Carbon Monoxide Poisoning

Introduction

• CO is a colorless, odorless gas that causes unintentional poisoning and is sometimes referred to as the “silent killer.”^1,2
• CO is found in many sources commonly used every day, including but not limited to: car and stove fuel, small engines, grills, fireplaces, methylene chloride, cigarette smoke, and more.¹
• CO poisoning affects upwards of 50,000 people per year within the United States, with a mortality rate between 1% and 3%.³
• CO historically has been regarded as a poison, due to the ability to cause tissue hypoxia and generate reactive oxygen species, resulting in general toxicity due to prolonged or high concentration exposure.⁴

Pathophysiology

• CO is in the gaseous form at room temperature.²
• Hb is a tetrameric protein in the blood that contains heme groups, which are iron-containing protoporphyrin rings that bind oxygen and transport it to tissues throughout the body.
• Once in the blood after inhalation, CO more readily binds to Hb in comparison to oxygen, yielding COHb.²
• CO binding to Hb results in cellular hypoxia by decreasing oxygen delivery to the tissues. This is associated with shifting the oxyhemoglobin dissociation curve to the left.^1,5
• COHb is not the only cause of poisoning.¹
  • CO causes direct cellular toxicity by interfering with myoglobin, cytochrome, and guanylate cyclase.
  • Binding to myoglobin leads to direct skeletal and heart muscle toxicity.
  • Impaired oxidative metabolism and free radical formation occur due to the binding of cytochrome, which causes metabolic acidosis.
  • Interference with guanylate cyclase leads to cerebral vasodilation, which can cause syncope.
• There is an increase in nitric oxide (NO) activity due to CO poisoning, leading to free radical formation, leukocyte adhesion in the brain, and oxidative damage from superoxide radicals.¹
  • NO binding to neutrophils causes adherence to the microvasculature in the brain, leading to xanthine oxidase activation, the formation of free radicals, and lipid peroxidation, which promotes delayed neurological sequelae.

Clinical Presentation

• Many patients are often found unconscious or severely ill by emergency medical services.³
• Patients with COHb concentrations exceeding 30% often present with a cherry-red skin color.²
• Symptoms often associated with acute CO poisoning include:⁶
  • Dizziness
  • Nausea
  • Vomiting
  • Headache
  • Confusion
  • Fatigue
  • Chest pain
  • Loss of consciousness
  • Shortness of breath
• Individuals who experience chronic lower-level CO exposure are often more challenging to diagnose and present with decreased cognitive function and neurological issues, with more unique symptoms in comparison to acute CO poisoning:^3,5
  • Vertigo
  • Paresthesia
  • Chronic fatigue
  • Polycythemia
  • Abdominal pain
  • Diarrhea
  • Recurrent infections
• Moderate to severe CO poisoning can cause myocardial injury, with higher levels of COHb associated with the development of myocardial infarction.^3,7
• CO poisoning impairs oxidative phosphorylation, increasing the risk of arrhythmias by disrupting repolarization and prolonging the QT interval.³
• Neurological deficits are seen up to 6 weeks after CO poisoning, with some resolution up to the 6-year mark, but they are often irreversible. No correlation has been observed between symptom severity and the development of neurological sequelae.^3,8

Diagnosis

• The diagnosis of CO poisoning requires three components.⁶
  • History of potential exposure to CO
  • Elevation of carboxyhemoglobin levels in the arterial or venous blood (more than 10% in smokers, more than 3-4% in nonsmokers)
  • Symptoms consistent with CO poisoning
• Measuring the amount of COHb in the blood could confirm the diagnosis if exposure is suspected.³
• Pulse co-oximetry can expedite time to treatment and distinguish between COHb and oxyhemoglobin, compared with conventional pulse oximetry.^3,9
• Co-oximetry readings need to be confirmed with laboratory measurements. Laboratory spectrophotometry uses a CO oximeter to measure the various Hb species by selecting wavelengths and absorbance values to determine the concentration in the sample.⁶
• COHb levels are associated with certain sets of symptoms:²
  • Patients with COHb greater than 10% exhibit neurological symptoms like nausea, headache, or dizziness.
  • Patients with COHb levels between 30-50% may present with respiratory and heart rate increase, syncope, motor paralysis, and confusion.
  • Patients with COHb levels exceeding 50% are deemed to be life-threatening, as well as indicative of CO poisoning.
• Clinical symptoms of acute poisoning might not correlate with COHb levels on admission, usually because of oxygenation en route to the emergency department (ED) or the time elapsed since removal of exposure to the CO source.²

