CO Poisoning
December 05, 2009, 19:40 Filed in: toxic gasses
Carbon Monoxide Poisoning
By Donald R. Elton, MD, FCCP
Lexington Pulmonary and Critical Care
Introduction
Carbon monoxide (CO) poisoning is primarily a diagnostic challenge. It is a diagnosis that is seldom made, primarily because it is seldom considered. The gas is insidious as inhaling as little as 0.1% CO can be fatal. The gas has no odor, color, taste, or irritating quality. CO poisoning accounts for about 3,500 deaths annually and is the mechanism of half of all suicides. The physician must be sensitized to the possibility of CO exposure in many patients if the diagnosis is to be made. It doesn't take a rocket scientist to consider CO exposure in fire victims but patients exposed via other mechanisms are easily missed.
Where does CO come from?
CO is a product of incomplete combustion (complete combustion producesCO2 and H2O.) This obviously includes exposures to fires by victims and fire fighters but also includes smokers (cigars produce more CO than cigarettes - up to 20% CO Hb possible). Exhaust fumes are a common source of CO exposure. A recent report detailed high levels of CO exposure in enclosed pickup truck beds from a backdraft of exhaust fumes into the back of the truck. This is particularly common in children. For this reason, passengers should not ride in the back of enclosed pickup trucks. A local case resulted when a local hospital's mammography truck parked too close to a building allowing the truck's exhaust to be entrained into the diagnostic area of the truck. A radiologic technician skipped lung, staying in the van because she didn't feel good. Her main symptoms were nausea and headache. She later collapsed and was taken to an ER where it took some time for the possibility of CO exposure to be considered. A few hours after removal from exposure she was found to have a CO Hb level exceeding 20%. Other less obvious sources of CO exposure are endogenous. Methylene Chloride, an ingredient of paint thinners, can be converted to CO by the liver during metabolism with a longer than normal half-life of excretion. Porphyrin breakdown accounts for a normal 1% CO Hb during normal turnover of hemoglobin.
Why is CO toxic?
Most of us were taught that CO is toxic because of its effect of displacing oxygen from hemoglobin thus causing hypoxia. This is probably not the primary mechanism of CO toxicity. In 1975, Goldbaum conducted a study where three groups of dogs were compared. One group was exposed to CO until their CO Hb saturation was 13% (leaving 87% available for oxygen). All dogs in this group died. A second group was made 68% anemic, reducing the oxygen carrying capacity to 32% of normal. All dogs in this group lived. A third group was transfused with CO exposed blood until their CO Hb saturation was 60% and all of these dogs survived. Another animal study by Geyer removed blood from rats and perfused them with an artificial solution capable of oxygen transport but that did not carry CO. Upon exposure to a 10% CO environment, the rats did well (remember that 0.1% CO would normally be fatal). This suggests that hemoglobin binding by CO is necessary but not sufficient to cause toxicity. Interference with oxygen transport by hemoglobin must play a minor role in CO's toxicity. One should not be surprised if measurement of COHb levels by co-oximetry is a poor method to quantify meaningful CO exposure as high levels may be survivable while low levels may result in serious injury. It is thought, that CO, in dissolved form, directly interferes with cellular metabolism by binding with cytochrome oxidase enzymes such as cytochrome a3, the terminal enzyme in the electron transport chain. CO has 200 to 250 times greater affinity for hemoglobin than oxygen but also shifts the oxyhemoglobin curve leftward which makes oxygen bind more tightly which makes it more difficult for oxygen to leave hemoglobin at the tissue level.
CO Exposure Physiology
CO levels (COHb%) have a time course of elimination from the body. The elimination half-life of CO while breathing room air is 320 minutes. This drops to 90 minutes while breathing 100% oxygen and to 23 minutes with 100% oxygen under 3 atmospheres pressure (hyperbaric chamber). A 1% CO atmosphere can allow lethal concentrations to develop within 10 minutes. Hemoglobin acts as a sink or vacuum that quickly removes any inhaled CO from the alveolar gas. Symptoms develop more quickly in children and the elderly. Sicker and/or more active patients also do worse. Exercise, stress, and anemia make individuals more susceptible. Higher atmospheric concentrations and longer durations of exposure are also factors to be considered. In CO exposure victims where the exposure is fire related, one must remember to consider the effects of other frequently fire-associated toxins such as cyanide. Because of their higher oxygen demands, the brain and heart are most sensitive to the hypoxic effects of CO exposure. CNS involvement accounts for many of the signs of CO exposure. COHb levels below 20% are usually associated with nausea, headache and mild dyspnea. From 20-40%, vomiting, poor judgement, and visual disturbances (including cortical blindness) develop. Above 40%, ataxia, confusion, syncope, coma, seizures and tachypnea are found. COHb levels are not, prognostic. Deaths have been reported with very low CO levels. About 12% of patients have delayed neurological deficits often following an initial asymptomatic period of several days. The onset of these delayed symptoms varies from 1 to 21 days with a mean of 6 days. These changes include memory impairment and personality changes as well as dementia, cerebellar ataxia and dystonias.
