Carbon Monoxide Toxicity

Etiology

The etiology of carbon monoxide is due to its effect on oxygen binding to the hemoglobin molecule. Carbon monoxide binds to hemoglobin, forming carboxyhemoglobin (COHb) with a 220 times greater affinity to hemoglobin than oxygen. This reduces the oxygen-carrying capacity of hemoglobin and leads to cellular hypoxia. Carboxyhemoglobin (COHb) increases the affinity of unbound hemoglobin for O_2, thus causing a leftward shift in the oxyhemoglobin dissociation curve. Additionally, carbon monoxide binds to the heme moiety of the cytochrome c oxidase in the electron transport chain and inhibits mitochondrial respiration. These effects cause a lower tissue and intracellular PO₂ than expected for a given blood oxygen concentration. The hemoglobin concentration and the PO₂ of blood may be normal, but the oxygen content of the blood is reduced significantly.[4][5]

Epidemiology

Annually, there are over 40,000 cases of carbon monoxide poisoning in the United States. There is a 0.5 to 1.0/1,000,000 person fatality rate. Carbon monoxide may be responsible for 50% of all fatal poisonings. Carbon monoxide poisoning is the major contributing cause of death in fire victims. Approximately 30% to 40% of carbon monoxide poisoning victims die before reaching the hospital. Of those hospitalized, approximately 2% die, 10% recover partially, and 23% to 47% suffer delayed neurologic sequelae.[6]

Pathophysiology

Carbon monoxide enters the body via the lungs. Direct interactions may damage the lung parenchyma without the need for delivery of blood-borne hemoglobin. Elsewhere in the body, carbon monoxide is delivered by hemoglobin. Carbon monoxide causes capillary leakage of macromolecules from the lungs and systemic vasculature, which can occur in humans exposed to relatively low concentrations of carbon monoxide for prolonged periods. As carboxyhemoglobin (COHgb) levels rise, the cerebral blood vessels dilate, and coronary blood flow and capillary density increase. If exposure continues, central respiratory depression develops, which may result from cerebral hypoxia. Cardiac effects, especially ventricular arrhythmias, occur. Ventricular arrhythmias are implicated as the cause of death, most often in carbon monoxide poisoning. There is evidence that myocardial impairment begins at a relatively low level of COHgb of 20%. The overall cause of death for most animals poisoned by carbon monoxide is combined hypoxia and ischemia during the acute event.[7]

Toxicokinetics

HGB combines with carbon monoxide 220 times more intensely than it does with oxygen. In the air in a standard room (21% O₂), the half-life of carbon monoxide is 320 minutes. In 100% O₂, the half-life of carbon monoxide is less than 90 minutes. With hyperbaric oxygen at a pressure of 3 ATA (atmospheres absolute), the half-life of carbon monoxide is decreased to 23 minutes. The only adequate treatment for significant carbon monoxide poisoning is hyperbaric oxygen therapy (HBOT).

History and Physical

The symptoms of carbon monoxide poisoning can be variable, which explains why only 5% to 6% of patients who present to the emergency department with carbon monoxide poisoning receive HBOT. Most commonly, patients present with headaches (more than 90%), dizziness, weakness, and nausea. Patients may be tachycardic and tachypneic. They may exhibit hypotension. Mental status changes such as confusion, altered level of consciousness, disorientation, and memory loss may occur. Intraocular findings may include retinal hemorrhages and congestion with papilledema. The kidneys are susceptible to ischemic injury from carbon monoxide poisoning. The classic symptoms of cherry red nail beds and mucous membranes are not "classic" and are usually post-mortem findings. Patients may also develop ataxia, apraxia, incontinence, and cortical blindness.

Evaluation

The standard ABCs (airway, breathing, and circulation) also apply to carbon monoxide-poisoned patients. Supplemental oxygen is the cornerstone of treatment. It is important to note that standard peripheral pulse oximeter devices cannot differentiate COHb from oxyhemoglobin; hence, oxygen saturation (SpO₂) does not show any abnormalities on the monitor.[7][8] Typically, an arterial blood gas sample with a co-oximetry analysis is the most useful initial step. The carboxyhemoglobin level is reported in this analysis. This number should not be the foundation upon which the treatment plan is built; however, because COHgB levels are loosely associated with symptoms, there is no direct correlation between COHgB levels and the severity of the symptoms or the risk of mortality and morbidity. COHb levels above 3% to 4% in non-smokers and 10% in smokers are typically considered outside normal limits. It is agreed that levels greater than 20 in adults indicate a significant poisoning, and levels greater than 15 in children are considered significant. The take-home point is to treat the patient, not the number. Other assessments should be assessed, such as a complete blood count, electrolytes, BUN, creatinine level, and baseline troponin. ECG should be checked for any signs of ischemia. New ischemia on ECG is indicative of severe carbon monoxide poisoning. Chest radiographs should be ordered as well. CT of the head is not required; however, carbon monoxide poisoning can manifest as globus pallidus hemorrhage; therefore, it may be useful.

Treatment / Management

The cornerstone of treatment for carbon monoxide poisoning is supplemental oxygen that should be initiated as soon as possible and continued throughout treatment. Patients with significant poisoning demonstrated by transient loss of consciousness, cardiac ischemia, mental status changes, tachycardia, and or hypotension, along with elevated carboxyhemoglobin levels, should be treated emergently with hyperbaric oxygen. Although present in every state, only several hundred hyperbaric oxygen centers currently exist in the United States of America. The best outcomes occur when patients receive their first treatment within 6 hours of the poisoning event. Most hyperbaric physicians prescribe 3 treatments in the first 24 hours and then reassess the patient's symptoms and response before continuing daily treatments. Despite hyperbaric therapy, up to 40% of patients can still develop chronic neurocognitive impairment, and hence, patients should be scheduled for neuropsychological evaluation approximately 1 to 2 months after recovery.[9][10][11] Alternate, more easily accessible, and useful therapies are still lacking. However, case reports and animal model studies are underway. These study therapies include lung phototherapy.(A1)

Differential Diagnosis

Differential diagnosis for carbon monoxide toxicity includes the following:

• Alcohol toxicity
• Depression and suicide
• Diabetic ketoacidosis (DKA)
• Encephalitis
• Hypothyroidism
• Labyrinthitis
• Meningitis
• Methemoglobinemia
• Migraine headache
• Opioid toxicity

Prognosis

The prognosis of patients with carbon monoxide poisoning does vary on the severity, other comorbidities, and laboratory values. Individuals with documented abnormal MRI and CT findings usually have a poor prognosis. Any patient with a persistent neurological deficit also had a guarded prognosis. Carbon monoxide poisoning can cause cognitive sequelae. Hyperbaric oxygen (HBO) reduces cognitive sequelae incidence in some patients.[12]

Complications

Complications with carbon monoxide toxicity include:

• Amnesia
• Dementia
• Irritability
• Psychosis
• Memory loss
• Loss of executive function
• Speech deficit
• Parkinson disease
• Depression
• Cortical blindness