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.


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.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.

Presenting Symptom % of Total Number of Patients Presenting with Elevated COHb levels (n=106)
Headache 35%
Dizziness 30%
Nausea 30%
Vomiting 24%
Altered Mentation 21%
Chest Pain 12%
Fatigue 7%
Syncope 6%

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

Symptom Disease Key Features
Headache Influenza Presentation: Headache, body ache, nausea, fever, potential history of exposure.

Evaluation: Can be evaluated with Rapid Influenza test, but typically a clinical diagnosis.

Management: Can be managed with supportive care and oseltamivir if within treatment window.

Tick Borne Illness


Presentation: Headache, body ache, nausea, fever, history of recent travel, hiking or camping trip. Presence of a rash may help distinguish from other illness (Erythema Migrans with Lyme, or centripetal rash of Rocky Mountain Spotted Fever)

Evaluation: Possible anemia, thrombocytopenia, electrolyte abnormalities on workup. Babesiosis (Peripheral blood smear with intraerythrocytic parasites). Consider antibody levels

Management: May be managed with supportive care and antibiotics depending on specific disease.



Babesiosis-Atovaquone/ Azithromycin

Intracranial Infection Presentation: Headache, nausea, fever, photophobia, seizure, nuchal rigidity, ophthalmoplegia, altered mental status, neurological deficit; recent instrumentation or recent sinus, URI, or middle ear infection can increase risk of intracranial infection.

Evaluation: Head jolt accentuation test, papilledema, focal neurological deficit on exam. Abnormal intracranial imaging. Abnormal lumbar puncture results.

Management: May be managed with supportive care and antibiotics and/or antivirals, and/or antifungal, and/or antiparasitic and in some cases neurosurgical intervention. Consider seizure prophylaxis.

Bacterial Meningitis: Ceftriaxone, Vancomycin, +/- Ampicillin, +/- Metronidazole

Viral Meningitis(HSV): Acyclovir, Valacyclovir

Fungal Meningitis: Amphotericin B

Toxoplasmosis: Pyrimethamine + sulfadiazine

Brain Abscess: Ceftriaxone and vancomycin OR cefotaxime and metronidazole

Intracranial Hemorrhage


Presentation: Headache, altered mental status, nausea, vomiting, focal neurological deficit

Evaluation: Coagulation studies, abnormal intracranial imaging

 Management: Supportive, reversal of any coagulopathy, possible neurosurgical intervention

Idiopathic intracranial hypertension


Presentation: Classically, young, obese female with headache, nausea, vomiting, and possible visual complaints. History may reveal use of oral contraceptives or vitamin A supplementation

Evaluation: Papilledema, increased ICP on LP

Management: Supportive, acetazolamide, steroids, and serial lumbar punctures. Possible neurosurgical intervention

Temporal Arteritis


Presentation: Classically, woman over the age of 50 years with head ache, eye discomfort, jaw claudication and vision changes

Evaluation: Tender temporal artery, possible APD, elevated ESR, elevated CRP, abnormal temporal artery biopsy

Management: Steroids, ophthalmology follow-up

Acute Mountain Sickness/High altitude cerebral edema(HACE)


Presentation: Classically, patient with recent altitude change, presents with headache, nausea, vomiting + cerebellar, CN deficit, and altered mental status in HACE

Evaluation: Tender temporal artery, possible APD, elevated ESR, elevated CRP, abnormal temporal artery biopsy

Management: Supportive, descent, supplemental oxygen, acetazolamide, steroids

Cyanide, Hydrogen Sulfide poisoning Presentation: Headache, syncope, nausea, vomiting, recent exposure (housefire, explosion, sewer), possible suicide attempt

Evaluation: Elevated lactic acid

Management: Supportive, hydroxocobalamin

Nausea/Vomiting Alcohol Intoxication


Presentation: Nausea, vomiting, inebriation, altered mental status, slurred speech, paresthesia (alcoholic with vitamin deficiency)

Visual changes (Methanol)

Evaluation: Blood alcohol level, elevated lactic acid, elevated anion gap/osmolal gap (ethylene glycol, methanol), oxalate crystals (ethylene glycol)


Ethanol/Isopropanol: Supportive

Ethylene glycol: Fomepizole, thiamine, pyridoxine, hemodialysis

Methanol: Fomepizole, folate, hemodialysis



Presentation: Classically, nausea, vomiting, diarrhea and either intermittent or persistent crampy abdominal pain

Evaluation: BMP, stool culture, stool O and P (consider in patient with prolonged symptoms or history suggestive of giardia exposure)

Management: Mainly supportive;

Hospitalization if severe dehydration

Invasive Diarrhea: Ciprofloxacin

Giardia: Metronidazole

C. diff: Oral vancomycin

Acute Coronary Syndrome Presentation: Classically, chest pain, shortness of breath associated with nausea, vomiting

Evaluation: EKG, cardiac biomarkers, cardiac catheterization,

Management: Supportive, aspirin, anticoagulation, antiplatelet, thrombolytics vs. PCI

DKA/HHS Presentation: Classically, patient with recent infection or noncompliance of medication presents with nausea, vomiting, abdominal pain, possibly altered mental status

Evaluation: VBG, anion gap, osmolar gap, infectious workup, ketone levels, EKGManagement: Supportive care, IV fluids, insulin, dextrose, potassium, magnesium, and treatment of potential underlying precipitant

Dyspnea/Fatigue/Syncope Pneumonia Presentation: Dyspnea, fatigue, productive cough, abdominal pain, chest pain, fever

Evaluation: Chest x-ray, chest CT

Management: Supportive, antibiotics

Congestive Heart Failure Presentation: Dyspnea, fatigue, orthopnea, cough, edema, chest pain

Evaluation: EKG, CXR, BNP, Echo, cardiac biomarkers

Management: Supportive, diuretics, non-invasive positive pressure ventilation

Pulmonary Embolism Presentation: Dyspnea, fatigue, hemoptysis, chest pain

Evaluation: EKG, echo with R heart strain, CTPA, V/Q scan, cardiac biomarkers

Management: Anticoagulation, thrombolytics (shock)

Aortic Dissection Presentation: Dyspnea, ripping/tearing chest pain, nausea, vomiting

Evaluation: EKG, chest x-ray, CT Aorta

Management: Supportive, heart rate and blood pressure control, surgical intervention



Presentation: Recent URI, presents with chest pain, shortness of breath, fever, nausea

Evaluation: EKG, chest x ray, echo, cardiac biomarkers

Management: Supportive care, Chrono/inotropic medications, IVIG, may need pericardiocentesis

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

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.

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