Carbon monoxide (CO) is a colorless, odorless gas produced by incomplete combustion of carbonaceous material. Commonly overlooked or misdiagnosed, CO intoxication often presents a significant challenge, as treatment protocols, especially for hyperbaric oxygen therapy, remain controversial because of a paucity of definitive clinical studies.
CO is formed as a by-product of burning organic compounds. Although most fatalities result from fires, stoves, portable heaters, and automobile exhaust cause approximately one third of deaths. These often are associated with malfunctioning or obstructed exhaust systems and suicide attempts. Cigarette smoke is a significant source of CO. Natural gas contains no CO, but improperly vented gas water heaters, kerosene space heaters, charcoal grills, hibachis, and Sterno stoves all emit CO. Other sources of CO exposure include propane-fueled forklifts, gas-powered concrete saws, inhaling spray paint, indoor tractor pulls, and swimming behind a motorboat.
CO intoxication also occurs by inhalation of methylene chloride vapors, a volatile liquid found in degreasers, solvents, and paint removers. Dermal methylene chloride exposure may not result in significant systemic effects but can cause significant dermal burns. Liver metabolizes as much as one third of inhaled methylene chloride to CO. A significant percentage of methylene chloride is stored in the tissues, and continued release results in elevated CO levels for at least twice as long as with direct CO inhalation.
Children riding in the back of enclosed pickup trucks seem to be at particularly high risk. Industrial workers at pulp mills, steel foundries, and plants producing formaldehyde or coke are at risk for exposure, as are personnel at fire scenes and individuals working indoors with combustion engines or combustible gases.
Pathophysiology:CO toxicity causes impaired oxygen delivery and utilization at the cellular level. CO affects several different sites within the body but has its most profound impact on the organs (eg, brain, heart) with the highest oxygen requirement.
Toxicity primarily results from cellular hypoxia caused by impedance of oxygen delivery. CO reversibly binds hemoglobin, resulting in relative anemia. Because it binds hemoglobin 230-270 times more avidly than oxygen, even small concentrations can result in significant levels of carboxyhemoglobin (HbCO).
An ambient CO level of 100 ppm produces an HbCO of 16% at equilibration, which is enough to produce clinical symptoms. Binding of CO to hemoglobin causes an increased binding of oxygen molecules at the 3 other oxygen-binding sites, resulting in a leftward shift in the oxyhemoglobin dissociation curve and decreasing the availability of oxygen to the already hypoxic tissues.
CO binds to cardiac myoglobin with an even greater affinity than to hemoglobin; the resulting myocardial depression and hypotension exacerbates the tissue hypoxia. Decrease in oxygen delivery is insufficient, however, to explain the extent of the toxicity. Clinical status often does not correlate well with HbCO level, leading some to postulate an additional impairment of cellular respiration.
CO binds to cytochromes c and P450 but with a much lower affinity than that of oxygen; very low levels of in vitro binding result. Additionally, the patient groups exhibiting neuropsychiatric deficits often are not acutely acidotic.
Studies have indicated that CO may cause brain lipid peroxidation and leukocyte-mediated inflammatory changes in the brain, a process that may be inhibited by hyperbaric oxygen therapy. Following severe intoxication, patients display central nervous system (CNS) pathology, including white matter demyelination. This leads to edema and focal areas of necrosis, typically of the bilateral globus pallidus. Interestingly, the pallidus lesions, as well as the other lesions, are watershed area tissues with relatively low oxygen demand, suggesting elements of hypoperfusion and hypoxia.
Recent studies have demonstrated release of nitric oxide free radical (implicated in the pathophysiology of atherosclerosis) from platelet and vascular endothelium, following exposure to CO concentrations of 100 ppm.
HbCO levels often do not reflect the clinical picture, yet symptoms typically begin with headaches at levels around 10%. Levels of 50-70% may result in seizure, coma, and fatality.