Clinical Diagnosis
As mentioned previously, a clinical suspicion is very important in diagnosing CO exposures. Symptoms are non-specific and include headache, dizziness, nausea and vomiting. CO exposures in the winter (when most accidental CO exposures occur) are frequently misdiagnosed as influenza, particularly when whole families are involved as they frequently are if there is a malfunctioning heater or fireplace.
Laboratory Diagnosis
The CO Hb level can be measured with co-oximetry. Remember that SaO2 levels from blood gas machines are normally calculated based on the pH and PO2 and will thus not reflect reduced levels in cases of CO poisoning. With routine blood gasses, PO2's and SaO2's will be normal (or very high if oxygen is being administered). If the exposure is significant, a metabolic acidosis will be present, reflecting tissue hypoxia. An anion gap will frequently be present and serum lactate levels may be elevated. CO Hb levels are frequently greater than 10% (up to 10% levels can be obtained from heavy smokers). CO Hb levels greater than 60% are almost always fatal but fatalities and severe brain damage can result from patients with normal CO levels. Remember that the damage may be done once levels have returned to normal from normal excretion. EKG's may show tachycardia and evidence of ischemia. Psychometric testing will frequently show mental deficits that resolve with treatment and may be the most sensitive method of detecting significant CO exposure and also provide for a means to evaluate the effects of therapy.
Therapy
Initially, all patients with suspected CO exposure should be treated with 100% oxygen delivered by a tight fitting mask (non-rebreather or demand valve device). Patients who are unconscious should be intubated. Associated conditions (burns, trauma, cyanide poisoning) should be treated. Hyperbaric oxygen therapy (HBO) is considered to be standard of care for patients with significant exposure defined as any patient who has been unconscious, neurological symptoms beyond simple headache, evidence of myocardial ischemia (symptoms or EKG), COHb levels greater than 25%, or unexpected abnormalities on psychometric testing. HBO therapy results in faster reductions in CO Hb levels (this is of uncertain importance), it increases tissue oxygen levels, and decreases cerebral edema. HBO therapy is normally given with 3 atmospheres of pressure using 100% oxygen for 90 minutes every 8 hours for 24 hours. HBO therapy almost totally eliminates the development of delayed neurologic sequelae. These effects are related to removal of CO from peripheral binding sites and not from reduction of CO Hb levels.
Follow-up
Part of treating CO poisoning is to prevent future exposures. It is not unheard of to treat a whole family for CO exposure from home and to have the family return to the same contaminated atmosphere because of a lack of understanding of the risks and need for corrective action. Follow-up must also be provided for to look for delayed results of CO exposure. Late treatment with HBO has been shown to reverse some symptoms in some cases.
References
Goldbaum LR, Ramirez RG, Absalon KB: What is the mechanism of carbon monoxide toxicity? Aviat Space Environ Med 1975; 46:1289-1291.
Myers RAM, Snyder SK, Emhoff TA: Subacute sequelae of carbon monoxide poisoning. AnnEmerg Med 1985; 14:1163-1167.
Norkool DM, Kirkpatrick JN: Treatment of acute carbon monoxide poisoning with hyperbaric oxygen: A review of 115 cases. Ann Emerg Med 1985; 14:1168-1171.
Turnbull, Timothy: Emergency Department Screening for Unsuspected Carbon Monoxide Exposure. Ann Emerg Med 17:478-489.
Stewart, RD: The Effect of Carbon Monoxide on Humans, J Occ Med 1976; 18:5.
Myers RAM: Are Arterial Blood Gases of Value in Treatment Decisions for Carbon Monoxide Poisoning? Crit Care Med 1989;17:139-142.
