Carbon Monoxide Toxicity Updated: Dec 26, 2017

Background

Carbon monoxide (CO) is a colorless, odorless gas produced by incomplete combustion of carbonaceous material. Clinical presentation in patients with CO poisoning ranges from headache and dizziness to coma and death. Hyperbaric oxygen therapy (see the image below) can significantly reduce the morbidity of CO poisoning, but a portion of survivors still suffer significant long-term neurologic and affective sequelae. [1]

See Clues on the Skin: Acute Poisonings, a Critical Images slideshow, to help diagnose patients based on their dermatologic presentations.

CO is formed as a by-product of burning organic compounds. Many cases of CO exposure occur in private residences. [2] CO toxicity is especially common during power outages due to storms, as a result of the improper use of gasoline-powered portable generators to provide electricity and indoor use of charcoal briquettes for cooking and heating. [3, 4] Exhaust from generators and propulsion engines on houseboats has also been linked to CO poisoning. [5]

Most fatalities from CO toxicity result from fires, but 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 the following [6, 7] :

Propane-fueled forklifts
Gas-powered concrete saws
Inhaling spray paint
Indoor tractor pulls
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. Rarely, methylene chloride is ingested, and can result in delayed CO toxicity. The 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.

Cellular hypoxia from CO toxicity is caused by impedance of oxygen delivery. CO reversibly binds hemoglobin, resulting in relative functional 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 three 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 CO toxicity. Clinical status often does not correlate well with HbCO level, leading some to postulate an additional impairment of cellular respiration.

CO can produce direct cellular changes involving immunological or inflammatory damage by a variety of mechanisms, including the following [3] :

Binding to intracellular proteins (myoglobin, cytochrome a,a 3)
Nitric oxide generation leading to peroxynitrite production
Lipid peroxidation by neutrophils
Mitochondrial oxidative stress
Apoptosis
Immune-mediated injury
Delayed inflammation

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. [8]

Studies have demonstrated release of nitric oxide free radicals (implicated in the pathophysiology of atherosclerosis) from platelet and vascular endothelium, following exposure to CO concentrations of 100 ppm. One study suggests a direct toxicity of CO on myocardium that is separate from the effect of hypoxia.[9]

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.

Epidemiology

Frequency

United States

Unintentional, non–fire-related CO poisoning is responsible for approximately 15,000 emergency department visits annually in the United States. In 2000-2009 the exposure site was reported as residence in 77.6% of cases and workplace in 12%. [10] The most common source of CO exposure in the home is furnaces (18.5%), followed by motor vehicles, stoves, gas lines, water heaters, and generators. [11] During 1999–2012, deaths from unintentional non–fire-related CO poisoning in the US totaled 6136, an average of 438 deaths per year.[12]

In 2016, the American Association of Poison Control Centers reported 12,239 single exposures to CO, 315 of which were intentional. Major outcomes occurred in 190 cases, and 48 deaths were reported. [13]

International

Quantifying the global incidence of CO poisoning is impossible because of the transient duration of symptoms in mild intoxication, the ubiquitous and occult nature of exposure, and the tendency of misdiagnosis. In contrast to findings in the United States, one Australian study of suicidal poisonings indicated no decrease following significantly lowered CO emissions from 1970-1996 and revealed no difference between the HbCO levels of occupants in cars with and without catalytic converters. [14]

Race

All ages, ethnic populations, and social groups are affected, yet particular groups may be at higher risk.

Earlier data stated that, for unintentional fatalities, race-specific death rates were 20% higher for blacks. More recent data reveal non-Hispanic whites and non-Hispanic blacks to have equally high death rates, significantly above that of Hispanic and those classified as Other. [15]
Conversely, intentional fatalities demonstrate that race-specific rates for blacks and other minority racial groups are 87% lower than for whites, revealing a cultural partiality to this form of suicide.

Two North American studies, from the 1990s and 2005, examined the incidence of CO toxicity from indoor heating devices used during severe winter storms. Both studies identified a strong association between CO toxicity and US immigrants who were non-English speaking. [16] However, a study of acute, severe CO poisoning from portable electric generators in the US from August 1, 2008 to July 31, 2011 found that 96% of patients spoke English. [4]

Sex

During 1999–2010, the average annual death rate from unintentional non–fire-related CO poisoning was more than three times higher for males than for females (0.22 versus 0.07 per 100,000 population, respectively). Males represented an overwhelming 74% of unintentional non–fire-related deaths. [15]

Age

Age-specific fatality rates increase with age and are highest in those older than 65 years. However, nonfatal exposures are more common in older teens and young adults (aged 15-34 y) than in older adults and are most common in young children (aged 0-4 y). [15, 11]

Individuals with pulmonary and cardiovascular disease tolerate CO intoxication poorly; this is particularly evident in those with chronic obstructive pulmonary disease (COPD) who have the additional concern of ventilation-perfusion abnormalities and possible respiratory depressive response to 100% oxygen therapy.

