• CO is toxic gas that is a byproduct of combustion, resulting in formation of carboxyHb (COHb). 
  • The COHb level in non-smoker is about 0.8%, while it is generally in the 3%-5% range in smokers.
  • CO binds to Hb with 200 to 250 times greater affinity compared to oxygen, resulting in a functional anemia.
  • Once bound to Hb, CO results in a left shift of the oxygen dissociation curve (reduced unloading of oxygen at tissues).
  • The combined effects of competitive Hb binding and left shift result in reduced oxygen delivery to tissues, increased erythropoietin production, and polycythemia.

Tobacco use

  • Cigarette use in 2011 was about 21%.
  • Cigarette smoking prevalence higher in patients with:
    • Unemployment
    • Low-income
    • Absence of high school diploma
    • Disability limiting daily function
    • Serious psychological illness
    • Heavy drinking

Carbon Monoxide: overview

  • Poisoning from carbon monoxide (CO) exposure causes about 600 to 6000 deaths/year in the US.
  • CO is a toxic gas that is:
    • A byproduct of combustion
    • Nonirritating, tasteless and odorless
  • The normal level of COHb in non-smokers is not zero; COHb is detectable in normal individuals and is derived from:
    • Exposure to CO in the environment
    • Degradation of heme, which releases a molecule of CO
  • Environmental and occupational exposures include:
    • Structure fires
    • Combustion motors
    • Fuel-burning heating and cooking devices
    • Charcoal fires
  • CO levels may be increased in patients with hemolytic anemia:
    • 3.5%-4.3% in sickle cell disease
    • 4.5% in malaria
    • 7.3% with antibiotic-associated hemolytic anemia
    • 9.7% in sepsis
  • In smokers, incomplete combustion of inhaled tobacco produces CO.

Carbon monoxide: hemoglobin binding

  • When CO is inhaled, it crosses the alveolar-capillary membrane and binds to hemoglobin (in the same iron-containing sites to which oxygen binds.) in circulating red blood cells (RBCs), forming carboxyhemoglobin (COHb).
  • Human hemoglobin has 200 to 250 times greater affinity for binding CO when compared to oxygen.
  • The majority of circulating COHb is the result of exogenous exposures, but endogenous production of CO from heme degradation accounts for a small amount of COHb.
  • Once bound to Hb, CO causes a left shit in the oxygen dissociation curve. In other words:
    • Hb has a higher avidity for oxygen.
    • P50 value is low.
  • Thus, there are two mechanisms by which CO reduces oxygen delivery:
    • CO competitively prevents oxygen binding (this is sometimes referred to as functional anemia).
    • CO reduces offloading of oxygen at tissues.
  • CO binding to hemoglobin is reversible; clearance half-time of COHb averages 320 minutes breathing normobaric air, with a range of 128-409 minutes.

Carbon monoxide/COHb in smokers

  • Cigarette, cigar, and pipe tobacco smoking can expose smokers and bystanders to CO. 
  • Reported COHb levels:
    • 11,368 individuals aged 3-74 year (NHANES II)
      • Nonsmokers averaged 0.83 ± 0.67%
      • Smokers (n=2,553) 4.3 ± 2.6%
      • > One pack of cigarettes daily 5.8%
      • For every pack of cigarettes smoked per day, the COHb level rises about 2.5%
    • Cohort of 601 cigarette smokers (Saudi Arabia):
      • Smokers 6.47%
      • Nonsmokers 1.60% 
    • Cohort of 228 individuals (Spain)
      • 1 to 10 cigarettes/day 5.2% 
      • greater than 20 cigarettes/day 9.6%
      • Nonsmokers 1.9%
  • Rarely, the COHb level in heavy smokers has been reported above 10%.

MILITARY MEDICINE, 185, 1/2:e61, 2020

Smoker’s polycythemia

  • Smoking a cause of secondary erythrocytosis/polycythemia

  • The combined effects of competitive binding of CO to Hb and the resulting left shift of the oxygen dissociation curve result in reduced oxygen delivery to tissues, increased erythropoietin production, and polycythemia.
  • The most comprehensive study of smoker’s polycythemia dates back to 1978.
    • 22 smokers with an elevated Hct (mean 54%, range 48% – 63%).
    • COHb 4.2-21.3% (mean 11.6%).
    • COHb levels were higher in cigar vs. cigarette smokers.
    • Progressive shift to left of the Hb oxygen dissociation curve represented by lower P50 (see below)
    • In those who stopped or reduced smoking, Hcts returned to normal. 




  • Suspect diagnosis of CO poisoning in patients with “cherry red” skin discoloration.
    • This finding is neither 100% sensitive nor specific for CO poisoning.
    • Among individuals dying of CO poisoning, fewer than one-half have red skin as measured by reflectance spectrophotometry.
  • Suspect diagnosis of smoker’s polycythemia in a patient who smokes and has an elevated Hct. 
  • Confirm diagnosis by demonstrating elevated COHb, typically 2-5% in the absence of other causes of primary and secondary polycythemia (a level over 9% is almost always due to exogenous carbon monoxide exposure, even among smokers).   
  • A typical order set for a patient with an elevated Hct is the following: 

  • Measuring COHb
    • Color of blood:
      • Objects such as blood do not have intrinsic color. Rather, color is based on wavelengths of light – typically from the sun – that the objects reflect. Oxygen-bound hemoglobin reflects red-orange light into our eyes, making normal blood appear red. 
      • The bright red color of COHb results from the fact that the absorption spectrum of COHb is different from that of either HbO2 or deoxyhemoglobin (Hb).
    • Cooximetry (multiple wavelength spectrophotometer):
      • By differentiating wavelength absorbance values, cooximetry measures concentrations of abnormal hemoglobins (eg, COHb and methemoglobin saturation) and measures (rather than calculates) total hemoglobin, oxyhemoglobin, and deoxyhemoglobin concentrations.
      • Venous or arterial blood samples are acceptable.
      • COHb levels are expressed as a percentage of the total hemoglobin.
      • COHb concentration could theoretically range from 0%-100.
    • Conventional pulse oximeter:
        • Inadequate to detect carbon monoxide poisoning because carboxyhemoglobin can be misinterpreted as oxyhemoglobin.
        • Pulse oximetry uses spectrophotometry to determine the proportion of hemoglobin that is saturated with oxygen based on preferential absorption of light at different wavelengths (660 nm and 940 nm). 
        • With only two wavelengths, these pulse oximeters must “assume” the presence of only two light absorbers in the blood: oxyhemoglobin and reduced hemoglobin; it does not differentiate COHb from oxyhemoglobin.
        • Carboxyhemoglobin has an absorption spectrum similar to HbO2 at one of the two wavelengths used by pulse oximeters (660 nm) and therefore tends to be counted as oxyhemoglobin. The result represents the approximate sum of both hemoglobins as Spo2
        • Thus, smokers may have falsely normal arterial oxygen saturation.

Undersea Hyperb Med. 2018 Mar-Apr;45(2):165-171

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