Carbon Monoxide Toxicity

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5 Interesting Facts of Carbon Monoxide Toxicity 

  1. Carbon monoxide toxicity results from exposure to carbon monoxide, a colorless, odorless gas produced as a byproduct of incomplete combustion of carbon-based products (eg, gas, coal) 
    • Exposure can be either unintentional (eg, poorly ventilated combustion sources, house fires) or intentional (suicide attempts)
  2. Presents with nonspecific signs and symptoms that include headache, dizziness, nausea, dyspnea, chest pain, and altered mental status; easily misdiagnosed as other conditions
  3. Diagnosis is made on basis of exposure history, clinical presentation, and elevated serum carboxyhemoglobin level
  4. First line treatment consists of 100% normobaric oxygen via face mask or endotracheal intubation, airway management, and cardiovascular support
  5. Hyperbaric oxygen is indicated in selected patients, including those with severe poisoning (eg, loss of consciousness, neurologic or cardiac manifestations) and pregnant patients

Pitfalls

  • Easily misdiagnosed in the absence of a clear exposure history; maintain high index of suspicion during winter months
  • Toxic effects on fetus are more severe than those on mother; therefore, pregnant patients should be treated with oxygen (possibly hyperbaric oxygen) even if clinical symptoms are mild
  • Carbon monoxide toxicity results from exposure to carbon monoxide, a colorless, odorless gas produced as a byproduct of incomplete combustion of carbon-based products (eg, gas, coal)
  • Causes an estimated 50,000 visits to emergency departments in the United States each year
    • Unintentional non–fire-related carbon monoxide poisoning (eg, from heaters, vehicles, or appliances) is responsible for an estimated 21,000 of these emergency department visits and is one of the leading causes of poisoning in the United States
  • May also be intentional (ie, by suicidal intent) or fire-related (eg, house fires)

Classification

  • Acute carbon monoxide poisoning
    • Cases that come to the attention of medical personnel immediately after exposure 
    • Presentation usually follows a single large exposure to carbon monoxide 
    • Incident may involve more than 1 patient (eg, household members) 
    • Most current knowledge of carbon monoxide poisoning is based on acute exposure 
  • Chronic carbon monoxide poisoning
    • Occurs when patients are exposed to carbon monoxide on multiple occasions, usually at low concentrations 
    • Symptoms occur if concentration of gas and duration of exposure are high enough; however, symptoms are usually nonspecific
    • Patients may seek medical attention after repeated exposure 
    • Diagnosis is easy to miss owing to not being considered by patient or provider 

Diagnosis

Clinical Presentation

History

  • Symptoms are vague, are nonspecific, and range in severity from mild to severe; easily mistaken for other illnesses 
    • Symptom severity does not necessarily correlate with carboxyhemoglobin level in blood
  • If related to malfunctioning heating unit, often occurs in late fall and early winter
  • History may indicate potential exposure to carbon monoxide source
    • Presence of more than 1 patient with similar symptoms raises index of suspicion 
      • Domestic animals are often symptomatic owing to higher metabolic rate
    • If symptoms occur only with car travel and worsen with longer rides, may be due to leaking automobile exhaust pipes
    • Elevated ambient carbon monoxide levels may have been measured by emergency personnel at site of exposure; however, measurement is not always possible or accurate, as ambient levels may fluctuate 
  • Acute carbon monoxide poisoning
    • Initial symptoms include:
      • Headache
      • Dizziness
      • Nausea 
      • Vomiting
      • Malaise 
    • With increasing exposure, symptoms become more pronounced:
      • Confusion
      • Altered level of consciousness 
      • Syncope 
      • Dyspnea
      • Weakness
      • Ataxia 
    • Severe manifestations include:
      • Palpitations
      • Coma
      • Seizures
      • Cardiorespiratory arrest
    • May exacerbate preexisting conditions (eg, angina, chronic obstructive pulmonary disease) 
  • Chronic low-level carbon monoxide poisoning
    • Headache
    • Dizziness
    • Anorexia
    • Lethargy/fatigue
    • Insomnia 
    • Personality changes
    • Flulike illness 
    • Impaired concentration 
    • Diarrhea 
    • Symptoms may resolve after time away from home or become worse on weekends (if more time is spent at home) 

