Another mini-review where I agree with the Cochrane Review that essentially concludes: too much cost/risk, not enough proven benefit.
Hyperbaric oxygen therapy is of proven value in rapidly clearing carboxyhemoglobin from the serum – half-life approaches 20 minutes at 3 atmospheres vs. 1 hour on 100% face mask and several hours at lower concentrations of oxygen. In addition, HBO has all sorts of beneficial effects in terms of preventing the damaging intracellular effects of carbon monoxide, including impairment of cytochrome oxidase a3 and of lipid peroxidation. Lipid peroxidation, as you might imagine, in a brain full of lipids, is where you really end up in trouble with permanent neurologic sequelae.
Unfortunately, the first animal models that prove how well HBO works go directly from CO poisoning into multiple atmospheres of therapy. As few HBO centers there are in the U.S., this is absolutely not a clinically relevant model because of the delays to therapy – and that’s why the human literature is less conclusive.
There are essentially three large studies that contribute most of the weight to the 2011 Cochrane Review – one from 1989 that demonstrates no benefit, a second from 2002 in the New England Journal of Medicine that has a broad following, and, finally, a 2011 publication in Intensive Care Medicine. Most toxicologists who are pro-HBO base their opinions on the 2002 Weaver article.
The good news about the Weaver article – it’s a great study. It enrolls a lot of patients, it enrolls all kinds of patients, it dives them to three atmospheres, it does three dives in a 24 hour period, and it has excellent objective testing and subjective evaluation follow-up. This study was well-designed to give us the answers. And, in the end, it finds a significant difference in objective neurologic function in the HBO group and a subjective difference in memory ability in the HBO group. What is odd, however, is that there were many objective tests of cognitive function. Most trended towards favoring the HBO group, but only one of them reached statistical significance – a trail marking test in which a line was drawn between similar numbers. The absolute change in cognitive function between treatment and follow-up wasn’t that much different between the two groups. And, unfortunately, the larger issue for me is the baseline difference between the two groups in amount of time exposed to CO which trended towards much higher in the NBO group – 22 +/- 64 hours in the NBO group and 13 +/- 41 hours in the HBO group.
This difference is much more important because animal studies have demonstrated it’s not the carboxyhemoglobin concentration that matters as much as the dissolved CO that diffuses intracellularly. There’s a fabulous study in dogs demonstrating this difference. In one group, they exposed dogs to CO to get their carboxyhemoglobin concentration to 68% – and they all died. In a second group, they bled dogs until they had lost 68% of their hemoglobin – in theory, the same level of deoxygenation as the CO group – and they all lived. Third, they bled dogs down until they had lost 68% of their hemoglobin, then exposed that hemoglobin to CO in vitro and re-transfused it back into the dogs – in theory, the same 68% carboxyhemoglobin level as group 1 – and those dogs lived. The difference between group 1 and 3 was the amount of dissolved CO in the blood and intracelluarly, and it was demonstrated that their cytochrome oxidase a3 activity was normal in group 3 despite the carboxyhemoglobin levels.
So, that’s where I can’t take the Weaver evidence as strong enough as the sole large study favoring HBO, even though it was well-designed. The 2011 evidence, as mentioned before, is a study by Annane in Intensive Care Medicine. This is the more recent study showing no benefit. However, if you thought the Weaver study had flaws, this one is even worse. They enrolled patients between 1989 and 2000 – but didn’t publish until 2011, which is a massive red flag. Their endpoint is fuzzier, as they simply have a questionnaire and a physical examination as their follow-up without a lot of details. But, for what it’s worth, they found HBO was futile in non-comatose patients and harmful in comatose patients. They also do not dive as low or as long as the patients in the Weaver study.
Each of these studies makes it in the Cochrane Review which finds a cumulative nonsignificant trend towards minimal improvement in the HBO group. The problem is, HBO therapy is expensive, causes hyperoxic seizures, barotrauma, anxiety, oxidative stress and both hyperthermia and hypothermia. Weak evidence for mild improvement in delayed neurologic sequelae at 6 weeks is not a strong enough motivator for me to be enthusiastic about subjecting someone to the risks of HBO therapy. I’d love to see more data.
“Hyperbaric Oxygen for Acute Carbon Monoxide Poisoning.”
www.ncbi.nlm.nih.gov/pubmed/12362006
“Hyperbaric Therapy for Acute Domestic Carbon Monoxide Poisoning: Two Randomized Controlled Trials.”
www.ncbi.nlm.nih.gov/pubmed/21125215
“Hyperbaric Oxygen for Carbon Monoxide Poisoning (Review).”
www.ncbi.nlm.nih.gov/pubmed/21491385