Carbon Monoxide Poisoning
Carbon Monoxide Poisoning
Authors: Colin G. Kaide, MD, FACEP, FAAEM, Clinical Assistant Professor of Emergency Medicine, Associate Director of Hyperbaric Medicine, The Ohio State University Medical Center, Columbus; Sorabh Khandelwal, MD, Clinical Associate Professor of Emergency Medicine, Director of Hyperbaric Medicine, The Ohio State University Medical Center; Erika Kube, MD; Emergency Medicine Resident, The Ohio State University Medical Center; Douglas A. Rund, MD, FACEP, Professor and Chairman of Emergency Medicine, The Ohio State University Medical Center.
Peer Reviewer: Ian R. Grover, MD, Assistant Clinical Professor of Medicine, Department of Emergency Medicine, University of California–San Diego Medical Center.
Carbon monoxide poisoning is a treatable condition when recognized prior to devastating consequences. Early on, carbon monoxide (CO) poisoning may be subtle and elusive, with vague, nonspecific symptoms that may be inappropriately contributed to other conditions. Particularly, viral syndromes may be confused with CO poisoning and it is important, particularly in the winter months, to screen patients who have isolated vomiting without fever and diarrhea. Also, it is unusual for a whole family to be symptomatic with the "flu" at the same time, and in these situations a careful history and consideration of testing may avert disaster. Early recognition may only occur if the diagnosis is considered in the differential and may be life-saving. The authors comprehensively review the presentation, diagnosis, and treatment of CO poisoning.
— The Editor
Introduction
"By turning the outside tap the room could be flooded with gas. With door and shutters closed and the tap full on I would not give two minutes of conscious sensation to anyone shut up in that little chamber."
—From the Sherlock Holmes story "The Adventure of the Retired Colourman" by Sir Arthur Conan Doyle, in which Josiah Amberley used coal gas to murder his wife. Coal gas is a gaseous mixture—mainly hydrogen, methane, and CO—formed by the destructive distillation (i.e., heating in the absence of air) of bituminous coal and used as a fuel.
The most devastating situation a physician may encounter is an easily treatable condition that is not recognized and results in a patient's death or permanent disability. Intentional CO poisoning may be obvious (in the case of a suicidal patient who presents comatose after inhaling car exhaust), but mild, unintentional CO poisoning presents with vague, nonspecific symptoms. Failure to make this diagnosis may result in a potentially treatable patient who is discharged back to the environment that sickened him in the first place, often with dire consequences.
Given that CO poisoning has higher morbidity and mortality rates than all other poisonings and is the most common poisoning overall, the likelihood of encountering a case in any practice is high. This review serves to make the emergency physician aware of the various presentations of CO poisoning as well as pitfalls surrounding diagnosis and management of the CO-poisoned patient.
Cases
Case 1: Daily Headaches. A healthy 30-year-old woman presented to an urgent care facility complaining of daily headaches associated with nausea for two weeks. The headaches were described as diffuse and aching in quality.
She notes that her symptoms began each day as she was driving to work and persisted for four to five hours, with complete resolution by the end of her work day. Her symptoms began again when she went home and lasted most of the evening. Her headache was lessened somewhat with ibuprofen. She denied fever, chills, vomiting, diarrhea, lethargy, stiff neck, confusion, or other systemic complaints.
Upon presentation, she did have a headache. Other than being slightly tachycardic with a heart rate of 110, her physical exam was essentially unremarkable. Her fingerstick glucose level was 90 mg/dL and her urine human chorionic gonadotropin was negative. Her headache improved with 600 mg of ibuprofen and 2 tablets of hydrocodone/acetaminophen (5/500); she was discharged with the diagnosis of tension headache.
She returned three days later with persistent but worsening headaches. Her presentation was similar to the prior visit. She was diagnosed with viral syndrome and a tension headache and discharged home.
She presented a third time after falling asleep at a traffic light on her way to work. She awoke when her car rear-ended another vehicle and went to the emergency department (ED) for further evaluation. The emergency physician, after obtaining a thorough history, established that her headaches always began as she traveled to and from work, a distance of 30 miles each way. Her headaches always improved after several hours and she did not have similar symptoms when taking short car trips. A carboxyhemoglobin (COHb) level was requested in the ED, which showed a level of 16%. (Normal levels are less than 2% for nonsmokers and less than 5% for smokers.) The fire department then tested her car with the engine running and the windows up. After 15 minutes, CO levels in the car reached 400 parts per million (ppm), which greatly exceeded the EPA standards for air quality.
The patient received 15 L oxygen by nonrebreather mask for 180 minutes, at which time her symptoms had resolved completely. She was discharged home with outpatient follow-up. Her car's exhaust system was repaired to prevent further CO poisoning.
Case 2: Flu-like Symptoms. A family of five (mother, father, and three children) presented to the ED on a Sunday morning with "flu-like symptoms." All family members described similar symptoms of fatigue, nausea, headache, and loss of appetite over the previous two days. Two of the three children had vomited several times over the previous day. The eldest child complained of a runny nose and discomfort around her eyes.
Physical examination findings were largely unremarkable for all of the family members. All vital signs were normal, with the eldest daughter having the highest temperature of 99.8°F. The family was diagnosed with flu/viral syndrome and discharged home.