Physical examination

  • Findings are often subtle but can include:
    • Tachypnea 
    • Tachycardia
    • Hypotension 
    • Respiratory depression 
    • Lung crackles and rales (owing to noncardiogenic pulmonary edema)
    • Neurologic signs ranging from mild to severe, including:
      • Reduction in visual perception 
      • Reduction in manual dexterity 
      • Ataxia 
      • Seizures 
      • Altered level of consciousness/coma 
      • Cognitive impairment
        • Neuropsychometric tests (eg, carbon monoxide neuropsychological screening battery, mini–mental status examination) can assess cognitive dysfunction 
    • Cherry red skin (once considered a hallmark feature) is rare except at death 
  • Physical findings may not be apparent with chronic low-level exposure
    • Subtle cognitive impairment may be detected

Causes

  • Inhalation of carbon monoxide—a colorless, odorless gas produced primarily as a result of incomplete combustion of carbon-based products, such as gas or coal—that has built up in an enclosed or semienclosed space 
    • Unintentional exposure
      • Non–fire-related causes
        • Major sources of carbon monoxide include motor vehicle exhaust, fuel-powered equipment (eg, electric generators, space heaters), and poorly maintained or inadequately ventilated home heating systems and cooking appliances
      • Fire-related causes
        • Structural fires (eg, house fires) emit carbon monoxide, posing a hazard to both victims and firefighters
    • Intentional exposure (ie, suicide attempt) 
  • Carbon monoxide poisoning results in a combination of pathophysiologic effects
    • Carbon monoxide binds hemoglobin with greater affinity than oxygen to form carboxyhemoglobin; produces a relative anemia with decreased oxygen delivery to tissues and tissue hypoxia 
    • Carbon monoxide exerts direct toxicity at a cellular level. It binds to proteins (eg, myoglobin, cytochromes, guanylate cyclase), causing direct skeletal muscle and myocardial toxicity, free radical formation, and cerebral vasodilation 
    • Exposure increases nitric oxide activity that results in cerebral vasodilation and oxidative damage to brain 

Risk factors and/or associations

Age
  • Rates of severe unintentional carbon monoxide poisoning, hospitalization, and mortality are higher in adults older than 65 years 
    • Increased risk of severe exposure in older adults may be due to delayed recognition of early nonspecific symptoms
  • Rates of nonfatal exposure and emergency department visits for exposure are higher in children and females 
    • Lower RBC count in these populations may result in earlier manifestation of symptoms, leading to shorter exposure periods and less severe poisoning
Sex
  • Rates of severe unintentional poisoning, hospitalization, and mortality are higher in males 
    • Increased risk is likely due to behaviors with increased risk (eg, using fuel-burning tools or appliances)
Other risk factors/associations
  • Seasonal pattern; unintentional, non–fire-related carbon monoxide poisoning is more common in winter months owing to increased use of home heating systems, improper use of portable generators during power outages from winter storms, and warming up motor vehicles in enclosed spaces 
    • Also accounts for geographic differences in rate of poisoning, with higher rates in regions experiencing prolonged, severe winters
  • More common during large-scale disasters (eg, hurricanes, floods) that lead to increased use of carbon monoxide–generating devices 
  • Pregnant patients, infants, and people with chronic heart disease, respiratory illness, or anemia are more susceptible to toxic effects of exposure 