By Donald R. Elton, MD, FCCP
Lexington Pulmonary and Critical Care
Introduction
Carbon monoxide (CO) poisoning is primarily a diagnostic challenge. It is a diagnosis that is seldom made, primarily because it is seldom considered. The gas is insidious as inhaling as little as 0.1% CO can be fatal. The gas has no odor, color, taste, or irritating quality. CO poisoning accounts for about 3,500 deaths annually and is the mechanism of half of all suicides. The physician must be sensitized to the possibility of CO exposure in many patients if the diagnosis is to be made. It doesn't take a rocket scientist to consider CO exposure in fire victims but patients exposed via other mechanisms are easily missed.
Where does CO come from?
CO is a product of incomplete combustion (complete combustion producesCO2 and H2O.) This obviously includes exposures to fires by victims and fire fighters but also includes smokers (cigars produce more CO than cigarettes - up to 20% CO Hb possible). Exhaust fumes are a common source of CO exposure. A recent report detailed high levels of CO exposure in enclosed pickup truck beds from a backdraft of exhaust fumes into the back of the truck. This is particularly common in children. For this reason, passengers should not ride in the back of enclosed pickup trucks. A local case resulted when a local hospital's mammography truck parked too close to a building allowing the truck's exhaust to be entrained into the diagnostic area of the truck. A radiologic technician skipped lung, staying in the van because she didn't feel good. Her main symptoms were nausea and headache. She later collapsed and was taken to an ER where it took some time for the possibility of CO exposure to be considered. A few hours after removal from exposure she was found to have a CO Hb level exceeding 20%. Other less obvious sources of CO exposure are endogenous. Methylene Chloride, an ingredient of paint thinners, can be converted to CO by the liver during metabolism with a longer than normal half-life of excretion. Porphyrin breakdown accounts for a normal 1% CO Hb during normal turnover of hemoglobin.
Why is CO toxic?
Most of us were taught that CO is toxic because of its effect of displacing oxygen from hemoglobin thus causing hypoxia. This is probably not the primary mechanism of CO toxicity. In 1975, Goldbaum conducted a study where three groups of dogs were compared. One group was exposed to CO until their CO Hb saturation was 13% (leaving 87% available for oxygen). All dogs in this group died. A second group was made 68% anemic, reducing the oxygen carrying capacity to 32% of normal. All dogs in this group lived. A third group was transfused with CO exposed blood until their CO Hb saturation was 60% and all of these dogs survived. Another animal study by Geyer removed blood from rats and perfused them with an artificial solution capable of oxygen transport but that did not carry CO. Upon exposure to a 10% CO environment, the rats did well (remember that 0.1% CO would normally be fatal). This suggests that hemoglobin binding by CO is necessary but not sufficient to cause toxicity. Interference with oxygen transport by hemoglobin must play a minor role in CO's toxicity. One should not be surprised if measurement of COHb levels by co-oximetry is a poor method to quantify meaningful CO exposure as high levels may be survivable while low levels may result in serious injury. It is thought, that CO, in dissolved form, directly interferes with cellular metabolism by binding with cytochrome oxidase enzymes such as cytochrome a3, the terminal enzyme in the electron transport chain. CO has 200 to 250 times greater affinity for hemoglobin than oxygen but also shifts the oxyhemoglobin curve leftward which makes oxygen bind more tightly which makes it more difficult for oxygen to leave hemoglobin at the tissue level.
CO Exposure Physiology
CO levels (COHb%) have a time course of elimination from the body. The elimination half-life of CO while breathing room air is 320 minutes. This drops to 90 minutes while breathing 100% oxygen and to 23 minutes with 100% oxygen under 3 atmospheres pressure (hyperbaric chamber). A 1% CO atmosphere can allow lethal concentrations to develop within 10 minutes. Hemoglobin acts as a sink or vacuum that quickly removes any inhaled CO from the alveolar gas. Symptoms develop more quickly in children and the elderly. Sicker and/or more active patients also do worse. Exercise, stress, and anemia make individuals more susceptible. Higher atmospheric concentrations and longer durations of exposure are also factors to be considered. In CO exposure victims where the exposure is fire related, one must remember to consider the effects of other frequently fire-associated toxins such as cyanide. Because of their higher oxygen demands, the brain and heart are most sensitive to the hypoxic effects of CO exposure. CNS involvement accounts for many of the signs of CO exposure. COHb levels below 20% are usually associated with nausea, headache and mild dyspnea. From 20-40%, vomiting, poor judgement, and visual disturbances (including cortical blindness) develop. Above 40%, ataxia, confusion, syncope, coma, seizures and tachypnea are found. COHb levels are not, prognostic. Deaths have been reported with very low CO levels. About 12% of patients have delayed neurological deficits often following an initial asymptomatic period of several days. The onset of these delayed symptoms varies from 1 to 21 days with a mean of 6 days. These changes include memory impairment and personality changes as well as dementia, cerebellar ataxia and dystonias.
