Carbon monoxide (CO) is an odourless, colourless gas that reduces the ability of haemoglobin to transport and deliver oxygen.

Occurrence. Carbon monoxide is produced when organic material, such as coal, wood, paper, oil, gasoline, gas, explosives or any other carbonaceous material, is burned in a limited supply of air or oxygen. When the combustion process takes place in an abundant supply of air without the flame contacting any surface, carbon monoxide emission is not likely to result. CO is produced if the flame contacts a surface which is cooler than the ignition temperature of the gaseous part of the flame. Naturally occurring sources produce 90% of atmospheric CO, and activity some 10%. Motor vehicules account for 55 to 60% of global man-made CO burden. The exhaust gas of gasoline-fuelled combustion engine (spark ignition) is a common source of ambient CO. The diesel engine (compression ignition) exhaust gas contains about 0.1% of CO when the engine is operating properly, but maladjusted, overloaded or badly maintained diesel engines may emit considerable amounts of CO. Thermal or catalytic afterburners in the exhaust pipes considerably reduce the amount of CO emitted. Other major sources of CO are cupolas in foundries, catalytic cracking units in petroleum refineries, distillation of coal and wood, lime kilns and the kraft recovery furnaces in kraft paper mills, manufacture of synthetic methanol and other organic compounds from carbon monoxide, the sintering of blast furnace feed, carbide manufacture, formaldehyde manufacture, carbon black plants, coke works, gas works and refuse plants.

Any process where incomplete burning of organic material may occur is a potential source of carbon monoxide emission.

Carbon monoxide is produced on an industrial scale by the partial oxidation of hydrocarbon gases from natural gas or by the gasification of coal or coke. It is used as a reducing agent in metallurgy, in organic syntheses, and in the manufacture of metal carbonyls. Several industrial gases that are used for heating boilers and furnaces and driving gas engines contain carbon monoxide.

Carbon monoxide is thought to be by far the most common single cause of poisoning both in industry and in homes. Thousands of persons succumb annually as a result of CO intoxication. The number of victims of non-fatal poisoning that suffer from permanent central nervous system damage can be estimated to be even larger. The magnitude of the health hazard due to carbon monoxide, both fatal and non-fatal, is huge, and poisonings are probably more prevalent than is generally recognized.

A sizeable proportion of the workforce in any country has a significant occupational CO exposure. CO is an ever-present hazard in the automotive industry, garages and service stations. Road transport drivers may be endangered if there is a leak of engine exhaust gas into the driving cab. Occupations with potential exposure to CO are numerous—for example, garage mechanics, charcoal burners, coke oven workers, cupola workers, blast furnace workers, blacksmiths, miners, tunnel workers, Mond process workers, gas workers, boiler workers, pottery kiln workers, wood distillers, cooks, bakers, firefighters, formaldehyde workers and many others. Welding in vats, tanks or other enclosures may result in production of dangerous amounts of CO if ventilation is not efficient. The explosions of methane and coal dust in coal mines produce “afterdamp” which contains considerable amounts of CO and carbon dioxide. If ventilation is decreased or CO emission increases owing to leaks or disturbances in process, unexpected CO poisonings may occur in industrial operations that usually do not create CO problems.

Toxic action

Small quantities of CO are produced within the human body from the catabolism of haemoglobin and other haem-containing pigments, leading to an endogenous carboxyhaemoglobin (COHb) saturation of about 0.3 to 0.8% in the blood. Endogenous COHb concentration is increased in haemolytic anaemias and after significant bruises or haematomas, which result in increased haemoglobin catabolism.

CO is easily absorbed through the lungs into the blood. The best understood biological effect of CO is its combination with haemoglobin to form carboxyhaemoglobin. Carbon monoxide competes with oxygen for the binding sites of the haemoglobin molecules. The affinity of human haemoglobin for CO is about 240 times that of its affinity for oxygen. The formation of COHb has two undesirable effects: it blocks oxygen transport by inactivating haemoglobin, and its presence in the blood shifts the dissociation curve of oxyhaemoglobin to the left so that the release of remaining oxygen to tissues is impaired. Because of the latter effect, the presence of COHb in the blood interferes with tissue oxygenation considerably more than an equivalent reduction of haemoglobin concentration, for example, through bleeding. Carbon monoxide also binds with myoglobin to form carboxymyoglobin, which may disturb muscle metabolism, especially in the heart.