Diagnostic Procedures

Primary diagnostic tools

  • Diagnosis is based on:
    • History of potential exposure to carbon monoxide source
    • Symptoms consistent with carbon monoxide toxicity (however, no particular combination of symptoms either proves or excludes a diagnosis of carbon monoxide poisoning) 
    • Elevated carboxyhemoglobin level 
  • Condition is easily misdiagnosed in the absence of a clear exposure history; maintain high index of suspicion during winter months
  • Measure serum carboxyhemoglobin levels in all patients with suspected carbon monoxide exposure 
    • Diagnosis can be based on measurement by fingertip pulse carbon monoxide–oximetry (not standard pulse oximetry) at scene of exposure; however, laboratory-based confirmation is recommended if hyperbaric oxygen therapy is being considered 
    • In multiple symptomatic patients who were in the same environment, documenting elevated carboxyhemoglobin level in a single patient is sufficient; testing all patients is not necessary 
  • Additional testing may be indicated to exclude other causes of presenting symptoms or to assess for potential complications of carbon monoxide poisoning, depending on the clinical scenario
    • Cardiac function tests (ECG with or without serum troponin level) to monitor myocardial effects of carbon monoxide poisoning 
    • Neuroimaging (CT or MRI) to exclude other causes of loss of consciousness or abnormal neurologic symptoms or signs
    • Chest radiography to assess for pulmonary edema
    • Blood glucose level to assess altered mental status
    • Serum levels of electrolytes, BUN, and creatinine 
    • CBC to assess for anemia
    • Consider toxicology screening if diagnosis is uncertain or carbon monoxide poisoning was intentional
      • In one study, 44% of patients with intentional carbon monoxide exposure had coingested drugs or ethanol 
      • At minimum, assess blood alcohol level if mental status changes do not appear to correlate with degree of carbon monoxide exposure 
    • Pregnancy test is recommended in patients of childbearing age owing to increased carbon monoxide risk to fetus 
    • Arterial blood gas analysis may be obtained to assess for metabolic acidosis (suggesting concomitant cyanide poisoning) if source of carbon monoxide poisoning was a house fire 

Laboratory

  • Serum carboxyhemoglobin level
    • Either arterial or venous blood can be used 
    • According to CDC, levels of 2% in nonsmokers and more than 9% in smokers strongly support diagnosis of carbon monoxide poisoning 
      • Other sources suggest diagnosis based on levels greater than 3% to 4% in nonsmokers and 10% in smokers 
    • Carboxyhemoglobin level
      • Clinical status of patient does not necessarily correspond with carboxyhemoglobin level 
      • Depends on duration of exposure, concentration of carbon monoxide inhaled, alveolar ventilation, and blood volume 
      • Does not predict symptoms or outcome 
      • Can be elevated in patients with hemolytic anemia or sickle cell disease without carbon monoxide exposure (owing to production of endogenous carbon monoxide)
  • Serum troponin levels
    • Measure serum troponin levels to assess for myocardial injury in patients with:
      • Abnormal ECG results
      • Cardiac or respiratory symptoms (eg, angina, dyspnea)
      • Severe carbon monoxide intoxication, defined as the presence of any of the following:
        • Carboxyhemoglobin level greater than 20% to 25% 
        • Loss of consciousness 
        • Severe metabolic acidosis
        • Signs or symptoms of cardiac ischemia (eg, angina, altered mental status, abnormal ECG result) 

Imaging

  • Chest radiography
    • Perform in all patients with smoke inhalation or severe carbon monoxide poisoning (eg, loss of consciousness, cardiorespiratory signs or symptoms) 
    • May show evidence of pulmonary edema 
  • Neuroimaging (CT or MRI)
    • Certain patterns of brain injury (eg, necrosis of globus pallidus region and other abnormalities of basal ganglia) are characteristic of carbon monoxide poisoning and may correlate with prognosis; abnormal findings are usually associated with poorer outcomes 
    • May show evidence of cerebral infarction secondary to hypoxia or ischemia 
    • Diffuse hypoxic-ischemic encephalopathy may develop in acute, severe cases 
    • Also used to exclude other causes of altered mental status, coma, or seizures

Functional testing

  • ECG
    • Perform in all patients with confirmed carbon monoxide poisoning
    • May show supraventricular or ventricular arrhythmia 
    • No correlation has been shown between levels of carboxyhemoglobin and ECG abnormalities 

