Scenario 1: A woman calls 9-1-1 after arriving at her father’s home and finding him unconscious in his car in an enclosed garage. The elderly man, suffering from terminal lung cancer, had written a suicide note, turned on his vehicle in the closed garage and then remained in his car.
Scenario 2: EMS transports a city employee to an emergency department (ED) after he suffers a headache and loses consciousness while working indoors at a water treatment plant. He had been working in a poorly ventilated, 60,000-cubic-foot room with an eight-horsepower, gasoline-powered pump when he became ill.
Scenario 3: A family doctor in a rural community asks the regional poison control center for advice after a family of five complains vaguely of nausea, fatigue and headaches. It is mid- December, and the symptoms began after the family moved into an older rental home with outdated heating and cooling systems.
Introduction
Despite the varying presentations of these three scenarios, all share an underlying causative agent: carbon monoxide (CO). CO poisoning is one of the leading agents of toxin-related deaths in the United States. A 10-year study tracking cases from 1979–1988 attributed a total of 56,133 U.S. deaths to CO poisoning. Suicides accounted for 25,889 of those cases; severe burns or house fires caused 15,523 of them; and 11,547 cases resulted from unintentional causes (1). Each year, 1,000–2,000 accidental deaths in the United States are related to CO(2). Even more common are nonlethal poisonings.
Although it’s difficult to track the exact number of cases related to CO poisoning that present to EDs across the United States, hospital surveys and data from national poison control centers indicate the number is upward of 40,000 visits. Although the number of CO-related injuries in the United States has declined in the past few years with the introduction of improved safety laws and increased public awareness, CO poisoning remains a significant source of morbidity and mortality in this country.
History
The toxic effects of human exposure to CO have been observed since ancient times. In the third century BC, Aristotle wrote, “Coal fumes lead to heavy head and death.” Ancient empires clearly knew the deadly effects of inhaling CO fumes, which were used for suicide and execution. It was not until 1842, however, that the French scientist LeBlanc identified CO as the toxic agent in coal gas.
Sources of CO
CO, dubbed the silent killer, is an odorless, colorless gas generated as a byproduct of incomplete combustion of nearly all carbon-containing products. Even the human body, through natural metabolism, produces low CO levels. A wide variety of environmental sources of CO exist. For years, automobile exhaust fumes have been known to be toxic and deadly, and CO is frequently used in suicide attempts, such as described in Scenario. In the home, other CO sources include faulty furnaces, blocked chimneys, cracked chimney flues, improperly installed water heaters, room heaters and other fuel-burning appliances. Studies implicate faulty furnaces in 80% of all accidental CO poisonings in the United States. Welding equipment, compressors, building generators, floor buffers, high-pressure washers, concrete cutting saws and many other gasoline powered tools have also been implicated, even when used in well-ventilated areas. Each year, about 30 deaths and 450 injuries from CO poisoning result from the use of portable camping heaters, lanterns, campers, charcoal grills and stoves inside tents. Several cases document severe injuries or death of families vacationing on houseboats or yachts due to faulty engine exhausts. Water skiing or swimming behind a running boat engine can also result in injury from CO inhalation. The prehospital provider or clinician must recognize that many different types of environmental hazards can lead to CO production and remain aware that CO poisoning takes many different forms. Location, population demographics, time of year and many other factors influence the incidence of CO-related injuries.
Pathophysiology
In the human body, hemoglobin in red blood cells carries oxygen. During inhalation, oxygen diffuses across pulmonary alveoli into the blood,
where hemoglobin picks it up and carries it to body tissues. Hemoglobin structure provides maximum oxygencarrying capacity. Each hemoglobin molecule comprises four globin chains, held together by weak chemical bonds. Each globin chain has its own heme molecule, composed of an iron atom, plus a distinctive ring called a protoporphyrin. Each iron atom can carry one oxygen molecule.10 The binding of oxygen by one heme group increases the affinity for oxygen of the remaining heme groups. In a normal adult, 96% of the body’s hemoglobin is composed of two types of globin chains: alpha (a) and beta (b). Each hemoglobin molecule has four heme groups and can carry four oxygen atoms.