Relatives were contacted the following Monday morning when the adults failed to report to work. Police were dispatched to the residence, where they found four of the family members and their two dogs dead. CO readings, as measured by the fire department, are typically done by averaging 2-3 samples taken in various places in the residence where the victims are found. Readings in this family's home were 890 ppm. The sole surviving family member, the eldest daughter, was found comatose in her bedroom, where the windows were open and CO levels were found to be 465 ppm. She was taken to a local ED, where her COHb level was 44%. She was flown to a tertiary referral center with hyperbaric oxygen therapy capabilities. Despite aggressive hyperbaric oxygen treatments (HBO2), she remained in a persistent vegetative state three weeks after the incident.
Case 3: Pregnant Woman. A 28-year-old pregnant mother presents to the ED with her two children, ages 2 and 4. The mother reports that the two children have been increasingly fussy and not eating or drinking well over the previous three days. Her husband is currently overseas serving in the United States Army. The mother states that she feels generally well, other than perhaps being more tired than usual and a little dizzy from time-to-time; both are symptoms that she attributes to being pregnant and caring for two small children.
Both children and the mother were afebrile on presentation, with the only abnormality being a slightly elevated pulse rate in all three. Upon further questioning about recent events, the mother reveals that some sort of "smoke detector" in her house had been going off because the battery in it had died; she was able to remove the old battery but was waiting for her husband to replace the new battery.
The emergency physician, being suspicious about an alarm going off and the presentation of the pregnant mother and children, decided to check a COHb level on all three. The mother's level was 26% and the children were 17% and 18%. Because the fetus is especially vulnerable to the effects of CO poisoning and likely had a level 10-15% higher than the mother, HBO2 was initiated. She was treated with 3 atmospheres absolute (ATA) of HBO2 for 60 minutes with a repeat dive at 2.4 ATA for 60 minutes and was discharged in good condition the following day. She delivered a healthy baby at term with no further sequelae. Additionally, she repaired the faulty water heater that caused the CO poisoning and replaced the battery in her CO detector, which she had mistaken for a smoke detector.
Case 4: Complicated CO Poisoning. A 47-year-old male is brought to the ED from a house fire. Paramedics report that the patient was found with agonal respirations in a closed room in the basement where the carpet and wall-paper had fully burned. On presentation to the ED his primary survey showed an intubated male with a blood pressure of 50 systolic and a pulse of 40. The respiratory rate with the assistance of bag-valve-mask was 18.
The patient received 3 mg of atropine with minimal response in heart rate. The patient was started on dopamine and titrated to 20 mcg/kg/min with the blood pressure increasing to 60 systolic. Lab values showed a pH of 7.0, PaO2 of 400 on FiO2 of 100%, PaCO2 of 30, and a HC03 of 3. The patient received a total of 4 amps of bicarb, with the resultant pH rising to 7.1. Serum lactate levels were 18 and the COHb was reported to be 25%.
The emergency medicine resident on the case noticed that the blood return from her central line placement was very bright red, such that she thought she had placed the line inadvertently in the femoral artery. After not finding pulsatile flow, she used the line and made a second stick in the groin to place an arterial line. This produced pulsatile flow that appeared to be the exact same color as the venous blood. At this point she made the connection between the similar colors and possible explanation of a decreased oxygen utilization manifesting in the bright red venous blood. She concluded that cyanide was a likely concomitant agent contributing to the patient's clinical picture. The patient was treated with sodium thiosulfate and sodium nitrite along with hyperbaric oxygen at 3 ATA for 60 minutes. The patient rapidly recovered with normalization of pH and vital signs.
Epidemiology
While CO poisoning is the leading cause of death and injury due to poisoning in the United States,1,2 the worldwide incidence of CO poisoning is estimated to be largely under-diagnosed, with more than one third of all cases going undetected. A 2001 study had emergency medical technicians use hand-held CO meters to screen for elevated levels of CO during emergency responses. Over a three-month period they obtained readings in 264 residences, of which nine (3.4%) were positive. In these nine homes, 35% of the residents had symptoms that could be attributed to CO exposure.3
In the United States, it is estimated that more than 40,000 presentations per year are related to CO poisoning, based on data obtained from three western states.4 The Centers for Disease Control and Prevention reported that CO poisoning contributed to an average of 1902 unintentional deaths and 2385 intentional suicides per year in the United States from 1968 through 1998.5,6 In the three-year period from 2001 through 2003, there were more than 15,000 annual ED visits related to CO exposure/poisoning and 500 annual deaths attributed to unintentional, non-fire-related CO exposure.7 Annual associated mortality rates are estimated to be as high as 31% in large series studies, while other studies have shown mortality rates as low as 1-2%.2
CO poisoning epidemics occur commonly during winter months with the misuse of non-electronic heating and cooking devices.8,9 Use of these devices also has been shown to increase CO poisoning incidence during natural disasters like hurricanes, where prolonged power outages are common.10
CO is the product of incomplete combustion of carbon-based products, such as gas or coal. Because it is colorless, odorless, and tasteless, CO is undetectable by human senses. While there are numerous potential sources (see Table 1) for CO, the two most common are motor vehicle exhaust and smoke. Of CO-related deaths between 1979 and 1988, 57% were caused by vehicle exhaust and 83% involved a stationary vehicle.11 Methylene chloride, a chemical found in some automotive cleaners, spray paints, and other household products, is converted into CO in the liver after the compound is ingested or inhaled.12
| Table 1. Exogenous Sources of Carbon Monoxide |
| • Car exhaust fumes • Paint removers containing methylene chloride • Pool heaters • Sterno fuel • Tobacco smoke • Wood-burning stoves • Underground electrical cable fires • Smoke from fires • Furnaces • Gas-powered engines • Home water heaters • Burning charcoal |