Differential Diagnosis

Most common

  • Influenza
    • Viral infection of respiratory tract
    • Similarly to carbon monoxide poisoning, can cause headache, nausea, fatigue, malaise, and weakness
    • Unlike carbon monoxide poisoning, can cause fever and swollen lymph nodes
    • Differentiated on basis of history, physical examination, absence of elevated carboxyhemoglobin levels, and positive serologic test results
  • Gastroenteritis
    • Infection of gastrointestinal tract of viral, bacterial, or parasitic origin
    • Similarly to carbon monoxide poisoning, may cause nausea and vomiting, fatigue, and weakness
    • Unlike carbon monoxide poisoning, can cause dehydration, fever, and diarrhea with blood or mucus
    • Differentiated on basis of history, physical examination, absence of elevated carboxyhemoglobin levels, and demonstration of pathogens in stool
  • Tension headache
    • Primary headache that can be episodic or chronic
    • Similarly to carbon monoxide toxicity, headache and sometimes mild nausea are present
    • Unlike carbon monoxide poisoning, does not cause cardiorespiratory symptoms, vomiting, or altered level of consciousness
    • Differentiated by history (eg, occurrence for over 5 years in patients diagnosed with chronic tension headache), physical examination, and absence of elevated carboxyhemoglobin levels
  • Migraine
    • Moderate to severe primary recurrent headaches
    • Similarly to carbon monoxide poisoning, presents with headache that may be accompanied by nausea and vomiting
    • Unlike carbon monoxide poisoning, does not cause cardiorespiratory symptoms or altered level of consciousness, and may include photophobia and phonophobia
    • Differentiated by history (eg, meets specific criteria including number and timing of attacks), physical examination, and absence of elevated carboxyhemoglobin levels
  • Acute coronary syndrome
    • Caused by myocardial ischemia
    • Similarly to carbon monoxide poisoning, may cause chest pain, dyspnea, nausea, and fatigue
    • Unlike carbon monoxide poisoning, does not generally cause headache or altered mental status
    • Differentiated on basis of history, physical examination, absence of elevated carboxyhemoglobin levels, characteristic ECG changes, and elevated cardiac enzyme levels
  • Subarachnoid hemorrhage
    • Bleeding in subarachnoid space; can be caused by arteriovenous malformation, coagulation disorder, cerebral aneurysm, or head injury
    • Similarly to carbon monoxide poisoning, causes headache, altered consciousness, and nausea
    • Unlike carbon monoxide poisoning, does not typically cause cardiorespiratory symptoms; may cause anisocoria
    • Diagnosed by brain imaging: cerebral angiography, CT angiography, transcranial Doppler ultrasound, or MRI angiography
  • Cerebral tumor
    • Includes gliomas, meningiomas, pituitary gland tumors, and others
    • Similarly to carbon monoxide poisoning, causes headache, nausea, and vomiting
    • Unlike carbon monoxide poisoning, may cause focal neurologic defects and does not typically cause cardiorespiratory symptoms
    • Differentiated on basis of history, physical examination, absence of elevated carboxyhemoglobin levels, and positive findings on neuroimaging
  • Central nervous system infection
    • Can be caused by viruses, bacteria, fungi, or protozoa
    • Similarly to carbon monoxide poisoning, can cause headache, altered level of consciousness, and vomiting
    • Unlike carbon monoxide poisoning, does not typically cause cardiorespiratory symptoms and may cause fever
    • Differentiated on basis of history, physical examination, absence of elevated carboxyhemoglobin levels, positive findings on cerebrospinal fluid analysis, and neuroimaging
  • Stroke
    • Cerebrovascular accident resulting from blocked blood flow to brain
    • Similarly to carbon monoxide poisoning, can cause coma, headache, and dizziness
    • Unlike carbon monoxide poisoning, does not typically cause cardiorespiratory symptoms
    • Differentiated on basis of history, physical examination, absence of elevated carboxyhemoglobin levels, and neuroimaging
  • Intoxication
    • Results from overdose of various substances, including alcohol, opioids, and cocaine
    • Similarly to carbon monoxide poisoning, can cause altered mental status or coma, depending on causative substance
    • Unlike carbon monoxide poisoning, may not cause cardiorespiratory symptoms (depending on causative agent)
    • Differentiated on basis of history, physical examination, and absence of elevated carboxyhemoglobin levels

