Carbon Monoxide

Carbon Monoxide

CHAPTER 45 Carbon Monoxide Leon Prockop CHAPTER CONTENTS Introduction 500 Neuropathology 505 Pathophysiology 501 Neuroimaging 505 Clinical F...

807KB Sizes 0 Downloads 37 Views

CHAPTER

45

Carbon Monoxide Leon Prockop CHAPTER CONTENTS Introduction

500

Neuropathology

505

Pathophysiology

501

Neuroimaging

505

Clinical Findings

502

Other Biochemical Markers of Carbon Monoxide Poisoning

510

Diagnosis

503

Treatment

510

Cardiac Effects

504

Conclusion

511

Other Toxic Mechanisms

505

INTRODUCTION Carbon monoxide (CO) intoxication is one of the most common types of poisoning in the modern world and a leading cause of death by poisoning in the United States, including intentional suicides and unintentional exposures from home heating, automobile exhaust, and smoke inhalaton.1–6 When not fatal, a spectrum of encephalopathy ranges from reversible dysfunction to severe irreversible dementia.7 Other features may include a parkinsonian syndrome8,9 and a delayed neuropsychiatric syndrome.10–12 Statistics on acute, nonfatal CO encephalopathy and the delayed CO-induced neuropsychiatric syndrome are imprecise. Sequelae of low-level exposure may be misdiagnosed or overlooked.4,6,13 CO is a tasteless, odorless, nonirritating but highly toxic gas. Because of these properties and because it often lacks a unique clinical signature, CO is difficult to detect and can mimic other common disorders. Therefore, the true incidence of CO poisoning is unknown and many cases probably go unrecognized. CO has been termed “the unnoticed poison of the 21st century.”14 An

environmental CO exposure is suggested when more than one person, animals, or both are affected; by a history of fire, presence of fireplace or combustion appliances, or occupation; and by the relation of symptoms to a possible exposure.5,14 CO is a byproduct of the incomplete combustion of hydrocarbons.15 Common sources include motor vehicle exhaust exposure in a poorly ventilated garage or areas close to garages and combustion appliances (e.g., heating units) in which partial combustion of oils, coal, wood, kerosene, and other fuels generate CO. A common scenario is that of a heating unit used only occasionally and not well maintained. Retrograde flow can occur in residential, occupational, or institutional settings in the presence of pressure problems and chimney or equipment malfunction. CO poisoning with immediate deaths may occur during a building fire or from fuel-powered generators and heaters, especially in poorly ventilated spaces. The latter causes are often reported during winter storms, hurricanes, earthquakes or other disasters after a power outage has occurred. Endogenous sources of CO include the heme degradation to bile pigments, catalyzed by heme oxygenases.16

Section 4

Constitutive and inducible isoforms (heme oxygenase-1, heme oxygenase-2) of the enzyme are known. Endogenously produced CO serves as a signaling molecule involved in multiple cellular functions, such as inflammation, proliferation, and apoptosis. CO, like nitric oxide, is a recently defined gaseous neurotransmitter in the central nervous system (CNS). Endogenous and exogenous sources of CO are contained in Table 1. The fatal effects of CO exposure are well recorded in past and recent history. For example, the ancient Greeks and Romans used CO to execute criminals. The deaths of two Byzantine emperors was related to CO produced by the burning of coal in braziers, the usual method of indoor heating then.17 In World War II, wood used widely as fuel caused many cases of acute or chronic CO poisoning.18 An article published in 2005 reported the death of one person among nine exposed to CO accidentally because of a faulty apartment house heating unit.19 CO was first prepared by the French chemist JosephMarie-François de Lassone in 1776. Because it burned with a blue flame, he mistakenly thought it to be hydrogen. In 1880, William Cruikshank identified it as a compound containing carbon and oxygen. In the middle of

Table 1: Sources of Carbon Monoxide ENDOGENOUS

Normal heme catabolism by heme oxygenase Increased in hemolytic anemia or sepsis EXOGENOUS

Incomplete combustion of carbonaceous fossil fuel Propane-powered vehicles, e.g., forklifts, ice-skating rink resurfacers



Neurotoxic Substances: Miscellaneous Neurotoxins

the 19th century, Claude Bernard recognized that CO causes hypoxia by interaction with hemoglobin (Hb). He poisoned dogs with the gas, noticing the scarlet appearance of their blood. Toward the end of the 19th century, John Scott Haldane demonstrated that a high partial pressure of oxygen can counteract the interaction between Hb and CO despite the high affinity for this interaction.20

PATHOPHYSIOLOGY CO binds rapidly to Hb, leading to the formation of carboxyhemoglobin (COHb). The oxygen-carrying capacity of the blood decreases, causing tissue hypoxia. COHb is red, which explains the “cherry-like” discoloration of victims. CO diffuses from the alveoli to the blood in the pulmonary capillaries across the alveolocapillary membrane that is composed of pulmonary epithelium, the capillary endothelium, and their fused basement membrane. CO is taken up by Hb at such a high rate that the partial pressure of CO in the capillaries stays low. Therefore, the CO transfer is diffusion limited. The affinity of Hb for CO is 210 times its affinity for oxygen. CO easily displaces oxygen from Hb. On the other hand, COHb liberates CO slowly. In the presence of COHb, the dissociation curve of the remaining hyperbaric oxygen (HBO) shifts to the left, further decreasing the amount of the oxygen released. The amount of COHb formed depends on the duration of exposure to CO, the concentration of CO in the inspired air, and the alveolar ventilation.21 CO toxicity is caused by impaired oxygen delivery and use, leading to cellular hypoxia. Body organs with poorly developed anastomotic vessels, high metabolic activity, or both, such as the heart and areas of the brain, are especially vulnerable to CO toxic damage. At least several pathophysiological effects occur. The relative contributions of each to resulting damage remains somewhat controversial22:

Gas-powered furnaces, ovens, fireplaces House fires Heaters Automobile exhaust Boat exhaust Indoor grills Camp stoves Cigarette smoke

1. Inhalation of CO replaces oxygen on the Hb molecule, leading to a relative anemia. The body requires 5 mL of oxygen dissolves per 100 mL of blood; the remaining 3 mL of oxygen per 100 mL blood (3 vol%) comes from the release of oxygen from Hb. Impairment of oxyhemoglobin formation by CO results in cellular hypoxia. 2. COHb impairs the release of oxygen from Hb by increasing oxygen binding to Hb. The result is a shift of the oxyhemoglobin dissociation curve to the left, which reduces unloading of oxygen in the tissues. 3. CO bind to cytochrome oxidase in vitro; however, the affinity of oxygen for cytochrome oxidase is so much greater than that of CO that in vivo binding 501