The effects of CO become apparent after an exposure period of 20 hours to ambient levels as low as 100 ppm. EPA guidelines for CO exposure in the workplace state that levels should not exceed 35 ppm over one hour or 9 ppm over eight hours. While steady state time depends on individual factors (including CO diffusing capacity and alveolar ventilation), in general, in the steady state after equilibrium, CO levels of 100 and 200 ppm produce average COHb levels of 16 and 30%, respectively.13 Exposure to levels near 1000 ppm for more than two hours can result in COHb levels of 50% or greater. Chimney smoke from a wood-burning stove contains approximately 5000 ppm CO. Warm, undiluted car exhaust contains 7000 to 8000 ppm CO. Undiluted cigarette smoke contains 16,000 to 30,000 ppm CO.14,15 A CO level of 1200 ppm is considered immediately dangerous to life.16
Pathophysiology
CO pathophysiology was accurately described as early as 1846, when Claude Bernard, a French physician and physiologist, referred to CO as a "poison that troubles the blood by displacing oxygen." The effects of CO have been appreciated since ancient times, when Roman and Greek empires used CO in state executions.17
CO toxicity is a result of tissue hypoxia and direct CO-mediated damage at the cellular level. CO binds competitively to hemoglobin; in fact, hemoglobin's affinity for CO is 240 times that of oxygen. This is why, even with low ambient levels of CO, significant toxicity can result over time with prolonged exposures. In addition to hemoglobin binding with CO with such great affinity, the binding of CO to hemoglobin causes a leftward shift of the oxyhemoglobin dissociation curve (the Haldane effect). This results in a decrease in oxygen delivery to the peripheral tissues. The net results are impaired oxygen delivery, cellular hypoxia, and increasing minute ventilation (respiratory rate X tidal volume). Increasing minute ventilation results in respiratory alkalosis that further shifts the oxyhemoglobin dissociation curve to the left, facilitating a vicious cycle of worsening tissue hypoxia. (See Figure 1.)
| Figure 1. Oxygen Dissociation Curves |
|
| A: Actual (solid line) and predicted (dashed line) oxygen (O2) dissociation curves of Hb at various levels (0%, 20%, 40%, and 60%) of HbCO. Nonlinear regression relationships for the parameters of Hill's equation [PO2 necessary to reach 50% Hb saturation (P50; B) and n (C)] as a function of HbCO level.
Used with permission from: Bruce EN, Bruce MC. A multicompartment model of carboxyhemoglobin and carboxymyoglobin responses to inhalation of carbon monoxide. J Appl Physiol 2003;95:1235-1247. |
In addition to binding hemoglobin, carbon monoxide binds cardiac and skeletal myoglobin, with a three times greater affinity for cardiac myoglobin than hemoglobin.18 Because carboxymyoglobin dissociation is slower than that of COHb due to its increased affinity, it is possible to see a rebound effect with late release of CO from myoglobin and its subsequent binding to hemoglobin.19
During pregnancy, the fetus is particularly vulnerable to CO exposure because fetal hemoglobin binds CO with a greater affinity than hemoglobin A. This, combined with slow transplacental transport and the fact that fetal oxyhemoglobin is naturally shifted to the left, can cause fetal CO levels to be deadly in exposures that would typically be nonfatal.20,21
Hypoxia can explain some of the effects of CO in the acute phase, particularly the cardiac and neurological symptoms seen frequently with the presentation of CO poisoning. Hypoxia alone, however, cannot explain all the pathophysiologic consequences of CO poisoning. CO interferes with peripheral oxygen utilization by combining with myoglobin, cytochromes, and triphosphopyridine nucleotide reductase, directly interfering with oxidative phosphorylation.22 CO also impairs tissue perfusion by inducing hypotension through myocardial depression, ventricular arrhythmias, and peripheral vasodilation.23 Postischemia reperfusion injury, brain lipid peroxidation, and subsequent demyelination of central nervous system (CNS) lipids are also seen with CO exposure.24 These CNS effects, which are reversible and occur after CO exposure, are mediated largely by leukocytes.25 Lastly, CO exposure creates oxidative stress on cells, leading to generation of oxygen free radicals, with implications for further cellular damage.26,27
It is not uncommon to see CO poisoning complicated by cyanide poisoning in victims of closed-space fires in which synthetic materials are burned. Cyanide worsens cellular hypoxia by binding of the cyanide to the mitochondrial cytochrome oxidase, thus preventing the ferric iron-dependent reduction of oxygen to water by cytochrome aa3. This effectively inhibits oxidative phosphorylation, preventing the conversion of adenosine diphosphate to adenosine triphosphate. The net effect is anaerobic metabolism and severe lactic acidosis.28
The standard treatment for cyanide toxicity is the cyanide antidote kit, which contains amyl nitrite, sodium nitrite, and sodium thiosulfate. When CO and cyanide poisoning are both suspected, the empiric administration of nitrites is cautioned due to the formation of a significant amount of methemoglobinemia, which further impairs the patient's oxygen carrying capacity. In a patient with severe COHb, HBO2 confers the benefit of increasing the amount of soluble oxygen many-fold, thus improving tissue oxygenation. However, the increased oxygen saturation would competitively inhibit the formation of methemoglobin, reducing the effectiveness of the cyanide antidote kit. This complicating issue of reducing the effectiveness of the cyanide antidote by treating the CO poisoning may no longer be an issue when hydroxocobalamin or ethylenediaminetetraacetic acid (EDTA) become approved as cyanide antidotes in the United States. Until that time, however, HBO2 remains the mainstay of therapy for severe CO poisoning, even at the expense of decreasing the amount of methemoglobinemia and the effects of cyanide toxicity.29
Presenting Features
The signs and symptoms of CO exposure depend on the amount of CO in inspired air, minute ventilation, and duration of exposure to CO. The diagnosis of CO poisoning can be easily missed because the clinical findings of CO poisoning are highly variable and nonspecific and can mimic a viral syndrome.30 (See Table 2.) The emergency physician must include CO poisoning in the differential diagnosis of every patient who presents with any of the common symptoms. This is especially true in winter months, when both viral syndromes and accidental CO poisonings occur with greater frequency.