Treatment Goals

  • Accelerate elimination of carboxyhemoglobin from body and alleviate tissue hypoxia 
  • Relieve symptoms 
  • Reduce risk of long-term sequelae 
  • Identify and eliminate source of exposure 

Disposition

Admission criteria

Begin treatment immediately while still in the emergency department 

For patients with moderate to severe symptoms (eg, altered mental status), comorbidities (eg, burns, cardiac disease), or carboxyhemoglobin level of 25% or greater, hospitalize and arrange transfer to hyperbaric facility

Criteria for ICU admission
  • Comatose patients
  • Patients who require intubation and mechanical ventilation
  • Patients with severe metabolic acidosis (pH less than 7.2 on arterial blood gas analysis) 

Recommendations for specialist referral

  • Refer to hyperbaric specialist if hyperbaric oxygen therapy is indicated
  • Refer to cardiologist if ECG results are abnormal or elevated cardiac enzyme levels are present 
  • Refer to burn specialist if concomitant cutaneous burns are present 
  • Refer for psychiatric follow-up if carbon monoxide exposure was a suicide attempt 

Treatment Options

Treat all patients presenting to emergency department with suspected carbon monoxide poisoning with 100% high-flow normobaric oxygen 

  • Administer by face mask or endotracheal tube (as determined on individual basis by physician) 
  • Continue until carboxyhemoglobin level has normalized (usually less than 3%) and symptoms have resolved (usually 4-6 hours) 

Provide supportive care, including airway management and hemodynamic stabilization 

Consider hyperbaric oxygen therapy

  • Consists of delivery of 100% oxygen in a pressurized chamber; may require transfer to specialized facility
  • Possible benefits include: 
    • Reduced elimination half-life of carbon monoxide 
    • Induction of cerebral vasoconstriction and reduced intracranial pressure/cerebral edema
    • Increased carbon monoxide dissociation from myoglobin and cytochromes; may reduce oxidative injury
  • Has not been shown to reduce short-term mortality compared with normobaric oxygen treatment 
  • Appears to reduce long-term neurologic and cognitive sequelae (eg, memory impairment)
    • However, results from randomized trials have been mixed, and published studies have significant limitations 
  • No widespread agreement regarding selection of patients; possible indications include:
    • Carboxyhemoglobin level of 25% or higher 
    • Loss of consciousness or coma
    • Cardiac involvement (eg, ischemia, infarction, arrhythmia)
    • Severe acidosis 
    • Neurologic deficits or abnormal neuropsychiatric testing 
    • Age of 36 years or older
    • Seizures 
    • Patients with carboxyhemoglobin levels less than 25% if clinical condition or exposure history warrants it (eg, symptoms persist despite normobaric oxygen therapy); decision is made on case-by-case basis
  • Indicated in pregnant patients, even with less severe poisoning (carboxyhemoglobin level greater than 15%-20% or patient is symptomatic)
  • Contraindicated in presence of untreated pneumothorax 
  • Optimally started within 12 hours of carbon monoxide exposure 
  • Optimal dose and frequency has not been established

Nondrug and supportive care

100% oxygen at normal barometric pressure

  • Administer by mask or endotracheal tube 
  • Administer until carboxyhemoglobin level has normalized (usually less than 3%) and symptoms have resolved (usually after 4-6 hours) 
Procedures
Hyperbaric oxygen therapy

General explanation

  • Delivery of 100% oxygen inside a chamber that is pressurized beyond 1 ATA
  • May require transfer to specialized center 
  • Optimal dose and frequency unknown; treatment is at discretion of hyperbaric specialist 
  • Generally safe to administer; most common adverse effects are painful barotrauma to ears and sinuses and claustrophobia 