Chapter 45



Carbon Monoxide

of CO to cytochrome oxidase may be small. Inhibition of cellular respiration may explain the poor correlation of toxicity to COHb in blood levels and justify the use of hyperbaric oxygen. 4. CO saturates myoglobin in three times higher concentration than skeletal muscle. The resultant myocardial depression and hypotension cause ischemia and potentiate the hypoxia induced by impaired oxygen delivery. Because of increased accumulation in fetal blood, the human fetus is especially vulnerable to CO poisoning. Furthermore, the fetal Hb dissociation curve lies to the left of the adult curve, resulting in greater tissue hypoxia at similar COHb levels. Neonates are even more susceptible, since fetal Hb constitutes 20% of the total at 3 months. Acute nonlethal maternal intoxication may cause fetal death or permanent neurological sequelae.23–25 Likewise, children may be especially vulnerable to acute and delayed effects of CO poisoining.26 The Normal COHb level for nonsmokers is less than 2% and for smokers is 5% to 13%. The Expert Panel on Air Quality Standard of the World Health Organization (WHO) in 1994 reported that blood COHb levels between 2.5% and 4% decrease the short-term maximal exercise duration in young healthy men. Decreased exercise duration because of increased chest pain and in patients with ischemic hearts occurred at levels from 2.7% to 4.1%. Levels between 2% and 20% can cause effects on visual perception, as well as on audition, motor, and sensory motor functions and behavior. Therefore, ambient air CO levels that produce blood COHb levels below 2.5% are recommended. The COHb levels depend not only on the CO level in ambient air but also on the duration of exposure. According to WHO guidelines, exposures to levels of ambient air carbon dioxide in parts per million (ppm) should conform to the following durations of exposure: 87.1 ppm (100 mg/m3) for 15 minutes; 52.3 ppm (60 mg/m3) for 30 minutes; 26.1 ppm (30 mg/m3) for 60 minutes; 8.7 ppm (10 mg/m3) for 80 minutes.27 Any exposure to ambient air with CO levels greater than 100 ppm is dangerous to human health.7,28,29 At equilibration, atmospheric CO levels of 50, 100, and 200 ppm produce average COHb levels of 8%, 16%, and 30% respectively.30 Perceptible clinical effects occur with a 20-hour exposure to concentrations as low as 0.01% (100 ppm). The industrial exposure limit, expressed as threshold limit value, is 35 ppm for an 8-hour day, allowing for a maximum COHb of 5% during an 8-hour period, assuming normal activity. The ceiling concentration to which a worker may be transiently exposed without changing the COHb level is 200 ppm. 502

CLINICAL FINDINGS Because of their high metabolic rate, the brain and the heart are most susceptible to CO toxicity. The clinical symptoms of CO poisoning are often nonspecific and can mimic various common disorders. The severity ranges from mild flulike symptoms to coma and death. About 50% of exposed people may develop weakness, nausea, confusion, and shortness of breath. Less often, abdominal pain, visual changes, chest pain, and loss of consciousness occur. Tachycardia and tachypnea develop to compensate from cellular hypoxia and cardiac output increases initially. Some potential complications of CO poisoning are contained in Table 2. Responses to cellular hypoxia vary depending on the premorbid condition of victims; those with underlying lung and heart diseases have little tolerance to even mild hypoxia. Hypoxia leads to increased intracranial pressure and cerebral edema, which is partly responsible for decreased level of consciousness, seizures, and coma. The classic cherry-red discoloration of the skin and cyanosis are rarely seen.5,15,20 Varying degrees of cognitive impairment have been reported.10–12,19,31 Headache is one of the most common presenting features of CO poisoning: it occurs in 84% of the victims and has been described as predominantly frontal, dull, sharp, continuous, throbbing, and intermittent in patients with a mean COHb level of 21.3% (⫹9.3%).32 There is not clear correlation between pain intensity and COHb levels.32 Some have reported tightness across the forehead at COHb levels of 10% to 20%, throbbing in the temples at 20% to 30%, and severe headache at 30% to 40%. Headaches, generalized weakness, fatigue, and sleepiness are part of the vague symptomatology observed in subjects with COHb levels below 20%. Headache is a frequent complaint not only with acute but also with chronic CO poisoning. Dizziness is a frequent companion of headache and can be seen in about 92% in victims of CO poisoning. In one report, 76% of 38 victims reported weakness with COHb levels greater than 30% to 40%.33 Chest pain as a symptom of myocardial ischemia can occur without underlying coronary artery disease. For example, 3 weeks after accidental exposure to CO, 34% of Swiss soldiers had chest pain.34 Cerebellar atrophy by magnetic resonance imaging (MRI) criteria and signs of cerebellar dysfunction have been reported.35 The delayed neuropsychiatric syndrome, also named “delayed neurological sequelae”, may occur in patients from 3 to 240 days after acute CO exposure and poses especially difficult diagnostic and therapeutic problems. Rarely this syndrome may present years after exposure.35a Even those victims without neurological and psychiatric symptoms immediately after an exposure accident may demonstrate features of delayed impairment ranging from subtle abnormalities such as personality changes or

Section 4

Table 2: Potential Complication of Carbon Monoxide Poisoning



Neurotoxic Substances: Miscellaneous Neurotoxins

DERMATOLOGICAL

Bullae

Cyanosis

Alopecia

Sweat gland necrosis

Pallor

Erythematous patches

NEUROLOGICAL AND/OR PSYCHIATRIC

Death

Coma

Stupor

Agitation

Confusion

Mutism

Leukoencephalopathy

Muscular rigidity

MUSCULOSKELETAL

Rhabdomyolysis

Myonecrosis

RENAL

Parkinsonism

Personality change

Dystonia and chorea

Behavioral disorder

Seizures

Psychosis

Dementia

Urinary incontinence

Ataxia

Fecal incontinence

Myoglobinuria

Proteinuria

METABOLIC

Lactic acidosis

Hypocalcemia

Diabetes insipidus

Polycythemia

Hyperglycemia Peripheral neuropathy

Headache

FETAL

CARDIOVASCULAR Angina

Arrhythmia

Tachycardia

Heart block

ST segment change

Death

Psychomotor retardation

Cerebral atrophy

Seizures

Microcephalus

Spasticity

Myocardial infarction Low birth weight

Hypotension PULMONARY Edema

Hemorrhage

OPHTHALMOLOGICAL Retinal hemorrhage

Cortical blindness

Decreased visual acuity

Papilledema

Decreased light sensitivity

Paracentral scotomas

Retrobulbar neuritis VESTIBULAR AND AUDITORY Central hearing loss

Vertigo

Tinnitus

Auditory nystagmus

mild cognitive deficit to severe dementia, gait disturbance, impaired coordination with cerebellar dysfunction, psychosis, parkinsonism, mutism, and fecal and urinary incontinence. Some authors report a “characteristic symptom triad” of mental deterioration, urinary incontinence, and gait disturbances in both humans and experimental animals.10,11,36 Urinary incontinence in children and adults has been reported as an especially distressing complication of CO poisoning.10,26,36–39 CO encephalopathy may cause several behavioral functional impairments, including alterations in attention, executive function, verbal fluency, motor abilities, visuospatial skills, learning, short-term memory, and mood and social adjustment. Formal neuropsychological testing usually confirms these impairments.28,39a

DIAGNOSIS

GASTROINTESTINAL Vomiting

Hepatic necrosis

Diarrhea

Melena

Diagnosis of CO poisoning requires a high level of suspicion. Epidemiological history with information about other affected individuals or pets, as well as circumstances 503

Chapter 45



Carbon Monoxide

suggestive of possible exposure, is of paramount importance. Ambient air CO levels should be obtained as soon as possible after the exposure. Because the half-life of COHb is 4 to 5 hours, a victim’s COHb level should also be obtained as soon as possible. Physicians who deal with CO intoxication should be aware that pulse oximetry is a colorimetric method, unreliable for the diagnosis of CO intoxication since it cannot distinguish oxyhemoglobin from COHb. Therefore, the pulse oximeters overestimate arterial oxygenation in patients with severe CO poisoning. Accurate assessment of arterial oxygenation in patients with severe CO poisoning can currently be performed only by analysis of arterial blood with a laboratory CO oximetry. High-flow oxygen should be administered to all patients suspected of significant CO exposure until direct measurement of CO levels can be performed, regardless of pulse oximetry readings.40 For clinical purposes, automated spectrophotometric CO-oximeter device are recommended. Spectrophotometry measures light intensity as a function of color and can differentiate the wavelengths of oxyhemoglobin and COHb. With an acceptable accuracy for COHb saturation levels above 5%, the device can simultaneously estimate total Hb and the percentage oxyhemoglobin and COHb. Gas chromatography, a more sensitive method, can be used for low-level exposure and for postmortem blood samples.41,42