| Table 2. Clinical Presentations of CO Poisoning |
|
While there is a correlation between the degree of a patient's symptoms and a rise in measured COHb levels, the actual COHb level does not predict the degree of symptoms that a patient may experience. One can generalize about symptomatology at the extremes of COHb levels. COHb levels between 3% and 10% are common in asymptomatic cigarette smokers.31 Levels greater than 25% are considered significantly elevated, with levels between 40% and 50% almost always causing overt symptoms.16
At lower COHb levels, acute CO poisoning usually presents with symptoms such as headache, dizziness, nausea, and weakness. As COHb levels increase, patients may become confused or have difficulty concentrating, which can proceed to lethargy and coma.30,32,33 Tachycardia and tachypnea may develop in response to cellular hypoxia. Additionally, the sensation of air hunger and agitation may be seen, which can progress in later stages to hypotension, bradycardia, and decreased respirations.
The extremes of age are at higher risk for morbidity and mortality from CO exposure. Patients with coronary artery disease may have anginal symptoms or actual myocardial infarction after CO exposure, due to the relative hypoxia at the cellular level.34 Patients with underlying pulmonary and cerebrovascular disease may also experience worsening of their conditions. The classically described cyanotic patient with cherry-red lips is actually rarely seen.35
It is not uncommon to have a patient awake and alert on ED presentation, despite having been described by rescuers as unconscious or barely conscious at the scene. Despite their grossly normal cognitive status on presentation, these patients have sustained hypoxia sufficient to cause end-organ injury and syncope and require aggressive treatment. Secondary ischemic injury frequently is seen in severe CO poisoning.
Since patients can be considered "alert and oriented × 3" and still have some degree of cognitive impairment, a neuropsychologic (NP) testing battery has been developed to help assess subtle cognitive changes that may be overlooked during routine ED examination. The Carbon Monoxide Neuropsychologic Screening Battery (CONSB), which takes up to 30 minutes to administer, consists of six different tests that together assess global cognitive function. (See Table 3.) Although some centers use this as criteria for HBO2 treatment, there is controversy as to whether the testing has the ability to predict which patients will develop delayed neurologic sequelae (DNS). Furthermore, some feel that the testing doesn't allow for differentiation between cognitive impairment from CO and cognitive impairment from other possible coingestants. Finally, it may be difficult to attribute abnormal NP testing to CO poisoning in patients with preexisting psychological and psychiatric illnesses.
| Table 3. Carbon Monoxide Neuropsychologic Screening Battery (CONSB) |
| Purpose of test: To determine if a patient has subtle neurologic symptoms in the acute care setting Six subtests: • General orientation • Digit span • Trail making • Digit symbol • Aphasia screening • Block design |
Specific Injury Patterns
There are three specific injury patterns that deserve special mention: cardiovascular sequelae, delayed neurological sequelae (DNS), and symptoms associated with long-term exposure.
As moderate to severe CO poisoning is associated with an increased risk of cardiovascular sequelae, an electrocardiogram (ECG) and cardiac biochemical markers should be obtained at presentation and followed throughout the hospitalization.36 A patient presenting with cardiac injury must be closely followed during hospitalization and at discharge as there does appear to be a correlation between myocardial injury at presentation and long-term mortality.37
A significant proportion of patients, up to 40%, with significant CO exposure develop a syndrome of DNS, characterized by variable degrees of cognitive deficits, movement disorders, personality changes, and focal neurological deficits. While onset of DNS is usually within 20 days of recovery from the initial insult, they have been shown to occur as many as 240 days afterward. These deficits may last for a year or longer, necessitating ongoing neurological and neuropsychiatric follow-up.38-40
Chronic CO poisoning from long-term exposure at low levels is frequently overlooked due to obscure and vague symptomatology, a wide range of presentations, and a general lack of awareness of the problem. The most commonly reported symptoms are: headache, dizziness, insomnia, anorexia, nausea, weight loss, apathy, and personality disturbance. Palpitations, impaired memory, decreased libido, increased sweating, impairment in sleep, and diminished alcohol tolerance also may be seen. Neurological signs including hyperreflexia, altered pain perception, nystagmus, ataxia, weakness, tremors, myoclonus, hemiplegia, anosmia, aphasia, and facial nerve palsies have been reported.41,42
Diagnosis
The diagnosis of acute CO poisoning requires diligence and an algorithmic approach. A history of potential exposure is the most reliable indicator, although this may be difficult to ascertain. Thus a high index of suspicion on the part of the emergency physician is paramount. (See Table 4.) In practical terms, this means that the emergency physician must at least consider CO poisoning in any patient who presents with nausea, headache, dizziness, or lethargy. While this consideration is vital, testing COHb levels on all patients with these symptoms is not appropriate.
| Table 4. Key Points for the Diagnosis of CO Poisoning |
| • High index of suspicion • Diagnosis is confirmed by venous or arterial carboxyhemoglobin level: > 5% for a non-smoker > 10% for a heavy smoker |
The emergency physician must consider the diagnosis of CO poisoning and choose whether or not to pursue it based on its apparent likelihood in a given patient. A patient, for example, who presents with a headache who lives with asymptomatic family members and whose home is heated with electricity is unlikely to have CO poisoning. In contrast, a patient with the same symptoms living alone in a home heated by gas would be a reasonable candidate for further testing.
