5: Diagnostic Imaging

Diagnostic imaging can play a significant role in the management of many patients with toxicologic emergencies. Radiography can confirm a diagnosis (eg, by visualizing the xenobiotic), assist in therapeutic interventions such as monitoring gastrointestinal (GI) decontamination, and detect complications of the xenobiotic exposure (Table 5–1).¹⁸⁰

Conventional radiography is readily available in the emergency department (ED) and is the imaging modality most frequently used in acute patient management. Other imaging modalities are used in certain other toxicologic emergencies, including computed tomography (CT); enteric and intravascular contrast studies; ultrasonography; transesophageal echocardiography (TEE); magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA); and nuclear scintigraphy, including ­positron emission tomography (PET) and single-photon emission tomography (SPECT).

A number of xenobiotics are radiopaque and can potentially be detected by conventional radiography. Radiography is most useful when a substance that is known to be radiopaque is ingested or injected. When the identity of the xenobiotic is unknown, the usefulness of radiography is very ­limited. When ingested, a radiopaque xenobiotic may be seen on an abdominal radiograph. Injected radiopaque xenobiotics are also amenable to radiographic detection. If the toxic material itself is available for examination, it can be radiographed outside of the body to detect any radiopaque contents (Fig. 105–2).⁷⁶

The radiopacity of a xenobiotic is determined by several factors. First, the intrinsic radiopacity of a substance depends on its physical density (g/cm³) and the atomic numbers of its constituent atoms. Biologic tissues are composed mostly of carbon, hydrogen, and oxygen and have an average atomic number of approximately 6. Substances that are more radiopaque than soft tissues include bone, which contains calcium (atomic number 20), radiocontrast agents containing iodine (atomic number 53) and barium (atomic number 56), iron (atomic number, 26), and lead (atomic number 82). Some xenobiotics have constituent atoms of high atomic number, such as chlorine (atomic number 17), potassium (atomic number 19), and sulfur (atomic number 16) that contribute to their radiopacity.

The thickness of an object also affects its radiopacity. Small particles of a moderately radiopaque xenobiotic are often not visible on a radiograph. Finally, the radiographic appearance of the surrounding area also affects the detectability of an object. A moderately radiopaque tablet is easily seen against a uniform background, but in a patient, overlying bone or bowel gas often obscures the tablet.

Compared with conventional radiography, ultrasonography theoretically is a useful tool for detecting ingested xenobiotics because it depends on echogenicity rather than radiopacity for visualization.³³ Solid pills within the fluid-filled stomach may have an appearance similar to gallstones within the gallbladder. In one in vitro study using a water-bath model, virtually all intact pills could be visualized.⁷ The authors were also successful at detecting pills within the stomachs of human volunteers who ingested pills. Nonetheless, reliably finding pills scattered throughout the GI tract, which often contains air and feces that block the ultrasound beam, is a formidable task. Ultrasonography, therefore, has limited clinical practicality.

Although a clinical policy issued by the American College of Emergency Physicians in 1995 suggested that an abdominal radiograph should be obtained in unresponsive overdosed patients in an attempt to identify the involved xenobiotic, the role of abdominal radiography in screening a patient who has ingested an unknown xenobiotic is questionable.⁶ The number of potentially ingested xenobiotics that are radiopaque is limited. In addition, the radiographic appearance of an ingested xenobiotic is not sufficiently distinctive to determine its identity (Fig. 5–1).²⁰⁵ However, when ingestion of a radiopaque xenobiotic such as ferrous sulfate tablets or another metal with a high atomic number is suspected, abdominal radiographs are ­helpful.⁵ In addition, knowledge of potentially radiopaque ­xenobiotics is useful in suggesting diagnostic possibilities when a radiopaque xenobiotic is discovered on an abdominal radiograph that was obtained for reasons other than ­suspected xenobiotic ingestion, such as in a patient with abdominal pain (Fig. 5–2).^179,186

Several investigators have studied the radiopacity of various ­medications.^{52,59,81,87,97,147,176,189,197} These investigators used an in vitro water-bath model to simulate the radiopacity of abdominal soft tissues.¹⁷⁶ The studies found that only a small number of medications exhibit some degree of radiopacity. A short list of the more consistently radiopaque xenobiotics is summarized in the mnemonic CHIPES—chloral hydrate, “heavy metals,” iron, phenothiazines, and enteric-coated and sustained-release preparations.