Clinical Diagnosis
As mentioned previously, a clinical suspicion is very important in diagnosing CO exposures. Symptoms are non-specific and include headache, dizziness, nausea and vomiting. CO exposures in the winter (when most accidental CO exposures occur) are frequently misdiagnosed as influenza, particularly when whole families are involved as they frequently are if there is a malfunctioning heater or fireplace.
Laboratory Diagnosis
The CO Hb level can be measured with co-oximetry. Remember that SaO2 levels from blood gas machines are normally calculated based on the pH and PO2 and will thus not reflect reduced levels in cases of CO poisoning. With routine blood gasses, PO2's and SaO2's will be normal (or very high if oxygen is being administered). If the exposure is significant, a metabolic acidosis will be present, reflecting tissue hypoxia. An anion gap will frequently be present and serum lactate levels may be elevated. CO Hb levels are frequently greater than 10% (up to 10% levels can be obtained from heavy smokers). CO Hb levels greater than 60% are almost always fatal but fatalities and severe brain damage can result from patients with normal CO levels. Remember that the damage may be done once levels have returned to normal from normal excretion. EKG's may show tachycardia and evidence of ischemia. Psychometric testing will frequently show mental deficits that resolve with treatment and may be the most sensitive method of detecting significant CO exposure and also provide for a means to evaluate the effects of therapy.
Therapy
Initially, all patients with suspected CO exposure should be treated with 100% oxygen delivered by a tight fitting mask (non-rebreather or demand valve device). Patients who are unconscious should be intubated. Associated conditions (burns, trauma, cyanide poisoning) should be treated. Hyperbaric oxygen therapy (HBO) is considered to be standard of care for patients with significant exposure defined as any patient who has been unconscious, neurological symptoms beyond simple headache, evidence of myocardial ischemia (symptoms or EKG), COHb levels greater than 25%, or unexpected abnormalities on psychometric testing. HBO therapy results in faster reductions in CO Hb levels (this is of uncertain importance), it increases tissue oxygen levels, and decreases cerebral edema. HBO therapy is normally given with 3 atmospheres of pressure using 100% oxygen for 90 minutes every 8 hours for 24 hours. HBO therapy almost totally eliminates the development of delayed neurologic sequelae. These effects are related to removal of CO from peripheral binding sites and not from reduction of CO Hb levels.
Follow-up
Part of treating CO poisoning is to prevent future exposures. It is not unheard of to treat a whole family for CO exposure from home and to have the family return to the same contaminated atmosphere because of a lack of understanding of the risks and need for corrective action. Follow-up must also be provided for to look for delayed results of CO exposure. Late treatment with HBO has been shown to reverse some symptoms in some cases.
References
Goldbaum LR, Ramirez RG, Absalon KB: What is the mechanism of carbon monoxide toxicity? Aviat Space Environ Med 1975; 46:1289-1291.
Myers RAM, Snyder SK, Emhoff TA: Subacute sequelae of carbon monoxide poisoning. AnnEmerg Med 1985; 14:1163-1167.
Norkool DM, Kirkpatrick JN: Treatment of acute carbon monoxide poisoning with hyperbaric oxygen: A review of 115 cases. Ann Emerg Med 1985; 14:1168-1171.
Turnbull, Timothy: Emergency Department Screening for Unsuspected Carbon Monoxide Exposure. Ann Emerg Med 17:478-489.
Stewart, RD: The Effect of Carbon Monoxide on Humans, J Occ Med 1976; 18:5.
Myers RAM: Are Arterial Blood Gases of Value in Treatment Decisions for Carbon Monoxide Poisoning? Crit Care Med 1989;17:139-142.