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Carbon monoxide (CO) is an insidious poison. It is an imperceptible gas produced by the incomplete combustion of carbon-based compounds such as wood, charcoal, gasoline, or kerosene. In children, CO poisoning is typically unintentional and most often results from malfunctioning home heating systems or proximity to inadequately ventilated generators, charcoal grills, or motor vehicles.3 Rarely, CO poisoning results from inhalation or ingestion of methylene chloride, a hydrocarbon commonly found in paint stripping products and metabolized to CO by the liver.4
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The pathophysiology of CO poisoning is complex and incompletely understood. It is rapidly absorbed through the alveoli and binds to heme iron with an affinity roughly 240 times that of oxygen, resulting in the formation of carboxyhemoglobin (COHb).5,6 This produces a functional anemia as well as a conformational change in the structure of the hemoglobin molecule that shifts the oxyhemoglobin dissociation curve to the left. Collectively, these effects reduce the oxygen carrying capacity of blood and impair the release of oxygen to tissues.
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In addition, CO produces a host of other cellular effects that contribute to toxicity by interfering with oxygen utilization and promoting inflammation.5 Notably, it binds to myoglobin and other heme-containingstructures including mitochondrial cytochromes, impairing cellular respiration and ATP generation.5,7 Predictably, the most prominent effects of CO poisoning involve the myocardium and brain, tissues with little ability to tolerate cellular asphyxia.6,8 The tissue-specific effects of CO are illustrated by the observation that CO-related myocardial dysfunction can occur even when oxygen delivery itself is normal.7 A major consequence of CO poisoning is peroxidation of brain lipids, which promotes inflammation and may underlie the neurologic sequelae seen in patients with severe CO poisoning.7,8
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The developing fetus is particularly sensitive to CO poisoning. The fetal oxyhemoglobin dissociation curve lies to the left of the adult curve, fetal hemoglobin binds CO more avidly than maternal hemoglobin, and the half-life of COHb is prolonged in utero.
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Clinical Presentation
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The clinical signs and symptoms of CO poisoning are notoriously nonspecific and correlate poorly with the COHb level at the scene of exposure.9 (Table 127-1) Moreover, symptoms can persist long after carboxyhemoglobin is undetectable. The diagnosis can, therefore, be difficultwhen a history of exposure is not readily apparent, or when CO poisoning is not considered until long after the patient is removed from the source of exposure. It is important to consider CO poisoning in patients with nonspecific or vague symptoms, particularly when multiple patients present simultaneously from the same location. Misdiagnosis of carbon monoxide poisoning as a viral illness such as influenza is particularly common in this setting.9
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Headache, nausea, dizziness, and impaired concentration are among the most common presenting symptoms in patients with CO poisoning.5 More severe exposures are characterized by confusion, altered mental status, seizures, and coma. Patients who survive CO poisoning may have long-term neurologic sequelae. Some experts classify these as either persistent neurologic sequelae (PNS) or delayed neurologic sequelae (DNS).10 The main distinction between the two is that DNS is characterized by a period of neurologic improvement (or even restoration of normalcy) prior to neurologic deterioration. The onset of DNS can be dramatic and accompanied by marked abnormalities on neuro-imaging.10,11In infants, the only suggestion of toxicity may be irritability or difficulty feeding. Children generally exhibit symptoms similar to those of adult patients but may become symptomatic sooner because of their higher metabolic rates.
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The physical examination in patients with CO poisoning is of limited utility in making the diagnosis. Vital signs are normal or minimally perturbed in many patients. Cherry red appearance of the skin is often touted as a clue to the diagnosis. While this is commonly seen in patients who have died from CO poisoning, it is rarely encountered in patients presenting to the emergency department.12 Neurologic abnormalities are sometimes subtle and may only be appreciated by a detailed neurologic examination that tests comprehension, recall, and attention. More severe cases may be characterized by delirium, coma, pulmonary edema, arrhythmias, and cardiovascular instability.