When considering CO poisoning in families or groups of people, it is important to remember that the patients usually have parallel presentations. On the other hand, viral syndromes tend to cause illness in an index member of the family who then passes the disease on to other group members. These other family members present serially and independently to their physicians. When an entire family presents with similar symptoms that fit the demographics and patterns for CO poisoning, this diagnosis must be pursued and excluded.
Emergency physicians must resist the tendency to describe a constellation of symptoms as "flu-like" when they lack the cardinal elements that characterize influenza, such as headache, myalgia, fever, and cough. Additionally, a diagnosis of gastroenteritis is inappropriate when only nausea and vomiting are present. True gastroenteritis is characterized by both vomiting and diarrhea, the latter of which is not a symptom of CO poisoning.
COHb levels may in fact be normal at presentation, particularly if the patient has been removed from the CO source for some time. Once CO poisoning is suspected, the COHb level can be measured in either venous or arterial blood samples, with venous usually being the preferred source.43 It is important to note that pregnancy and hemolytic anemia can increase COHb levels to 5%, and heavy smoking can elevate levels to as high as 13%.44
Pulse oximetry has no role in the screening or diagnosis of CO poisoning, because pulse oximeters misread COHb for oxyhemoglobin and give falsely elevated oxygen saturation values. There is a new noninvasive CO oximeter on the market, which if proven in the acute setting, will greatly facilitate screening for CO toxicity.45 If a patient's COHb levels are normal at the time of evaluation but the index of suspicion for CO toxicity remains high, it is not unreasonable to send police, emergency medical services, or the local gas company to test ambient CO levels at the site in question.
Treatment
Prompt removal of the patient from the source of CO poisoning and high-flow oxygen by nonrebreather mask at 15 L/min is the mainstay of treatment for acute CO poisoning. (See Table 5.) It is important to remember that the highest attainable percentage of oxygen delivery by a nonrebreather mask in conventional treatment settings is 75% fraction of inspired oxygen (FiO2). This is due to the entrainment of room air into the mask during inspiration. The use of 100% FiO2 would be ideal to hasten the removal of CO from the hemoglobin molecule; however, this is only attainable in the operating room by way of an anesthesia circuit.46 Breathing this concentration of oxygen effectively reduces the half-life of COHb from 300 minutes at ambient atmospheric conditions to 90 minutes. Seizures, cardiac ischemia, hypotension, and other complications of acute CO poisoning can be managed supportively.
| Table 5. Treatment of CO Poisoning |
|
The use of HBO2 in the treatment of CO poisoning is widely accepted due to a clear scientific rationale for its use, but controversy does exist in some circles regarding its clinical efficacy. At 3 ATA, which is three times ambient atmospheric pressure, HBO2 decreases the half-life of COHb to less than 30 minutes.47 HBO2 also increases the amount of oxygen dissolved in blood from 0.3 mL/dL with 100% FiO2 to 6 mL/dL under hyperbaric conditions, which is enough to sustain life even in the absence of hemoglobin. In animal studies, HBO2 has been shown to promote the dissociation of CO from cytochrome-c oxidase, inhibit leukocyte adhesion, and reduce brain lipid peroxidation.48-50 These effects appear to play a role in limiting direct cellular toxicity and decreasing the incidence of DNS.
The results of six prospective, randomized trials have been reported to date comparing normobaric O2 versus hyperbaric O2 in patients presenting with acute CO poisoning. Of these, four have demonstrated positive results51-54 while two have shown no effect.55,56 The two studies that have generated the most discussion in the past several years are the ones headed by Scheinkestel's group from Australia and Weaver's group from the United States. The former study concluded that there was no benefit from HBO2 in CO poisoning. However, there are numerous criticisms of the study, which affect its validity: poor followup at one month (46%) and poor followup long-term (38%); use of cluster randomization; unconventional treatment regimens that could result in pulmonary oxygen toxicity, including a minimum of three days of normobaric oxygen; delay in initiating hyperbaric treatment for acutely poisoned patients; poor outcomes in both treatment arms when compared to other trials; and the presence of psychoactive substances and depression in a significant percentage of the study population, likely influencing the results of neuropsychiatric testing.57 Weaver's study demonstrated that HBO2 therapy reduces cognitive sequelae after acute CO poisoning. Criticisms of this study include the control group having a disproportionately higher CO exposure, a higher incidence of pretreatment cerebellar neurologic deficits, and treatment with less normobaric oxygen than in other major published studies. Outcomes also have been called into question after using different criteria to analyze the data.58 These criticisms are discussed by the respective authors in detail and the reader is encouraged to review these papers.58-60
A recent Cochrane Database of Systematic Reviews maintains that data from existing randomized trials do not show that HBO2 reduces the incidence of adverse neurological outcomes and neurological sequelae in patients with CO poisoning.61 However, they emphasize that their results should be interpreted cautiously because methodology varied significantly among the trials, and all trials had flaws in design and analysis. The authors of a recent systematic review concluded that HBO2 should not be used routinely; however, it may benefit patients with moderate to severe CO poisoning.62 Reviewers from The New England Journal of Medicine, and commentaries in Journal Watch–Emergency Medicine, Journal Watch–Internal Medicine, and the ACP Journal Club all appear to accept Weaver's conclusions.
