SAN FRANCISCO--Which is better for managing carbon monoxide (CO) poisoning patients: hyperbaric or normobaric oxygen therapy? Both have been in use for decades, yet clinicians are still asking this question.

To help answer it, two experts faced off in a pro/con debate at the annual meeting of the American College of Chest Physicians. Neil B. Hampson, MD, presented data in favor of hyperbaric oxygen, while Lon W. Keim, MD, argued that the jury is still out.

Hyperbaric medicine is sometimes criticized for a lack of prospective, randomized, double-blind, controlled clinical trials to support its use in CO poisoning. “That is an unjust criticism,” stated Dr. Hampson, Medical Director of the Hyperbaric Department at the Virginia Mason Medical Center, in Seattle. “We have six trials so far comparing hyperbaric to normobaric oxygen.” Four of the trials have been published in the peer–reviewed literature; the other two have been presented in abstract form.[1– 6]

“I admit that the clinical trials are not in total agreement, but I think they support the use of hyperbaric oxygen therapy in total,” said Dr. Hampson. Two of these are conflicting French studies, a large and a small trial with 343 and 26 CO poisoning victims, respectively.[1,2] The small trial found that at the three–week follow–up, the hyperbaric oxygen group was more likely than the patients given normobaric oxygen to experience symptom resolution and less likely to have abnormalities on quantitative electroencephalography or to have decreased cerebral blood flow reactivity to acetazolamide challenge.

The large trial showed no difference in outcome between the hyperbaric and normobaric oxygen groups. However, this study had several major weaknesses, Dr. Hampson said, the most important being the exclusion of severely poisoned patients—possibly the group most likely to benefit from hyperbaric oxygen therapy. Moreover, this therapy was given at a lower pressure than is commonly used in clinical practice, and the method of assessing outcomes was quite weak, consisting primarily of telephone interview follow–up.

A trial by University of Pennsylvania researchers found in favor of hyperbaric oxygen therapy, despite the fact that it, too, excluded severe cases of CO poisoning.[3] Of 30 patients with mild–to–moderate CO poisoning who were treated with hyperbaric oxygen, none developed memory loss, cognitive impairment, or other delayed neurologic sequelae (DNS) during the three–month follow–up; however, seven of the 30 patients given normobaric oxygen experienced such complications–a statistically significant difference. All of the patients with DNS fully recovered within a year.

That conclusion is consistent with the results of one of the trials presented to date only as an abstract: a multicenter French study comparing a single hyperbaric oxygen treatment with 12 hours of normobaric oxygen administration in 575 patients with CO poisoning.[4] At three–month follow–up, there were significantly fewer neurologic sequelae in the hyperbaric oxygen group than in the normobaric group. This difference decreased after six months, however, and disappeared completely at one year.

Dr. Hampson refuted the results of an Australian trial widely hailed as strong proof of hyperbaric oxygen’s lack of value. In this trial, which included 191 patients with various degrees of CO poisoning, the hyperbaric oxygen group performed no better than the normobaric oxygen group on seven posttreatment neuropsychologic tests and, in fact, did worse on one.[5]

Several factors, however, limit interpretation of these findings, argued Dr. Hampson. In most of the cases in this study, he explained, CO poisoning resulted from a suicide attempt, often preceded by drug or alcohol use. Thus, drug or alcohol co–intoxication and, quite possibly, depression influenced the studyÕs outcome.

“We do not know what happened to the majority of the patients in this study,” he added, pointing out that only 46% of the patients were available for the one–month follow–up, which was the basis for the study’s conclusions. Furthermore, all patients received additional high–flow oxygen that was apt not only to mask any difference between the two treatment groups but also to cause pulmonary oxygen toxicity.

The sixth randomized study of hyperbaric versus normobaric oxygen for the treatment of CO poisoning was conducted in Salt Lake City.[6] “At the blinded interim analysis, one treatment group had experienced one half the incidence of neurological sequelae as the other did,” said Dr. Hampson.“ The trial was continued in an attempt to achieve statistical significance and was recently concluded.

Results are scheduled to be presented at the American Thoracic Society meeting in San Francisco in May 2001,” he explained. “I am hopeful that this study will be the fourth [one] demonstrating the value of hyperbaric oxygen for treatment of acute CO poisoning.”

Thus, Dr. Hampson concluded that the evidence, although not uniform, supports the use of hyperbaric oxygen administration—if for no other reason than to ameliorate short–term morbidity. However, he believes that more research should be done to identify which patient subgroups are most likely to derive benefit from this form of treatment.

Clinical trials do not support hyperbaric over normobaric oxygen for CO poisoning, said Dr. Keim, Medical Director of the Barrow Medical Unit in Pulmonary Medicine Services at Nebraska Health Systems, in Omaha. Two of the trials found these therapies comparable,[2,5] he pointed out, as did a retrospective review of 213 CO poisoning cases.[7] Although results of the University of Pennsylvania trial favored hyperbaric oxygen therapy, the study only included mildly poisoned patients not usually considered for such therapy, Dr. Keim said.

Regardless of their findings, the clinical trials should be interpreted with caution, Dr. Keim warned, since they typically used different protocols for hyperbaric oxygen administration and different outcome measurements. In fact, there are 44 different treatment protocols used by the more than 350 centers that provide hyperbaric oxygen, he noted.

It is, therefore, still unknown whether hyperbaric oxygen is preferable to normobaric oxygen in CO poisoning, Dr. Keim concluded. He advised clinicians to rely on sound clinical judgment until research produces a definitive answer.

His specific recommendations included:

• Start all patients with CO poisoning on 100% oxygen through a high–flow or nonrebreathing mask.

• Consider subsequent hyperbaric oxygen administration when poisoning is severe or if symptoms persist after four to six hours of 100% oxygen.

• No further treatment is necessary if symptoms resolve with 100% oxygen. In fact, in most of these cases, simply discharge the patient.

--Timothy Begany

References
1. Raphael JC, Elkharrat D, Jars–Guincestre MC, et al. Trial of normobaric and hyperbaric oxygen for acute carbon monoxide intoxication. Lancet. 1989;2:414-419.

2. Ducasse JL, Celsis P, Marc-Vergnes JP. Non–comatose patients with acute carbon monoxide poisoning: hyperbaric or normobaric oxygenation? Undersea Hyperb Med. 1995;22:9-15.

3. Thom SR, Taber RL, Mendiguren II, et al. Delayed neuropsychologic sequelae after carbon monoxide poisoning: prevention by treatment with hyperbaric oxygen. Ann Emerg Med. 1995;25:474-480.

4. Mathieu D, Wattel F, Mathieu–Nolf M, et al. Randomized prospective study comparing the effect of HBO versus 12 hours NBO in non–comatose CO poisoned patients: results of the interim analysis [abstract]. Undersea Hyperb Med. 1996;23(suppl):7.

5. Scheinkestel CD, Bailey M, Myles PS, et al. Hyperbaric or normobaric oxygen for acute carbon monoxide poisoning: a randomised controlled clinical trial. Med J Aust. 1999;170:203-210.

6. Weaver LK, Hopkins RO, Larson–Lohr V, et al. Double–blind, controlled, prospective, randomized clinical trial in patients with acute carbon monoxide poisoning: outcome of patients treated with normobaric oxygen or hyperbaric oxygen–an interim report [abstract]. Undersea Hyperb Med. 1995;22(suppl):14.

7. Myers RA, Snyder SK, Emhoff TA. Subacute sequelae of carbon monoxide poisoning. Ann Emerg Med. 1985;14:1167.

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