CARDIAC EFFECTS Even though this chapter focuses upon the toxic effects of CO on the brain, some discussion of its toxic cardiac effects is important, especially because cardiac stress may shed light on brain effects. CO binds to the intracellular myoglobin of the myocardium and impairs the oxygen supply to the mitochondria. This negatively affects the oxidative phosphorylation and, consequently, the energy source of heart muscle. Patients with underlying cardiac conditions are at risk for death from arrhythmias, and fatal heart attacks can occur. Henry et al. studied mortality risk in patients with moderate to severe CO poisoning. In those at low risk for cardiovascular diseases, 37% suffered acute myocardial injury and 38% of them were dead within 7.6 years. The mortality rate was three times higher than the United States expected by age and sex.43 After CO exposure, angina attacks, arrhythmias, and increased level of cardiac enzymes often occur. This has led to a search for morphological changes that could be attributed to CO, especially because the myocardium binds more CO than skeletal muscle. Ultramicroscopic lesions have been reported, but the relative roles of general tissue hypoxia and specific CO toxicity are unknown. 504

In addition to the COHb effects, binding of CO to cytochromes is significant and is thought to be responsible for the cytotoxic phenomena. Combined ultrastructural and cytochemical studies have enabled differentiation among toxic, hypoxic, and mixed alteration. The marked decrease in cytochrome oxidase in experimental studies suggests a direct toxic effect.44 Myocardial injury with ischemic changes on electrocardiogram (ECG) and elevated cardiac biomarkers were found in 37% of 230 patients with moderate to severe CO poisoning, with 5% in-hospital mortality.45 Therefore, patients admitted to the hospital with CO poisoning should have a baseline ECG and serial cardiac enzymes. Myocardial fiber necrosis was described in a 26-year-old patient with accidental CO poisoning and blood concentration of COHb of 46.6%.46 Electron microscopy of left ventricular biopsies of a 25-year-old woman with functional evidence of cardiac failure after acute CO poisoning, and otherwise normal myocardial perfusion showed slight ultrastructural changes in the myocytes, large glycogen deposits, and swollen mitochondria. The preceding changes have been thought to be signs of impaired energy metabolism of the myocardial cells.47 In the rat heart, CO causes vasodilatation and increased coronary flow that are not mediated by simple hypoxia.48 CO exposure in the fetal period in rats causes myocyte hyperplasia and cardiomegaly. This cellular response is sustained through the early neonatal period in animals exposed to CO both in utero and postpartum.49 Although hemorrhages and areas of necrosis in the heart, mostly in the septum and the papillary muscles, were described with CO poisoning as early as 1865, only a few human cases of acute, fatal CO intoxication, with small foci of coagulation necrosis, have been reported.50,51 Cardiac function must be monitored closely by ECG, two-dimensional echocardiogram, and cardiac enzymes. Patients with underlying cardiac disorders, whose reserves are impaired at baseline, are at higher risk than are normal individuals. Cardiac arrest and sudden cardiac death can be expected. Chest pain due to myocardial ischemia or infarction is a consequence of decreased oxygen supply to the cardiac muscle. Features of ischemia, as well as other abnormalities, such as tachycardia, bradycardia, atrial and ventricular fibrillation, premature ventricular contractions, and conduction abnormalities, can be easily detected on ECG. Noninvasive devices that can be used to screen firefighters and victims and can estimate the COHb levels in the exhaled alveolar breath have been suggested.11 A noninvasive, high-resolution method of measuring COHb fraction using expiratory gas analysis in patients without evidence for pulmonary edema or atelectasis has been found to have accuracy equivalent to that of CO oximetry.40–42

Section 4

OTHER TOXIC MECHANISMS Investigations suggest other mechanisms of COmediated toxicity. One hypothesis is that CO-induced tissue hypoxia may be followed by reoxygenation injury to the CNS. Hyperoxygenation facilitates the production of partially reduced oxygen species, which in turn can oxidize essential proteins and nucleic acids, resulting in typical reperfusion injury. In addition, CO exposure has been shown to cause lipid preoxygenation, i.e., degradation of unsaturated fatty acids leading to reversible demyelination of CNS lipids. CO exposure also creates substantial oxidative stress on cells, with production of oxygen radicals resulting from the conversion of xanthine dehydrogenase to xanthine oxidase.52 Acute disturbances of brain function predominate in acute CO intoxication, ranging from transient confusion to severe dementia and death. As stated, delayed neurological effects also occur. Tissue hypoxia is the end result of intoxications with CO and many other physical and chemical agents. Some brain regions are sensitive to hypoxic damage, including the cerebral cortex, particularly its second and third layers; the white matter; the basal nuclei; and the Purkinje cells of the cerebellum. Attempts have been made to relate this “selective vulnerability” to the cause of the hypoxia, but the nature and distribution of the lesions appear to depend on the severity, suddenness, and duration of the oxygen deprivation, as well as on its mechanism (hypoxemia or ischemia), rather than on its cause. Regions with relatively poor vascularization and “watershed” areas between two sources of blood supply, such as the globus pallidus, may be more vulnerable, especially during periods of hypotension. The effects of hypoxia on the brain, therefore, do not reflect it cause, and neither the character of the lesions nor the areas affected are regarded as pathognomonic for CO.

NEUROPATHOLOGY The neuropathology of CO toxicity has been well described in postmortem studies by Lasprele and Fardeau.53 Lesions can be separated into four categories: multifocal necrosis, multifocal necrosis involving the cortex, myelinopathy with discrete globus pallidus and cortical lesions, and white matter lesions. When bilateral globus pallidus damage occurs, it is usually asymmetrical. It can extend anteriorly, superiorly, or into the internal capsule. Occasionally, a small linear focus of necrosis at the junction of the internal capsule and the internal nucleus of the globus pallidus was noted. Less commonly, hemorrhages in the hippocampus were seen.



Neurotoxic Substances: Miscellaneous Neurotoxins

Relatively spared were the hypothalamus, walls of the third ventricle, thalamus, striatum, and brainstem. In acute cases, petechial hemorrhages of the white matter involved in particular the corpus callosum; in cases surviving more than 48 hours, there is multifocal necrosis involving the globus pallidus, hippocampus, pars reticularis of the substantia nigra, laminar necrosis of the cortex, and loss of Purkinje cells in the cerebellum, along with white matter lesions. The typical pallidal lesions are well-defined, bilateral globus pallidus macroscopic infarctions, usually asymmetrical, extending anteriorly, superiorly, or into the internal capsule. Occasionally, only a small linear focus of necrosis is found at the junction of the internal capsule and the internal nucleus of the globus pallidus. CO intoxication usually spares the hypothalamus, walls of the third ventricle, thalamus, striatum, and brainstem. Myelin damage ranges from discrete, perivascular foci in corpus callosum, internal–external capsule and optic tracts usually seen in comatose patients who died within 1 week to extensive periventricular demyelination and axonal destruction observed in comatose subjects with longer survival, sometimes leading to formation of plaques of demyelination.

NEUROIMAGING A distinct constellation of brain and MRI abnormalities appears premortem and in those surviving exposure. It includes globus pallidus lesions, white matter changes, and diffuse low-density lesions throughout the brain. In general, computerized tomography (CT) and magnetic resonance neuroimaging findings reflect the neuropathological changes described by Laspresle and Fardeau (Figures 45-1 to 45-4). Differences between neuroimaging findings and neuropathological findings include findings of MRI thalamic lesions.54 Although some authors suggest that CT findings correlate with long-term outcome after CO poisoning,55 others questions their prognostic value. However, the database that correlates patient outcome to serial CT, MRI, or both types of studies is limited.56,57 Tom et al.58 reported neuroimaging studies in 18 patients with CO toxicity, age 19 to 70 years (mean 35.6 years). CO exposure occurred by four routes: suicide attempt with car exhaust, 44%; portable heater, 33%; smoke inhalation, 17%; and hotel heating systems, 6%. COHb levels on hospital admission ranged from 1.9% to 40% (mean 18.49%). The most common findings were low-density lesions in the globus pallidus, deep white matter changes, generalized edema, and low-density lesions in the mesial temporal lobes 505

Chapter 45



Carbon Monoxide

A

B Figure 45-1. Brain computerized tomography (CT) and magnetic resonance imaging (MRI) scans in the same patient. (A) CT findings. The arrows show low-density areas. (B) T2weighted MRI. Cortical areas are more affected than the subcortical areas. (Murata S, Asaba H, Hiraishi K, et al. Magnetic resonance imaging findings on carbon monoxide intoxication. J Neuroimaging. 1993;3:128–131.)

