Carbon monoxide poisoning
Carbon monoxide poisoning typically occurs from breathing in carbon monoxide at excessive levels. Symptoms are often described as "flu-like" and commonly include headache, dizziness, weakness, vomiting, chest pain, and confusion. Large exposures can result in loss of consciousness, arrhythmias, seizures, or death. The classically described "cherry red skin" rarely occurs. Long-term complications may include chronic fatigue, trouble with memory, and movement problems.
CO is a colorless and odorless gas which is initially non-irritating. It is produced during incomplete burning of organic matter. This can occur in cooking equipment, motor vehicles, or heaters which use carbon-based fuels. Carbon monoxide primarily causes adverse effects by combining with hemoglobin to form carboxyhemoglobin, which prevents the blood from carrying oxygen and expelling carbon dioxide as carbaminohemoglobin. Additionally, many other hemoproteins such as myoglobin, Cytochrome P450, and mitochondrial cytochrome oxidase are affected, along with other metallic and non-metallic cellular targets.
Diagnosis is typically based on a HbCO level of more than 3% among nonsmokers and more than 10% among smokers. The biological threshold for carboxyhemoglobin tolerance is typically accepted to be 15% COHb, meaning toxicity is consistently observed at levels in excess of this concentration. The FDA has previously set a threshold of 14% COHb in certain clinical trials evaluating the therapeutic potential of carbon monoxide. In general, 30% COHb is considered severe carbon monoxide poisoning. The highest reported non-fatal carboxyhemoglobin level was 73% COHb.
Efforts to prevent poisoning include carbon monoxide detectors, proper venting of gas appliances, keeping chimneys clean, and keeping exhaust systems of vehicles in good repair. Treatment of poisoning generally consists of giving 100% oxygen along with supportive care. This procedure is often carried out until symptoms are absent and the HbCO level is less than 3%/10%.
Carbon monoxide poisoning is relatively common, resulting in more than 20,000 emergency room visits a year in the United States. It is the most common type of fatal poisoning in many countries. In the United States, non-fire related cases result in more than 400 deaths a year. Poisonings occur more often in the winter, particularly from the use of portable generators during power outages. The toxic effects of CO have been known since ancient history. The discovery that hemoglobin is affected by CO emerged with an investigation by James Watt and Thomas Beddoes into the therapeutic potential of hydrocarbonate in 1793, and later confirmed by Claude Bernard between 1846 and 1857.
Background
Carbon monoxide is not toxic to all forms of life, and the toxicity is a classical dose-dependent example of hormesis. Small amounts of carbon monoxide are naturally produced through many enzymatic and non-enzymatic reactions across phylogenetic kingdoms where it can serve as an important neurotransmitter and a potential therapeutic agent. In the case of prokaryotes, some bacteria produce, consume and respond to carbon monoxide whereas certain other microbes are susceptible to its toxicity. Currently, there are no known adverse effects on photosynthesizing plants.The harmful effects of carbon monoxide are generally considered to be due to tightly binding with the prosthetic heme moiety of hemoproteins that results in interference with cellular operations, for example: carbon monoxide binds with hemoglobin to form carboxyhemoglobin which affects gas exchange and cellular respiration. Inhaling excessive concentrations of the gas can lead to hypoxic injury, nervous system damage, and even death.
As pioneered by Esther Killick, different species and different people across diverse demographics may have different carbon monoxide tolerance levels. The carbon monoxide tolerance level for any person is altered by several factors, including genetics, behavior such as activity level, rate of ventilation, a pre-existing cerebral or cardiovascular disease, cardiac output, anemia, sickle cell disease and other hematological disorders, geography and barometric pressure, and metabolic rate.