The Undersea and Hyperbaric Medical Society (UHMS), using an evidenced-based approach, has published its recommendations concerning the use of HBO2 in the treatment of acute CO poisoning, and they recommend HBO2 for patients presenting with transient or prolonged unconsciousness, cardiovascular dysfunction, neurologic signs, or severe acidosis.29 (See Table 6.)
| Table 6. UHMS Indications for Hyperbaric Oxygen Therapy |
| • Air or gas embolism • Carbon monoxide poisoning • Carbon monoxide poisoning complicated by cyanide poisoning • Clostridial myositis and myonecrosis (gas gangrene) • Crush injury, compartment syndrome, and other acute traumatic ischemias • Decompression sickness • Enhancement of healing in selected problem wounds • Exceptional blood loss (anemia) • Intracranial abscess • Necrotizing soft tissue infections • Osteomyelitis (refractory) • Delayed radiation injury • Skin grafts and flaps • Thermal burns |
While HBO2 may not be appropriate in every patient, its potential clinical benefit coupled with its minimal side-effect profile (primarily middle ear barotrauma) should result in its administration to patients who demonstrate any of the following: coma; acidosis with a pH below 7.1; history of loss of consciousness (even if awake on presentation); any neurological abnormality; evidence of cardiac dysfunction. Pregnant women would benefit from HBO2 with COHb levels above 15% or if they exhibit any signs of fetal distress. Patients with persistent neurological symptoms despite normobaric oxygen therapy, patients with neuropsychometric abnormalities, or patients with severely elevated COHb levels may also derive benefit from HBO2.
Despite the general acceptance of HBO2 for the treatment of severe CO poisoning, no single, universally accepted protocol for pressure and duration of treatments has been established within the hyperbaric community. Protocols generally range from a single treatment for 60 minutes at a pressure of 2.8-3.0 ATA to multiple treatments at varying pressures. There is evidence to support a multi-treatment regimen based on work by Gorman and Runciman that showed lower mortality and less residual neurological deficits with multiple treatments.63
Cyanide Toxicity
Cyanide is by itself a rare cause of poisoning; however cyanide exposure occurs relatively commonly in patients that are victims of smoke inhalation from either residential or industrial fires. Cyanide may be released when many synthesized (e.g., polyacrylonitrile, polyurethane, polyamide) or natural (e.g., wool, silk) compounds are burned. (See Table 7.)
| Table 7. Cyanide Toxicity |
|
Cyanide adversely affects all body tissues and principally inactivates cytochrome oxidase, which uncouples mitochondrial oxidative phosphorylation and inhibits cellular respiration. Rapidity of onset of symptoms is dependent on the type of cyanide involved, route of entry and the dose. Presenting symptoms may include general weakness, neurologic symptoms (headache, vertigo dizziness, confusion, seizures, coma), gastrointestinal symptoms and cardiopulmonary symptoms (apnea, shortness of breath). Although the onset of symptoms may be dramatic, the physical examination findings are typically nonspecific. The patient may have cherry-red skin coloring. The smell of bitter almonds on the breath may be suggestive, but 60% of the population cannot detect the smell. Pulse oximetry may be high and falsely reassuring.
Laboratory testing may include arterial and venous blood gases and blood lactate level. A metabolic acidosis, frequently severe, associated with a reduced arterial-venous oxygen saturation difference (< 10 mmHg) suggests the diagnosis. A plasma lactate level greater than 10 mmol/L, in a victim of smoke inhalation, suggests significant cyanide exposure. Cyanide blood concentrations are typically not available in time to aid in the treatment of acute poisoning.
In addition to supportive care, treatment for cyanide toxicity should be initiated as soon as the diagnosis is suspected. Sodium bicarbonate should be given if the patient is unconscious, hemodynamically unstable and acidotoc (elevated lactates). The cyanide antidote kit should then be administered and contains amyl nitrite pearls, sodium nitrite and sodium thiosulfate. The sodium nitrite portion should not be given in patients with smoke inhalation unless the carboxyhemoglobin level is very low (< 10%).
Conclusion
Every emergency physician should expect to encounter a patient with CO poisoning. It is vital to maintain a high index of suspicion because this complicated and often lethal entity is associated with highly variable clinical presentations. (See Table 8.) Intervening in the ED may inhibit or decrease the pathophysiologic consequences that are mediated by multiple mechanisms at the cellular level.
| Table 8. Pitfalls and Perils |
| • Avoid basing treatment on CO levels and accidentally underestimating the degree of cognitive impairment. • Syncope, even in a currently awake patient, represents end-organ injury and should be treated as a severe CO poisoning. • Pregnancy with CO levels > 15% are severe poisonings, owing to increased fetal uptake of CO. • Do not diagnose patients with "the flu" with absence of fever, cough, headache, myalgia or with gastroenteritis in the absence of diarrhea. • Pulse-oximetry is of no value in diagnosing CO poisoning • Remember to ensure that other family members who may still be in a CO-poisoned environment are warned to leave the affected area. |
Measuring the COHb level using a venous sample or CO oximeter can help the physician confirm a suspected diagnosis of CO poisoning. Normobaric, high-flow oxygen is the standard treatment, with hyperbaric oxygen reserved for select cases. Additionally, the emergency physician should provide patients information regarding CO toxicity and ways to prevent this common poisoning.
All emergency physicians should be intimately familiar with the varied clinical presentations of CO poisoning to make a life-saving diagnosis and avoid missing it. When a patient presents with headache, lethargy, vomiting, nonspecific dizziness, or an afebrile viral-like illness without signs of upper-respiratory tract infection, the emergency physician should ask the vital question, "Why isn't this CO poisoning?"
