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A. Introductionnavigator

  1. One of the most common causes of morbidity due to poisoning in USA
  2. About 600 accidental deaths per year in USA
  3. From 3000-6000 suicides per year with carbon monoxide in USA
  4. Carbon monoxide (CO) formed from incomplete combustion of hydrocarbons
    1. Normal catabolism of hemoglobin yields very low levels of CO
    2. Tobacco smoke is the most common cause of elevated CO in humans
    3. CO levels in smokers are 10% or higher, compared with 1-3% in non-smokers
    4. Air pollution is the second most common cause of chronically elevated CO
    5. Acute intoxication from car exhaust, heating systems, inhaled smoke most common
    6. Methylene chloride, a solvent, is converted to CO by normal metabolism
  5. Properties of CO
    1. Colorless, oderless, nonirrant toxic gas
    2. Easily absorbed through lungs
    3. Very high affinity for hemoglobin (Hb)
  6. Metabolism of CO
    1. Inhaled CO is absorbed and eliminated through the lungs
    2. <1% is oxidized to carbon dioxide
    3. 10-15% is bound to proteins (including myoglobin and cytochrome c oxidase)
  7. CO Toxicity
    1. Binding to Hb accounts for a good deal of the toxicity of CO
    2. There is also direct CO toxicity to tissues

B. Pathophysiology [3] navigator

  1. Hemoglobin (Hb)
    [Figure] "O2-Hb Dissociation Curve"
    1. Protein found in red blood cells, essential for oxygen transport
    2. Normal Hb consists of two alpha and two beta polypeptides
    3. Also contains a porphyrin ring with ferrous (Fe2+ iron) atom
    4. Molecular weight is 64.5K
    5. Deoxyhemoglobin is in a tense (T) conformation with low O2 affinity
  2. Formation of carboxyhemoglobin (Hb-CO)
    1. Hemoglobin's (Hb) affinity for CO is ~240 times that for Oxygen (O2)
    2. Binding of CO to Hb will increase its affinity for O2 (shift dissociation curve to the left)
    3. CO binding sites are the same as O2 binding sites on Hb
    4. Therefore, during pulmonary transit, Hb binds alveolar CO preferentially over O2
    5. CO binding also increases Hb affinity for O2 and reduces ability of Hb to release O2
    6. Therefore, CO reduces Hb's O2 carrying capacity as well as ability to deliver O2
    7. Blood carboxyHb concentration underestimates true tissue O2 deficit
  3. Other effects of carbon monoxide
    1. Dissolved CO binds iron containing cytochromes leading to further tissue hypoxia
    2. CO binds to cytochrome c oxidase and inhibits its functions
    3. CO may also activate neutrophils to release toxic compounds
    4. CO can induce lipid peroxygenation which can cause CNS problems
    5. CO creates significant oxidative stress on cells
    6. Particularly concerning effects in pregnant women, with marked toxicity to fetus
  4. Hb-CO levels may not correlate with the clinical status since dissolved CO at cytochrome level is unmeasured
  5. Pulse oximetry saturation meters do not reliably give O2 saturation (Hb-CO cross reacts)
  6. Smokers often have Hb-CO levels 3-8% at baseline
    1. CO is especially harmful in the placental circulation
    2. Smoking tobacco and chronic smoke inhalation are serious problems during pregnancy
    3. Smoking 1 pack per day, fetal arterial O2 saturation drops from 75% (normal) to ~58%
  7. Drug-Induced Methemoglobinemia
    1. Rare consequence of exposure of normal red cells to various oxidizing drugs
    2. Benzocaine
    3. Dapsone
    4. Nitrates
    5. Sulfonamides
    6. Treatment with oxygen and drug-binding agents if possible (such as methylene blue)

C. Symptoms and Signsnavigator

  1. Aysymptomatic (Levels <10%) - dyspnea only on extreme exertion (DOE)
  2. Mild (Hb-CO level 11-20%)
    1. Normal mental status and no cardiac abnormalities
    2. Throbbing headache, fatigue, difficulty thinking, increased DOE
    3. Dizziness, nausea
  3. Moderate (Hb-CO level 21-30%)
    1. Increased headache, nausea
    2. Mild confusion
    3. Dyspnea on mild exertion
    4. No syncope
  4. Moderately Severe (Hb-CO level 31-40%)
    1. Visual dimming
    2. Dizziness (continued headache)
    3. Irritability
    4. Nausea with vomiting
    5. Tachycardia
  5. Severe
    1. Tachypnea
    2. Syncope
    3. Neurologic abnormalities including seizures
    4. Dyspnea at rest, cardiac ischemia, arrhythmias
    5. Myocardial injury is common in moderate to severe CO poisoning [6]
    6. Myocardial injury portends poor long term outcomes [6]
  6. Extreme (Hb-CO level >50)
    1. Respiratory failure
    2. Acute Myocardial Infarction
    3. Sustained hypotension
    4. Seizures, Coma
  7. Complicated
    1. Pregnancy - fetal hemoglobin has higher affinity for CO than adult hemoglobin
    2. Coronary Artery Disease, pulmonary disease, anemia, elderly patients
    3. Children
  8. Blood will appear extremely red - seen in hue of lips and skin ("cherry red")
  9. Respiratory alkalosis with metabolic acidosis
  10. Delayed Neuropsychiatric Syndrome [2]
    1. Delayed onset of neuropsychiatric symptoms in 10-30% of victims
    2. Recovery occurs in 50-75% of those who have the syndrome
    3. Occurs 3-240 days after exposure
    4. Symptoms are variable:
    5. Cognitive and personality changes
    6. Parkinsonism
    7. Incontinence
    8. Dementia
    9. Psychosis
    10. CT or MRI or SPECT scanning can show variable abnormalities
    11. Unclear etiology; no specific treatment