Neonates and the in utero fetus are more vulnerable to CO toxicity because of the natural leftward shift of the dissociation curve of fetal hemoglobin, a lower baseline PaO2, and levels of HbCO at equilibration that are 10-15% higher than maternal levels.

Climate and weather

Age-adjusted fatality rates are higher in cold and mountainous Midwestern and Western states and peak in the winter months. However, multiple incidents of CO poisoning were reported in Southern states following the Katrina and Rita hurricanes of 2005, and in Northeastern states following Hurricane Sandy in 2012. [17, 18]

History

Misdiagnosis of carbon monoxide (CO) toxicity 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 (see Background and Causes).

For nonfatal nonintentional non–fire-related exposures, the most common symptom was headache (37%) followed by dizziness (18%) and nausea (17%). [11]However, any of the following symptoms should alert suspicion in the winter months, especially when the patient has a history compatible with CO exposure and when more than one patient in a group or household presents with similar complaints:

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 exposure also produces the above symptoms; however, patients with chronic CO exposure may present with loss of dentition, 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 may include the following:

Tachycardia
Hypertension or hypotension
Hyperthermia
Marked tachypnea (rare; severe intoxication often associated with mild or no tachypnea)

Although so-called cherry-red skin has traditionally been considered a sign of CO poisoning (ie, "When you're cherry red, you're dead"), it is in fact rare. [3]Pallor is present more often

Ophthalmologic findings include the following:

Flame-shaped retinal hemorrhages
Bright red retinal veins (a sensitive early sign)
Papilledema
Homonymous hemianopsia
Noncardiogenic pulmonary edema

Neurologic and/or neuropsychiatric findings may include the following;

Memory disturbance (most common), including retrograde and anterograde amnesia with amnestic confabulatory states
Emotional lability, impaired judgment, and decreased cognitive ability
Stupor, coma, gait disturbance, movement disorders, and rigidity
Brisk reflexes, apraxia, agnosia, tic disorders, hearing and vestibular dysfunction, blindness, 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.

Causes

See the list below:

