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POSTED: December 17th, 2021
POSTED IN: EM Pulse - The Official Newsletter of MOCEP, November/December 2021,

Written by Evan Schwarz, MD, FACEP, FACMT

               Yes, it’s that time of year again as the leaves begin to change and the temperatures starts to drop. So, what time of year is it? Time for the National Dog Show? The College Football Championship games? Black Friday? Well, yes, all of those things; however, I’m referring to the time of the year when we must think of carbon monoxide poisoning. As the temperature drops and more of us start to turn on our heaters, more people will accidentally be poisoned by carbon monoxide due to malfunctioning heaters or using inappropriate heating sources to stay warm.

               As many of us know, carbon monoxide poisoning is a difficult diagnosis to make.¹ The symptoms are vague and include anything from headache and nausea and vomiting to syncope to arrhythmia, seizure, neurologic deficits (i.e. a stroke) and death. What’s more is that patients with mild poisoning have similar presentations to those with viral illnesses, something we see commonly in the winter. Furthermore, many patients will start to feel better after sitting in the waiting room for a few hours further making the diagnosis challenging.

               Of course, the diagnosis is only half the battle; what you do after making the diagnosis is just as challenging.² The easy answer is to start oxygen, generally a non-rebreather. Others have proposed more complex oxygen sources, but in general, a non-rebreather is the appropriate initial therapy.³ The question is, what else? Well, we learn pretty early in our emergency medicine training that hyperbaric oxygen (HBO) is the treatment of choice.⁴ Well, this is a little tricky. Many believe HBO is beneficial as it more rapidly lowers the amount of carbon monoxide in our system. It is true that it does, and thereby, maybe prevents lipid peroxidation, free radical formation, and neurologic injury in the brain.^5,6 However, the proposed benefit is that HBO prevents delayed neurologic sequelae (DNS), or long-term cognitive impairment, from carbon monoxide poisoning.^4,5,7 Much of this is based on a study by Weaver et al. which had a very impressive number needed to treat of 5 to prevent one case of DNS.⁴ While that seems fantastic, it is more complicated. First, patients in this study in the HBO group received three HBO treatments within 24 hours. In my experience, very few patients actually receive this many treatments. Additionally, while the Weaver study and a few other randomized controlled trials (RCTs) demonstrated benefit of HBO, other RCTs did not.^2,7–9 Unfortunately, these trials differ in inclusion and exclusion criteria, HBO protocols, and outcome assessments making combining them into a meta-analysis less than helpful.²

               This is why I was initially very excited about a recent trial by Lee et all in Critical Care Medicine that concluded that we should dive (provide HBO) early in these patients to improve cognitive outcomes.¹⁰ The blog analyzing the study even led with the sexy headline, “Time=Brain in Carbon Monoxide Poisoning.”¹¹ So, case closed, right? Well, like everything else, not exactly. The authors aimed to retrospectively study the effectiveness of HBO in patients receiving treatment within 6 hours of exposure compared to those that received it 6-12 hours and 12-24 hours after exposure. Patients were included if they had a carboxyhemoglobin (CO-Hb) concentration greater than 5% in nonsmokers or 10% in heavy smokers (by the way, smoking as a source of significant CO-Hb elevation has been debunked outside of extreme examples¹²). Propensity scoring was used to control for variables. They found that patients that received HBO within 6 hours did better on the global deterioration score (GDS) than those that received late treatment.

Again, case closed, right? Well, not exactly. While the authors should be commended for doing propensity score matching to try to compare patients that received HBO prior to six hours and those that received it afterwards, there are likely some significant problems. Sticking to the big ones, the control group should have been those that only received oxygen in the ED without HBO and not just comparing the hyperbaric groups to one another. It is possible, that no HBO may have had similar results to the group that received treatment within six hours, i.e. HBO didn’t make a difference. Second, why did some patients receive HBO sooner than others? This was likely because sicker patients had to wait until being stabilized to get to a chamber. While propensity scoring still demonstrated improved outcomes in GDS in the early group, it is still possible (and likely) that the matching didn’t account for everything, and in the end, the delayed group was just sicker. As such, you’d expect them to do worse no matter if or when they received HBO.

That being said, it is certainly reasonable to refer for HBO sooner than later if you are going to do it. Whether we should be referring patients to HBO is not answered by this study. For now, the answer is still debatable and likely depends on many factors. For now, I’d recommend consulting the poison center, a medical toxicologist, or a specialist in hyperbarics to help you make the decision.

References:

1.            Eichhorn L, Thudium M, Jüttner B. The Diagnosis and Treatment of Carbon Monoxide Poisoning. Dtsch Arzteblatt Int. 2018;115(51-52):863-870. doi:10.3238/arztebl.2018.0863

2.            Buckley NA, Juurlink DN, Isbister G, Bennett MH, Lavonas EJ. Hyperbaric oxygen for carbon monoxide poisoning. Cochrane Database Syst Rev. 2011;(4):CD002041. doi:10.1002/14651858.CD002041.pub3

3.            Roth D, Mayer J, Schreiber W, Herkner H, Laggner AN. Acute carbon monoxide poisoning treatment by non-invasive CPAP-ventilation, and by reservoir face mask: Two simultaneous cases. Am J Emerg Med. 2018;36(9):1718.e5-1718.e6. doi:10.1016/j.ajem.2018.05.066

4.            Weaver LK, Hopkins RO, Chan KJ, et al. Hyperbaric oxygen for acute carbon monoxide poisoning. N Engl J Med. 2002;347(14):1057-1067. doi:10.1056/NEJMoa013121

5.            Thom SR, Taber RL, Mendiguren II, Clark JM, Hardy KR, Fisher AB. Delayed neuropsychologic sequelae after carbon monoxide poisoning: prevention by treatment with hyperbaric oxygen. Ann Emerg Med. 1995;25(4):474-480. doi:10.1016/s0196-0644(95)70261-x

6.            Piantadosi CA, Zhang J, Levin ED, Folz RJ, Schmechel DE. Apoptosis and delayed neuronal damage after carbon monoxide poisoning in the rat. Exp Neurol. 1997;147(1):103-114. doi:10.1006/exnr.1997.6584

7.            Annane D, Chadda K, Gajdos P, Jars-Guincestre MC, Chevret S, Raphael JC. Hyperbaric oxygen therapy for acute domestic carbon monoxide poisoning: two randomized controlled trials. Intensive Care Med. 2011;37(3):486-492. doi:10.1007/s00134-010-2093-0

8.            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(5):203-210. doi:10.5694/j.1326-5377.1999.tb140318.x

9.            Raphael JC, Elkharrat D, Jars-Guincestre MC, et al. Trial of normobaric and hyperbaric oxygen for acute carbon monoxide intoxication. Lancet Lond Engl. 1989;2(8660):414-419. doi:10.1016/s0140-6736(89)90592-8

10.         Lee Y, Cha YS, Kim SH, Kim H. Effect of Hyperbaric Oxygen Therapy Initiation Time in Acute Carbon Monoxide Poisoning. Crit Care Med. 2021;49(10):e910-e919. doi:10.1097/CCM.0000000000005112

11.         Rebecca White. Time=Brain in Carbon Monoxide Poisoning. Accessed November 28, 2021. https://journalfeed.org/article-a-day/2021/time-brain-in-carbon-monoxide-poisoning

12.         Schimmel J, George N, Schwarz J, Yousif S, Suner S, Hack JB. Carboxyhemoglobin Levels Induced by Cigarette Smoking Outdoors in Smokers. J Med Toxicol Off J Am Coll Med Toxicol. 2018;14(1):68-73. doi:10.1007/s13181-017-0645-1