Indication

  • No widespread agreement regarding selection of patients; possible indications include:
    • Carboxyhemoglobin level 25% or higher
      • Also may be indicated for patients with carboxyhemoglobin level less than 25% if clinical condition or exposure history warrants it (eg, symptoms persist despite normobaric oxygen therapy); decision is made on case-by-case basis 
    • Loss of consciousness or coma 
    • Cardiac involvement (eg, ischemia, infarction, arrhythmia) 
    • Severe acidosis 
    • Neurologic deficits or abnormal neuropsychiatric test results 
    • Age of 36 years or older 
    • Seizures 
  • Treatment of choice for pregnant patients, even if they are less severely poisoned 

Contraindications

  • Absolute
    • Untreated pneumothorax
  • Relative
    • Asthma
    • Congenital spherocytosis
    • History of bleomycin treatment
    • Chronic obstructive airway disease 
    • Claustrophobia 
    • Bowel obstruction 
    • Otosclerosis 

Complications

  • Inner ear barotrauma
  • Oxygen toxicity
  • Confinement anxiety
  • Tension pneumothorax 

Comorbidities

  • Smoke inhalation
    • Upper airway and lung injuries result from inhalation of superheated air, smoke, and/or chemical products of combustion in house fire
    • May require intubation, mechanical ventilation, aggressive fluid resuscitation, bronchoscopic evaluation, and removal of foreign particles and secretions 
  • Cyanide toxicity
    • Concomitant cyanide poisoning may be present when source of carbon monoxide exposure is smoke inhalation in house fires 
    • Causes severe metabolic acidosis 
    • Provide aggressive supportive therapy and supplemental oxygen
    • Consider empirical treatment with antidote for cyanide toxicity (hydroxocobalamin) if severe metabolic acidosis is present (arterial blood pH is less than 7 or plasma lactate level is 10 mmol/L or greater) and source of carbon monoxide exposure was a house fire 
      • Avoid traditional cyanide antidote kit
        • Methemoglobinemia exacerbates carboxyhemoglobinemia

Special populations

  • Pregnant patients
    • Toxic effects on fetus are more severe than those on mother
    • Hyperbaric oxygen is treatment of choice, even with less severe poisoning 
    • Prolonged oxygen therapy may be required 

Monitoring

  • Provide follow-up at 2 weeks to 2 months to assess for delayed neuropsychiatric sequelae 

Complications

  • Cardiac complications (described in 37% of patients)
    • Myocardial ischemia/infarction
    • Arrhythmia
    • Cardiac arrest 
  • Neuropsychiatric sequelae (occurring in up to 50% of patients )
    • Cognitive impairment
    • Memory loss
    • Anxiety 
    • Depression 
    • Attention disorders 
    • Parkinsonism 
    • Tinnitus
    • Hearing loss
    • Vestibular and balance problems
    • Peripheral neuropathy
    • Persistent headaches
    • Sleep problems

Prognosis

  • Outcome depends on concentration of carbon monoxide, duration of exposure, and underlying health status of patient 
  • Mortality ranges between 1% and 3%, depending on severity of poisoning 
  • Poorer prognosis is seen with higher carboxyhemoglobin levels, elderly patients, and patients with preexisting cardiovascular disease, carbon monoxide–induced metabolic acidosis, or structural changes on neuroimaging
  • Long-term neurocognitive deficits occur in 15% to 40% of patients 
  • Long-term mortality is increased after unintentional poisoning; may be partly due to long-term neurologic injury 

Prevention

  • Public education campaigns about the dangers of carbon monoxide, especially during power outages 
  • Proper maintenance and operation of home heating systems, cooking appliances, and other carbon monoxide–emitting equipment 
  • Use of residential carbon monoxide monitors/detectors, with proper maintenance 
    • Minimum of 1 detector per home, located near sleeping area
    • Batteries replaced semiannually, unless label clearly states otherwise
      • Some detectors are sealed for multiyear life of unit; at expiry date, whole unit must be replaced; intent is to better protect public from failure to replace batteries and failure to replace detector
    • Monitor replaced periodically according to manufacturer’s instructions (most detectors should be replaced after 1 decade)

References

Harper A et al: Carbon monoxide poisoning: undetected by both patients and their doctors. Age Ageing. 33(2):105-9, 2004

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