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 datafrom 1986-1991 revealed that leading sources of 1149 unintentional nonfatal CO poisonings were residential furnaces (40%), automobile exhaust (24%), and fires (12%); however, furnaces were responsible for onlly 10% of fatal poisonings [19]
In the setting of structure fires, AntibioticsClass SummaryEmpiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.Penicillin G (Pfizerpen)View full drug informationPenicillin G is used for IE caused by S viridans or S bovis with a penicillin G minimum inhibitory concentration (MIC) of 0.1 mcg/mL or less.Oxacillin (Bactocil in Dextrose)View full drug informationOxacillin is a bactericidal antibiotic that inhibits cell wall synthesis. It is used to treat infections caused by penicillinase-producing staphylococci. It is used to initiate therapy when MSSA infection is present.Ceftriaxone (Rocephin)View full drug informationCeftriaxone is given as once-daily treatment of S viridans or HACEK (ie, H aphrophilus, A actinomycetemcomitans, C hominis, E corrodens, K kingae) IE. It is a third-generation cephalosporin with broad-spectrum gram-negative activity. It has lower efficacy against gram-positive organisms and higher efficacy against resistant organisms. It arrests bacterial growth by binding to one or more penicillin-binding proteins.VancomycinView full drug informationVancomycin is the drug of choice for patients who are allergic to penicillin who have streptococcal or enterococcal endocarditis, those with methicillin-resistant S aureus (MRSA) IE, and those with other beta-lactam–resistant gram-positive IE infections.It is important to achieve adequate trough levels of 15-20 mcg/mL. If theMIC of the isolate is 2 mcg/mL or greater, vancomycin should not be administered.The duration of treatment is 4 weeks in penicillin-susceptible streptococcal IE and 4-6 weeks for staphylococcal infections, prosthetic valve infections, or enterococcal IE.GentamicinView full drug informationGentamicin is an aminoglycoside used in combination therapy to attain bactericidal activity against enterococci and resistant streptococcal species, to shorten treatment of penicillin-susceptible streptococcal IE, and for prosthetic staphylococcal IE.The duration of treatment is 2 weeks for penicillin-susceptible streptococcal IE and 4-6 weeks for penicillin-resistant streptococci and enterococci.StreptomycinView full drug informationStreptomycin is an aminoglycoside antibiotic that has bacteriocidal activity and acts by inhibiting protein synthesis. It may be used for the treatment of streptococcal or enterococcal endocarditisAmpicillinView full drug informationAmpicillin is used for treatment of enterococcal IE, IE caused by HACEK organisms, or as a penicillin G substitute for penicillin-susceptible organisms.For enterococcal endocarditis, duration of treatment is 4-6 weeks in combination with gentamicin.Ampicillin and sulbactam (Unasyn)View full drug informationAmpicillin and sulbactam is a drug combination consisting of a beta-lactamase inhibitor with ampicillin. It interferes with bacterial cell wall synthesis during active replication, causing bactericidal activity against susceptible organisms.CefazolinView full drug informationCefazolin is a first-generation cephalosporin that is used for staphylococcal endocarditis susceptible to methicillin/oxacillin. It may be substituted for penicillin G or ampicillin for penicillin-susceptible streptococcal endocarditis. It is used if the patient develops a mild rash to penicillins but no anaphylaxis or severe immediate hypersensitivity reactions.Ceftazidime (Fortaz, Tazicef)View full drug informationCeftazidime is a third-generation cephalosporin with broad-spectrum, gram-negative activity, including against pseudomonas. It has lower efficacy against gram-positive organisms and higher efficacy against resistant organisms. It arrests bacterial growth by binding to one or more penicillin-binding proteins, which, in turn, inhibits the final transpeptidation step of peptidoglycan synthesis in bacterial cell wall synthesis, thus inhibiting cell wall biosynthesis. The condition of the patient, severity of the infection, and susceptibility of the microorganism should determine the proper dose and route of administration.Cefepime (Maxipime)View full drug informationCefepime is a fourth-generation cephalosporin with gram-negative coverage comparable to ceftazidime, but it has better gram-positive coverage (comparable to ceftriaxone). Cefepime is a zwitter ion and rapidly penetrates gram-negative cells.Nafcillin (Nallpen in Dextrose)View full drug informationNafcillin is used for staphylococcal IE caused by organisms susceptible to methicillin/oxacillin.Linezolid (Zyvox)View full drug informationLinezolid prevents formation of functional 70S initiation complex, which is essential for bacterial translation process. It is bacteriostatic against enterococci and staphylococci and bactericidal against most strains of streptococci. It is used as an alternative in patients allergic to vancomycin and for treatment of vancomycin-resistant enterococci (VRE).The FDA warns against the concurrent use of linezolid with serotonergic psychiatric drugs, unless indicated for life-threatening or urgent conditions. Linezolid may increase serotonin CNS levels as a result of MAO-A inhibition, increasing the risk of serotonin syndrome.Daptomycin (Cubicin)View full drug informationDaptomycin is a cyclic lipopeptide antibiotic that is used for Staphylococcus aureus bacteremia, including those with right-sided infective endocarditis caused by MSSA or MRSA. There is a risk of developing eosinophilic pneumonia with daptomycin use. Immediate discontinuation of daptomycin is recommended if eosinophilic pneumonia is suspected.Rifampin (Rifadin)View full drug informationRifampin is used synergistically in the treatment of staphylococcal infections associated with a foreign body, such as a prosthetic heart valve.Rifampin inhibits DNA-dependent RNA polymerase activity in susceptible cells. Specifically, it interacts with bacterial RNA polymerase but does not inhibit the mammalian enzyme. Cross-resistance has been shown only with other rifamycins.Ciprofloxacin (Cipro, Cipro XR)View full drug informationCiprofloxacin is a fluoroquinolone antibiotic that inhibits bacterial DNA synthesis and, consequently, growth, by inhibiting DNA gyrase and topoisomerases, which are required for replication, transcription, and translation of genetic material. Quinolones have broad-spectrum activity against gram-positive and gram-negative aerobic organisms. It has no activity against anaerobes.Doxycycline (Adoxa, Doryx, Monodox, Vibramycin)View full drug informationDoxycycline is a broad-spectrum, synthetically derived bacteriostatic antibiotic in the tetracycline class. It is almost completely absorbed, concentrates in bile, and is excreted in urine and feces as a biologically active metabolite in high concentrations. It inhibits protein synthesis and, thus, bacterial growth by binding to the 30S and possibly 50S ribosomal subunits of susceptible bacteria. It may block dissociation of peptidyl t-RNA from ribosomes, causing RNA-dependent protein synthesis to arrest.Sulfamethoxazole and Trimethoprim (Bactrim, Bactrim DS, Septra DS, Sulfatrim)View full drug informationTrimethoprim and sulfamethoxazole inhibit bacterial growth by inhibiting the synthesis of dihydrofolic acid.Quinupristin and dalfopristin (Synercid)View full drug informationQuinupristin and dalfopristin belong to the macrolide/lincosamide/streptogramin group of antibiotics. The combination inhibits protein synthesis and is usually bacteriostatic. This drug combination is effective against Enterococcus faecium, but not Enterococcus faecalis strains. It is an option for the treatment of vancomycin-resistant E faecium infections.Ticarcillin-clavulanate (Timentin)View full drug informationTicarcillin-clavulanate inhibits the biosynthesis of cell wall mucopeptide and is effective during the stage of active growth. The drug combination includes an antipseudomonal penicillin plus a beta-lactamase inhibitor that provides coverage against most gram-positive, most gram-negative, and most anaerobic organisms.Piperacillin and Tazobactam sodium (Zosyn)View full drug informationcombination includes an antipseudomonal penicillin plus beta-lactamase inhibitor. It inhibits biosynthesis of cell wall mucopeptide and is effective during the stage of active multiplication.
In most developing countries, cooking or heating is often done with unvented cookstoves, wood, charcoal, animal dung, or agricultural waste, wwhich has been linked with elevated HbCO levels
Boats and houseboats represent a significant and underappreciated source of exposure, with multiple case reports and studies [5]