CO interacts with deoxyhemoglobin to form carboxyhemoglobin (COHb). Heme groups prefer CO to oxygen: CO binds to hemoglobin with an affinity 250 times greater than oxygen. This causes cellular hypoxia because no new oxygen can bind to the hemoglobin molecules. CO further impairs oxygen delivery by preventing release of oxygen molecules already bound to heme molecules. When two of the four heme sites on the hemoglobin molecule are bound by CO, the molecular shape of the molecule alters, making it difficult for the hemoglobin molecule to release bound oxygen into tissues. Although CO’s detrimental effects, caused by its interaction with hemoglobin, are well-known, recent studies indicate that CO may cause damage to the human body by several other mechanisms. Evidence indicates that CO acts as an intracellular toxin, interfering with structures responsible for energy production.2 Myoglobin, which plays an important role in oxygen transport in muscle cells, also binds with CO. Studies of lab animals show that CO binds to myoglobin in cardiac and muscle cells at COHb levels less than 2%, which can significantly impair muscle performance.
Other studies show that CO can interfere with molecules responsible for various enzymatic functions throughout the body, interrupt normal
platelet function and may even lead to apoptosis in various organs, including the brain. Although much of this evidence has been derived from investigations using laboratory animals, many of the noxious effects likely occur in humans as well.
Clinical presentation
Symptoms can result from chronic exposure to low CO levels over a period of time or from acute exposure to higher CO levels. Major disability may result from either type of exposure. The presence of other toxins affects the severity of CO poisoning. Concentrations as low as 0.005% (50–100 parts per million [ppm]) can cause mild symptoms in the human body, 0.1% (1,000 ppm) may be potentially fatal, and a level of 1,200 ppm is considered an immediate threat to humans.
In a working environment, safety commissions limit exposure to 25 ppm in an eight-hour period. Patient factors, such as age and underlying medical conditions (especially respiratory, cardiovascular and hematological diseases), also affect the severity of CO poisoning. Headache is the most common symptom of CO poisoning. Other common symptoms include fatigue, dizziness, nausea, vomiting and diarrhea. More severe exposures can cause confusion, shortness of breath and fainting. In severe cases, cardiac arrhythmias, hypotension, seizures, coma and even death may occur. A patient’s COHb level doesn’t always reflect the severity of CO poisoning. Smokers commonly have a COHb level of up to 10% because of the CO in cigarette smoke. Research has even shown that if a COHb measurement occurs hours after an acute exposure, a patient can have a normal COHb level despite suffering significant CO poisoning. Treating a patient’s signs and symptoms is much more important than relying on a laboratory value to assess the need for therapy. The textbook appearance of a CO poisoning patient is a cherry-red coloration of the skin and mucous membranes, secondary to the bright-red color of COHb. However, this finding is inconsistent and often doesn’t present, even in patients with severe CO intoxication.
These may improve after the patient is removed from the poisoned environment. Complications from hypoxia and tissue ischemia can include cardiac ischemia, myocardial infarction or metabolic acidosis. Because CO doesn’t affect the amount of dissolved oxygen in serum, the partial pressure of oxygen (PaO2) and calculated oxygen saturation (SaO2) will be normal. Peripheral oxygen saturation (SpO2), such as readings from a pulse oximeter, also prove unreliable. Because pulse oximeters measure only two wavelengths of light, the machine separates hemoglobin molecules into two groups, oxyhemoglobin and deoxyhemoglobin. COHb is misread as oxyhemoglobin. The signs and symptoms of CO poisoning are often vague, and the possibility of CO exposure may be overlooked, unless the patient or bystanders offer a clear history. Patients with other medical conditions may have similar clinical presentations. Studies attempting to distinguish between the classic throbbing, diffuse headache of CO exposure and non-CO related headaches haven’t shown any specific pattern to differentiate CO exposure from other causes of headache. Thus, the diagnosis of CO poisoning remains difficult in many cases.
Treatment
The most important initial treatment is to remove the victim from the toxic environment without exposing rescuers to unsafe environments. Promptly administer 100% oxygen through a properly fitted oxygen or nonrebreather mask. If the patient is unconscious or has unstable vital signs, perform endotracheal (ET) intubation, and administer 100% oxygen via the ET tube. Establish an IV line, and administer crystalloid fluid if the patient is hypotensive. On arrival at the ED, assessment of arterial blood gas, electrolytes, COHb level and an ECG should be performed. Metabolic acidosis should be treated only for a pH of less than 7, because an acidotic environment actually aids oxygen delivery to the tissues.
High-dose oxygen delivery facilitates patient recovery in two ways. First, it increases the total oxygen content of the blood and, in turn, increases oxygen delivery to the tissues. Although the hemoglobin molecule has a higher affinity for the CO molecules, the oxygen molecules effectively compete with the CO molecules by outnumbering them. The other mechanism by which 100% oxygen helps is by decreasing the half-life of CO in the blood.