References
1. Gasman J, Varon J, Gardner J. Revenge of the barbecue grill–Carbon monoxide poisoning. West J Med 1990;153:656-657.
2. Thom S, Keim L. Carbon monoxide poisoning: A review. Epidemiology, pathophysiology, clinical features, and treatment options including hyperbaric therapy. Clin Toxicol 1989;27:141-156.
3. Jaslow D, Ufberg J, Ukasik J, et al. Routine carbon monoxide screening by emergency medical technicians. Acad Emergency 2001;8:288-291.
4. Hampson NB. Emergency department visits for carbon monoxide poisoning in the Pacific Northwest. J Emerg Med 1998;16:695-698.
5. Mott JA, Wolfe MI, Alverson CJ, et al. National vehicle emissions policies and practices and declining US carbon monoxide-related mortality. JAMA 2002;288:988-995.
6. Center for Disease Control and Prevention. WONDER compressed mortality database. Available at http://wonder.cdc.gov.
7. Unintentional non-fire-related carbon monoxide exposures—United States, 2001-2003. MMWR Morb Mortal Wkly Rep 2004;53:920-922.
8. Geehr EC, Saluzzo R, Braaten J, et al. Emergency health impact of a severe storm. Am J Emerg Med 1989;7:598-604
9. Sternbach G, Varon J. Winter storms and great imitators. J Emerg Med 1997;15:531-532.
10. Centers for Disease Control and Prevention. Carbon monoxide poisoning from hurricane-associated use of portable generators–Florida, 2004. MMWR Morb Mortal Wkly Rep 2005;294:1482-1483.
11. Anonymous. Centers for Disease Control and Prevention. Deaths from motor-vehicle-related unintentional carbon monoxide poisoning—Colorado: 1996; New Mexico: 1980-1995, and United States: 1979-1992. JAMA 1996;276:1942-1943.
12. Horowitz BZ. Carboxyhemoglobinemia caused by inhalation of methylene chloride. Am J Emerg Med 1986;4:48-51.
13. Peterson JE, Steward RD. Adsorption and elimination of carbon monoxide by inactive young men. Arch Environ Health 1970;21:165-171.
14. Gosink T. What do carbon monoxide levels mean? Alaska Science Forum 1983;Jan:Article 588.
15. K. Jaffe D, Chavasse L. Comparing the CO content of cigarette smoke and auto exhaust using gas chromatography. J Coll Sci Teach 1999;Dec:172-176.
16. Olson KR. Carbon monoxide. In: Olson KR (ed). Poisoning and Drug Overdose: A Lange Clinical Manual, 4th Ed. New York:Lange Medical Books/McGraw-Hill;2004.
17. Sternbach GL, Varon J. The resuscitation greats. Claude Bernard: On the origin of carbon monoxide poisoning. Resuscitation 2003;58:127-130.
18. Coburn R. Carbon monoxide body stores. Ann NY Acad Sci 1970;174:11-22.
19. Anderson G. Treatment of carbon monoxide poisoning with hyperbaric oxygen. Military Med 1978;143:538-541.
20. Farrow J, Davis G. Fetal death due to nonlethal maternal carbon monoxide poisoning. J Forens 1990;35:1448-1452.
21. Longo LD, Hill EP. Carbon monoxide uptake and elimination in fetal and maternal sheep. Am J Physiol 1977;232:H324-H330.
22. Hardy KR, Thom SR. Pathophysiology and treatment of carbon monoxide poisoning. J Toxicol Clin Toxicol 1994;32:613-629.
23. Zhang J, Piantadosi CA. Mitochondrial oxidative stress after carbon monoxide hypoxia in the rat brain. J Clin Invest 1992;90:1193-1199.
24. Thom SR. Carbon monoxide-mediated brain lipid peroxidation in the rat. J Appl Physiol 1990;68:997-1003.
25. Thom SR. Leukocytes in carbon monoxide-mediated brain oxidative injury. Toxicol Appl Pharmacol 1993;123:234-247.
26. Penney DG. Acute carbon monoxide poisoning: Animal models: A review. Toxicology 1990;62:123-160.
27. Thom SR. Dehydrogenase conversion to oxidase and lipid peroxidation in brain after carbon monoxide poisoning. J Appl Physiol 1992;73:1584-1589.
28. Kindwall EP, Whelan HT. Hyperbaric Medicine Practice, 2nd Ed. Flagstaff, AZ:Best Publishing Co.;2004:509.
29. The Hyperbaric Oxygen Therapy Committee. Hyperbaric Oxygen 2003: Indications and Results. Dunkirk, MD:Undersea and Hyperbaric Medical Society, 2003.
30. Ernst A, Zibrak JD. Carbon monoxide poisoning. N Engl J Med 1998;339:1603-1608.
31. Hee J, Callais F, Momas I, et al. Smokers' behaviour and exposure according to cigarette yield and smoking experience. Pharmacol Biochem Behav 1995;52:195-203.
32. Ely EW, Moorehead B, Haponik EF. Warehouse workers' headache: Emergency evaluation and management of 30 patients with carbon monoxide poisoning. Am J Med 1995;98:145-155.
33. Burney RE, Wu SC, Nemiroff MJ. Mass carbon monoxide poisoning: Clinical effects and results of treatment in 184 victims. Ann Emerg Med 1982;11:394-399.
34. Williams J, Lewis RW II, Kealey GP. Carbon monoxide poisoning and myocardial ischemia in patients with burns. J Burn Care Rehabil 1992;13:210-213.
35. Hardy KR, Thom SR. Pathophysiology and treatment of carbon monoxide poisoning. J Toxicol Clin Toxicol 1994;32:613-629.