Laboratory Studies

The clinical diagnosis of acute carbon monoxide (CO) poisoning should be confirmed by demonstrating an elevated level of carboxyhemoglobin (HbCO). Either arterial or venous blood can be used for testing. [3]

Analysis of HbCO requires direct spectrophotometric measurement in specific blood gas analyzers. Bedside pulse carbon monoxide (CO)-oximetry is now available but requires a special unit and is not a component of routine pulse oximetry. A 2012 study showed that noninvasive pulse CO-oximetry correlates with more rapid diagnosis and initiation of hyperbaric oxygen therapy than laboratory CO-oximetry. However, the impact on clinical outcome is still not proven. [21] A 2017 clinical policy statement from the American College of Emergency Physicians (ACEP) recommends against using pulse CO-oximetry to diagnose CO toxicity in patients with suspected acute CO poisoning (level B recommendation). [22]

Elevated CO levels of at least 3–4% in nonsmokers and at least 10% in smokers are significant. [3] 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. HbCO levels in cigarette smokers typically range from 3-5%, but may be as high as 10% in some heavy smokers. [3] Presence of fetal hemoglobin, as high as 30% at 3 months, may be read as an elevation of HbCO level to 7%.[23] Symptoms may not correlate well with HbCO levels.

Findings on arterial blood gas measurement include the following:

Partial pressure of oxygen (PaO 2) levels should remain normal; oxygen saturation is accurate only if directly measured but not if calculated from PaO 2, which is common in many blood gas analyzers.
As with pulse oximetry, estimate PCO 2 levels by subtracting the carboxyhemoglobin (HbCO) level from the calculated saturation. PCO 2level may be normal or slightly decreased. Metabolic acidosis occurs secondary to lactic acidosis from ischemia.

The ACEP recommends obtaining an electrocardiogram and cardiac biomarker levels in emergency department patients with moderate to severe CO poisoning (level B recommendation). [22] Cardiac marker results include the following:

Elevated high-sensitive troponin I levels often indicate cardiomyopathy, including reversible global dysfunction and a Takotsubo-like pattern [24]
Myocardial ischemia is common in patients hospitalized for moderate-to-severe CO exposure and is a predictor of mortality. [25]
Patients with preexisting cardiovascular disease can experience increased exertional angina with HbCO levels of just 5-10%; at high HbCO levels, even young healthy patients develop myocardial depression

Other test results include the following:

