Should hyperbaric oxygen be used for carbon monoxide poisoning?

Journal Club

CJEM 2006;8(1):43-46

Clinical question

Does hyperbaric oxygen therapy (HBO) provide clinical benefit by reducing neurologic sequelae after 1 year for non-pregnant patients presenting with carbon monoxide (CO) poisoning?

Search

A MEDLINE search from 1966-2005. MESH headings:

1. exp/carbon monoxide poisoning: 3114
2. exp/hyperbaric oxygenation: 7481
3. 1 and 2: 459
4. limit 3 to clinical trial: 12

Articles chosen

The 12 studies identified by the search were narrowed down to the 5 chosen for discussion here.^1-5 The other 7 studies were either comments, did not measure clinically relevant outcomes, only looked at fetuses or were not clinical trials. A recently published Cochrane review6 revealed 1 additional article, which we also discuss here.⁷

Objective

To determine if there is evidence of improved clinical outcome during the first 4-6 weeks following treatment with HBO compared with treatment with normobaric oxygen (NBO) for CO poisoning.

Background

Carbon monoxide is an imperceptible gas generated during the incomplete combustion of carbon-based compounds⁶ and has an affinity approximately 240 times greater than oxygen for the hemoglobin molecule. Inhaled CO exerts its toxic effect by displacing oxygen and binding to deoxyhemoglobin to form carboxyhemoglobin; by shifting the hemoglobin-oxygen dissociation curve to the left, impairing cellular oxygen delivery; and by interfering with cellular oxygen storage, thus impairing cellular metabolism.

At high concentrations, oxygen competes with CO for hemoglobin binding sites and is therefore a mainstay of therapy for CO poisoning. Carboxyhemoglobin's 4-8-hour half-life falls to approximately 2 hours in the presence of 100% oxygen, and to 30 minutes if 100% oxygen is delivered at 3 atmospheres of pressure. However, despite physiologic rationale supporting the value of HBO therapy, its use in CO poisoning remains controversial and it is typically recommended only for the most severe cases.^8,9 The objective of this review was to determine if there is evidence that HBO improves clinical outcomes more than NBO in patients being treated for CO poisoning.

Populations studied and study design

Table 1 illustrates the settings, population, study designs, interventions, comparison protocol, outcome measures, results, conclusions and limitations of the 6 assessed studies.^1-5,7 All studies evaluated non-pregnant adults.

View Table 1

Results

The studies in this analysis used clinical findings, neuropsychological tests, or the electroencephalogram (EEG) to assess the development of neurologic sequelae. Clinically significant neurologic sequelae were detected using physical examination or self-assessment questionnaires. The neuropsychological tests used to identify neurologic sequelae measured attention, information processing, memory, learning, reaction time, temporal-spatial orientation, visual discrimination and visual-spatial functioning.

Figure 1 shows key outcomes, stratified by time after exposure.^1-5,7 Results that used neuropsychological tests to determine the presence of neurologic sequelae showed no effect over a 12-month course. Results that used clinical findings showed no effect after 6 weeks.

Fig. 1. (enlarge) Neurological sequelae over 1 year for the 6 studies chosen for this assessment. Diamonds = studies that used neuropsychological testing; Squares = studies that used physical examination, self-assessment questionnaires or EEG. White diamonds and squares = Weaver et al¹; light grey diamond = Scheinkestel et al²; dark grey diamonds = Mathieu et al⁴; black diamonds = Thom et al⁷; dark grey squares = Ducasse et al³; black square = Raphael et al⁵

Comments

The Cochrane reviewers, also using 4-6 weeks as the end point for their analysis, were not able to demonstrate unequivocal benefits for HBO therapy and did not recommend it routinely for CO poisoning. In light of this uncertainty, they recommend that a multi-centre trial be performed to define the role, if any, for HBO therapy in CO poisoning. Examination of all the data points drawn from both strategies over a year reveals that although neuropsychological test scores took up to 12 months to return to normal, the self-reporting of symptoms, clinical assessments and activities of daily living had returned to normal after 6 weeks.

All of the published studies to date have numerous limitations that compromise their validity, including lack of blinding, significant loss to follow-up, HBO therapy at below standard treatment levels, difficulty in interpreting reported results, and exclusion of patients with severe CO poisoning.¹⁰

With 14 hospital-based HBO chambers in Canada and over 200 in the United States, most of which are single chamber, accessing a hyperbaric chamber for a patient with CO poisoning can be difficult. Even if available, the limited number of facilities means that most eligible patients would require transportation. Furthermore, HBO therapy has potential risks including decompression sickness, cerebral gas embolism, oxygen toxicity, tympanic membrane rupture, sinus barotrauma and pneumothorax.⁹

Even though the Undersea and Hyperbaric Medical Society and others recommend the use of HBO for CO poisoning,¹¹ a thorough review of the evidence does not support this practice in medicine.

References

1. Weaver LK, Hopkins RO, Chan KJ, et al. Hyperbaric oxygen for acute carbon monoxide poisoning. N Engl J Med 2002;347:1057-67.
2. 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;170:203-10.
3. DucassÉ 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.
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 patients: results of the interim analysis [abstract]. Undersea Hyperb Med 1996;23:S7-8.
5. Raphael JC, Elkharrat D, Jars-Guincestre MC, et al. Trial of normobaric and hyperbaric oxygen for acute carbon monoxide intoxication. Lancet 1989;2:414-9.
6. Juurlink DN, Buckley NA, Stanbrook MB, et al. Hyperbaric oxygen for carbon monoxide poisoning. The Cochrane Database of Systematic Reviews. 2005 Issue 4.
7. 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;25:474-80.
8. Nelson LS, Hoffman RS. Inhaled toxins. In: Marx, JA, Hockberger RS, Walls RM, et al, editors. Rosen's emergency medicine: concepts and clinical practice. 5th ed. St. Louis: Mosby; 2002. p. 2169-70.
9. Kao LW, Nanagas KA. Carbon monoxide poisoning. Emerg Med Clin North Am 2004;22:985-1018.
10. Buckley NA, Isbister GK, Stokes B, et al. Hyperbaric oxygen for carbon monoxide poisoning: a systematic review and critical analysis of the evidence. Toxicol Rev 2005;24:75-92.
11. Feldmeier J, chairman and editor. Hyperbaric oxygen 2003: indications and results: the Hyperbaric Oxygen Therapy Committee Report. Kensington (MD): Undersea and Hyperbaric Medical Society; 2003.