Carbon monoxide poisoning

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 (subcategorized as a gasotransmitter) 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, The carbon monoxide tolerance level for any person is altered by several factors, including genetics (hemoglobin mutations), 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. Aside from physiological signaling, most carbon monoxide is stored as carboxyhemoglobin at non-toxic levels below 3% HbCO. 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 (3.5 ppm at 20 °C). Acute exposure should not exceed 10 mg/m3 (8.7 ppm at 20 °C) in 8 hours, 35 mg/m3 (31 ppm at 20 °C) in one hour and 100 mg/m3 (87 ppm at 20 °C) in 15 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. 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. 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. 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. Chronic exposure may worsen cardiovascular symptoms in some people. 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. The colorant effect of carbon monoxide in such postmortem circumstances is thus analogous to its use as a red colorant in the commercial meat-packing industry. == Epidemiology ==

The true number of cases of carbon monoxide poisoning is unknown, since many non-lethal exposures go undetected. Poisoning is typically more common during the winter months. This is due to increased domestic use of gas furnaces, gas or kerosene space heaters, and kitchen stoves during the winter months, which if faulty and/or used without adequate ventilation, may produce excessive carbon monoxide. Carbon monoxide detection and poisoning also increases during power outages, when electric heating and cooking appliances become inoperative and residents may temporarily resort to fuel-burning space heaters, stoves, and grills (some of which are safe only for outdoor use but nonetheless are errantly burned indoors). It has been estimated that more than 40,000 people per year seek medical attention for carbon monoxide poisoning in the United States. 95% of carbon monoxide poisoning deaths in Australia are due to gas space heaters. In many industrialized countries, carbon monoxide is the cause of more than 50% of fatal poisonings. Carbon monoxide poisoning contributes to the approximately 5,613 smoke inhalation deaths each year in the United States. The CDC reports, "Each year, more than 500 Americans die from unintentional carbon monoxide poisoning, and more than 2,000 commit suicide by intentionally poisoning themselves." For the 10-year period from 1979 to 1988, 56,133 deaths from carbon monoxide poisoning occurred in the United States, with 25,889 of those being suicides, leaving 30,244 unintentional deaths. In South Korea, 1,950 people had been poisoned by carbon monoxide with 254 deaths from 2001 through 2003. A report from Jerusalem showed 3.53 per 100,000 people were poisoned annually from 2001 through 2006. In Hubei, China, 218 deaths from poisoning were reported over a 10-year period with 16.5% being from carbon monoxide exposure. Causes Carbon monoxide is a product of combustion of organic matter under conditions of restricted oxygen supply, which prevents complete oxidation to carbon dioxide (CO2). Sources of carbon monoxide include cigarette smoke, house fires, faulty furnaces, heaters, wood-burning stoves, internal combustion vehicle exhaust, electrical generators, propane-fueled equipment such as portable stoves, and gasoline-powered tools such as leaf blowers, lawn mowers, high-pressure washers, concrete cutting saws, power trowels, and welders. Exposure typically occurs when equipment is used in buildings or semi-enclosed spaces. Idling automobiles with the exhaust pipe blocked by snow has led to the poisoning of car occupants. Any perforation between the exhaust manifold and shroud can result in exhaust gases reaching the cabin. Generators and propulsion engines on boats, notably houseboats, have resulted in fatal carbon monoxide exposures. Poisoning may also occur following the use of a self-contained underwater breathing apparatus (SCUBA) due to faulty diving air compressors. In caves carbon monoxide can build up in enclosed chambers due to the presence of decomposing organic matter. In coal mines incomplete combustion may occur during explosions resulting in the production of afterdamp. The gas is up to 3% CO and may be fatal after just a single breath. Another source of poisoning is exposure to the organic solvent dichloromethane, also known as methylene chloride, found in some paint strippers, as the metabolism of dichloromethane produces carbon monoxide. In November 2019, an EPA ban on dichloromethane in paint strippers for consumer use took effect in the United States. Prevention Detectors Prevention remains a vital public health issue, requiring public education on the safe operation of appliances, heaters, fireplaces, and internal-combustion engines, as well as increased emphasis on the installation of carbon monoxide detectors. The United States Consumer Product Safety Commission has stated, "carbon monoxide detectors are as important to home safety as smoke detectors are", and recommends each home have at least one carbon monoxide detector, and preferably one on each level of the building. and widely available, are either battery- or AC-powered, with or without battery backup. In buildings, carbon monoxide detectors are usually installed around heaters and other equipment. If a relatively high level of carbon monoxide is detected, the device sounds an alarm, giving people the chance to evacuate and ventilate the building. Unlike smoke detectors, carbon monoxide detectors do not need to be placed near ceiling level. The use of carbon monoxide detectors has been standardized in many areas. In the US, NFPA 720–2009, the carbon monoxide detector guidelines published by the National Fire Protection Association, mandates the placement of carbon monoxide detectors/alarms on every level of the residence, including the basement, in addition to outside sleeping areas. In new homes, AC-powered detectors must have battery backup and be interconnected to ensure early warning of occupants at all levels. Legal requirements The NFPA standard is not necessarily enforced by law. As of April 2006, the US state of Massachusetts requires detectors to be present in all residences with potential CO sources, regardless of building age and whether they are owner-occupied or rented. This is enforced by municipal inspectors and was inspired by the death of 7-year-old Nicole Garofalo in 2005 due to snow blocking a home heating vent. Other jurisdictions may have no requirement or only mandate detectors for new construction or at time of sale. World Health Organization recommendations The following guideline values (ppm values rounded) and periods of time-weighted average exposures have been determined in such a way that the carboxyhemoglobin (COHb) level of 2.5% is not exceeded, even when a normal subject engages in light or moderate exercise: • 100 mg/m3 (87 ppm) for 15 min • 60 mg/m3 (52 ppm) for 30 min • 30 mg/m3 (26 ppm) for 1 h • 10 mg/m3 (9 ppm) for 8 h • 7 mg/m3 (6 ppm) for 24 h (for indoor air quality, so as not to exceed 2% COHb for chronic exposure) == Diagnosis ==