(Figures 45-3 to 45-6). In 5 patients, multiple CT findings appeared acutely; however, those patients did not have higher COHb levels than those with less prominent CT findings. A typical noncontrasted CT scan (see Figure 45-4) showed bilateral low-density lesions in the globus pallidus with calcification, cortical atrophy, enlargement of the quadrigeminal cistern, and left choroid plexus calcification. Overall the most common positive findings were low-density lesions in the globus pallidus (7 of 18 patients, 39%) and deep white matter changes (5 patients, 28%). Six brain CT scans showed no acute changes. Tom et al.58 provided representative CT or magnetic resonance images in this series. A 24-year-old man accidentally exposed to CO was admitted to the hospital with a COHb of 24%. The brain CT scan showed only low-density lesions in the globus pallidus bilaterally without generalized edema, deep white matter changes, or low-density lesions in the mesial temporal lobes. Brain MRI was obtained 7 days later. The T1-weighted transaxial (see Figure 45-3A) and coronal views (see Figure 45-3B) showed globus pallidus hemorrhages bilaterally. A 49-year-old woman accidentally exposed to CO was admitted to the hospital 506

Figure 45-2. T1-weighted magnetic resonance imaging. High-signal regions are seen in both globi pallidi (arrows). (Murata S, Asaba H, Hiraishi K, et al. Magnetic resonance imaging findings on carbon monoxide intoxication. J Neuroimaging. 1993;3:128–131.)

with a COHb of 13.7%. Noncontrasted brain CT (see Figure 45-6) showed bilateral low-density lesions in the globus pallidus, cortical atrophy, and enlargement of the quadrigeminal cistern. A 30-year-old man suffered accidental CO exposure with COHb of only 1.9%. His T2-weighted brain magnetic resonance image (see Figure 45-5) showed hyperintense bilateral deep white matter changes. Brain CT showed low-density lesions in the globus pallidus. He was in persistent coma. A 41-year-old woman inhaled CO in a suicide attempt, attaining a 33.7% COHb. A noncontrasted brain CT scan demonstrated a finding consistent with generalized edema with effacement of the cortical suprasella and quadrigeminal cistern. There was also attenuation within the quadrigeminal, ambient, and suprasella cisterns representing subarachnoid hemorrhage (see Figure 45-6). She died. In this series of 18 patients, 4 died. None of them showed globus pallidus lesions on CT. However, 2 suffered generalized edema, 1 had deep white matter changes, and 1 had low-density lesions in the mesial temporal lobe. Both patients in coma had globus pallidus lesions and deep white matter changes. One also

Section 4

A



Neurotoxic Substances: Miscellaneous Neurotoxins

B

Figure 45-3. (A) Proton density brain magnetic resonance imaging (MRI), transaxial view, shows bilateral hemorrhage in the globus pallidus. (B) T1-weighted brain MRI, coronal view. (Tom T, Abedon S, Clark RI, Wong W. Neuroimaging characteristics in carbon monoxide toxicity. J Neuroimaging. 1996:161–166.)

Figure 45-5. T2-weighted brain magnetic resonance image showing bilateral hyperintense white matter lesion, most prominent in the left frontal lobe. (Tom T, Abedon S, Clark RI, Wong W. Neuroimaging characteristics in carbon monoxide toxicity. J Neuroimaging. 1996:161–166.)

had low-density lesions in the mesial temporal lobes. Tom et al.58 concluded the following: 1. Advanced age, method of exposure (i.e., whether intentional or accidental), and severity of COHb levels did not predict neuroimaging or clinical outcomes. 2. Although CT findings always predicted clinical courses in this patient population, negative CT findings usually were associated with a good outcome. 3. Because 17 of the 18 patients received HBO therapy, the data cannot be used to assess the value of this therapy and the prevention of CT findings.

Figure 45-4. Noncontrast head computerized tomograph showing bilateral low-density lesions of the globus pallidus with calcification (right), enlargement of the quadrigeminal cistern, and choroid plexus calcification (left). (Tom T, Abedon S, Clark RI, Wong W. Neuroimaging characteristics in carbon monoxide toxicity. J Neuroimaging. 1996:161–166.)

Gotoh et al. obtained sequential brain MRI studies in two patients 4 days, 1 month, 2 months, and 4 months after CO exposure.57 The serial changes were coagulation necrosis with surrounding edema, decrease in lesion size and edema in both patients, and development of gliotic tissue and evidence of neovascularization. MRI offered the best prognostic index at the 1— to 2-month mark. Brain MRI and changes in the level of consciousness in one of the patients are depicted in Figure 45-7. In 19 patients, Jones et al.59 reported CT findings similar 507

Chapter 45



Carbon Monoxide

Figure 45-6. Noncontrasted heat computerized tomography scan showing generalized edema evidenced by effacement of the sulci, as well as the quadrigeminal, ambient, and suprasellar cisterns whose effacement represents subarachnoid hemorrhage. (Tom T, Abedon S, Clark RI, Wong W. Neuroimaging characteristics in carbon monoxide toxicity. J Neuroimaging. 1996:161–166.)

to those noted by Tom et al.58 The mean COHb level of these patients was 35%. There were no direct relationships among age, admission COHb level, and neuroimaging abnormalities. Diffusion-weighted brain MRI shows white matter high-signal intensities consistent with restricted diffusion in the acute CO poisoning. Follow-up MRI performed 16 days later reveals disappearance of white matter lesions, suggesting the white matter can be more sensitive to hypoxia than gray matter in the acute phase.60 T2-weighted brain MRI shows increased signal intensity bilaterally in the putamen and the caudate nucleus, as well as high-signal intensity in the globus pallidus.61 Initially, unilateral low attenuation areas in the right putamen, globus pallidus, and thalamus were observed on CT in a patient after CO exposure, followed by transient bilateral appearance on subsequent CT examination. Hemorrhagic infarction of the right putamen and ischemic lesions in both thalami were visualized on MRI 2 weeks later.62 Diffusion-weighted MRI in a case of 508

CO poisoning revealed pallidoreticular damage and delayed leukoencephalopathy characterized by a restricted water diffusion pattern in the early stage. Diffusionweighted brain MRI is more sensitive than brain CT and is useful for early identification of the effects of acute CO poisoning.63,64 Brain MRI changes after CO poisoning are variable and reflect the neuropathological lesions. Most unconscious patients present with abnormalities of globus pallidus or the entire lentiform nucleus (globus pallidus and putamen), putamen alone, caudate nucleus, thalamus, periventricular and subcortical white matter, cerebral cortex hippocampus, and cerebellum. Brain CT and MRI may appear to be normal in some victims who have suffered CO brain damage.58,64 Previously unreported brain MRI findings in CO poisoning included a bilateral diffuse high signal in the centrum semiovale and bilateral high-intensity lesions in the anterior thalami.65 Extensive bilateral cerebellar white matter signal change, with sparing of the overlying cortex, consistent with demyelination was reported 6 years previously after CO poisoning.35 In a study of patients with severe CO intoxication, coma on admission, and normobaric 100% oxygen, persistent changes on the MRI were found 1 to 10 years after exposure independently of the neuropsychiatric findings. T2-weighted and fluid-attenuated inversion recovery (FLAIR) images showed bilateral symmetrical hyperintensity of the white matter, more often involving the centrum semiovale, with relative sparing of the temporal lobes and anterior parts of the frontal lobes. There was also atrophy of the cerebral cortex, cerebellar hemispheres, vermis, and corpus callosum, as well as T1 hypointensities and T2 and FLAIR hyperintensities in the globus pallidus.66 Kim et al.11 studied the delayed effects of CO on the cerebral white mater 25 to 95 days after the exposure, with initial recovery followed by relapse of neuropsychiatric symptoms. T2-weighted images, diffusion-weighted images, and FLAIR sequences demonstrate bilateral, diffuse, and confluent lesions in the periventricular white matter and centrum semiovale; more prominent changes were present in the frontal lobes than elsewhere. The effects of CO poisoning in acute stages can be evaluated by diffusion-weighted images on brain MRI.11 A restricted water diffusion pattern in the globus pallidus and substantia nigra can be seen.63 Cerebral edema occurs early. Clinical status and outcome correlate with diffuse white matter changes.62 Long term (25 years) after CO exposure, MRI has demonstrated symmetrical globus pallidus and white matter changes in most patients.67 Temporal, parietal, and occipital lobes are usually affected with asymmetrical cortical and subcortical lesions.68