The approximate relation of carboxyhaemoglobin (COHb) and oxyhaemoglobin (O₂Hb) in blood can be calculated from the Haldane’s equation. The ratio of COHb and O₂Hb is proportional to the ratio of the partial pressures of CO and oxygen in alveolar air:

The equation is applicable for most practical purposes to approximate the actual relationship in equilibrium state. For any given CO concentration in the ambient air, the COHb concentration increases or decreases towards the equilibrium state according to the equation. The direction of the change in COHb depends on its starting level. For example, continuous exposure to ambient air containing 35 ppm of CO would result in equilibrium state of about 5% COHb in blood. After that, if the air concentration remains unchanged there will be no change in COHb level. If the air concentration increases or decreases, the COHb also changes towards the new equilibrium. A heavy smoker may have a COHb concentration of 8% in his or her blood at the beginning of a work shift. If he or she is continuously exposed to a 35 ppm CO concentration during the shift, but is not allowed to smoke, his or her COHb level gradually decreases towards the 5% COHb equilibrium. At the same time, the COHb level of non-smoking workers gradually increases from the starting level of about 0.8% endogenous COHb towards the 5% level. Thus, absorption of CO and build up of COHb is determined by gas laws, and the solution of Haldane’s equation will give the approximate maximum value of COHb for any ambient air CO concentration. It should be remembered, however, that the equilibrium time for humans is several hours for air concentrations of CO usually encountered at worksites. Therefore, when judging the potential health risk of exposure to CO it is important that the exposure time is taken into account in addition to CO concentration in the air. Alveolar ventilation is also a major variable in the rate of CO absorption. When alveolar ventilation increases—for example, during heavy physical work—the equilibrium state is approached more rapidly than in a situation with normal ventilation.

The biological half-life of COHb concentration in the blood of sedentary adults is about 3 to 4 h. The elimination of CO becomes slower with time and the lower the initial level of COHb, the slower the rate of excretion.

Acute poisoning

The appearance of symptoms depends on the concentration of CO in the air, the exposure time, the degree of exertion and individual susceptibility. If the exposure is massive, loss of consciousness may take place almost instantaneously with few or no premonitory signs and symptoms. Exposure to concentrations of 10,000 to 40,000 ppm leads to death within a few minutes. Levels between 1,000 and 10,000 ppm cause symptoms of headache, dizziness and nausea in 13 to15 min and unconsciousness and death if exposure continues for 10 to 45 min, the rapidity of onset depending on the concentrations. Below these levels the time before the onset of symptoms is longer: levels of 500 ppm cause headache after 20 min and levels of 200 ppm after about 50 min. The relation between carboxyhaemoglobin concentrations and the main signs and symptoms is shown in table 1.

Table 1. Principal signs and symptoms with various concentrations of carboxyhaemoglobin.

¹ There is considerable individual variation in the occurrence of symptoms.

The victim of poisoning is classically described as being cherry red. In the early stages of poisoning, the patient may appear pale. Later, the skin, nailbeds and mucous membranes may become cherry red due to a high concentration of carboxyhaemoglobin and a low concentration of reduced haemoglobin in the blood. This sign may be detectable above 30% COHb concentration, but it is not a reliable and regular sign of CO poisoning. The patient’s pulse is rapid and bounding. Little or no hyperpnoea is noticed unless COHb level is very high.

Where the symptoms or signs described above occur in a person whose work may expose him or her to carbon monoxide, poisoning due to this gas should be immediately suspected. Differential diagnosis from drug poisoning, acute alcohol poisoning, cerebral or cardiac accident, or diabetic or uraemic coma may be difficult, and the possibility of carbon monoxide exposure is often unrecognized or simply overlooked. Diagnosis of carbon monoxide poisoning should not be considered established until it is ascertained that the body contains abnormal quantities of CO. Carbon monoxide is readily detectable from blood samples or, if a person has healthy lungs, an estimate of blood COHb concentration can be rapidly made from samples of exhaled end-alveolar air which is in equilibrium with blood COHb concentration.

