CO Toxicity: A Potentially Elusive Diagnosis

Author: Patrick C. Ng, MD (EM Chief Resident, SAUSHEC Emergency Medicine Department) // Edited by: Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UT Southwestern Medical Center / Parkland Memorial Hospital) and Brit Long, MD (@long_brit)

It is flu season and the dead of winter, and temperatures are at a record low. You just get on shift and are trying to get warm after that brisk walk from the parking lot to the ED when you see two-family-members, an 89-year-old female and her 40-year-old daughter, pop up on the tracker board with a chief complaint of ‘flu like symptoms’. You get a sip of your lukewarm coffee in before you see those two new patients. Both have very similar HPIs: gradual onset of headache, nausea/vomiting, and body aches. They ask you how they could have possibly contracted the flu, as they have been inside their home by the heater for the past few days secondary to the cold.

As part of your work-up, you obtain a co-oximetry level to realize that both of their carboxyhemoglobin levels are abnormal.  Your older patient has a level of 13% and is a nonsmoker, while her daughter has a level of 20%. Given that your younger patient is 38 weeks pregnant, you arrange for her to be transported to another facility to start hyperbaric oxygen therapy, while you order your elderly patient 100% oxygen and arrange for admission for carbon monoxide toxicity.

Background

Carbon monoxide (CO) poisoning is an important topic for emergency physicians to understand. It is a common exposure and can lead to significant morbidity and mortality.¹ According to the Centers for Disease Control and Prevention (CDC), more than 20,000 visits to the emergency department are related to carbon monoxide poisoning.² CO poisoning has been associated with both intentional and accidental poisonings.^3,4 Approximately 600 accidental deaths due to CO poisoning are reported annually.⁵

CO is produced by the burning of fuels/organic material and is produced in the human body in low amounts. A normal carboxyhemoglobin level in the body is <1.5%. This number can increase up to 15% in smokers.⁶  Carbon monoxide is also produced by the burning of fuels. Exposures to higher levels of carbon monoxide can occur in building fires, industrial plants, garages with engines running, or in the home with gas stoves/heating appliances. In these potential environments, associated exposures to cyanide, carbon dioxide, hydrogen sulfide, phosgene, and nitrogen dioxide have been reported.^6-7

How does Carbon Monoxide Cause Toxicity?

Carbon monoxide interferes with oxygen transport and delivery to cells. It has greater affinity for hemoglobin when compared to oxygen, thus impairing oxygen transport and delivery in the blood stream leading to cellular hypoxia. Morbidity classically involves the cardiovascular and neurological systems.^3-10

How does a patient exposed to carbon monoxide present?

Patients with carbon monoxide poisoning may present with a variety of non-specific symptoms. Headache is one of the most common symptoms reported. Other symptoms such as nausea, vomiting, dizziness, weakness, or confusion are also commonly reported.^12-13 The table below demonstrates these findings. In severe toxicity, patients can present with syncope, altered mental status, myocardial ischemia, and even cardiac arrest.

Table 1: Frequency of presenting symptoms in patients presenting with elevated COHb levels. From Deniz et al.

Due to the non-specific signs and symptoms of carbon monoxide poisoning, the diagnosis can be delayed and mistaken for other pathologies. By sign/symptoms, here are some conditions on the differential one should consider:^14-30

As seen, the differential is broad with the common signs and symptoms of carbon monoxide toxicity. The history and exam, along with several diagnostic tests, can assist.

An Approach

In the ED, historical clues such as winter time, exposure to CO in a fire, gas appliances in the home, and multiple patients from the same household presenting with similar symptoms can help the emergency physician narrow the differential diagnosis down to carbon monoxide poisoning. Once suspected, as always, ABCs should be evaluated and supported.

CO-Oximetry should be obtained in CO toxicity is on the differential. Elevated carbon monoxide levels via CO-Oximetry can help make the diagnosis. Because pulse oximetry cannot distinguish between carboxyhemoglobin and oxyhemoglobin, pulse oximetry readings can be normal in carbon monoxide poisoning. Patients may also have a lactic acidosis, and a lactate level should be obtained. CBC, CMP, LFT, troponin, EKG, and targeted imaging such as a chest x-ray can also be considered depending on the clinical situation.  Of note, troponin may be elevated.