CO is eliminated through the lungs. Half-life of CO at room air temperature is 3-4 hours. One hundred percent oxygen reduces the half-life to 30-90 minutes; hyperbaric oxygen at 2.5 atm with 100% oxygen reduces it to 15-23 minutes.
History: Misdiagnosis commonly occurs because of the vagueness and broad spectrum of complaints; symptoms often are attributed to a viral illness. Specifically inquiring about possible exposures when considering the diagnosis is important. Any of the following should alert suspicion in the winter months, especially in relation to the previously named sources and when more than one patient in a group or household presents with similar complaints. Symptoms may not correlate well with HbCO levels.
Acute poisoning
Malaise, flulike symptoms, fatigue
Dyspnea on exertion
Chest pain, palpitations
Lethargy
Confusion
Depression
Impulsiveness
Distractibility
Hallucination, confabulation
Agitation
Nausea, vomiting, diarrhea
Abdominal pain
Headache, drowsiness
Dizziness, weakness, confusion
Visual disturbance, syncope, seizure
Fecal and urinary incontinence
Memory and gait disturbances
Bizarre neurologic symptoms, coma
Chronic exposures also present with the above symptoms; however, they may present with loss of dentation, gradual-onset neuropsychiatric symptoms, or, simply, recent impairment of cognitive ability.
Physical: Physical examination is of limited value. Inhalation injury or burns should always alert the clinician to the possibility of CO exposure.
Vital signs
Tachycardia
Hypertension or hypotension
Hyperthermia
Marked tachypnea (rare; severe intoxication often associated with mild or no tachypnea)
Skin: Classic cherry red skin is rare (ie, "When you're cherry red, you're dead"); pallor is present more often.
Ophthalmologic
Flame-shaped retinal hemorrhages
Bright red retinal veins (a sensitive early sign)
Papilledema
Homonymous hemianopsia
Noncardiogenic pulmonary edema
Neurologic and/or neuropsychiatric
Patients display memory disturbance (most common), including retrograde and anterograde amnesia with amnestic confabulatory states.
Patients may experience emotional lability, impaired judgment, and decreased cognitive ability.
Other signs include stupor, coma, gait disturbance, movement disorders, and rigidity.
Patients display brisk reflexes, apraxia, agnosia, tic disorders, hearing and vestibular dysfunction, blindness, and psychosis.
Long-term exposures or severe acute exposures frequently result in long-term neuropsychiatric sequelae. Additionally, some individuals develop delayed neuropsychiatric symptoms, often after severe intoxications associated with coma.
After recovery from the initial incident, patients present several days to weeks later with neuropsychiatric symptoms such as those just described. Two thirds of patients eventually recover completely.
MRI changes may remain long after clinical recovery. Predicting and preventing long-term complications and delayed encephalopathy have been the object of recent studies, many of which focus on the role of hyperbaric oxygen therapy.
Causes:
Most unintentional fatalities occur in stationary vehicles from preventable causes such as malfunctioning exhaust systems, inadequately ventilated passenger compartments, operation in an enclosed space, and utilization of auxiliary fuel-burning heaters inside a car or camper.
Most unintentional automobile-related CO deaths in garages have occurred despite open garage doors or windows, demonstrating the inadequacy of passive ventilation in such situations.
Colorado state data revealed that sources of 1149 poisonings were residential furnaces (40%), automobile exhaust (24%), and fires (12%).
Furnaces were determined to be the source in 46% of nonfatal CO poisonings but in only 10% of fatal poisonings. This suggests that the role of home heating appliances is prominent in the large group of underreported nonfatal exposures.
Most developing countries utilize unvented cookstoves, burning wood, charcoal, animal dung, or agricultural waste. Studies have shown a concurrent rise in HbCO with these types of exposure in developing countries.
Lab Studies:
HbCO analysis requires direct spectrophotometric measurement in specific blood gas analyzers. CO can be measured with a handheld analyzer, although less accurately.