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It is important for clinicians to recognize that the usual methods of assessing oxygenation not only fail to detect carboxyhemoglobin, they produce falsely reassuring measurements. Conventional pulse oximetry does not distinguish COHb from oxyhemoglobin. Because both are reddish pigments, COHb is perceived as oxyhemoglobin and will artificially elevate the estimated percentage of hemoglobin that exists as oxyhemoglobin. However, oximeters capable of measuring COHb are available13 and have been used for hospital and pre-hospital point of care diagnosis. Similarly, because routine arterial blood gas analyzers measure the partial pressure of oxygen dissolved in plasma to estimate hemoglobin saturation, they also produce falsely elevated estimates of hemoglobin saturation. They will, however, provide accurate information about acid–base status and ventilation. Most laboratories use co-oximetry to measure COHb.5 This can be performed on a venous blood sample, obviating the need for arterial puncture.
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The measurement of COHb is subject to several interpretive cautions. While its presence at more than trace percentages is indicative of CO exposure, these values correlate poorly with clinical signs. Because COHb concentrations decline once exposure ceases, the value obtained in hospital may be significantly lower than peak values. Importantly, severe neurologic toxicity can be present in the absence of measurable COHb if measurement was delayed, particularly when high-flow oxygenation has been administered prior to COHb measurement.
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Significant acidemia is an uncommon manifestation of isolated CO toxicity but can occur in severely poisoned patients. In victims of structural fires, elevated serum lactate should prompt consideration of concomitant cyanide toxicity (discussed below). Electrocardiography and myocardial enzymes may provide evidence of cardiac injury.14 Computed tomography and, in particular, magnetic resonance imaging may reveal characteristic low-density changes in the globus pallidus and sub-cortical white matter in cases of CO poisoning.15,16
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Following removal from exposure, meticulous supportive care is the mainstay of treatment. If the patient has been extricated from a fire, clinicians should maintain a high index of suspicion for concomitant cyanide poisoning, which is often accompanied by mental status abnormalities, lactic acidosis, and hemodynamic instability. Patients with obvious evidence of inhalational injury such as singed nasal hair, soot in the oropharynx, and carbonaceous sputum should be intubated immediately.
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High-flow supplemental oxygen is the standard treatment of the CO-poisoned patient (Fig. 127-1). The administration of 100% oxygen (sometimes described as normobaric oxygen or NBO) significantly hastens the elimination of carboxyhemoglobin, with a mean t1/2 of 74 minutes.17 This is a safe and low-cost intervention that many authorities recommend as standard of care. Typically, 4–6 hours of 100% oxygen will suffice although it is prudent to ensure that COHb is below 5% before supplemental oxygen is discontinued. Extended treatment for pregnant women is sometimes advocated although there is no strong evidence supporting this practice.
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The role of hyperbaric oxygen (HBO) in the management of CO poisoning remains the subject of considerable debate.18,19 Compared to high-flow supplemental oxygen, HBO clearly hastens the elimination of COHb, with a mean elimination half-life of 24 minutes at 3 atmospheres of pressure. Other surrogate measures cited by proponents of HBO include a reduction in neuronal disruption and apoptosis from reperfusion injury, as well as a 10–20-fold increase in the amount of oxygen dissolved in blood.5,18 Several randomized trials have attempted to determine the benefits of HBO in CO poisoning. All are hampered by significant methodologic limitations, as outlined in two, recent reviews,19,20 which conclude that there is insufficient evidence to recommend the use of HBO in the treatment of acute CO poisoning, and that additional, well-designed trials should be conducted.
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Nevertheless, many hyperbaric physicians and toxicologists advocate the use of HBO in selected patients, in part because HBO carries few risks.18 While there is no absolute indication for HBO therapy in patients with CO poisoning, commonly quoted indications include a very elevated COHb percentage (typically greater than 25–30% although many centers advise treatment at lower values in the setting of pregnancy), coma, syncope, seizure, or evidence of myocardial ischemia. Unstable patients should not be placed in a hyperbaric chamber or transferred to another center solely for that purpose. The decision to institute HBO therapy should be made in conjunction with a medical toxicologist or other physician with carbon monoxide poisoning expertise and should take into consideration the patient's clinical status as well as the risks of treatment and transfer to a facility with a hyperbaric chamber.
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Children who are asymptomatic can be discharged after oxygen therapy has lowered COHb below 5%, provided they will not return to an environment where ongoing exposure is likely. Parents should be advised of the potential for delayed neuropsychiatric sequelae, including persistent headaches, memory lapses, irritability, and personality changes. Such changes are occasionally sudden and dramatic, but it is difficult to predict, which patients will develop sequelae. Hospitalization solely for observation is generally not warranted. Some experts suggest psychometric testing 4–6 weeks after an episode of significant CO exposure.