Experimental studies show that healthy adult humans who breathe room air at sea level have an average COHb half life of 320 minutes. When 100% oxygen is inhaled, the half-life shortens to 40–80 minutes. Studies show that the use of hyperbaric oxygen (HBO) may shorten the half-life of CO to 20 minutes or less. However, the use of HBO therapy in CO-poisoned patients remains controversial. Patients with severe acute CO toxicity can have a normal recovery without HBO therapy, and patients who do receive HBO therapy can suffer severe neurological disabilities. Only recently have randomized, controlled trials been performed to compare HBO treatment with that of 100% oxygen delivered
under normal pressure, normobaric oxygen (NBO). Two important studies in the last decade found no difference in outcome between HBO and NBO therapies in patients with all severities of CO poisoning.
Problems exist with HBO therapy that don’t occur with NBO therapy. First, HBO therapy isn’t available in all institutions. As previously mentioned, when 100% oxygen is delivered by a mask or ET tube, the half-life of CO is drastically reduced; the COHb level may have already dropped to a low level by the time a patient is transferred to a proper facility. The actual transfer of a potentially unstable patient to another facility isn’t without risk, especially in the presence of cardiac arrhythmias and hypotension. Also, the efficacy of HBO treatment appears to decline when utilized more than six hours after exposure. HBO therapy is expensive and has side effects. Example: Otic barotrauma, although generally reversible, is the most common side effect. One study demonstrated a seizure incidence of 1–3% in CO poisoned patients treated with HBO therapy, a much higher rate than found in patients treated with NBO. Many authorities use certain clinical criteria to determine which patients should receive HBO therapy, although its benefit has not been scientifically proven.
Pregnant patients and young children are generally considered candidates for HBO therapy. Fetal hemoglobin (HbF) is composed of alpha and gamma chains (rather than the alpha and beta chains found in adult hemoglobin) and has an even higher affinity for CO.1,15 Fetal CO poisoning has been associated with significant morbidity and mortality. Because HBO therapy appears safe during pregnancy and for children, many clinicians suggest initiating HBO therapy in pregnant patients and young children with a COHb level of 15% or greater. The appropriate dose of HBO therapy has also not yet been determined. An Undersea and Hyperbaric Medical Society Committee Report suggests treating CO poisoning at 2.5–3.0 atmospheres (atms) for 120 minutes for a maximum of five treatments. Opinions vary among institutions as to the appropriate number and length of treatments.
Long-term outcome
Many different studies have shown that CO poisoning can cause long-term problems. Neurological injury may persist in up to 40% of patients. Examples of long-term problems include malaise, memory disturbances, blindness, deafness, seizures, ataxia and Parkinsonian symptoms. Affective symptoms, such as depression, anxiety and personality changes, can persist even one year after poisoning. These symptoms sometimes improve over time, but patients may never return to prepoisoning states. Neuro-imaging studies have shown lesions in various regions of the brain. Patients at a higher risk for permanent neurological injuries often have abnormal computer tomography (CT) or magnetic resonance imaging (MRI) scans on hospital admission.16 Recent studies have attempted to study the long-term effects of CO poisoning in children. Researchers have found that acute neurological problems prove common after CO exposure, but usually resolve with therapy. Hypoxic brain injuries are generally responsible for most neurological injuries in CO-exposed children, and delayed sequelae are
uncommon after CO exposure.
The role of EMS personnel
A study published in 1999 surveyed directors of 618 U.S. paramedic training programs to determine the number of lecture hours devoted to toxicology subjects and the number of paramedic rotations through poison control centers. The results indicated that toxicology lectures account for only 2% of all paramedic lectures and that 19% of training programs discussed CO poisoning for less than 10 minutes. Also, although 81% of programs had access to a regional poison control center, only 11% of students actually trained there.18 EMS providers can play a critical role in the recognition and early treatment of CO poisoning if they receive appropriate training and get involved in prevention programs.
However, because CO poisoning often proves difficult to diagnose, hospital employees rely on EMS to provide an accurate patient history, especially for unconscious patients. EMS personnel are often the only medical staff to actually observe the setting in which a patient is found. Also, the immediate initiation of 100% oxygen is very important in managing CO-exposed patients. A patient may complain of nausea, vomiting, malaise or other flulike symptoms, rather than shortness of breath, seizures or syncope; therefore, oxygen therapy may not immediately be initiated. Consequently, EMS providers must consider CO poisoning early in their assessment.
Lee Ann Koster, MD, is a third-year resident in the Emergency Medicine Residency Training Program at the University of Texas Southwestern Medical Center at Dallas. She graduated from the University of South Alabama School of Medicine in 2000.