saturation monitor (SpCO%). Note: This is not the same as a pulse oximeter (SpO2%), although some models (such as this one) do measure both the oxygen and carbon monoxide saturation. As many symptoms of carbon monoxide poisoning also occur with many other types of poisonings and infections (such as the flu), the diagnosis is often difficult. A history of potential carbon monoxide exposure, such as being exposed to a residential fire, may suggest poisoning, but the diagnosis is confirmed by measuring the levels of carbon monoxide in the blood. This can be determined by measuring the amount of carboxyhemoglobin compared to the amount of hemoglobin in the blood. In symptomatic poisoned people they are often in the 10–30% range, while persons who die may have postmortem blood levels of 30–90%. As people may continue to experience significant symptoms of CO poisoning long after their blood carboxyhemoglobin concentration has returned to normal, presenting to examination with a normal carboxyhemoglobin level (which may happen in late states of poisoning) does not rule out poisoning. Measuring Carbon monoxide may be quantitated in blood using spectrophotometric methods or chromatographic techniques in order to confirm a diagnosis of poisoning in a person or to assist in the forensic investigation of a case of fatal exposure. A CO-oximeter can be used to determine carboxyhemoglobin levels. Pulse CO-oximeters estimate carboxyhemoglobin with a non-invasive finger clip similar to a pulse oximeter. These devices function by passing various wavelengths of light through the fingertip and measuring the light absorption of the different types of hemoglobin in the capillaries. The use of a regular pulse oximeter is not effective in the diagnosis of carbon monoxide poisoning as these devices may be unable to distinguish carboxyhemoglobin from oxyhemoglobin. Breath CO monitoring offers an alternative to pulse CO-oximetry. Carboxyhemoglobin levels have been shown to have a strong correlation with breath CO concentration. However, many of these devices require the user to inhale deeply and hold their breath to allow the CO in the blood to escape into the lung before the measurement can be made. As this is not possible in people who are unresponsive, these devices may not appropriate for use in on-scene emergency care detection of CO poisoning. Differential diagnosis There are many conditions to be considered in the differential diagnosis of carbon monoxide poisoning. The earliest symptoms, especially from low level exposures, are often non-specific and readily confused with other illnesses, typically flu-like viral syndromes, depression, chronic fatigue syndrome, chest pain, and migraine or other headaches. Carbon monoxide has been called a "great mimicker" due to the presentation of poisoning being diverse and nonspecific. Other conditions included in the differential diagnosis include acute respiratory distress syndrome, altitude sickness, lactic acidosis, diabetic ketoacidosis, meningitis, methemoglobinemia, or opioid or toxic alcohol poisoning. == Treatment ==

Initial treatment for carbon monoxide poisoning is to immediately remove the person from the exposure without endangering further people. Those who are unconscious may require CPR on site. Due to the possible severe effects in the baby, pregnant women are treated with oxygen for longer periods of time than non-pregnant people. Hyperbaric oxygen Hyperbaric oxygen is also used in the treatment of carbon monoxide poisoning, as it may hasten dissociation of CO from carboxyhemoglobin to a greater extent than normal oxygen. Hyperbaric oxygen at three times atmospheric pressure reduces the half life of carbon monoxide to 23 minutes, compared to 80 minutes for oxygen at regular atmospheric pressure. There have been randomized controlled trials in which the two treatment options have been compared; of the six performed, four found hyperbaric oxygen improved outcome and two found no benefit for hyperbaric oxygen. Some of these trials have been criticized for apparent flaws in their implementation. A review of all the literature concluded that the role of hyperbaric oxygen is unclear and the available evidence neither confirms nor denies a medically meaningful benefit. The authors suggested a large, well designed, externally audited, multicentre trial to compare normal oxygen with hyperbaric oxygen. Cardiac dysrhythmias are treated with standard advanced cardiac life support protocols. Treatment of acidosis may only need to consist of oxygen therapy. Extensive follow up and supportive treatment is often required for delayed neurological damage. especially people who have symptoms of cardiac arrest, coma, metabolic acidosis, or have high carboxyhemoglobin levels. A device that also provides some carbon dioxide to stimulate faster breathing (sold under the brand name ClearMate) may also be used. == Pathophysiology ==

