Justifying Hyperbaric Oxygen Delivery for Carbon Monoxide Poisoning
2017; Elsevier BV; Volume: 152; Issue: 5 Linguagem: Inglês
10.1016/j.chest.2017.07.022
ISSN1931-3543
Autores Tópico(s)High Altitude and Hypoxia
ResumoFOR RELATED ARTICLE SEE PAGE 943Carbon monoxide (CO) exposure, both accidental and suicidal, accounts for thousands of deaths worldwide each year and remains an important public health issue.1Buckley N.A. Juurlink D.N. Isbister G. Bennett M.H. Lavonas E.J. Hyperbaric oxygen for carbon monoxide poisoning.Cochrane Database Syst Rev. 2011; : CD002041PubMed Google Scholar Because of its very strong affinity with hemoglobin to create carboxyhemoglobin, even relatively low concentrations of the gas can result in tissue hypoxia and cellular destruction through a variety of mechanisms.2Olson K.R. Carbon monoxide poisoning: mechanisms, presentation, and controversies in management.J Emerg Med. 1984; 1: 233-243Abstract Full Text PDF PubMed Scopus (96) Google Scholar The use of hyperbaric oxygen therapy (HBOT) to treat CO exposure has been controversial since its inception, hinging on a debate about whether 100% normobaric oxygen delivery by nonrebreathing mask or endotracheal intubation produces more effective clinical outcomes than HBOT for patients with CO poisoning. FOR RELATED ARTICLE SEE PAGE 943 Researchers in the field of hyperbaric medicine have produced a number of compelling manuscripts to address appropriate clinical indications for this technology in the past several decades, but thanks to some of its early historical promoters, who tended to place hyperbaric treatment ahead of strong supporting data, wholehearted acceptance of the science has been slow to follow for some indications, including treatment of CO poisoning. For example, although hyperbaric environments were shown early on to be effective for treating decompression illness related to gas embolism in divers, the use of HBOT to treat a cornucopia of clinical ailments received the scientific equivalent of a black eye dating as far back as 1662, when the British physician Nathaniel Henshaw developed his domicilium, a large sealed chamber driven by organ bellows with valves to control the flow of air. Despite lacking any scientific basis for his theories, Henshaw believed that patients with certain conditions would benefit from increased air pressure and wrote, “In times of good health this domicilium is proposed as a good expedient to help digestion, to promote insensible respiration, to facilitate breathing and expectoration and consequently, of excellent use for prevention of most affections of the lungs.”3Simpson A. Compressed Air As a Therapeutic Agent in the Treatment of Consumption, Asthma, Chronic Bronchitis and Other Diseases. Sutherland and Knox, Edinburgh1857: 1-4Google Scholar In the 1920s, Orval J. Cunningham operated a large hyperbaric chamber in Kansas City, treating hundreds of victims of Spanish influenza and promoted the chamber to treat maladies such as syphilis, hypertension, diabetes mellitus, and cancer without one shred of scientific evidence to justify its efficacy. A very expensive and very publically visible boondoggle, funded in 1928 by industrial tycoon H. H. Timken at a price tag of more than $1 million, involved the development of a giant chamber shaped like a massive steel ball with windows to be used as a sort of hyperbaric “hotel.” Masterminded by Cunningham, the chamber being built in Cleveland would theoretically house long-term patients who would live inside the chamber for weeks or months at a time, each receiving prolonged HBOT for various ailments.4Edwards M.L. Hyperbaric oxygen therapy. Part 1: history and principles.J Vet EmergCrit Care. 2010; 20: 284-288Crossref PubMed Scopus (54) Google Scholar During the construction of the chamber, the American Medical Association repeatedly requested that Cunningham document his claims of treatment success, but he made no meaningful efforts to describe or discuss his technique in the medical literature. He was eventually censured by the American Medical Association in 1928 in the midst of construction with a report that stated, “Under the circumstances, it is not to be wondered that the medical profession looks askance at the 'tank treatment' and intimates that it seems tinctured much more strongly with economics than with scientific medicine. It is the mark of the scientist that he is ready to make available the evidence on which his claims are based.”5Brown O.R. Oxygen, the Breath of Life: Boon and Bane in Human Health, Disease, and Therapy”. Bentham Books, Sharjah, UAE2017: 162-163Google Scholar Cunningham was given repeated opportunities to present such evidence but never did so, and the chamber, the bellwether of exaggerating the capability of the technology, was eventually dismantled for scrap in 1937. The early efforts at perfecting HBOT were met with the disdain of academic