Reply: Better Studies Are Needed to Guide Treatment of Carbon Monoxide Poisoning

From the Authors:

We appreciate the comments of Dr. Juurlink and colleagues, who summarize the limitations of the currently available clinical trials data supporting the efficacy of hyperbaric oxygen therapy (HBO₂). Although there are several clinical trials testing the efficacy of HBO₂, pooled analysis is difficult owing to heterogeneity among the different trials (1, 2). The Weaver and colleagues study is the best designed trial and most resembles clinical practice (3). Although we do not provide an in-depth critical review of the Weaver and colleagues trial (3), we certainly recognize the urgent need for new therapies for carbon monoxide (CO) poisoning (4).

Even if HBO₂ is as effective in general clinical practice as in the Weaver and colleagues trial—a number needed to treat of five to prevent one case of delayed neurologic sequelae—there would still be thousands of survivors of CO poisoning suffering from significant long-term morbidity every year (1, 3). We thus have focused much of our discussion on new therapies being developed that can be used at the point of care (1). One of the limitations of HBO₂ is treatment delay due to the transportation of a patient to a facility capable of emergent therapy. The development of antidotal agents, such as CO scavengers or hydroxocobalamin, that could be delivered on site or en route to a hospital would drastically cut time to treatment, if proven successful in further studies (1, 4, 5).

Our research team has recently published studies evaluating a potential antidote, based on a mutationally engineered recombinant neuroglobin molecule that binds CO with approximately 500 times higher affinity than hemoglobin binds CO (4). This molecule clears CO in vitro from human red blood cells and in vivo from mouse blood with a half-life of only 25 seconds, compared with even the shortest half-life using HBO₂ of 20 minutes (1, 4). The antidote improved cardiovascular function, lactic acid clearance, and survival in a lethal CO poisoning mouse model (4). We are hopeful there may one day be improved strategies to address the important public health issue of CO poisoning. Overall, we strongly agree that further research in this area is necessary.