Section 4



Neurotoxic Substances: Miscellaneous Neurotoxins

Figure 45-7. Changes in the level of consciousness and the magnetic resonance images of a 20-year-old woman acutely exposed to carbon monoxide. The disappearance of the lesions in the cerebral white matter coincided with amelioration of the patient’s clinical neurological condition. The globus pallidus lesions, which became obscure on magnetic resonance images 2 months after exposure, reappeared on the magnetic resonance images 4 months after the incident. (A) The T1-weighted images 4 days after exposure demonstrating areas of hypointensity in the globus pallidus bilaterally; areas appear hyperintense on the T2-weighted images. (B) The T1-weighted images 1 month after exposure still show distinct, but diminished, areas of hypointensity in the globus pallidus bilaterally. In addition, areas of abnormal signal intensity are seen in the subcortical white matter; areas are more clearly seen and appear hyperintense on T2-weighted images. (C) The T1- and T2-weighted images 2 months after exposure showing diminution of the lesions in the globus pallidus and the subcortical white matter. (D) The T1- and T2-weighted images 4 months after exposure showing distinct lesions in the globus pallidus bilaterally. (Gotoh M, Kuyama H, Asari S, Ohmoto T, Akioka T, Lai, MY. Sequential changes in MR images of the brain in acute carbon monoxide poisoning. Comput Med Imaging Graph. 1993;17:55–59.)

Magnetic resonance spectroscopy (MRS) examines brain metabolites. The major resonances of MRS are Nacetyl aspartate (NAA), choline, and creatine. NAA is located within neurons and is a specific neuronal and axonal marker. Choline is part of the membrane constituent phosphatidyl choline. Based on previous studies of demyelinating brains, choline increases are due to an increase in phosphatidyl choline, which in turn is due to demyelination or gliosis. The NAA decreases in the demyelinated white matter presumably represent axonal and neuronal loss.69 MRS provides evidence for COinduced brain damage, including decreased NAA that can be found in the basal ganglia and elsewhere.70 Proton magnetic resonance spectroscopy (1H-MRS) is a noninvasive method that can provide biochemical information about brain tissues. In early CO poisoning 1 H-MRS studies showed a persistent increase in choline related to progressive demyelination. In irreversible injury, lactate appears and NAA decreases.70 1H-MRS studies of

frontal lobe white matter revealed increases in the cholinecontaining compounds, and reductions of NAA in all cases. Normalization of the findings was found in a subclinical case. In two cases with akinetic mutism, presenting increased lactate was noted to persist. These results indicate the 1H-MRS is a useful indicator in the clinical evaluation of patients with the interval form of CO poisoning when compared to MRI, electroencephalogram, and N-isopropyl-p-[123]iodoamphetamine singlephoton emission computed tomography (SPECT).71 Kamada et al.72 reported that MRS in patients with delayed sequelae of CO exposure precisely reflects the severity of symptoms. With severe clinical dysfunction, marked lowering of the NAA-to-creatine ratio and a slightly increased choline-to-creatine ratio are noted, with subsequent return of the NAA- and choline-tocreatine ratios to normal with clinical improvement. 1 H-MRS appears to be superior to conventional radiological examinations in CO poisoning. 509

Chapter 45



Carbon Monoxide

Differential Diagnosis on Neuroimaging The globus pallidus CT and MRI findings are common in but not pathognomonic of CO toxicity. Other diseases may mimic CO toxicity. Bilateral basal ganglia lesions similar to those described in CO poisoning are also present in Leigh’s disease and in Hallervorden-Spatz disease. Basal ganglia infarcts and lesions can also appear in other metabolic disorders (e.g., propionic academia). Basal ganglia hamartomas associated with neurofibromatosis may appear similar to the lesions seen in CO toxicity.68 Prockop73 reported a young man suffering occupational exposure to mixed volatile organic compounds. He suffered cerebral edema documented by CT scan and later developed bilateral globus pallidus lesions almost identical to those noted in CO toxicity. Likewise, white matter hyperintensities are not pathognomonic of CO toxicity but are sometimes seen in healthy aging individuals.74 They occur more often and to a greater degree in cerebrovascular insufficiency, i.e., hypoxia, ischemia, or both. As such, these white matter hyperintensities are often considered markers of cerebral ischemia. However, white matter hyperintensities, especially of the centru semiovale regions, are significantly associated with CO induced cognitive impairments.

OTHER BIOCHEMICAL MARKERS OF CARBON MONOXIDE POISONING Very high levels of S100B protein, a structural astroglial protein in the astroglia, have been found in patients who died; elevated levels have been found in unconscious patients; and normal levels have been found in those without loss of consciousness. It was proposed that S100B protein levels could be used as a biochemical marker of brain injury in CO poisoning.75 However, Rasmussen et al. failed to find significant increase in blood concentrations of neuron-specific enolase and S100 protein and found no correlation with level of consciousness in CO poisoning.76 Overall, brain CT, MRI, and MRS, as well as neuropsychological testing, are useful tools in diagnosis of CO toxicity and its severity. In addition, positron emission tomography and SPECT may provide additional information.77,78

TREATMENT Tissue hypoxia is the major outcome of CO intoxication. Therefore, based on chemical and pathophysiological data, oxygen is the “natural antidote.”79 Since the clinical signs and symptoms of CO toxicity are nonspecific, all 510

suspected victims should be treated with oxygen inhalation immediately after blood is drawn for COHb content. Individual responses to similar levels of CO exposure vary widely, ranging from death, to a parkinsonian syndrome, to mild or moderate intellectual impaiment.19 Therefore, immediately after securing the airway and adequate ventilation, administration of normobaric oxygen is the cornerstone of therapy, reducing the half-life of COHb from a mean of 5 hours (range 2 to 7 hours) to about 1 hour. HBO at 2.5 atmospheres reduces it to 20 to 30 minutes and has other benefits, at least in animal models. For example in rat brains, it prevents lipid peroxidation and leukocyte adherence to brain microvascular endothelium while accelerating regeneration of inactivated cytochrome oxidase. Therefore, usually at 2.5 to 3 atmospheres absolute for 90 to 120 minutes, it is considered the treatment of choice for those who present with syncope, coma, or seizure; a focal neurological deficit; or COHb greater than 25% (15% in pregnancy).80–85 In theory, normobaric oxygen should be the treatment for the least severely poisoned patients, reserving HBO therapy for severe intoxications. However, there are problems with this policy: (1) COHb levels do not correlate with the clinical severity of CO poisoning. (2) There is no universally accepted severity scale of CO poisoning, although loss of consciousness and neurological deficits generally indicate severe poisoning. (3) All victims of CO poisoning are at risk for delayed neuropsychological sequelae. Therefore, in general, the following approach is appropriate: (1) Patients with presumed CO poisoning should be placed on 100% oxygen. (2) Patients with severe poisoning must receive HBO regardless of COHb level. (3) Pregnant women must be treated with HBO irrespective of signs and symptoms. (4) In patients with lesser degrees of poisoning, careful evaluation is advised before deciding that 100% normobaric oxygen for more than 6 hours is the adequate therapy.79 Administration of more than one course of HBO for those who remain in coma is controversial. There are several practical considerations because not all treatment facilities, e.g., hospital emergency rooms, can measure COHb or administer HBO. For example, in one recent study, only 44% of acute care hospitals had the capability of measuring COHb.86 HBO is 100% oxygen at two to three times the atmospheric pressure at sea level. The oxygen tension in the arteries increases to about 2000 mm Hg and that of the tissues—to almost 400 mm Hg. The pressure is expressed in multiples of the atmospheric pressure, which is 1 at sea level. At sea level, the blood oxygen concentration is 0.3 mL/dL. At 100% oxygen at ambient (normobaric) pressure, the amount of the dissolved oxygen in the blood increases fivefold to 1.5 mL/dL. At 3 atmospheres, the dissolved-oxygen content reaches 6 mL/dL. HBO decreases the bubble formation in the blood and replaces inert gases with oxygen, which is