scientists and placed on the shelf of quackery next to snake oil liniment and electromagnetic coils. Despite its academic nadir in years past, the field of hyperbaric medicine has gradually demonstrated efficacy for a number of indications in clinical medicine through a variety of published reports over the past several decades—from studies showing mobilization of bone marrow-derived stem/progenitor cells by a free radical mechanism in a hyperbaric environment6Heyboer M. Milovanova T.N. Wojcik S. et al.CD34+/CD45-dim stem cell mobilization by hyperbaric oxygen—changes with oxygen dosage.Stem Cell Res. 2014; 12: 638-645Crossref PubMed Scopus (33) Google Scholar to the use of hyperbaric therapies as an adjunctive measure in the treatment of malignancies.7Hartford A.C. David T.H. Buckey J.C. et al.Hyperbaric oxygen as radiation sensitizer for locally advanced squamous cell carcinoma of the oropharynx: a phase 1 dose-escalation-escalation study.Int J Radiat Oncol Biol Phys. 2017; 97: 481-486Abstract Full Text Full Text PDF PubMed Scopus (5) Google Scholar, 8Stepien K. Ostrowski R.P. Matyja E. Hyperbaric oxygen as an adjunctive therapy in treatment of malignancies, including brain tumors.Med Oncol. 2016; 33: 101Crossref PubMed Scopus (72) Google Scholar, 9Tequh D.N. Bol Raap R. Struikmans H. et al.Hyperbaric oxygen therapy for late radiation-induced tissue toxicity: prospectively patient-reported outcome measures in breast cancer patients.Radiat Oncol. 2016; 11: 130Crossref PubMed Scopus (15) Google Scholar Although administration of supplemental oxygen is the primary treatment for CO exposure, the use of HBOT to deliver supplemental oxygen remains inconclusive as a primary treatment strategy. Following several unblinded studies concluding that neurologic outcomes were more favorable in patients receiving HBOT compared with those receiving standard normobaric oxygen therapies for CO poisoning, a meta-analysis published in 2005 and updated in 2011 concluded that there was no significant alteration in neurologic sequelae involving four of six randomized controlled trials (RCTs) involving the use of HBOT for treatment of CO exposure at that time.1Buckley N.A. Juurlink D.N. Isbister G. Bennett M.H. Lavonas E.J. Hyperbaric oxygen for carbon monoxide poisoning.Cochrane Database Syst Rev. 2011; : CD002041PubMed Google Scholar Regardless, HBOT speeds carboxyhemoglobin dissociation when compared with breathing 100% oxygen in a normobaric environment.10Pace N. Strajman E. Walker E.L. Acceleration of carbon monoxide elimination in man by high pressure oxygen.Science. 1950; 111: 652-654Crossref PubMed Scopus (154) Google Scholar, 11Roughton F. Darling R. T he effect of carbon monoxide on oxyhemoglobin dissociation curve.Am J Physiol. 1944; 141: 17-31Google Scholar The optimal benefit from supplemental oxygen therapy seems to be in rapidity of treatment.12Gorman D.F. Huang Y.L. Williams C. Prolonged exposure to one percent carbon monoxide causes a leucoencephalopathy in un-anaesthetized sheep.Toxicology. 2001; 165: 97-107Crossref PubMed Scopus (18) Google Scholar Animal models have shown positive effects with the use of HBOT at the cellular level after CO exposure as it impacts neurologic function, with theoretical improvement in mitochondrial oxidative mechanisms, temporary inhibition of lipid peroxidation, and attenuation of leukocyte adhesion to microvascular structures.13Weaver L.K. Hopkins R.O. Chan K.J. et al.Hyperbaric oxygen for acute carbon monoxide poisoning.N Engl J Med. 2002; 347: 1057-1067Crossref PubMed Scopus (746) Google Scholar, 14Thom S.R. Carbon monoxide-mediated brain lipid peroxidation in the rat.J ApplPhysiol. 1990; 68: 997-1003Google Scholar Although HBOT has shown promise in the treatment of CO poisoning victims, critics charge that some HBOT studies have suffered from soft end points, poorly defined populations, and paltry cohort sizes.15Juurlink D.N. Buckley N.A. Eddleston M. Better studies are needed to guide treatment of carbon monoxide poisoning.Am J Respir Crit Care Med. 2017; 195: 693-694Crossref Scopus (3) Google Scholar In this issue of CHEST, Huang et al16Huang C.-C. Ho C.-H. Chen Y.-C. et al.Hyperbaric oxygen therapy is associated with lower short- and long-term mortality in patients with carbon monoxide poisoning.Chest. 