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prn8099 - Number 36, October 2002

THE SILENT KILLER 

Since January, several cases of intentional carbon monoxide poisoning from various parts of the country have made headlines in major newspapers. In the Utusan Malaysia of January 30, 2002, a 24 year old lady was found dead in her car reportedly due to excessive inhalation of carbon monoxide. The poisonous gas from the car’s exhaust fumes was directed into the back of the car through a rubber hose in a suicide attempt. Similar suicide attempts have also been exposed by the media in at least three other separate incidents involving two university undergraduates and a middle-aged couple. All four victims did not survive. 

Earlier in September 2001,the nation was saddened by a tragic incident involving a pregnant mother and her three kids who perished while waiting in an idle Perodua Kancil with the engine and air-conditioning running continuously for about two hours. The Chemistry Department of  Johore later confirmed that their death was due to excessive inhalation of carbon monoxide which had leaked into the car as a result of malfunctioning of the exhaust system.

The cases quoted above represent only a small fraction of acute carbon monoxide fatalities due to automobile exhaust emissions worldwide. The majority of known morbidity and mortalities are due to smoke from fires while others are caused by faulty heating equipment, methylene chloride in paint removers, tobacco smoke inhalation, and other indoor and outdoor activities.

The danger of carbon monoxide lies in its ubiquity and lack of warning properties. In fire accidents, carbon monoxide and cyanide gases are the leading causes of death, and can kill a victim long before the flames reach him. Workers involved in chemical manufacturing and paint spraying are obviously the industrial portion of the population most heavily exposed while cigarette smokers mainly constitute the non-industrial portion.

The true incidence of carbon monoxide exposures is unknown and may be greatly underestimated. It has been known for decades that carbon monoxide poisoning can produce long-lasting health harm, mainly through its destructive effects on the central nervous system. Some studies found that 25-40% of people died during acute exposure, while 15-40% of the survivors suffered immediate or delayed neurological effects. Carbon monoxide poisoning has also been linked to asthma in young children, retardation of fetal development and aggravation of chronic medical conditions such as coronary heart disease, and congestive heart failure particularly in senior citizens.

Awareness of the source of carbon monoxide exposure can decrease the risk of morbidity and mortality. To prevent carbon monoxide intoxication, continuous maintenance of combustion appliances and vehicle exhaust systems are necessary. Carbon monoxide detectors with minimum sensitivity and alarm characteristic standards should be used indoors while adequate ventilation should be maintained in areas of carbon monoxide production and potential exposure. 


Review on

Carbon Monoxide Poisoning (Part I)

By Dr Syed Azhar Syed Sulaiman, PharmD, Clinical Pharmacy Discipline, School of Pharmaceutical Sciences, Universiti Sains Malaysia.

Introduction: Carbon monoxide (CO) is a colorless, odorless gas produced by incomplete combustion of carbonaceous material. Commonly overlooked or misdiagnosed, CO intoxication often presents a significant challenge, as treatment protocols, especially for hyperbaric oxygen therapy, remain controversial because of a paucity of definitive clinical studies.

CO is formed as a by-product of burning organic compounds. Although most fatalities result from fires, 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 propane-fueled forklifts, gas-powered concrete saws, inhaling spray paint, indoor tractor pulls, and 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. 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 indoor with combustion engines or combustible gases.

How will carbon monoxide affect our body?

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 with the highest oxygen requirement (e.g., brain, heart).

Toxicity primarily results from cellular hypoxia caused by impedance of oxygen delivery. CO reversibly binds hemoglobin, resulting in relative 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 3 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 toxicity. Clinical status often does not correlate well with HbCO level, leading some to postulate an additional impairment of cellular respiration.

CO binds to cytochromes C and P450, but with a much lower affinity than that of oxygen; very low levels of in vitro binding result. Additionally, the patient groups exhibiting neuropsychiatric deficits often are not acutely acidotic.

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.

Recent studies have demonstrated release of nitric oxide free radical (implicated in the pathophysiology of atherosclerosis), from platelet and vascular endothelium, following exposure to CO concentrations of 100 ppm.

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.

Age-specific fatality rates are equivalent for individuals aged 15-74 years; rates increase for persons older than 75 years and decline for persons younger than 15 years.

  • Age-adjusted fatality rates are higher in cold and mountainous locations.
  • 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.

What are the signs and symptoms of carbon monoxide poisoning?

Misdiagnosis 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. Any of the following should alert suspicion in the winter months, especially in relation to the previously named sources and when more than one patient in a group or household presents with similar complaints. Symptoms may not correlate well with HbCO levels.  Table I listed some of the most common symptoms occurring with carbon monoxide poisoning.

Table I: Common symptoms of carbon monoxide poisoning in acute and chronic exposure

Acute poisoning
    • Malaise, flu-like 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 exposures Also present with the above symptoms; however, they may present with loss of dentation, gradual onset neuropsychiatric symptoms, or, simply, recent impairment of cognitive ability

 Physical Examination

Physical examination is of limited value. Inhalation injury or burns should always alert the clinician to the possibility of CO exposure.

  • Vital signs
    • Tachycardia
    • Hypertension or hypotension
    • Hyperthermia
    • Marked tachypnea (rare; severe intoxication often associated with mild or no tachypnea)
  • Skin: Classic cherry red skin is rare (i.e., “When you're cherry red, you're dead”); pallor is present more often.
  • Ophthalmologic
    • Flame-shaped retinal hemorrhages
    • Bright red retinal veins (a sensitive early sign)
    • Papilledema
    • Homonymous hemianopsia
  • Noncardiogenic pulmonary edema
  • Neurologic and/or neuropsychiatric
    • Patients display memory disturbance (most common), including retrograde and anterograde amnesia with amnestic confabulatory states.
    • Patient may experience emotional lability, impaired judgment, and decreased cognitive ability.
    • Other signs include stupor, coma, gait disturbance, movement disorders, and rigidity.
    • Patients display brisk reflexes, apraxia, agnosia, tic disorders, hearing and vestibular dysfunction, blindness, and 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.
    • MRI changes may remain long after clinical recovery. Predicting and preventing long-term complications and delayed encephalopathy have been the object of recent studies, many of which focus on the role of hyperbaric oxygen therapy.

 What are the common causes of carbon monoxide poisoning?

Some of the most common causes are as follow:

  • 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.
  • Furnaces were determined to be the source in 46% of nonfatal CO poisonings but in only 10% of fatal poisonings. This suggests that the role of home heating appliances is prominent in the large group of underreported nonfatal exposures.
  • Most developing countries utilize unvented cook stoves, burning wood, charcoal, animal dung, or agricultural waste. Studies have shown a concurrent rise in HbCO with these types of exposure in developing countries.


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