The CHIPES mnemonic has several limitations.¹⁷⁶ It does not include all of the pills that are radiopaque in vitro such as acetazolamide and ­busulfan. Most radiopaque medications are only moderately radiopaque, and when ingested, they dissolve rapidly, becoming difficult or impossible to detect. “Psychotropic medications” include a wide variety of compounds of varying radiopacity.^147,176 For example, whereas trifluoperazine (containing fluorine; atomic number 9) is radiopaque in vitro, chlorpromazine (containing chlorine; atomic number 17) is not.¹⁷⁶

Finally, sustained-release preparations and those with enteric coatings have variable composition and radiopacity. Pill formulations of ­fillers, binders, and coatings vary among manufacturers, and even a specific product can change depending on the date of manufacture. Furthermore, the insoluble matrix of some sustained-release preparations is radiopaque, and when seen on a radiograph, these tablets may no longer contain active ­medication. Some sustained-release cardiac medications such as verapamil and nifedipine have inconsistent radiopacity.^119,188,199

When a xenobiotic that is known to be radiopaque is involved in an exposure, radiography plays an important role in patient care.⁵ Radiography can confirm the diagnosis of a radiopaque xenobiotic exposure, quantify the approximate amount of xenobiotic involved, and monitor its removal from the body. Examples include ferrous sulfate, sustained-release potassium chloride,¹⁹³ and heavy metals.

Iron Tablet Ingestion

Adult-strength ferrous sulfate tablets are readily detected radiographically because they are highly radiopaque and disintegrate slowly when ingested. Aside from confirming an iron tablet ingestion and quantifying the amount ingested, radiographs repeated after whole-bowel irrigation help to determine whether further GI decontamination is needed (Fig. 5–3).^{51,61,101,146,151,153,205} Nonetheless, caution must be exercised in using radiography to exclude an iron ingestion. Some iron preparations are not radiographically detectable. Liquid, chewable, or encapsulated (“Spansule”) iron preparations rapidly fragment and disperse after ingestion. Even when intact, these preparations are less radiopaque than ferrous sulfate tablets.⁵²

Metals

Metals, such as arsenic, cesium, lead, manganese, mercury, potassium, and thallium, can be detected radiographically. Examples of metal exposure include leaded ceramic glaze (Fig. 5–4),¹⁶⁸ paint chips containing lead (Fig. 96–6),^112,133 mercuric oxide and elemental mercury (Fig. 98–1),¹²² thallium salts (atomic number 81),^44,134 and zinc (atomic number 30).²³ Arsenic (Fig. 5–5)^77,116,203 with a lower atomic number (atomic number 33) is also radiopaque.

Mercury.

Unintentional ingestion of elemental mercury can occur when a glass thermometer or a long intestinal tube with a mercury-containing balloon breaks. Liquid elemental mercury can be injected subcutaneously or intravenously. Radiographic studies assist débridement by detecting mercury that remains after the initial excision. Elemental mercury that is injected intravenously produces a dramatic radiographic picture of pulmonary embolization (Fig. 5–6).^{23,26,112,126,130,143}

Lead.

Ingested lead can be detected only by abdominal radiography, such as in a child with lead poisoning who has ingested paint chips (Fig. 96–6). Metallic lead (eg, a bullet) that is embedded in soft tissues is not usually systemically absorbed. However, when the bullet is in contact with an acidic environment such as synovial fluid or cerebrospinal fluid (CSF), there may be significant absorption. Over many years, mechanical and chemical action within the joint causes the bullet to fragment and gradually dissolve.^{43,45,53,192,196} Radiography can confirm the source of lead poisoning by revealing metallic material in the joint or CSF (Fig. 5–7).

Xenobiotics in Containers

In some circumstances, ingested xenobiotics can be seen even though they are of similar radiopacity to surrounding soft tissues. If a xenobiotic is ingested in a container, the container itself may be visible.

Body Packers.