Critical organs in respect to CO action are the brain and the heart, both of which are dependent on an uninterrupted supply of oxygen. Carbon monoxide burdens the heart by two mechanisms—the heart’s work is increased in order to provide the peripheral oxygen demand, while its own oxygen supply is reduced by CO. Myocardial infarction may be precipitated by carbon monoxide.

Acute poisoning may result in neurological or cardiovascular complications which are evident as soon as the patient recovers from the initial coma. In severe poisoning, pulmonary oedema (excess fluid in the lung tissues) may emerge. Pneumonia, sometimes due to aspiration, may develop after a few hours or days. Temporary glycosuria or albuminuria may also occur. In rare cases acute renal failure complicates the recovery from poisoning. Various cutaneous manifestations are occasionally encountered.

After severe CO intoxication the patient may suffer from cerebral oedema with irreversible brain damage of varying extent. The primary recovery may be followed by a subsequent neuropsychiatric relapse, days or even weeks after poisoning. Pathology studies of fatal cases show the predominant nervous system lesion in white matter rather than in neurons in those victims who survive a few days after the actual poisoning. The degree of brain damage after CO poisoning is determined by the intensity and duration of exposure. On regaining consciousness after severe CO poisoning, 50% of the victims have been reported as presenting an abnormal mental state manifested as irritability, restlessness, prolonged delirium, depression or anxiety. A three-year follow-up of these patients revealed that 33% had personality deterioration and 43% had persistent memory impairment.

Repeated exposures. Carbon monoxide does not accumulate in the body. It is completely excreted after each exposure if sufficient time in fresh air is allowed. It is possible, however, that repeated mild or moderate poisonings which do not lead to unconsciousness would result in death of brain cells and ultimately lead to central nervous system damage with a multitude of possible symptoms, such as headache, dizziness, irritability, impairment of memory, personality changes and a state of weakness of the limbs.

Individuals repeatedly exposed to moderate concentrations of CO are possibly adapted to some extent against the action of CO. Mechanisms of adaptation are thought to be similar to the development of tolerance against hypoxia in high altitudes. An increase in the haemoglobin concentration and in haematocrit has been found to occur in exposed animals, but neither the time course nor the threshold of similar changes in exposed humans has been accurately quantified.

Altitudes. At high altitudes the possibility of incomplete burning and greater CO production increases because there is less oxygen per unit of air than at sea level. The adverse body responses also increase due to reduced oxygen partial pressures in breathed air. The oxygen deficiency present at high altitudes and the effects of CO apparently are additive.

Methane-derived halogentated hydrocarbons. Dichloromethane (methylene chloride), which is a major component of many paint strippers and other solvents of this group, is metabolized in the liver with the production of CO. Carboxyhaemoglobin concentration may increase up to moderate poisoning level by this mechanism.

Effects of low level exposure to carbon monoxide. In recent years considerable efforts of investigation have been focused on biological effects of COHb concentrations below 10% upon both healthy persons and patients with cardiovascular diseases. Patients with severe cardiovascular disease may lack compensatory reserve at about 3% COHb level, so that the chest pain of angina pectoris patients is provoked by less exertion. Carbon monoxide readily crosses the placenta to expose the foetus, which is sensitive to any extra hypoxic burden in such a way that its normal development may be endangered.

Susceptible groups. Particularly sensitive to the action of CO are individuals whose oxygen transport capacity is decreased due to anaemia or haemoglobinopathias; those with increased oxygen needs due to fever, hyperthyroidism or pregnancy; patients with systemic hypoxia due to respiratory insufficiency; and patients with ischemic heart disease and cerebral or generalized arteriosclerosis. Children and young individuals whose ventilation is more rapid than that of adults attain the intoxication level of COHb sooner than healthy adults. Also, smokers whose starting COHb level is higher than that of non-smokers would more rapidly approach dangerous COHb concentrations at high exposures.

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