Elevated levels are significant; however, low levels do not rule out exposure, especially if the patient already has received 100% oxygen or if significant time has elapsed since exposure.
Individuals who chronically smoke may have mildly elevated CO levels as high as 10%. Presence of fetal hemoglobin, as high as 30% at 3 months, may be read as an elevation of HbCO level to 7%.
Arterial blood gas
PaO2 levels should remain normal. Oxygen saturation is accurate only if directly measured but not if calculated from PaO2, which is common in many blood gas analyzers.
As with pulse oximetry, estimate PCO2 levels by subtracting the carboxyhemoglobin (HbCO) level from the calculated saturation. PCO2 level may be normal or slightly decreased. Metabolic acidosis occurs secondary to lactic acidosis from ischemia.
Myocardial ischemia frequently is associated with CO exposure.
Patients with preexisting disease can experience increased exertional angina with HbCO levels of just 5-10%. At high HbCO levels, even young healthy patients develop myocardial depression.
Creatinine kinase, urine myoglobin: Nontraumatic rhabdomyolysis can result from severe CO toxicity and can lead to acute renal failure.
Complete blood count
Look for mild leukocytosis.
Disseminated intravascular coagulation (DIC) and thrombotic thrombocytopenic purpura (TTP) require further hematologic studies.
Electrolytes and glucose level - Lactic acidosis, hypokalemia, and hyperglycemia with severe intoxication
BUN and creatinine levels - Acute renal failure secondary to myoglobinuria
Liver function tests - Mild elevation in fulminant hepatic failure
Urinalysis - Positive for albumin and glucose in chronic intoxication
Methemoglobin level - Included in the differential diagnosis of cyanosis with low oxygen saturation but normal PaO2
Toxicology screen - For instances of suicide attempt
Ethanol level - A confounding factor of intentional and unintentional poisonings
Cyanide level - If cyanide toxicity also is suspected (eg, industrial fire); cyanide exposure suggested by an unexplained metabolic acidosis; rapid determinations rarely are available. Smoke inhalation is the most common cause of acute cyanide poisoning.
Imaging Studies:
Chest radiography
Obtain a chest radiograph with significant intoxications, pulmonary symptoms, or if hyperbaric oxygen is to be used.
Findings usually are normal.
Changes such as ground-glass appearance, perihilar haze, peribronchial cuffing, and intra-alveolar edema imply a worse prognosis than normal findings.
CT scan
Obtain a CT scan of the head with severe intoxication or change in mental status that does not resolve rapidly.
Assess cerebral edema and focal lesions; most are typically low-density lesions of the basal ganglia.
Positive CT scan findings generally predict neurologic complications.
In one study, 53% of patients hospitalized for acute CO intoxication had abnormal CT scan findings; all of these patients had neurologic sequelae. Of those patients with negative scan results, only 11% had neurologic sequelae.
MRI is more accurate than CT scans for focal lesions and white matter demyelination and is often used for follow-up care.
Serial CT scans may be necessary, especially with mental status deterioration.
A recent report describes the evolution of acute hydrocephalus in a child poisoned with CO, documented by serial CT scans.
Other Tests:
Electrocardiogram
Sinus tachycardia is the most common abnormality.
Arrhythmias may be secondary to hypoxia, ischemia, or infarction.
Even low HbCO levels can have severe impact on patients with cardiovascular disease.
Neuropsychologic testing
Formal neuropsychologic testing of concentration, fine motor function, and problem solving consistently reveal subtle deficits in even mildly poisoned patients.
Abridged versions of these tests, more applicable to the emergency department (ED) setting, have been developed as possible means to assess the risk of delayed neurologic sequelae, to assess the need for hyperbaric oxygen therapy, and to determine the success of hyperbaric therapy in preventing delayed sequelae.
These tests are used in some institutions, but studies prospectively confirming the conclusions are lacking.
Abridged tests can be performed in about 30 minutes by a well-trained examiner.