2017; 152: 943-953Abstract Full Text Full Text PDF PubMed Scopus (59) Google Scholar report data from a very large database covering more than 25,000 patients in Taiwan with CO exposure. In this study, researchers were able to compare mortality rates in more than 7,000 patients who received HBOT over a 13-year time frame with those who received standard therapy and, unlike prior studies, were able to adjust for age, sex, underlying comorbidities, and even monthly income. They found statistically significant improvement in mortality rates for the cohort receiving HBOT, even after adjusting for multiple variables. The data are compelling for several reasons. First, it appears to be the first large-scale study that looks at short- and long-term mortality specifically targeting individuals encountering CO toxicity across an entire nation rather than a single institution or multiple centers but with a small cohort of study subjects. Also, although certain parameters that contribute to mortality, such as lifestyle, smoking status, or BMI, were not available, adjustment for major comorbidities likely minimized this effect. Second, although the database used for the study did not have specific carboxyhemoglobin levels measured or access to documented concentrations of CO at the time of exposure, the study found more favorable mortality rates in a subpopulation with respiratory failure, a probable surrogate for more serious CO exposures. Third, mortality is generally a solid end point, whereas attempting to measure neurologic sequelae by more qualitative parameters is plagued by subjectivity. Finally, although there is no single standard for HBOT across all centers in Taiwan (or in any other nation), most treatment paradigms involve a standard single treatment table involving pressures of 2 to 3 ATA. The variation noted by these researchers focused more on the number of treatments than on the amount of atmospheric pressure applied in each therapy session. Have we reached the point of clearly establishing that delivery of pure oxygen in a high-pressure environment is more effective in treating patients who have CO poisoning than is normobaric supplemental oxygen alone? Probably not. The retrospective database study by Huang et al,16Huang C.-C. Ho C.-H. Chen Y.-C. et al.Hyperbaric oxygen therapy is associated with lower short- and long-term mortality in patients with carbon monoxide poisoning.Chest. 2017; 152: 943-953Abstract Full Text Full Text PDF PubMed Scopus (59) Google Scholar despite its large size and interesting findings, remains distant from the ideal of a large blinded multicenter RCT using a standardized protocol to compare normobaric supplemental oxygenation with HBOT delivery for this cohort; however, its size, scale, and findings add credibility to the mounting data supporting HBOT for this indication. Efficacy of therapy in CO poisoning regarding neurologic sequelae seems to hinge on the rapidity of applying supplemental oxygen, regardless of whether it is applied in a normobaric or hyperbaric environment. It is time to answer the research question of efficacy in the treatment of this cohort starting with clear definitions of what constitutes a successful clinical outcome. Although the cost of coordinating RCTs can be exorbitant and will take time, responding to the need for a definitive trial is critical, partly due to the high cost of hyperbaric technology itself. In addition to analyzing rigid end points such as mortality and other more qualitative variables such as neurologic outcomes and quality of life indicators, other factors, such as accessibility, cost of therapy, staffing, and safety aspects of treatment (particularly for critically ill CO poisoning victims with comorbidities) will need to be considered in any multicenter randomized trial being designed in the future. Hyperbaric medicine has come a long way from its controversial beginnings, and the article by Huang et al16Huang C.-C. Ho C.-H. Chen Y.-C. et al.Hyperbaric oxygen therapy is associated with lower short- and long-term mortality in patients with carbon monoxide poisoning.Chest. 2017; 152: 943-953Abstract Full Text Full Text PDF PubMed Scopus (59) Google Scholar adds important data to a clinical question in which life and death for those exposed to CO hangs in the balance. Efficacy of Hyperbaric Oxygen for Carbon Monoxide PoisoningCHESTVol. 153Issue 3PreviewDespite inaccuracies in Cowl’s1 recent editorial in CHEST (November 2017) on the use of hyperbaric oxygen treatment (HBOT) for carbon monoxide poisoning (Henshaw’s 17th century domicilium, if ever constructed according to his specification, with windows in brick or stone walls, could not have been pressurized; Cunningham’s efforts in the 1920s used hyperbaric air equivalent to 50% to 60% normobaric oxygen, not HBOT), he should be applauded for endorsing the conduct of a multicenter clinical trial. Full-Text PDF ResponseCHESTVol. 153Issue 3PreviewIt is reassuring to be applauded by two giants in the field of hyperbaric medicine regarding my observation that there is a clear need for a definitive multicenter clinical trial to further delineate the efficacy of hyperbaric oxygen therapy in the treatment of carbon monoxide poisoning.1 Collecting adequate trial numbers to establish the statistical power to appropriately assess subsets of individuals with generally less severe symptoms as Moon and Hampson suggest will be the imperative moving forward. Full-Text PDF
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