Creatinine kinase, urine myoglobin - Nontraumatic rhabdomyolysis can result from severe CO toxicity and can lead to acute renal failure
Complete blood count - Mild leukocytosis may be present; disseminated intravascular coagulation (DIC) and thrombotic thrombocytopenic purpura(TTP) require further hematologic studies
Electrolytes and glucose level - Hypokalemia and hyperglycemia occur with severe intoxication
Blood lactate level - Elevation is an indication of severity [3, 26] ; if the source of the CO was a house fire and the lactate level is 10 mmol/L or higher, the patient may have concomitant cyanide poisoning [3]
Blood urea nitrogen (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 PaO 2
Toxicology screen - For instances of suicide attempt
Ethanol level - A confounding factor of both intentional and unintentional poisonings
Cyanide level - If cyanide toxicity also is suspected (eg, industrial fire); cyanide exposure is suggested by an unexplained metabolic acidosis; rapid determinations rarely are available. Smoke inhalation is the most common cause of acute cyanide poisoning.

Imaging Studies

Obtain a chest radiograph in patients with significant intoxications, pulmonary symptoms, evidence of hypoxia, or if hyperbaric oxygen is to be used. Findings usually are normal. Changes such as the following imply a worse prognosis than normal findings:

Ground-glass appearance
Perihilar haze
Peribronchial cuffing
Intra-alveolar edema

Computed tomography

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.

Serial CT scans may be necessary, especially with mental status deterioration. One report describes the evolution of acute hydrocephalus in a child poisoned with CO, documented by serial CT scans. [27]

Magnetic resonance imaging

MRI is more accurate than CT scans for detection of focal lesions and white matter demyelination and is often used for follow-up care. The progression from conventional MRI to diffusion-weighted imaging (DWI) and then diffusion tensor imaging (DTI) has enabled increasingly sensive evaluation of damage from CO poisoning. DTI can visualize progressive pathologic changes in the early stage of CO toxicity, allowing prediction of chronic conditions. [8]

Other Tests

On electrocardiography, sinus tachycardia is the most common abnormality. Arrhythmias may be secondary to hypoxia, ischemia, or infarction. Even low HbCO levels can have a 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 are available that can be performed in about 30 minutes by a well-trained examiner. These are more applicable to the emergency department (ED) setting. These tests 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. The tests are used in some institutions, but studies prospectively confirming the conclusions are lacking.

Research indicates a specific link to deficits in context-aided memory in CO poisoing.Use of such specific testing in the ED has been proposed, as a tool for measuring the severity of neurologic involvement.

Prehospital Care

Promptly remove the patient from continued exposure and immediately institute oxygen therapy with a nonrebreather mask.
Institute cardiac monitoring. Pulse oximetry, although not useful in detecting carboxyhemoglobin (HbCO), is still important because a low saturation causes even greater apprehension in this setting.
Perform intubation for the comatose patient or, if necessary for airway protection, and provide 100% oxygen therapy.
Give notification to the emergency department for comatose or unstable patients because rapid or direct transfer to a hyperbaric center may be indicated.
If possible, obtain ambient carbon monoxide (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

Considerations in emergency department (ED) care include the following:

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. However, pulse CO-oximetry units are available that can screen for CO toxicity at the bedside.
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.
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. Pregnant patients should be considered for hyperbaric treatment at lower carboxyhemoglobin levels (above 15%). Complicated issues of treatment of fetomaternal poisoning are discussed in Special Concerns.
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 PCO 2 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 as contributing factors. 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.

Hyperbaric Oxygen Therapy

Locate the nearest hyperbaric oxygen center by contacting the Divers Alert Network (DAN) at Duke University at (919) 684-2948. However, note that a survey of hyperbaric programs in the United States found that only 43 of 361 centers (11.9%) had equipment, intravenous infusion pumps and ventilators, and staff necessary to treat high-acuity patients. [28]

Hyperbaric oxygen (HBO) therapy 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. Despite these individual claims, systematic reviews have not revealed a clear benefit of HBO. [29, 30] A 2017 clinical policy statement from the American College of Emergency Physicians (ACEP) concluded that it remains unclear whether HBO therapy is superior to normobaric oxygen therapy for improving long-term neurocognitive outcomes.[22]

Presently, universal treatment criteria do not exist; however, a survey of directors of North American HBO facilities with 85% responding demonstrates some consensus. The most common selection criteria (regardless of HbCO level) include the following:

Coma (98%)
Transient loss of consciousness (77%)
Ischemic ECG changes (91%)
Focal neurologic deficits (94%)
Abnormal neuropsychiatric test results (91%).