The precise mechanisms by which the effects of carbon monoxide are induced upon bodily systems are complex and not yet fully understood. Hemoglobin Carbon monoxide has a higher diffusion coefficient compared to oxygen, and the main enzyme in the human body that produces carbon monoxide is heme oxygenase, which is located in nearly all cells and platelets. However, certain mutations such as the Hb-Kirklareli mutation has a relative 80,000 times greater affinity for carbon monoxide than oxygen resulting in systemic carboxyhemoglobin reaching a sustained level of 16% COHb. At toxic concentrations, carbon monoxide as carboxyhemoglobin significantly interferes with respiration and gas exchange by simultaneously inhibiting acquisition and delivery of oxygen to cells and preventing formation of carbaminohemoglobin which accounts for approximately 30% of carbon dioxide exportation. Therefore, a patient with carbon monoxide poisoning may experience severe hypoxia This binding interferes with aerobic metabolism and efficient adenosine triphosphate synthesis. Cells respond by switching to anaerobic metabolism, causing anoxia, lactic acidosis, and eventual cell death. The rate of dissociation between carbon monoxide and cytochrome oxidase is slow, causing a relatively prolonged impairment of oxidative metabolism. The result of these effects is lipid peroxidation, which causes delayed reversible demyelination of white matter in the central nervous system known as Grinker myelinopathy, which can lead to edema and necrosis within the brain. Hallmark pathological changes following poisoning are bilateral necrosis of the white matter, globus pallidus, cerebellum, hippocampus and the cerebral cortex. Pregnancy Carbon monoxide poisoning in pregnant women may cause severe adverse fetal effects. Poisoning causes fetal tissue hypoxia by decreasing the release of maternal oxygen to the fetus. Carbon monoxide also crosses the placenta and combines with fetal hemoglobin, causing more direct fetal tissue hypoxia. Additionally, fetal hemoglobin has a 10 to 15% higher affinity for carbon monoxide than adult hemoglobin, causing more severe poisoning in the fetus than in the adult. The level of fetal morbidity and mortality in acute carbon monoxide poisoning is significant, so despite mild maternal poisoning or following maternal recovery, severe fetal poisoning or death may still occur. == History == Humans have maintained a complex relationship with carbon monoxide since first learning to control fire circa 800,000 BC. Primitive cavemen probably discovered the toxicity of carbon monoxide upon introducing fire into their dwellings. The early development of metallurgy and smelting technologies emerging circa 6,000 BC through the Bronze Age likewise plagued humankind with carbon monoxide exposure. Apart from the toxicity of carbon monoxide, indigenous Native Americans may have experienced the neuroactive properties of carbon monoxide through shamanistic fireside rituals. Emperor Lucius Verus used smoke to execute prisoners. In the fifteenth century, coal miners believed sudden death was caused by evil spirits; carbon monoxide poisoning has been linked to supernatural and paranormal experiences, witchcraft, etc. throughout the following centuries Georg Ernst Stahl mentioned carbonarii halitus in 1697 in reference to toxic vapors thought to be carbon monoxide. Friedrich Hoffmann conducted the first modern scientific investigation into carbon monoxide poisoning from coal in 1716, notably rejecting villagers attributing death to demonic superstition. Herman Boerhaave conducted the first scientific experiments on the effect of carbon monoxide (coal fumes) on animals in the 1730s. Over 50 people are suspected to have died from smoke inhalation as a result of the Branch Davidian Massacre during the Waco siege in 1993. On 14 December 2024 12 individuals died by carbon monoxide poisoning in Gudauri (Georgia) as electric generators using fuel oil were placed in a closed area near their rooms. Weaponization In ancient history, Hannibal executed Roman prisoners with coal fumes during the Second Punic War. As part of the Holocaust during World War II, the Nazis used gas vans at Chelmno extermination camp and elsewhere to murder an estimated 700,000 or more people by carbon monoxide poisoning. This method was also used in the gas chambers of several death camps such as Treblinka, Sobibor, and Belzec. Gassing with carbon monoxide started in Action T4. The gas was supplied by IG Farben in pressurized cylinders and fed by tubes into the gas chambers built at various mental hospitals, such as Hartheim Euthanasia Centre. Exhaust fumes from tank engines, for example, were used to supply the gas to the chambers. == References ==