possible medical audience. Until that time, demands for retraction seem to me to be posturing, rather than an attempt to improve patient management. Eugene D. Robin, M.D., Stanford University Medical School, Stanford, CA
REFERENCES 1 Demling RH. Medical progress: burns. N Engl J Med 1985; 313: 1389-98
2 Esterhal JL Jr, Pisarello J, Brighton C1: Heppenstall RB, Gellman
H, Goldstein G. Adjunctive hyperbaric oxygen therapy in the treatment of chronic refractory osteomyelitis. J Trauma 1987; 27:763-68
To the Editor: We have read with interest the risk-benefit analysis column in Chest and in particular the analysis of hyperbaric oxygen therapy (Gabb G, Robin ED. 1987; 92:1074-82) which we consider to be an excellent example of how not to do a risk-benefit analysis. A risk-benefit analysis is a formal technique for structuring problems which require decision-making under conditions of uncertainty; 1-4 It involves explicit structuring of the clinical problem CHEST / 94 f 3 / SEPTEMBER, 1988
671
3
4 5 6
7
8
9 10 11 12 13 14
15 16
wounds. In: Davis JC, Hunt TK, eds. Hyperbaric oxygen therapy. Bethesda, MD: Undersea Medical Society 1978; 229-48 Ketchum FA, Thomas AN, Hall AD. Angiographic studies of the effects of hyperbaric oxygen on burn wound revascularization. In: Wada J, Iwa 1: eds. Proceedings of the Fourth International Congress on Hyperbaric Medicine. Baltimore, MD: The Williams and Wilkins Co, 1970; 383-94 Manson PN, Im MJ, Myers RAM, Hoopes JE. Improved capillaries by hyperbaric oxygen in skin flaps. Surg Forum 1980; 31:564-66 McFarlane RM, Wermuth RE. The use of hyperbaric oxygen to prevent necrosis in experimental pedicle flaps and composite skin grafts. Plast Reconstr Surg 1966; 37:422-30 Champion WM, McSherry CK, Goulian D. Effects ofhyperbaric oxygen on survival of pedicled skin flaps. J Surg Res 1967; 7:58386 Arturson GG, Khanna NN. The effects of hyperbaric oxygen, dimethyl sulfoxide and complamin on survival of experimental skin flaps. Scand J Plast Reconstr Surg 1970; 4:8-10 Jurell G, Kaijser L. The influence of varying pressure and duration of treatment with hyperbaric oxygen on the survival of skin flaps: an experimental study; Scand J Plast Reconstr Surg 1973; 7:25-28 Nemiroff PM, Merwin GE, Brant 1: Cassisi NJ. Effects of hyperbaric oxygen and irradiation on experimental skin flaps in rats. Otolaryngol Head Neck Surg 1985; 93:485-91 Nemiroff PM, Lungu AL. The influence of hyperbaric oxygen and irradiation on vascularity in skin flaps: a controlled study; Surg Forum 1987; 38:565-67 Hunt TK, Zerderfeldt BH, Goldstick TK. Oxygen and healing. Am J Surg 1969; 118:521-26 Hunt TK, Pai MP. The effect of varying ambient oxygen tensions on wound metabolism and collagen synthesis. Surg Gynecol Obstet 1972; 135:561-67 Niinikoski JD, Hunt TK. Oxygen tension in human wounds. J Surg Res 1972; 12:77-82 Mader J1: Brown GL, Guckian JC, Wells CH, Reinarz JA. A mechanism for the amelioration by hyperbaric oxygen of experimental staphlococcal osteomyelitis in rabbits. J Infect Dis 1980; 142:915-22 Marx RE, Ames JR. The use of hyperbaric oxygen therapy in bony reconstruction of the irradiated and tissue deficient patient. J Oral Maxillofac Surg 1982; 40:412-20 Marx RE. Osteoradionecrosis of the jaws: review and update. HBO Rev 1984; 5:78-126
To the Editor: Dr. Nemiroff makes several fundamental errors in his letter. He implicitly proposes the following syllogism: 1) An adequate oxygen supply is required for wound healing. (This premise is reasonable and supported by the relevant literature.) 2) Hyperbaric oxygen increases Pa02' (This premise is obviously correct for the period during which HBO is used.) 3) Hyperbaric oxygen increases tissue P0 2 (This premise is not obviously valid. For example, ifHBO produces arteriolar vasoconstriction or increases capillary flow resistance, the net impact on oxygen supply would be unpredictable. It is also not predictable that the hypothesized increases in tissue P0 2 for one or several hours per day would impact favorably on wound healing. In fact, one authority states, "the best environment for wound healing therefore appears to be one in which the partial pressure of oxygen -is low at the wound surface, thereby stimulating angiogenesis, and high at the subsurface, increasing the secretion of macrophagederived growth factor and fibroblasts." 4) Therefore, HBO improves wound healing in patients with slow wound healing. Whether the first three premises are correct, the fourth premise does not follow The only valid way to determine whether or not premise 4 is correct would be to perform a prospective, randomized, controlled clinical trial. None of the 16 references supplied by the correspondent provide such data. I don't believe that it is too