“Body packers” are individuals who smuggle large quantities of illicit drugs across international borders in securely sealed packets.^{3,15,16,25,36,56,95,109,125,132,156,181,183,201} The uniformly shaped, oblong packets can be seen on abdominal radiographs either because there is a thin layer of air or metallic foil within the container wall or because the packets are outlined by bowel gas (Fig. 5–8). In some cases, a “rosette” representing the knot at the end of the packet is seen.¹⁸³ Intraabdominal calcifications (pancreatic calcifications and bladder stones) have occasionally been misinterpreted as drug-containing packets.^201,217

The sensitivity of abdominal radiography for such packets is high, in the range of 85% to 90%. The major role of radiography is as a rapid screening test to confirm the diagnosis in individuals suspected of smuggling drugs, such as persons being held by airport customs agents. However, because packets are occasionally not visualized and the rupture of even a single packet can be fatal, abdominal radiography should not be relied on to exclude the diagnosis of body packing. Ultrasonography has also been used to rapidly detect packets, although it also should not be relied on to exclude such a life-threatening ingestion.^33,78,136 After intestinal decontamination, an upper GI series with oral contrast or CT with or without enteric contrast can reveal any remaining packets.^80,91,148

Body Stuffers.

A “body stuffer” is an individual who, in an attempt to avoid imminent arrest, hurriedly ingests contraband in insecure ­packaging.¹⁷⁰ The risk of leakage from such haphazardly constructed ­containers is high. Unfortunately, radiographic studies cannot reliably ­confirm or exclude such ingestions.¹⁸⁷

Occasionally, a radiograph will demonstrate the ingested container (Fig. 5–9). If the drug is in a glass or in a hard-plastic crack vial, the container may be seen.⁹⁰ If the body stuffer swallows soft plastic bags containing the drug, the containers are not usually visible. However, in three reported cases, “baggies” were visualized by abdominal CT.^{37,48,83,85,105,157,180}

Halogenated Hydrocarbons

Some halogenated hydrocarbons can be visualized radiographically.^31,38 Radiopacity is proportionate to the number of chlorine atoms. Both carbon tetrachloride (CCl₄) and chloroform (CHCl₃) are radiopaque. Because these liquids are immiscible in water, a triple layer may be seen within the stomach on an upright abdominal radiograph—an uppermost air bubble, a middle radiopaque chlorinated hydrocarbon layer, and a lower gastric fluid layer. However, these ingestions are rare, and the quantity ingested is usually too small to show this effect. Other halogenated hydrocarbons such as methylene iodide are highly radiopaque.²¹⁶

Mothballs

Some types of mothballs can be visualized by radiography. Whereas relatively nontoxic paradichlorobenzene mothballs (containing chlorine; atomic number 17) are moderately radiopaque, more toxic naphthalene mothballs are radiolucent.¹⁹⁴ If the patient is known to have swallowed mothballs, the difference in radiopacity may help determine the type. However, if mothball ingestion is not already suspected, the more toxic naphthalene type may not be detected. Radiographs of mothballs outside of the patient can help distinguish these two types (Fig. 105–2).

Radiolucent Xenobiotics

A radiolucent xenobiotic may be visible because it is less radiopaque than surrounding soft tissues. Hydrocarbons such as gasoline are relatively radiolucent when embedded in soft tissues. The radiographic appearance resembles subcutaneous gas as seen in a necrotizing soft tissue infection (Fig. 5–10).

Extravasation of intravenous (IV) radiographic contrast material is a common occurrence. In most cases, the volume extravasated is small, and there are no clinical sequelae.^17,35,54,169 Rarely, a patient has an extravasation large enough to cause cutaneous necrosis and ulceration.

Recently, the incidence of sizable extravasations has increased because of the use of rapid-bolus automated power injectors for CT studies.²⁰⁸ Fortunately, nonionic low-osmolality contrast solutions are currently nearly always used for these studies. These solutions are far less toxic to soft tissues than older ionic high-osmolality contrast materials.