Once the diagnosis of carbon monoxide poisoning is made, oxygen supplementation should be started. For mild to moderate toxicity, supplemental oxygen via non-rebreather can be considered. For more severe toxicity, or in select patient populations (pregnancy), hyperbaric oxygen can be considered.^12-16,30

The diagnostic and therapeutic approach can be further reviewed at http://www.emdocs.net/carbon-monoxide-poisoning/.

Of note, ACEP recently published updated recommendations for CO toxicity evaluation and management.³¹ The clinical policy evaluates three questions:

1) In emergency department patients with suspected acute carbon monoxide poisoning, can noninvasive carboxyhemoglobin measurement be used to accurately diagnose carbon monoxide toxicity?

– With level B evidence, the ACEP clinical policy does not recommend the use of noninvasive COHb measurement to diagnose CO toxicity with suspected acute CO poisoning.

2) In emergency department patients diagnosed with acute carbon monoxide poisoning, does hyperbaric oxygen therapy as compared with normobaric oxygen therapy improve long-term neurocognitive outcomes?

– With Level B recommendations, the authors recommend that HBO₂ therapy or high-flow normobaric therapy should be used by emergency physicians for acute CO-poisoned patients but that the effects of HBO₂ versus normobaric therapy on long-term neurocognitive outcomes remain unclear.

3) In emergency department patients diagnosed with acute carbon monoxide poisoning, can cardiac testing be used to predict morbidity or mortality?

– With Level B recommendations, the authors recommend that an ECG and cardiac biomarker levels be obtained in ED patients with moderate to severe CO poisoning to identify acute myocardial injury.

Key points

-Carbon monoxide poisoning can be an elusive diagnosis.

–Headache, nausea, fatigue, and chest pain are non-specific, but common complaints in patients poisoned with CO.

-Historical clues such as high risk exposure environments (garages, heaters) and multiple family members with the same symptoms can narrow the differential to CO poisoning.

-Management can include supportive care, normobaric and hyperbaric oxygen.