Recent research indicates a specific link to deficits in context-aided memory; such specific testing has been proposed as a tool for measuring the severity of neurologic involvement in the ED.
Prehospital Care:
Promptly remove from continued exposure and immediately institute oxygen therapy with a nonrebreather mask.
Perform intubation for the comatose patient or, if necessary, for airway protection.
Institute cardiac monitoring. Pulse oximetry, although not useful in detecting HbCO, is still important because a low saturation causes an even greater apprehension in this setting.
Give notification for comatose or unstable patients because rapid or direct transfer to a hyperbaric center may be indicated.
If possible, obtain ambient CO measurements from fire department or utility company personnel, when present.
Early blood samples may provide much more accurate correlation between HbCO and clinical status; however, do not delay oxygen administration to acquire them.
Obtain an estimate of exposure time, if possible.
Avoid exertion to limit tissue oxygen demand.
Emergency Department Care:
Cardiac monitor: Sudden death has occurred in patients with severe arteriosclerotic disease at HbCO levels of only 20%.
Pulse oximetry: HbCO absorbs light almost identically to that of oxyhemoglobin. Although a linear drop in oxyhemoglobin occurs as HbCO level rises, pulse oximetry will not reflect it. Pulse oximetry gap, the difference between the saturation as measured by pulse oximetry and one measured directly, is equal to the HbCO level.
Continue 100% oxygen therapy until the patient is asymptomatic and HbCO levels are below 10%. In patients with cardiovascular or pulmonary compromise, lower thresholds of 2% have been suggested.
Calculate a gross estimate of the necessary duration of therapy using the initial level and half-life of 30-90 minutes at 100% oxygen. Complicated issues of treatment of fetomaternal poisoning are discussed in Special Concerns.
In uncomplicated intoxications, venous HbCO levels and oxygen therapy are likely sufficient. Evaluate patients with significant cardiovascular disease and initial HbCO levels above 15% for myocardial ischemia and infarction.
Consider immediate transfer of patients with levels above 40% or cardiovascular or neurologic impairment to a hyperbaric facility, if feasible. Persistent impairment after 4 hours of normobaric oxygen therapy necessitates transfer to a hyperbaric center.
Serial neurologic examinations, including funduscopy, CT scans, and, possibly, MRI, are important in detecting the development of cerebral edema. Cerebral edema requires intracranial pressure (ICP) and invasive blood pressure monitoring to further guide therapy. Head elevation, mannitol, and moderate hyperventilation to 28-30 mm Hg PCO2 are indicated in the initial absence of ICP monitoring. Glucocorticoids have not been proven efficacious, yet the negative aspects of their use in severe cases are limited.
Do not aggressively treat acidosis with a pH above 7.15 because it results in a rightward shift in the oxyhemoglobin dissociation curve, increasing tissue oxygen availability. Acidosis generally improves with oxygen therapy.
In patients who fail to improve clinically, consider other toxic inhalants or thermal inhalation injury. Be aware that the nitrites used in cyanide kits cause methemoglobinemia, shifting the dissociation curve leftward and further inhibiting oxygen delivery at the tissue level. Combined intoxications of cyanide and CO may be treated with sodium thiosulfate 12.5 g intravenously to prevent the leftward shift.
Admit patients to a monitored setting and evaluate acid-base status if HbCO levels are 30-40% or above 25% with associated symptoms.
Consultations:
Hyperbaric oxygen therapy
Locate the nearest hyperbaric oxygen center by contacting the Divers Alert Network (DAN) at Duke University at (919) 684-2948.
Hyperbaric oxygen therapy (HBO) currently rests at the center of controversy surrounding management of CO poisoning. Increased elimination of HbCO clearly occurs. Certain studies proclaim major reductions in delayed neurologic sequelae, cerebral edema, pathologic central nervous system (CNS) changes, and reduced cytochrome oxidase impairment.