The treatment of contrast extravasation has not been studied in a large series of human subjects and is therefore controversial. Various strategies have been proposed. The affected extremity should be elevated to promote drainage. Although topical application of heat causes vasodilation and could theoretically promote absorption of extravasated contrast material, the intermittent application of ice packs has been shown to lower the incidence of ulceration.³⁵ Rarely, an extremely large volume of liquid is injected into the soft tissues, which requires surgical decompression when there are signs of a compartment syndrome. A radiograph of the extremity will demonstrate the extent of extravasation (Fig. 5–11).³⁵

Precautions should be taken to prevent extravasation. A recently placed, well-running IV catheter should be used. The distal portions of the extremities (hands, wrist, and feet) should not be used as IV sites for injecting contrast. Patients who are more vulnerable to complications and those whose veins may be more fragile, such as infants, debilitated patients, and those with an impaired ability to communicate, must be closely monitored to prevent or determine if extravasation occurs.

Summary

Obtaining an abdominal radiograph in an attempt to identify pills or other xenobiotics in a patient with an unknown ingestion is unlikely to be helpful and is, in general, not warranted. Radiography is most useful when the suspected xenobiotic is known to be radiopaque, as is the case with iron tablets and heavy metals. The xenobiotic can be radiographed within the patient’s abdomen; elsewhere in the patient’s body; or, if the material is available, outside of the patient.

The lungs, central nervous system (CNS), GI tract, and skeleton are the organ systems that are most amenable to diagnostic imaging. Disorders of the lungs and skeletal system are seen by plain radiography. For abdominal pathology, contrast studies and CT are more useful, although plain radiographs can diagnose intestinal obstruction, perforation, and radiopaque foreign bodies. Imaging of the CNS uses CT, MRI, and nuclear scintigraphy (PET and SPECT).

Skeletal Changes Caused by Xenobiotics

A number of xenobiotics affect bone mineralization. Toxicologic effects on bone result in either increased or decreased density (Table 5–2). Some xenobiotics produce characteristic radiographic pictures, although exact diagnoses usually depend on correlation with the clinical scenario.^10,145 Furthermore, alterations in skeletal structure develop gradually and are usually not visible unless the exposure continues for at least 2 weeks.

Increase in Bone Density

Lead poisoning.

Skeletal radiography may suggest the diagnosis of chronic lead poisoning even before the blood lead concentration is obtained. With lead poisoning, the metaphyseal regions of rapidly growing long bones develop transverse bands of increased density along the growth plate (Fig. 5–12).^{21,160,163,174} Characteristic locations are the distal femur and proximal tibia. Flaring of the distal metaphysis also occurs. Such lead lines are also seen in the vertebral bodies and iliac crest. Detected in approximately 80% of children with a mean lead concentration of 49 ± 17 µg/dL, lead lines usually occur in children between the ages of 2 and 9 years.²¹ In most children, it takes several weeks for lead lines to appear, although in very young infants (2–4 months old), lead lines may develop within days of exposure.²²¹ After exposure ceases, lead lines diminish and may eventually disappear.

Lead lines are caused by the toxic effect of lead on bone growth and do not represent deposition of lead in bone. Lead impedes resorption of calcified cartilage in the zone of provisional calcification adjacent to the growth plate. This is termed chondrosclerosis.^21,47 Other xenobiotics that cause metaphyseal bands are yellow phosphorus (Chap. 116), bismuth (Chap. 90), and vitamin D (Chap. 47).

Fluorosis.

Fluoride poisoning causes a diffuse increase in bone mineralization. Endemic fluorosis occurs where drinking water contains very high levels of fluoride (≥2 or more parts per million), as an occupational exposure among aluminum workers handling cryolite (sodium–aluminum fluoride), or with excessive tea drinking. The skeletal changes associated with fluorosis are osteosclerosis (hyperostosis deformans), osteophytosis, and ligament calcification (Fig. 5–13). Fluorosis primarily affects the axial skeleton, especially the vertebral column and pelvis. Thickening of the vertebral column may cause compression of the spinal cord and nerve roots. Without a history of fluoride exposure, the clinical and radiographic findings can be mistaken for osteoblastic skeletal metastases. The diagnosis of fluorosis is confirmed by histologic examination of the bone and measurement of fluoride levels in the bone and urine.^22,210

Bisphosphonates.