References/Further Reading

1. Weaver LK, Hopkins RO, Chan KJ, et al. Hyperbaric oxygen for acute carbon monoxide poisoning. N Engl J Med 2002;347:1057–1067
2. Igbal S, Clower JH, Boehmer TK, et al. Carbon monoxide-related hospitalizations in the U.S.: evaluation of a web-based query system for public health surveillance. Public Health Rep. 2010 May-Jun;125(3):423-32.
3. Tibbles PM, Perrotta PL. Treatment of carbon monoxide poisoning: a critical review of human outcome studies comparing normobaric oxygen with hyperbaric oxygen. Ann Emerg Med. 1994;24:269-276.
4. Arensman E, Bennardi M, Larkin C, et al. Suicide among Young People and Adults in Ireland: Method Characteristics, Toxicological Analysis and Substance Abuse Histories Compared. PLoS One. 2016 Nov 29;11(11).
5. Ernst A, Zibrak JD. Carbon Monoxide Poisoning. N Engl J Med 1998;339:1603-1608.
6. Deniz T, Kandis H, Eroglu O, et al. Carbon monoxide poisoning cases presenting with non-specific symptoms. Toxicology and Industrial Health. 2017, Vol 33(1) 53-60.
7. Higgins EA, Fiorica, V, Thomas AA, et al. Acute Toxicity of Brief Exposure to HF, HC, NO₂, and HCN with and without CO. Fire Technology 1972(8), 120-130.
8. Hardy KR, Thom SR. Pathophysiology and treatment of carbon monoxide poisoning. J Toxicol Clin Toxicol. 1994; 32(6):613-29.
9. Satran D, Henry CR, Adkinson C, et al. Cardiovascular manifestations of moderate to severe carbon monoxide poisoning. J Am Coll Cardiol. 2005;45:1513-1516.
10. Choi IS. Delayed neurologic sequelae in carbon monoxide intoxication. Arch Neurol. 1983;40:433-435.
11. Kwon OY, Chung SP, Ha YR, et al. Delayed postanoxic encephalopathy after carbon monoxide poisoning. Emerg Med J. 2004;21:250-251.
12. Lavonas EJ. Carbon monoxide poisoning. In: Shannon M, Borron S, Burns M, eds. Haddad and Winchester’s Clinical Management of Poisoning and Drug Overdose. Philadelphia, Pa: Elsevier; 2007:1297-1307.
13. Macnow TE, Waltzman ML. Carbon Monoxide Poisoning in Children: Diagnosis and Management In The Emergency Department. Pediatr Emerg Med Pract. 2016 Sep;13(9):1-24.
14. Hampson NB. Myth busting in carbon monoxide poisoning. Am J Emerg Med. 2016 Feb;34(2):295-7.
15. Zijlstra WG. Standardisation of haemoglobinometry: History and new challenges. Comparative Haematology International. 1997;7(3),125-132.
16. Brunelle JA, Degtiarov AM, Moran RF, et al. Simultaneous measurement of total hemoglobin and its derivatives in blood using CO-oximeters: analytical principles; their application in selecting analytical wavelengths and reference methods; a comparison of the results of the choices made. Scad J Clin Lab Invest Suppl. 1996;224:47-69.
17. Beigel JH. Influenza. Crit Care Med 2008;36:2660–2666.
18. Piantadosi CA. Diagnosis and treatment of carbon monoxide poisoning. Respir Care Clin N Am. 1999;5:183-202.
19. Mosquera GA, Iridoy ZM, Azcona GG, et al. Pseudotumour cerebri in children: Aetiology, clinical features, and progression. Neurologia. 2017 Jan 9.
20. Elsterova J, Palus M, Sirmarova J, et al. Tick-borne encephalitis virus neutralization by high dose intravenous immunoglobulin. Ticks Tic Borne Dis. 2017 Feb;8(2):253-258.
21. Johnson NJ, Luks AM. High-Altitude Medicine. Med Clin North Am. 2016 Mar;100(2):357-69.
22. Shah NM, Hussain S, Cooke M, et al. Wilderness medicine at high altitude: recent developments in the field. Open Access J Sports Med. 2015 Sep 24;6:319-28.
23. Hofheinz K, Bertz S, Wacker J, et al. Fever of unknown origin, giant cell arteritis and aortic dissection. Z Rheumatol. 2017 Jan 10.
24. Cabral AG, Lesczynsky A, Climaco VM, et al. Cerebral venous sinuses thrombosis in both transverse sinus and torcula: Multistep endovascular treatment and stenting. Interv Neuroradiol, 2016 Oct 26.
25. Ahmed A, Rezai H, Boradway-Stringer S. Evidence-Based Revised View of the Pathophysiology of Preeclampsia. Adv Exp Med Biol. 2016 Nov 22.
26. Schmidt KJ, Doshi MR, Holzhausen JM, et al. Treatment of Severe Alcohol Withdrawal. Ann Pharmacother. 2016 May;50(5):389-401.
27. Bradford AL, Crider CC, Xu X, et al. Predictors of Recurrent Hospital Admission for Patients Presenting With Diabetic Ketoacidosis and Hyperglycemia Hyperosmolar State. J Cin Med Res. 2017 Jan;9(1):35-39.
28. Kostic T, Momciovic S, Perisic ZD, et al. Manifestations of Lyme carditis. Int J Cardiol. 2016 Dec 27.
29. Ben Khelil M, Chkirbene Y, Mlika M, et al. Penicillin-Induced Fulminant Myocarditis: A Case Report and Review of the Literature. Am J Forensic Med Pathol. 2016 Dec 21.
30. Pietrus M, Paprota P, Radziszewska R, et al. Carbon monoxide poisoning in pregnant woman. Przegl Lek. 2015;72(9):482-4.
31. Wolf SJ, Maloney GE, Shih RD, et al. Clinical Policy: Critical Issues in the Evaluation and Management of Adult Patients Presenting to the Emergency Department With Acute Carbon Monoxide Poisoning. Ann Emerg Med 2017;69:98-107.