D. Diagnosisnavigator

  1. High suspicion in appropriate clinical situation
  2. Must measure carboxyhemoglobin (Hb-CO) with blood sample
    1. Normal non-smokers: 1-3%
    2. Smokers: <15% in most cases
    3. May be difficult to distinguish mild CO intoxication from chronic smoker CO levels
  3. Venous blood is adequate, and can estimate acidosis level
  4. Pulse oximetry is not acceptable because it cannot distinguish Hb-O from Hb-CO
  5. Increased levels of Hb-CO are diagnostic in most cases
  6. CT scan of the brain may be useful only to rule out other causes of mental status changes

E. Treatmentnavigator

  1. Inhalation of 100% O2 is preferred treatment
    1. This therapy decreases the half-life of Hb-CO by >50%
    2. Must follow arterial blood glass O2 saturation and Hb-CO level
    3. Intubation and placement of arterial blood catheter usually required
  2. Hyperbaric O2 at 3 Atmospheres (Atm) is very effective [3]
    1. Normal half life of Hb-CO in room air oxygen is 5-6 hours
    2. Treatments for carbon monixde poisoning should last ~45 minutes
    3. Three hyperbaric treatments within 24 hour period reduced risk of cognitive sequellae at 12 months [4]
  3. Indications for Hyperbaric Oxygen [2,4]
    1. Hb-CO >20-40%
    2. Any symptomatic carbon monoxide poisoning [4]
    3. Pregnancy and Hb-CO level >15%
    4. History of coronary artery disease and Hb-CO level >20%
  4. For smoke inhalation, consider concomitant cyanide poisoning
  5. Supportive therapy, vasopressors, anti-ischemics, blood transfusions
  6. Complications: rhabdomyolysis, late neuropsychiatric sequellae

F. Hyperbaric Oxygen Therapy [4,5]navigator

  1. Principle
    1. Oxygen carrying capacity of blood depends mainly on hemoglobin (Hb)
    2. However, oxygen itself can dissolve in blood
    3. At 1 Atm pressure (760mm Hg), 1.5mL oxygen is dissolved in blood itself
    4. Normal resting oxygen requirements are 5-6mL oxygen per mL of blood
    5. At 3 Atm oxygen pressure, ~6mL oxygen is dissolved per mL of blood
    6. Thus, at elevated oxygen pressures (hyperbaric), Hb is not required for oxygen delivery
  2. Interaction of Hyperbaric Oxygen with HbCO
    1. The half life of HbCO (carboxyhemoglobin) in room air is 4-5 hours
    2. Half life of Hb-CO in 100% oxygen is ~80 minutes
    3. At 2.5 Atm hyperbaric oxygen, the half-life of HbCO is reduced to <25 minutes
    4. Thus, hyperbaric oxygen substantially reduces the longevity of HbCO in the blood
  3. Other effects of Hyperbaric Oxygen
    1. Reduces half-life of CO-cytochrome c oxidase complex
    2. Inhibits release of toxic metabolits from neutrophils
  4. Utility of Hyperbaric Oxygen
    1. Symptomatic Carbon Monoxide poisoning
    2. Decompression Sickness - due to dissolve nitrogen, air embolism
    3. Radiation induced tissue injury
    4. Myonecrosis and Necrotizing Fasciitis
    5. Problem Wounds
  5. Side Effects
    1. Generally minimal for treatments <120 minutes at 3 Atm
    2. Middle ear rupture, sinus pain, myopia (lens effects), chest tightness

Resources navigator

calcAlveolar Gas Equation

References navigator

  1. Kales SN and Christiani DC. 2004. NEJM. 350(8):800 abstract
  2. Ernst A and Zibrak JD. 1998. NEJM. 339(22):1603 abstract
  3. Hsia CCW. 1998. NEJM. 338(4):239 abstract
  4. Weaver LK, Hopkins RO, Chan KJ, et al. 2002. NEJM. 347(14):1057 abstract
  5. Tibbles PM and Edelsberg JS. 1996. NEJM. 334(25):1642 abstract
  6. Henry CR, Satran D, Lindgren B, et al. 2006. JAMA. 295(4):398 abstract