Bisphosphonates such as alendronate (Fosamax) are commonly used to treat osteoporosis. They increase bone density by inhibiting osteoclast activity and decreasing bone resorption. However, by suppressing bone turnover and fracture healing, bisphosphonates are associated with accumulated microdamage to bone and skeletal weakening, which makes the bone vulnerable to fractures. Radiographically, there is thickening of the cortex of diaphyseal bone, typically the proximal femoral shaft. Such bone is associated with atypical proximal femoral shaft and subtrochanteric fractures after low-energy injuries such as a fall from standing. The fractures are transverse and have a characteristic “beaked” appearance caused by the cortical thickening (Fig. 5–14).

Focal Loss of Bone Density.

Skeletal disorders associated with focal diminished bone density (or mixed rarefaction and sclerosis) include osteonecrosis, osteomyelitis, and osteolysis. Osteonecrosis, also known as avascular necrosis, most often affects the femoral head, humeral head, and proximal tibia.¹²⁷ There are many causes of osteonecrosis. Xenobiotic causes include long-term corticosteroid use and alcoholism. Radiographically, focal skeletal lucencies and sclerosis are seen, ultimately with loss of bone volume and collapse (Fig. 5–15A).

Acroosteolysis.

Acroosteolysis is bone resorption of the distal pha­lan­ges and is associated with occupational exposure to vinyl chloride monomer. Protective measures have reduced its incidence since it was first described in the early 1960s.¹⁶⁴

Osteomyelitis.

Osteomyelitis is a serious complication of injection drug use. It usually affects the axial skeleton, especially the vertebral bodies, as well as the sternomanubrial and sternoclavicular joints (Figs. 5–15B and C).^74,79 Back pain or neck pain in injection drug users warrants careful consideration. A spinal epidural abscess causing spinal cord compression may accompany vertebral osteomyelitis.^92,125 Radiographic findings are negative early in the disease course before skeletal changes are visible and the diagnosis is confirmed by MRI or CT (Fig. 5–15D).

Soft Tissue Changes

Certain abnormalities in soft tissues, predominantly as a consequence of infectious complications of injection drug use, are amenable to radiographic diagnosis.^{74,75,79,99,198} In an injection drug user who presents with signs of local soft tissue infections, radiography is indicated to detect a retained metallic foreign body, such as a needle fragment, or subcutaneous gas, as may be seen in a necrotizing soft tissue infection such as necrotizing fasciitis. CT is more sensitive at detecting soft tissue gas than is conventional radiography. CT and ultrasonography can also detect subcutaneous or deeper abscesses that require surgical or percutaneous drainage.

Pulmonary and Other Thoracic Problems

Many xenobiotics that affect intrathoracic organs produce pathologic changes that can be detected on chest radiographs.^{9,12,24,49,63,75,140,172,219} The lungs are most often affected, resulting in dyspnea or cough, but the pleura, hilum, heart, and great vessels may also be involved.⁶ Patients with chest pain may have a pneumothorax, pneumomediastinum, or aortic dissection. Patients with fever, with or without respiratory symptoms, may have a focal infiltrate, pleural effusion, or hilar lymphadenopathy.

Chest radiographic findings may suggest certain diseases, although the diagnosis ultimately depends on a thorough clinical history. When a specific xenobiotic exposure is known or suspected, the chest radiograph can confirm the diagnosis and help in assessment. If a history of ­xenobiotic exposure is not obtained, a patient with an abnormal chest radiograph may initially be misdiagnosed as having pneumonia or another disorder that is more common than xenobiotic-mediated lung disease.¹⁶⁶ Therefore, patients with chest radiographic abnormalities should be carefully questioned regarding possible xenobiotic exposures at work or at home, as well as the use of medications or other drugs.

Many pulmonary disorders are radiographically detectable because they result in fluid accumulation within the normally air-filled lung. Fluid may accumulate within the alveolar spaces or interstitial tissues of the lung, producing the two major radiographic patterns of pulmonary disease: airspace filling and interstitial lung disease (Table 5–3). Most xenobiotics are widely distributed throughout the lungs and produce a diffuse rather than a focal radiographic abnormality.

Diffuse Airspace Filling.