36. Satran MD, Henry CR, Adkinson C, et al. Cardiovascular manifestations of moderate to severe carbon monoxide poisoning. J Am Coll Cardiol 2005;45:1513-1516.
37. Henry CR, Satran D, Lindgren B, et al. Myocardial injury and long-term mortality following moderate to severe carbon monoxide poisoning. JAMA 2006;295:398-402.
38. Thom SR, Taber RL, Mendiguren II, et al. Delayed neurolopsychologic sequelae after carbonmonoxide poisoning: Prevention by treatment with hyperbaric oxygen. Ann Emerg Med 1995;25:474-480.
39. Choi IS. Delayed neurologic sequelae in carbon monoxide intoxication. Arch Neurol 1983;40:433-435.
40. Kwon OY, Chung SP, Ha YR, et al. Delayed postanoxic encephalopathy after carbon monoxide poisoning. Emerg Med J 2004;21:250-251.
41. Katz MD. Carbon monoxide asphyxia: A common clinical entity. Can Med Assoc J 1958;78:182-186.
42. Gilbert GJ, Glaser GH. Neurologic manifestations of chronic carbon monoxide poisoning. N Engl J Med 1959;261:1217-1220.
43. Touger M, Gallagher EJ, Tyrell J. Relationship between venous and arterial carboxyhemoglobin levels in patients with suspected carbon monoxide poisoning. Ann Emerg Med 1995;25:481-483.
44. Ernst A, Zibrak JD. Carbon monoxide poisoning. N Engl J Med 1998;339:1603-1608.
45. Hampson NB, Scott KL. Use of a noninvasive pulse CO-oximeter to measure blood carboxyhemoglobin levels in bingo players. Respir Care 2006;51:758-760.
46. Walls RM, Luten RC, Murphy MF, et al (eds). Manual of Emergency Airway Management 2nd Ed. Philadelphia:Lippincott, Williams & Wilkins; 2004.
47. Pace N, Strajman E, Walker E. Acceleration of carbon monoxide elimination in man by high pressure oxygen. Science 1950;111:652-654.
48. Thom SR. Antagonism of carbon monoxide-mediated brain lipid peroxidation by hyperbaric oxygen. Toxicol Appl Pharmacol 1990;105:340-344.
49. Brown SD, Piantadosi CA. Recovery of energy metabolism in rat brain after carbon monoxide hypoxia. J Clin Invest 1992;89:666-672.
50. Thom SR. Functional inhibition of leukocyte B2 integrins by hyperbaric oxygen in carbon monoxide-mediated brain injury in rats. Toxicol Appl Pharmacol 1993;123:248-256.
51. Ducasse JL, Celsis P, Marc-Vergnes JP. Non-comatose patients with acute carbon monoxide poisoning: Hyperbaric or normobaric oxygenation? Undersea Hyperb Med 1995;22:9-15.
52. Thom SR, Taber RL, Mendiguren II, et al. Delayed neuropsychologic sequelae after carbon monoxide poisoning: Prevention by treatment with hyperbaric oxygen. Ann Emerg Med 1995;25:474-480.
53. Mathieu D, Wattel F, Mathieu-Nolf M, et al. Randomized prospective study comparing the effect of HBO versus 12 hours of NBO in non-comatose CO poisoned patients [abstract]. Undersea Hyperb Med 1996;23(suppl):7-8.
54. Cobb N, Etzel R. Unintentional carbon monoxide-related deaths in the United States, 1979-1988. JAMA 1991;266:659-663.
55. Raphael JC, Elkharrat D, Jars-Guincestre MC, et al. Trial of normobaric and hyperbaric oxygen for acute carbon monoxide intoxication. Lancet 1989;2:414-419.
56. Scheinkestel CD, Bailey M, Myles PS, et al. Hyperbaric or normobaric oxygen for acute carbon monoxide poisoning: A randomized controlled clinical trial. Med J Aust 1999;170:203-210.
57. Thom SR. Carbon monoxide-induced deficits in cognitive performance of mice and lack of effect of hyperbaric oxygen treatment. Acad Emerg Med 2002;9:75-77.
58. Scheinkestel CD, Jones K, Myles PS, et al. Where to now with carbon monoxide poisoning? Emerg Med 2004;16:151-154.
59. Weaver LK, Hopkins RO, Chan KJ, et al. Carbon Monoxide Research Group. LDS Hospital, Utah in reply to Scheinkestel et al and Emerson: The role of hyperbaric oxygen in carbon monoxide poisoning. Emerg Med Australas 2004:16;394-399.
60. Weaver LK, Hopkins RO, Chan KJ, et al. Hyperbaric oxygen for acute carbon monoxide poisoning. N Engl. J. Med 2002;347:1057-1067.
61. Juurlink DN, Buckley NA, Stanbrook MB, et al. Hyperbaric oxygen for carbon monoxide poisoning. Cochrane Database of Systematic Reviews 2005;Issue 1:Article CD002041.pub2.
62. Judge BS, Brown MD. To dive or not to dive? Use of hyperbaric oxygen therapy to prevent neurologic sequelae in patients acutely poisoned with carbon monoxide. Ann Emerg Med 2005:46:462-464.
63. Gorman DF, Runciman WB. Carbon monoxide poisoning. Anaes Int Care 1991;19:506-511.
Carbon monoxide poisoning is a treatable condition when recognized prior to devastating consequences. Early on, carbon monoxide (CO) poisoning may be subtle and elusive, with vague, nonspecific symptoms that may be inappropriately contributed to other conditions.Subscribe Now for Access
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