Section 4

rapidly taken up and used by the tissues. HBO can be bactericidal or bacteriostatic, or it can suppress toxin production, increasing tissues resistance against infections. HBO is more effective than normobaric oxygen in promoting collagen formation and angiogenesis and thus can facilitate wound healing. HBO inhibits neutrophil adherence to the walls of the ischemic vessels, which decreased free radical production, vasoconstriction, and tissue destruction. HBO is commonly delivered in a monoplace chamber or less often in a multioccupant chamber. The duration of a single treatment for CO poisoning is about 45 minutes. HBO with oxygen pressures of up to 3 atmospheres for a maximum of 120 minutes is safe. Adverse effects include reversible myopia, cataract, tracheobronchial symptoms, self-limited seizures, and barotraumas to the middle ear, cranial sinuses, and rarely teeth or lungs. Claustrophobia can be an issue in monoplace chambers. Despite the conflicting results from the literature regarding the effect of HBO versus normobaric oxygen, Tibbles and Edelsberg84 determined that patients with severe CO poisoning should receive at least one HBO treatment at 2.5 to 3.0 atmospheres because this therapy is the fastest method of treatment of the potentially reversible life-threatening effects. The treatment of a patient with CO poisoning should not be based solely on the COHb levels. The clinical manifestations, COHb levels, and importantly, the patient’s underlying medical history should be taken into account. In patients with suspected CO poisoning, 100% oxygen should be given immediately by a mask. The goal is to raise the PaO2 levels, decrease the half-life of CO, and facilitate its dissociation from Hb, thus allowing oxygen to attach to the freed binding sites. Strict bed rest should be provided, since it decreases oxygen demand and consumption. Patients with respiratory distress and decreased level of consciousness should be intubated and ventilated. Chest radiographs, blood lactate levels, and arterial blood gases should be performed in the emergency department. Headache improved before HBO treatment in 72%, resolving entirely in 21%. Of those with residual headache, pain improved with hyperbaric oxygen in 97%, resolving entirely in 44%. Even though deaths from CO poisoning have decreased in the United States in recent years, the total burden, including fatal and nonfatal cases, has not significantly changed.87 Juurlink et al.88 analyzed available data from six randomized controlled trials involving nonpregnant adults acutely poisoned with CO. At 1 month follow-up after treatment, symptoms possibly related to CO poisoning were present in 34.2% not of those treated with HBO, compared with 37.2% not treated with HBO.88 They found no evidence that unselected use of HBO in the treatment of acute CO poisoning reduces the frequency of neurological symptoms at 1 month. Because of insufficient



Neurotoxic Substances: Miscellaneous Neurotoxins

evidence, they recommend further research for defining the role of HBO in treatment of CO poisoning. Five years later, the same group examined the evidence for the effectiveness of the HBO for prevention of neurological sequelae in patients with acute CO poisoning. Four out of six trials found no benefit of HBO for the reduction of neurological sequelae, while two others found HBO beneficial. The authors conclude that the existing randomized trials have not been able to establish reduction of neurological sequelae with the administration of HBO to patients with CO poisoning.89 Close monitoring of serum pH and lactic acid levels is required, since anaerobic metabolism in the presence of tissue hypoxia generates lactic acidosis. Acidosis below 7.15 pH should be treated with sodium bicarbonate. Caution has to be exercised with the administration of sodium bicarbonate because carbon dioxide, a byproduct of its metabolism, could lead to respiratory acidosis and has to be eliminated by proper ventilation.

CONCLUSION CO, a highly toxic gas produced by incomplete combustion of hydrocarbons, is a relatively common cause of damage to humans. Because CO is tasteless and odorless and its clinical symptoms and signs are nonspecific, human toxicity is often overlooked. The brain and the heart may be severely affected after exposure to COHb levels exceeding 20%. Such damage occurs because the affinity of Hb for CO is 210 times higher than for oxygen. Hypoxic damage in the brain predominates in the cerebral cortex, cerebral white matter, and basal ganglia, especially the globus pallidus. Diagnosis requires clinical acumen and a high index of suspicion, often combined with epidemiological data, a careful clinical examination, analysis of ambient air CO and patient COHb levels, cardiological evaluations including ECG, and neurological evaluations including brain imaging (CT, MRI, MRS) and neuropsychological testing. SPECT and positron emission tomography may also be useful. Although immediate oxygen breathing is sometimes an adequate treatment, HBO treatment is favored. Subsequently, only symptomatic therapy is available for sequelae occurring in the course of long-term follow-up evaluations. An especially perplexing and unresolved issue is establishment of therapy or therapies to prevent the development of long-term sequelae in victims, e.g., the delayed neuropsychiatric syndrome and neurological dysfunction in children exposed to CO while they were in utero. Because prevention is the best treatment, our society should be on high alert in its attempts to prevent cases of CO poisoning. 511

Chapter 45



Carbon Monoxide

REFERENCES 1. Hardy KR, Thom SR. Pathophysiology and treatment of carbon monoxide poisoning. J Toxicol Clin Toxicol. 1994;32:613–629. 2. Centers for Disease Control and Prevention. Deaths from motor-vehicle-related unintentional carbon monoxide poisoning: Colorado 1996, New Mexico 1980–1995, and United States 1979–1988. MMWR. 1996;45:1029–1032. 3. Cobb N, Etzel RA. Unintentional carbon monoxide–related deaths in the United States, 1979–1988. JAMA. 1991;266:659–663. 4. Abelsohn A, Sanborn MD, Jessiman BJ, Weir F. Identifying and managing adverse environmental health effects: VI. Carbon monoxide poisoning. CMAJ. 2002;166:1685–1690. 5. Kao LW, Nanagas KA. Carbon monoxide poisoning. Emerg Med Clin North Am. 2004;22:985–1018. 6. Prockop LD, Chichkova R. Carbon monoxide intoxication: An environmental updated review. In: Román GC, Reis J, Defer G, Prockop L, eds. Special Issue on Environmental Neurology. J Neurol Sci. 2007; 262:122–130. 7. Mimura K, Harada M, Sumiyoshi S, et al. Long-term follow-up study on sequelae of carbon monoxide poisoning: serial investigation 33 years after poisoning. Seishin Shinkeigaku Zashi. 1999;101:592–618. 8. Klawans HL, Stein RW, Tanner CM, Goetz CG. A pure parkinsonian syndrome following acute carbon monoxide intoxication. Arch Neurol. 1982;39:302–304. 9. Sohn YH, Jeong T, Kim HS, Im JH, Kim JS. The brain lesion responsible for parkinsonism after carbon monoxide poisoning. Arch Neurol. 2000;57:1214–1218. 10. Choi S. Delayed neurological sequelae in carbon monoxide intoxication. Arch Neurol. 1982;40:433–435. 11. Kim JH, Chang KH, Song IC, et al. Delayed encephalopathy of acute carbon monoxide intoxication: diffusivity of cerebral white matter lesions. Am J Neuroradiol. 2003;24:1592–1597. 12. Min SK. A brain syndrome with delayed neuropsychiatric sequelae following acute carbon monoxide intoxication. Acta Psychiatry Scand. 1986;73:80–86. 13. Candura SM, Fonte R, Finozzi E, et al. Indoor pollution: a report of 2 clinical cases of occult carbon monoxide poisoning. G Ital Med Lav. 1993;15:1–4. 14. Carbon Monoxide: The Unnoticed Poison of the 21st Century. Proceedings of Satellite Meeting: International Union of Toxicology, 8th International Congress of Toxicology. Universite de Bourgogne, Dijon, France; 1998. 15. Wikipedia contributors. Carbon Monoxide. Available at: http:// en.wikipedia.org/wiki/Carbon_monoxide_poisoning. Accessed 2008. 16. Ryter SW, Alam J, Choi AM. Heme oxygenase-1/carbon monoxide: from basic science to therapeutic applications. Physiol Rev. 2006;86(2):583–650. 17. Lascaratos JG, Marketos SG. The carbon monoxide poisoning of two Byzantine emperors. J Toxicol Clin Toxicol. 1998;36(1–2):103–107. 18. Tvedt B, Kjuus H. Chronic CO poisoning: use of generator gas during the Second World War and recent research. Tidsskr Nor Laegeforen. 1997;117(17):2454–2457. 19. Prockop LD. Carbon monoxide brain toxicity: clinical, magnetic resonance imaging, magnetic resonance spectroscopy, and neuropsychological effects in 9 people. J Neuroimaging. 2005;15(2):144–149. 20. Chance BC, Erecinska M, Wanger M. Mitochondrial responses to carbon monoxide toxicity. Ann NY Acad Sci. 1970 Oct 5;174(1):193–204. 21. Tomaszewski C. Carbon monoxide. In: Ford MD, Delaney KA, Ling LS, Erickson T, eds. Clinical Toxicology. Philadelphia: WB Saunders; 2001:57–667.