Timothy Rupp, MD, FACEP, is an assistant professor in the Department of Surgery, Division of Emergency Medicine at the University of Texas Southwestern Medical Center at Dallas. Rupp graduated from Temple University School of Medicine in 1995 and the Emergency Medicine Residency Training Program at Thomas Jefferson University Hospital in 1998. He is the associate director of the Emergency Medicine Residency Training Program at the University of Texas Southwestern Medical Center at Dallas.
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References & Additional Reading:
1. Harwood-Nuss A: The Clinical Practice of Emergency Medicine. Philadelphia: Lippincott Williams and Wilkins, 2001.
2. Weaver LK: “Carbon monoxide poisoning.” Critical Care Clinics. 15(2):297–317, 1999.
3. Hampson NB: “Emergency department visits for carbon monoxide poisoning in the Pacific Northwest.” Journal of Emergency Medicine.
16(5):695–698, 1998.
4. Penney DG (ed): Carbon Monoxide Headquarters. 1998. www.phymac.med.wayne.edu/facultyProfile/penney/COHQ/co1/htm.
Accessed Aug. 22, 2002.
5. Marx J, Hockberger RS, Walls R: Rosen’s Emergency Medicine: Concepts and Clinical Practice. Philadelphia: Mosby Inc. 2002.
6. Rakel RE: Conn’s Current Therapy 2002. Philadelphia: W.B. Saunders Co., 2002.
7. “The ‘senseless’ killer.” U.S. Environmental Protection Agency: Indoor Air-Publications. 2002. www.epa.gov/iedweb00/pubs/senseless.html. Accessed Aug. 14, 2002.
8. “Preventing carbon monoxide poisoning from small gasoline-powered engines and tools.” U.S. Environmental Protection Agency: Indoor
Air-Publications. 2002. www.epa.gov/iedweb00/pubs/senseless.html. Accessed Aug. 14, 2002.
9. “CPSC warns of carbon monoxide poisoning with camping equipment.” Consumer Product Safety Commission Document #5008. www.cpsc.gov/cpscpub/5008.html. Accessed Aug 10, 2002.
10. Becker WM, Deamer DW: The World of the Cell. Redwood City, CA: The Benjamin/Cummings Publishing Company Inc. 1991.
11. Robbins SL, Cotran RS, Kumar V: Robbins Pathological Basis of Disease. Philadelphia: W.B. Saunders Company. 1994.
12. Thom SR, Taber RL, Mendiguren II, et al: “Delayed neurological sequelae after carbon monoxide poisoning: Prevention by treatment with hyperbaric oxygen.” Annals of Emergency Medicine. 24(4):474–480, 1995.
13. Hampson NB: “Characteristics of headache associated with acute carbon monoxide poisoning.” Headache. 42(3):220–223, 2002.
14. Pracyk JB, Stolp BW, Fife CE, et al: “Brain computerized tomography after hyperbaric oxygen therapy for carbon monoxide poisoning.” Journal of the Undersea and Hyperbaric Medicinal Society. 22(suppl):1–7, 1995.
15. Hampson NB, Simonson SG, Kramer CC, et al: “Central nervous system toxicity during hyperbaric treatment of patients with carbon monoxide poisoning.” Journal of the Undersea and Hyperbaric Medicinal Society. 23(4):215–219, 1996.
16. Zagami AS, Lethlean AK, Mellick R: “Delayed neurological deterioration following carbon monoxide poisoning: MRI findings.” Journal of Neurology. 240(2):113, 1993.
17. Meert KL, Heidemann SM, Sarnaik AP: “Outcome of children with carbon monoxide poisoning treated with normobaric oxygen.” Journal of Trauma. 44(1):149–154, 1998.
18. Davis CO, Cobaugh DJ, Leahey NF, et al: “Toxicology training of paramedic students in the United States.” American Journal of Emergency Medicine.
17(2):138–140, 1999. A. Lascaratos JG, Marketos SG: “The carbon monoxide poisoning of two Byzantine emperors.” Journal of Clinical Toxicology. 36(1–2):103–107, 1998.
B. Sancton T, Macleod S: “Mystery in the details.” Time. 152(9):64–66. 1998.
C. Scheinkestel CD, Bailey M, Myles PS, et al: “Hyperbaric or normobaric oxygen
for acute carbon monoxide poisoning: a randomized controlled clinical
trial.” Medical Journal of Australia. 170(5): 203–210, 1999.
D. Weaver LK, et al: “Double-blind, controlled, prospective, randomized clinical
trial in patients with acute carbon monoxide poisoning: Outcome of patients
treated with normobaric oxygen or hyperbaric oxygen. An interim report.”
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