demanding a requirement that a faculty member at a modern medical school understand such an elementary concept. An example from a similar problem involves the treatment of chronic refractory osteomyelitis. Any number of papers can be cited to support a beneficial effect of HBO in that disorder. However, when a prospective controlled (not randomized or double blind) clinical trial was performed, the results were as follows." "Hyperbaric oxygen therapy had no effect on length of hospitalization, rapidity of wound repair, initial clinical outcome, or recurrence of infection noted to date." Even if HBO worked in refractory osteomyelitis, this would not mean it would work in wound healing. Conversely though it is not effective in osteomyelitis, this does not mean that it might not be effective in wound healing. There is no way of knowing without an appropriate clinical trial. It will now be of interest to note the rate at which HBO proponents give up HBO therapy for chronic osteomyelitis. You might also be interested in the comments of one of the discussors of this paper: "In conclusion, I think we can say that the primary indication for hyperbaric oxygen treatment remains a marketing gimmick by the hospital and also by physicians. This study I think, shows that hyperbaric oxygen does not work in osteomyelitis and until we have a better study that proves otherwise we should not use it." The final statement seems to me to be applicable to all of the communciations we have received. It is uncomfortable for me to see Ms. Gabb singled out as the focus of wrath. All she did was to look at HBO with unbiased and fresh eyes. Perhaps the entire field of HBO could benefit from her example. I estimate that HBO is used to treat some 30 or 40, or more, disorders (as of 1985). I trust that it will not be necessary to counter the claims made by HBO proponents for each of these conditions, most not supported by adequate validation. These claims conform to a stereotypic pattern. Finally I know of no "hidden agenda" on my part. I would have thought that my "agenda" was quite obvious. It is to analyze the appropriateness of the data base used to rationalize the use of HBO, to bring the analysis to the attention of the chest community; and to stimulate the performance of adequate clinical trials by the HBO community; Nor are my conclusions hidden in Aesopian language. I find that, for most indications, there is no acceptable data base which supports its use. If and when such data are made available, I would be eager to expose the data to the widest possible medical audience. Until that time, demands for retraction seem to me to be posturing, rather than an attempt to improve patient management. Eugene D. Robin, M.D., Stanford University Medical School, Stanford, CA
REFERENCES 1 Demling RH. Medical progress: burns. N Engl J Med 1985; 313: 1389-98
2 Esterhal JL Jr, Pisarello J, Brighton C1: Heppenstall RB, Gellman
H, Goldstein G. Adjunctive hyperbaric oxygen therapy in the treatment of chronic refractory osteomyelitis. J Trauma 1987; 27:763-68
To the Editor: We have read with interest the risk-benefit analysis column in Chest and in particular the analysis of hyperbaric oxygen therapy (Gabb G, Robin ED. 1987; 92:1074-82) which we consider to be an excellent example of how not to do a risk-benefit analysis. A risk-benefit analysis is a formal technique for structuring problems which require decision-making under conditions of uncertainty; 1-4 It involves explicit structuring of the clinical problem CHEST / 94 f 3 / SEPTEMBER, 1988
671