Anesthesia-Induced CO Poisoning

• Low-flow endotracheal anesthesia has been shown to result in low-concentration CO exposure. This leads to exogenous CO production within the breathing circuit due to the degradation of the anesthetic. Production may occur in the following situations:⁴
  • The absorbent’s water content is low, which increases CO production due to the inverse correlation between water and CO production.
  • The type of volatile agent affects the amount of CO produced, with higher-volatility agents, such as desflurane, having higher peak CO concentrations. However, the relationship between the CO-generating capacity of each agent depends on other variables and conditions, such as temperature or the absorbent used.
  • The degradation of the anesthetic increases with increased temperature. When the anesthetic breaks down, it raises the temperature of the absorbent through exothermic heat loss, further degrading the anesthetic.
  • Patients with higher overall CO production are at greater risk of increased CO production during anesthesia.
  • Absorbents with strong alkali hydroxides, like potassium hydroxide, produce more CO due to base-catalyzed proton abstraction. Newer carbon dioxide absorbents are composed of these strong alkali hydroxides, which lower overall CO production.
• Anesthesia providers should adhere to the Anesthesia Patient Safety Foundation recommendations to help minimize the risk of CO toxicity, know which carbon dioxide absorbent is being used, and maintain vigilance during the procedure to ensure proper use of the substance.⁴

Treatment and Prevention

Who Should Be Treated?

• All individuals who are suspected of CO poisoning should be treated with high-flow oxygen.^3,6
• Individuals who experience loss of consciousness, neurological deficits, ischemia-related cardiac changes, have a COHb greater than 25% or are in severe metabolic acidosis should be receiving hyperbaric oxygen.⁶
• Pediatric poisonings appear to have no marked differences in clinical manifestation compared to adult poisonings and are generally treated as adults.⁶
• Patients with significant burns should be treated for their burns due to the greater risk of mortality compared to CO poisoning.⁶

Short-Term Management

• Short-term management is administration of normobaric oxygen via a nonrebreather face mask at high flow, ensuring prompt elimination of CO while being taken to the ED.^5,6
• Patients should be evaluated for cardiac abnormalities with an electrocardiogram and cardiac enzyme labs due to CO’s impact on the heart muscle. If there is evidence of cardiac injury, a cardiology consult should be obtained.⁵
• Belief of intentional CO exposure should prompt a toxicology investigation to detect for alcohol or drugs such as benzodiazepines, narcotics, or other agents, as well as a potential psychiatric referral.⁵
• Patients who are considered eligible for hyperbaric oxygen should receive that treatment; if it is not available, administer 100% normobaric oxygen in the ED until the patient’s COHb is normal (≤3%).⁶

Long-Term Management

• Individuals should be monitored after discharge due to variable rates of recovery after poisoning.⁵
• Survivors of CO poisoning were found to have increased mortality compared to the standard population, with intentional poisonings having more mortality than accidental poisonings.¹⁰
• There are no specific therapies for CO poisoning sequelae; rather, symptoms are managed as they arise.⁵
• Pregnant women and young children are more likely to experience permanent sequelae of CO poisoning.⁶

Hyperbaric Oxygen Treatment

• Hyperbaric oxygen treatment is often considered by providers in the ED for cases of serious acute CO poisoning.⁵
• The goal of hyperbaric oxygen treatment is to prevent long-term neurocognitive dysfunction. There is no improvement in short-term survival with the use of hyperbaric oxygen.⁶
  • There are often methodological limitations in studies on the efficacy of hyperbaric oxygen, which affect the conclusions drawn from them.
• Please see the OA summary on “Hyperbaric Oxygen Therapy” for more details. Link
• Hyperbaric treatment in pregnant women has been deemed safe, but there are no studies of efficacy.⁶
• For burn patients, treatment with hyperbaric oxygen should be at the discretion of the burn surgeon.⁶
• Roughly 1/4 of the population carries the apolipoprotein E4 allele, which is involved in cholesterol transport in the brain and in neuronal growth and repair. It is upregulated with brain injury. In the case of CO poisoning, individuals with the E4 allele have shown no benefit from hyperbaric treatment in comparison to individuals without the allele, who do show benefit from treatment with cognitive sequelae.^5,6
• There is no optimal dose or frequency established in hyperbaric treatment, which is ultimately left at the discretion of the hyperbaric medicine physician.⁶
• The American College of Emergency Physicians recommends hyperbaric oxygen for treatment of CO poisoning but does not mandate it, again leaving it to the discretion of hyperbaric medicine physicians.³

Prevention

• Numerous states have legislation mandating the installation of residential CO alarms and smoke alarms to help alert residents to an increase in CO.⁶
  • The alarms are set to alert the individual when COHb levels exceed 10%.⁵
  • There are no current studies demonstrating the efficacy of CO alarms in reducing morbidity or mortality.³
• The introduction of catalytic converters in cars has been shown to reduce CO emissions by 75%, helping lower motor-vehicle-related poisonings.³
• Implementing periodic furnace inspections may also help prevent cases of CO poisoning.⁵