512

22. Ellenhorn MJ, Schonwald S, Ordog G, Wasserberger J, eds. Respiratory Toxicology in Ellenhorn’s Medical Toxicology. 2nd ed. Philadelphia: Williams & Wilkins; 1997:1448–1531. 23. Longo LD. The biological effects of carbon monoxide on the pregnant woman, fetus, and newborn infant. Am J Obstet Gynecol. 1997;129:69–103. 24. Cramer CR. Fetal death due to accidental maternal carbon monoxide poisoning. J Toxicol Clin Toxicol. 1982;19: 297–301. 25. Margulies JL. Acute carbon monoxide poisoning during pregnancy. Am J Emerg Med. 1986;4:515–519. 26. Kim JK, Coe CJ. Clinical study on carbon monoxide intoxication in children. Yonsei Med J. 1987;28:266–273. 27. Department of the Environment. Expert Panel on Air Quality Standard. London: Her Majesty’s Stationery Office, 1994. 28. White RF, Feldman RG, Proctor SP. Neurobehavioral effects of toxic exposure. In: White RF, ed. Clinical Syndrome in Adult Neuropsychology: The Practitioner’s Handbook. New York: Elsevier; 1992:1–51. 29. Townsend CL, Maynard RI. Effects on health of prolonged exposure to low concentrations of carbon monoxide. Occup Environ Med. 2002:59(10):708–711. 30. Peterson JE, Steward RD. Absorption and elimination of carbon monoxide by active young men. Arch Environ Health. 1970;21:165–171. 31. Handa PK, Tai DY. Carbon monoxide poisoning: a five year review at Tan Tock Seng Hospital, Singapore. Ann Acad Med Singapore. 2005;34(10):611–614. 32. Hampson NB, Hampson LA. Characteristics of headache associated with acute carbon monoxide poisoning. Headache. 2002;42(3):220–223. 33. Choi IS. Carbon monoxide poisoning: systemic manifestations and complication. J Korean Med Sci. 2001;16(3):253–261. 34. Henz S, Maeder M. Prospective study of accidental carbon monoxide poisoning in 38 Swiss soldiers. Swiss Med Wkly. 2005;135(27–28):398–408. 35. Durak AC, Coskun A, Yikilmaz A, Erdogan F, Mavili E, Guven M. Magnetic resonance imaging findings in chronic carbon monoxide intoxication. Acta Radiol. 2005;46:322–327. 35a. Prockop, LD. Unpublished data, 2008. 36. Ginsberg MD, Myers RE, McDonagh BF. Experimental carbon monoxide encephalopathy in the primate: II. Clinical aspects, neuropathology, and physiologic correlation. Arch Neurol. 1974;30:209–216. 37. Cohen RE. Behavioral treatment of incontinence in a profoundly neurologically impaired adult. Arch Phys Med Rehabil. 1986;67(12):883–884. 38. Kwon, OY, Chung SP, Ha YR, Yoo IS, Kim SW. Delayed postanoxic encephalopathy after carbon monoxide poisoning. Emerg Med J. 2004;21:250–251. 39. Hu MC, Shiah IS, Yeh CB, Chen HK, Chen CK. Ziprasidone in the treatment of delayed carbon monoxide encephalopathy. Prog Neuropsychopharmacol Biol Psychiatry. 2006;30:755–757. 39a. Chambers CA, Hopkins RO, Weaver LK, Kay C. Cognitive and affective outcomes of more severe compared to less severe carbon monoxide poisoning. Brain Injury.2008;22(5):387–395. 40. Hampson NB. Pulse oximetry in severe carbon monoxide poisoning. Chest. 1998;114(4):1036–1041. 41. Bozeman WP, Hampson NB. Pulse oximetry in CO poisoning: additional data. Chest. 2000;117(1):295–296. 42. Widdop B. Analysis of carbon monoxide. Ann Clin Biochem. 2002;39(Pt 4):378–391. 43. Henry CR, Satran D, Lindgren B, Adkinson C, Nicholson CI, Henry TD. Myocardial injury and long-term mortality following moderate to severe carbon monoxide poisoning. JAMA. 2006;295(4):398–402.