Ninety-two percent of HBO facility directors use HBO for headache, nausea, and HbCO levels above 40%; yet only 62% have a specific minimum HbCO level in asymptomatic patients. One half of the centers place a time limit on delay of treatment in patients with transient loss of consciousness alone.

HBO at 3 atm raises the amount of oxygen dissolved in the serum to 6.8%, enough to sustain cerebral metabolism. Elimination half-life is reduced to 15-23 minutes. Elimination half-life of CO from methylene chloride intoxication of 13 hours at room air temperature is reduced to 5.8 hours.

Chambers are small monoplace hulls, allowing space for a single patient in a supine position who can be viewed through a window at the head, or they are acrylic walled and allow full visualization. Many of these monoplace chambers allow for care of critically ill patients, including intravenous lines, arterial lines, and ventilator. Others are large multiplace chambers that permit ventilation equipment and allow medical teams to accompany the patient. A monoplace chamber is shown below.

Treatment regimens usually involve 100% oxygen at 2.4-3 atm for 90-120 minutes. Re-treatment, although controversial, may be performed for acutely and chronically persistent symptoms. One study suggests that degree of metabolic acidosis can predict the need for re-treatment. [31]

Complications of therapy include decompression sickness, sinus and middle ear barotrauma, seizure, progression of pneumothorax to tension pneumothorax, gas embolism, reversible visual refractive changes, and complications related to transport of unstable patients.

For treatment of complications from therapy, decongestants are useful, prophylactic myringotomy is common and a requirement for intubated patients, and chest tube placement is mandatory with pneumothorax. Exercise caution in patients who have experienced chest compressions, central venous catheterization, intubation, and positive pressure ventilation. Seizures are most often secondary to oxygen toxicity and do not mandate anticonvulsant therapy or discontinuation of HBO therapy.

In multiplace chambers, seizure therapy consists of removing the oxygen mask. In monoplace chambers, decompression lowers oxygen concentration. It is crucial not to do this during the tonic phase of the seizure because it may cause pulmonary barotrauma secondary to gas expansion in the lungs.

A 10-year retrospective study found that transfer to an HBO facility did not need to be delayed for concern of cardiac arrest, respiratory arrest, myocardial infarction, or worsening mental status if they had not occurred during initial resuscitation; however, hypotension, dysrhythmia, seizure, emesis, and agitation were of concern in transit as well as in initial resuscitation. [32]

Complications

Survivors of CO poisoning are at risk for a range of neurologic and psychiatric complications, including the following [33] :

Impaired intellectual function
Short-term memory loss
Dementia
Amnesia
Psychosis
Irritability
Dysfunctional gait
Speech disorders
Parkinson disease [34]
Cortical blindness
Depression

Survivors of intentional CO poisoning are at extreme risk for subsequent completion of suicide. [3]

Further Outpatient Care

Asymptomatic patients with HbCO levels below 10% may be discharged. In cases of accidental CO poisoning, patients should be followed up in 4-6 weeks to screen for cognitive sequelae. With intentional poisoning, psychiatric follow-up is mandatory, given the high rate of subsequent completed suicide. [3]

Further Inpatient Care

See the list below:

Admitted patients generally require monitored settings, telemetry beds, or cardiac care unit/medical intensive care unit (CCU/MICU) beds for more severe cases.
Patients with cerebral edema may be most appropriately treated in a neurosurgical ICU setting; this may dictate transfer to another facility. Admission or consult by toxicology service is helpful in these cases.

Prognosis

Considerations regarding prognosis include the following:

Variability of clinical severity, laboratory values, and outcome limits prognostic accuracy
Cardiac arrest, coma, metabolic acidosis, and high HbCO levels are associated with poor outcome
Abnormal CT or MRI findings are associated with persistent neurologic impairment
Neuropsychiatric testing may have prognostic efficacy in determining delayed sequelae

Patient Education

See the list below:

Carbon monoxide (CO) detectors: Home CO detectors with audible alarms are available. One study of 911 calls for suspected CO poisoning showed in 80% of calls for detector alarms, verifiable ambient CO levels were present in the home; the mean concentration of CO was 18.6 ppm in homes tested because of detector alarms but was 96.6 ppm in homes without alarms where calls were prompted by suspicious symptoms. [35]
Discuss the possibility of delayed neurologic complications, although they are much more common in patients with toxicity severe enough to require hospital admission.
Suggest minimizing physical activity for 2-4 weeks.
Advise patient to stop smoking.
For patient education information, see the First Aid and Injuries Center, as well as Carbon Monoxide Poisoning.