Physiology
Carbon monoxide is produced naturally by many physiologically relevant enzymatic and non-enzymatic reactions best exemplified by heme oxygenase catalyzing the biotransformation of heme into biliverdin and eventually bilirubin. Aside from physiological signaling, most carbon monoxide is stored as carboxyhemoglobin at non-toxic levels below 3% HbCO.Therapeutics
Small amounts of CO are beneficial and enzymes exist that produce it at times of oxidative stress. A variety of drugs are being developed to introduce small amounts of CO, these drugs are commonly called carbon monoxide-releasing molecules. Historically, the therapeutic potential of factitious airs, notably carbon monoxide as hydrocarbonate, was investigated by Thomas Beddoes, James Watt, Tiberius Cavallo, James Lind, Humphry Davy, and others in many labs such as the Pneumatic Institution.Signs and symptoms
On average, exposures at 100 ppm or greater is dangerous to human health. The WHO recommended maximum levels of indoor CO exposure in 24 hours is 4 mg/m3. Acute exposure should not exceed 10 mg/m3 in 8 hours, 35 mg/m3 in one hour and 100 mg/m3 in 15 minutes.| Concentration | Symptoms |
| 35 ppm, | Headache and dizziness within six to eight hours of constant exposure |
| 100 ppm, | Slight headache in two to three hours |
| 200 ppm, | Slight headache within two to three hours; loss of judgment |
| 400 ppm, | Frontal headache within one to two hours |
| 800 ppm, | Dizziness, nausea, and convulsions within 45 min; insensible within 2 hours |
| 1,600 ppm, | Headache, increased heart rate, dizziness, and nausea within 20 min; death in less than 2 hours |
| 3,200 ppm, | Headache, dizziness and nausea in five to ten minutes. Death within 30 minutes. |
| 6,400 ppm, | Headache and dizziness in one to two minutes. Convulsions, respiratory arrest, and death in less than 20 minutes. |
| 12,800 ppm, | Unconsciousness after 2–3 breaths. Death in less than three minutes. |
Acute poisoning
The main manifestations of carbon monoxide poisoning develop in the organ systems most dependent on oxygen use, the central nervous system and the heart. The initial symptoms of acute carbon monoxide poisoning include headache, nausea, malaise, and fatigue. These symptoms are often mistaken for a virus such as influenza or other illnesses such as food poisoning or gastroenteritis. Headache is the most common symptom of acute carbon monoxide poisoning; it is often described as dull, frontal, and continuous. Increasing exposure produces cardiac abnormalities including fast heart rate, low blood pressure, and cardiac arrhythmia; central nervous system symptoms include delirium, hallucinations, dizziness, unsteady gait, confusion, seizures, central nervous system depression, unconsciousness, respiratory arrest, and death. Less common symptoms of acute carbon monoxide poisoning include myocardial ischemia, atrial fibrillation, pneumonia, pulmonary edema, high blood sugar, lactic acidosis, muscle necrosis, acute kidney failure, skin lesions, and visual and auditory problems. Carbon monoxide exposure may lead to a significantly shorter life span due to heart damage.One of the major concerns following acute carbon monoxide poisoning is the severe delayed neurological manifestations that may occur. Problems may include difficulty with higher intellectual functions, short-term memory loss, dementia, amnesia, psychosis, irritability, a strange gait, speech disturbances, Parkinson's disease-like syndromes, cortical blindness, and a depressed mood. Depression may occur in those who did not have pre-existing depression. These delayed neurological sequelae may occur in up to 50% of poisoned people after 2 to 40 days. It is difficult to predict who will develop delayed sequelae; however, advanced age, loss of consciousness while poisoned, and initial neurological abnormalities may increase the chance of developing delayed symptoms.
Chronic poisoning
Chronic exposure to relatively low levels of carbon monoxide may cause persistent headaches, lightheadedness, depression, confusion, memory loss, nausea, hearing disorders and vomiting. It is unknown whether low-level chronic exposure may cause permanent neurological damage. Typically, upon removal from exposure to carbon monoxide, symptoms usually resolve themselves, unless there has been an episode of severe acute poisoning. However, one case noted permanent memory loss and learning problems after a three-year exposure to relatively low levels of carbon monoxide from a faulty furnace.Chronic exposure may worsen cardiovascular symptoms in some people. Chronic carbon monoxide exposure might increase the risk of developing atherosclerosis. Long-term exposures to carbon monoxide present the greatest risk to persons with coronary heart disease and in females who are pregnant.
In experimental animals, carbon monoxide appears to worsen noise-induced hearing loss at noise exposure conditions that would have limited effects on hearing otherwise. In humans, hearing loss has been reported following carbon monoxide poisoning. Unlike the findings in animal studies, noise exposure was not a necessary factor for the auditory problems to occur.