Hyperbaric Oxygen in Acute Carbon Monoxide Poisoning

Abstract & Commentary

Synopsis: Hyperbaric oxygen therapy used within 24 hours of acute symptomatic CO poisoning decreases the risk of cognitive sequelae at 6 weeks and 12 months.

Source: Weaver LK, et al. N Engl J Med. 2002;347:1057-1067.

Carbon monoxide (CO) poisoning is a serious and common public health problem leading to unfavorable neurological sequelae and death. CO has greater affinity for hemoglobin than oxygen and displaces oxygen from hemoglobin causing severe tissue hypoxia. The organs most commonly affected are those that have the highest oxygen demands (eg, brain and heart). Between 23-47% of patients exposed to CO develop delayed neurological sequelae within 2-28 days.2,3 Overall, despite the serious sequelae associated with CO, the mechanisms of injury and methods of treatment remain poorly understood.

Weaver and colleagues conducted a prospective double-blind, randomized, controlled trial to evaluate the effect of hyperbaric oxygen treatment in symptomatic acute CO poisoning. One hundred fifty-two patients over 7 years met the enrollment criteria of documented exposure to CO or an obvious exposure to CO with presence of signs and symptoms suggestive of CO poisoning, elevated carboxyhemoglobin (COHB), or metabolic acidosis. Exclusion criteria included > 24 hours elapsed since CO exposure had ended, age < 16 years, pregnancy, and morbidly ill patients. Patients were randomized to either hyperbaric or normobaric protocols. In the hyperbaric group, 3 chamber sessions of hyperbaric oxygen were administered at 6-12 hour intervals within a 24-hour period. In the first session, 3 atmospheres (ATA) of 100% oxygen were administered for 1 hour and decreased to 2 ATA of 100% oxygen for the next hour. The second and third chamber sessions consisted of hyperbaric oxygen at 2 ATA for 2 hours. In the normobaric group, the first session consisted of 100% oxygen at 1 ATA. The second and third sessions consisted of normobaric room air. Neurological and neuropsychological tests were administered at enrollment, after the first and third treatment sessions, and at 2 weeks, 6 weeks, 6 months, and 12 months after enrollment. Primary end points were the incidence of cognitive sequelae at 6 weeks after CO poisoning. Patients were followed for 12 months although it was not included in the study design.

Seventy six patients were randomly assigned to each treatment group. Of the 76 in each group, 75 in the hyperbaric group, and 72 in the normobaric oxygen group completed the study. Baseline characteristics were similar in both groups except for cerebellar dysfunction before treatment, which was worse in the normobaric group (15% vs 4%; P = 0.03). The presence of cerebellar dysfunction before treatment was associated with a higher incidence of cognitive sequelae (odds ratio, 5.71 [95% CI, 1.69-19.31]; P = 0.005). Cognitive sequelae at 6 weeks were less frequent in the hyperbaric oxygen group than the normobaric oxygen group (25% vs 46.1%; P = 0.007). Cognitive sequelae were less frequent in the hyperbaric oxygen group at 12 months according to intention-to-treat analysis (18% vs 33%; P = 0.04). Even when baseline characteristics such as incidence of cerebellar dysfunction were accounted for, this remained statistically significant. Weaver et al concluded that treatment of patients with acute symptomatic CO poisoning with 3 hyperbaric oxygen treatments within 24 hours appears to reduce the rate of cognitive sequelae at 6 weeks and 12 months later.

Comment by David Ost, MD, and Gnanaraj Joseph, MD

Previous studies done on the use of hyperbaric oxygen treatment were inconclusive due to methodological difficulties.1 Practice guidelines were developed based on clinical experience and uncontrolled studies. This study supports the use of hyperbaric oxygen treatment. No adverse effects due to hyperbaric oxygen treatment were reported.

The serum COHB was mildly elevated at the time of hyperbaric oxygen, and treatment benefits may not have been from removal of carbon monoxide alone but also from prevention of cellular damage due to CO exposure. Animal studies have shown that hyperbaric oxygen preserves adenosine triphosphate, prevents lipid peroxidation of the cell wall and decreases neutrophil adherence in the brain.4

Limitations to the use of hyperbaric oxygen are the limited availability of facilities and the risk of adverse effects. Adverse effects of hyperbaric oxygen are uncommon. The most severe complication is convulsions.

This study strengthens the rationale for using hyperbaric oxygen in acute CO poisoning but some important clinical issues remain unanswered. First, better predictive factors are needed for determining the risk of delayed and permanent effects of CO poisoning. Second, the optimum frequency, dose and duration of treatment, as well as the therapeutic window of opportunity need to be defined. Third, the role of hyperbaric oxygen in mild CO poisoning needs to be elucidated. Finally, prevention is a key part of the public health issue.

Dr. Ost, Assistant Professor of Medicine, NYU School of Medicine, Director of Interventional Pulmonology, Division of Pulmonary and Critical Care Medicine, Northshore University Hospital, Manhasset, NY, is Associate Editor of Internal Medicine Alert. Dr. Joseph is Fellow of Pulmonary and Critical Care Medicine, North Shore University Hospital, Manhasset, NY.


1. Scheinkestel CD, et al. Med J Aust. 1999;170:203-210.

2. Gorman DE, et al. Anaesth Intern Care. 1992;20:311-316.

3. Weaver LK. Crit Care Clin. 1999;15:297-317.

4. Thom SR. Toxicol Appl Pharmacol. 1990;105:340-344.