Section 4 44. Somogyi E, Balogh I, Rubanyi G, Sotonyi P, Szegedi L. New findings concerning the pathogenesis of acute carbon monoxide (CO) poisoning. Am J Forensic Med Pathol. 1981;2(1):31–39. 45. Satran D, Henry CR, Adkinson C, Nicholson CI, Bracha Y, Henry TD. Cardiovascular manifestations of moderate to severe carbon monoxide poisoning. J Am Coll Cardiol. 2005;3;45(9): 1513–1516. 46. Kumazawa T, Watanabe-Suzuki K, Seno H, Ishii A, Suzuki O. A curious autopsy case of accidental carbon monoxide poisoning in a motor vehicle. Leg Med (Tokyo). 2000;2(3):181–185. 47. Tritapepe L, Macchiarelli G, Rocco M, et al. Functional and ultrastructural evidence of myocardial stunning after acute carbon monoxide poisoning. Crit Care Med. 1998;26(4):797–801. 48. Lin H, McGrath JJ. Responses of the working rat heart to carbon monoxide. Physiol Behav. 1989;46(1):81–84. 49. Clubb FJ Jr, Penney DG, Baylerian MS, Bishop SP. Cardiomegaly due to myocyte hyperplasia in prenatal rats exposed to 200 ppm carbon monoxide. J Mol Cell Cardiol. 1986;18(5):477–486. 50. Anderson RF, Allensworth DC, DeGroot WJ. Myocardial toxicity from carbon monoxide poisoning. Ann Intern Med. 1967;67(6):1172–1182. 51. Fineschi V, Agricola E, Baroldi G, et al. Myocardial findings in fatal carbon monoxide poisoning: a human and experiment morphometric study. Int J Legal Med. 2000;113(5):276–282. 52. Ernst A, Zibrak JD. Current concepts: Carbon monoxide poisoning. N Engl J Med. 1998;339(22):1603–1608. 53. Lasprele J, Fardeau M. The central nervous system and carbon monoxide poisoning: II. Anatomical study of brain lesions following intoxication with carbon monoxide (22 cases). Prog Brain Res. 1967;24:31–74. 54. Tuchman RF, Moser FG, Moshe SL. Carbon monoxide poisoning: bilateral lesions in the thalamus on MR imaging of the brain. Pediatr Radiol. 1990;20(6):478–479. 55. Sawada Y, Ahashi N, Maenura K, et al. Computerized tomography as an indication of long–term outcome after carbon monoxide poisoning. Lancet. 1980;1:783–786. 56. Murata S, Asaba H, Hiraishi K, et al. Magnetic resonance imaging findings on carbon monoxide intoxication. J Neuroimaging. 1993;3:128–131. 57. Gotoh M, Kuyama H, Asari S, Ohmoto T, Akioka T, Lai, MY. Sequential changes in MR images of the brain in acute carbon monoxide poisoning. Comput Med Imaging Graph. 1993;17:55–59. 58. Tom T, Abedon S, Clark RI, Wong W. Neuroimaging characteristics in carbon monoxide toxicity. J Neuroimaging. 1996:161–166. 59. Jones JS, Lagasse J, Zimmerman G. Computed tomographic findings after acute carbon monoxide poisoning. Am J Emerg Med. 1994;12:448–451. 60. Sener RN. Acute carbon monoxide poisoning: diffusion MR imaging findings. Am J Neuroradiol. 2003;24(7):1475–1477. 61. Ferrier D, Wallace CJ, Fletcher WA, Fong TC. Magnetic resonance features in carbon monoxide poisoning. Can Assoc Radiol J. 1994;45(6):466–468. 62. Schils F, Cabay JE, Flandroy P, Dondelinger RF. Unusual CT and MRI appearance of carbon monoxide poisoning. JBR-BTR. 1999;82(1):13–15. 63. Kinoshita T, Sugihara S, Matsusue E, Fujii S, Ametani M, Ogawa T. Pallidoreticular damage in acute carbon monoxide poisoning: diffusion-weighted MR imaging findings. AJNR Am J Neuroradiol. 2005;26(7):1845–1848. 64. O’Donnell P, Buxton PJ, Pitkin A, Jarvis LJ. The magnetic resonance imaging appearances of the brain in acute carbon monoxide poisoning. Clin Radiol. 2000;55(4):273–280. 65. Mascalchi M, Petruzi P, Zampa V. MRI of cerebellar white matter damage due to carbon monoxide poisoning: case report. Neuroradiology. 1996;38(Suppl 1):S73–S74.



Neurotoxic Substances: Miscellaneous Neurotoxins

66. Kawada N, Ochiai N, Kuzuhara S. Diffusion MRI in acute carbon monoxide poisoning. Intern Med. 2004;43(7):639–640. 67. Inagaki T, Ishino H, Seno H, Umegae N, Aoyama T. A long-term follow-up study of serial magnetic resonance images in patients with delayed encephalopathy after acute carbon monoxide poisoning. Psychiatry Clin Neurosci. 1997;51(6):4213. 68. Prockop LD, Naidu KA. Brain CT and MRI findings after carbon monoxide toxicity. J Neuroimaging. 1999;9(3):175–181. 69. Van Zijl PCM, Barker PB. Magnetic resonance spectroscopy and spectroscopic imaging for the study of brain metabolism. Ann NY Acad Sci. 1997;820:75–96. 70. Murata T, Itoh S, Koshino Y, et al. Serial proton magnetic resonance spectroscopy in a patient with the interval form of carbon monoxide poisoning. J Neurol Neurosurg Psychiatry. 1995;58:100–103. 71. Murata T, Kimura H, Kado H, et al. Neuronal damage in the interval form of carbon monoxide determined by serial diffusionweighted magnetic resonance imaging plus 1H-magnetic resonance spectroscopy. J Neurol Neurosurg Psychiatry. 2001;71(2):250–253. 72. Kamada K, Houkin K, Aoki T, et al. Cerebral metabolic changed in delayed carbon monoxide sequelae studied by proton MR spectroscopy. Neuroradiology. 1994;36(2):104–106. 73. Prockop LD. Neuroimaging in neurotoxicology. In: L Chang, ed. Handbook of Neurotoxicology. New York: M Dekker; 1995: 753–763. 74. Frazeka F, Schmidt R, Offenbacker H, et al. Prevalence of white matter and periventricular magnetic resonance hyperintensity in asymptomatic volunteers. J Neuroimaging. 1991:1:27–30. 75. Brvar M, Mozina H, Osredkar J, et al. S100B protein in carbon monoxide poisoning: a pilot study. Resuscitation. 2004;61(3):357–360. 75a. Parkinson RB, Hopkins RO, Cleavinger LK, et al. White matter hyperintensities and neuropsychological outcome following carbon monoxide poisoning. Neurology. 2002;58:1525–1532. 76. Rasmussen LS, Poulsen MG, Christiansen M, Jansen EC. Biochemical markers from brain damage after carbon monoxide poisoning. Acta Anaesthesiol Scand. 2004;48(4):469–473. 77. Tengvar C, Johansson B, Sorensen J. Frontal lobe and cingulated cortical metabolic dysfunction in acquired akinetic mutism: a PET study of the interval form of carbon monoxide poisoning. Brain Inj. 2004;18(6):615–625. 78. Gale SD, Hoskins RO, Weaver LK, Bigler ED, Booth EJ, Blatter DD. MRI, quantitative MRI, SPECT, and neuropsychological findings following carbon monoxide poisoning. Brain Inj. 1999;13(4):229–243. 79. Elkharrat D. Indications of Normobacic and Hyperbaric Oxygen Therapy in Acute CO intoxication. Proceedings of Satellite Meeting: International Union of Toxicology, 8th International Congress of Toxicology. International Congress of Toxicology. Dijon, France, July 3–4, 1998. 80. Tibbles PM, Perotta PL. Treatment of carbon monoxide poisoning: a critical review of human outcome studies comparing normobaric oxygen with hyperbaric oxygen. Ann Emerg Med. 1994;24:269–276. 81. Weaver LK, Hopkins RO, Larson-Lorh V, Howe S, Haberstock D. Double blind, controlled, prospective, randomized clinical trial (RCT) in patients with acute carbon monoxide (CO) poisoning: outcome of patients tested with normobaric oxygen or hyperbaric oxygen (HBO2), an interim report. Undersea Hyperb Med. 1995;22(Suppl):14. 82. Thom SR, Taber RI, Mediguren II, Clark JM, Hardy KR, Fisher AB. Delayed neuropsychological sequelae after carbon monoxide poisoning: prevention by treatment with hyperbaric oxygen. Ann Emerg Med. 1995;25:479–486.

513

Chapter 45



Carbon Monoxide

83. Van Meter KW, Weiss L, Harch PE, et al. Should the pressure be off or on with use of oxygen in the treatment of carbon monoxide poisoned patients? Ann Emerg Med. 1994;24: 283–288. 84. Tibbles PM, Edelsberg JS. Hyperbaric-oxygen therapy. N Engl J Med. 1996;334:1642–1648. 85. Weaver LK, Hopkins RO, Chan KJ, et al. Hyperbaric oxygen for acute carbon monoxide poisoning. N Engl J Med. 202;347:1057–1067. 86. Hampson NB, Scott KL, Zmaeff JL. Carboxyhemoglobin measurement by hospitals: implications for the diagnosis of carbon monoxide poisoning. J Emerg Med. 2006;31(1):13–16.

514

87. Hampson NB. Trends in the incidence of carbon monoxide poisoning in the United States. Am J Emerg Med. 2005;23(7):838–841. 88. Juurlink DN, Stanbrook MB, McGuigan MA. Hyperbaric oxygen for carbon monoxide poisoning. Cochrane Database Syst Rev. 2000;(2):CD002041. 89. Juurlink DN, Buckley NA, Stanbrook MB, Isbister GK, Bennett M, McGuigan MA. Hyperbaric oxygen for carbon monoxide poisoning. Cochrane Database Syst Rev. 2005;(1): CD002041 [review].