Overdose with various xenobiotics, including salicylates, opioids, and paraquat, may cause acute respiratory distress syndrome (ARDS) (formerly known as noncardiogenic pulmonary edema or acute lung injury) with or without diffuse alveolar damage and characterized by leaky capillaries (Fig. 5–16).^{75,85,89,123,184,191,218} There are, of course, many other causes of ARDS, including sepsis, anaphylaxis, and major trauma.²¹³ Other xenobiotic exposures that may result in diffuse airspace filling include inhalation of irritant gases that are of low water solubility such as phosgene (COC1₂), nitrogen dioxide (silo filler’s disease), chlorine, hydrogen sulfide, and sulfur dioxide (Chaps. 124 and 126).^79,102 Organic phosphorus insecticide poisoning causes cholinergic hyperstimulation, resulting in bronchorrhea (Chap. 113). Smoking “crack” cocaine is associated with diffuse alveolar hemorrhage (Chap. 78).^{60,75,79,165,219}

Focal Airspace Filling.

Focal infiltrates are usually caused by bacterial pneumonia, although aspiration of gastric contents also causes localized airspace disease.^75,195 Aspiration may occur during sedative–hypnotic or alcohol intoxication or during a seizure. During ingestion, low-viscosity hydrocarbons often enter the lungs while they are being swallowed (Figs. 5–17 and 108–1). There may be a delay in the development of radiographic abnormalities, and the chest radiograph may not appear to be abnormal until 6 hours after the ingestion.⁸ During aspiration, the most dependent portions of the lung are affected. When the patient is upright at the time of aspiration, the lower lung segments are involved. When the patient is supine, the posterior segments of the upper and lower lobes are affected.⁶²

Multifocal Airspace Filling.

Multifocal airspace filling occurs with septic pulmonary emboli, which is a complication of injection drug use and right-sided bacterial endocarditis. The foci of pulmonary infection often undergo necrosis and cavitation (Fig. 5–18).^75,79

Interstitial Lung Diseases.

Toxicologic causes of interstitial lung disease include hypersensitivity pneumonitis, use of medications with direct pulmonary toxicity, and inhalation or injection of inorganic particulates.⁷⁵ Interstitial lung diseases may have an acute, subacute, or chronic course. On the chest radiograph, acute and subacute disorders cause a fine reticular or reticulonodular pattern (Fig. 5–19). Chronic interstitial disorders cause a coarse reticular “honeycomb” pattern.

Hypersensitivity Pneumonitis.

Hypersensitivity pneumonitis is a delayed-type hypersensitivity reaction to an inhaled or ingested allergen.^40,96,166 Inhaled organic allergens such as those in moldy hay (farmer’s lung) and bird droppings (pigeon breeder’s lung) cause hypersensitivity pneumonitis in sensitized individuals. There are two clinical syndromes: an acute, recurrent illness and a chronic, progressive disease. The acute illness presents with fever and dyspnea. In these cases, the chest radiograph findings are normal or may show fine interstitial or alveolar infiltrates. Chronic hypersensitivity pneumonitis causes progressive dyspnea, and the radiograph shows interstitial fibrosis.

The most common medication causing hypersensitivity pneumonitis is nitrofurantoin. Respiratory symptoms occur after taking the medication for 1 to 2 weeks. Other medications that may cause hypersensitivity pneumonitis include sulfonamides and penicillins.

Chemotherapeutics.

Various chemotherapeutic agents, such as busulfan, bleomycin, cyclophosphamide, and methotrexate, cause pulmonary injury by their direct cytotoxic effect on alveolar cells.^39,65 The radiographic pattern is usually interstitial (reticular or nodular) but may include airspace filling or mixed patterns. The patient presents with dyspnea, fever, and pulmonary infiltrates that begin after several weeks of therapy. Other causes of these clinical and radiographic findings must be considered, including opportunistic infection, pulmonary carcinomatosis, pulmonary edema, and intraparenchymal hemorrhage. Symptoms usually resolve with discontinuation of the offending medication.

Amiodarone.

Amiodarone toxicity causes phospholipid accumulation within alveolar cells and may result in pulmonary fibrosis. An interstitial radiographic pattern is seen, although airspace filling may also occur (Fig. 5–19) (Chap. 64).

Particulates.

Inhaled inorganic particulates, such as asbestos, silica, and coal dust, cause pneumoconiosis. This is a chronic interstitial lung disease characterized by interstitial fibrosis and loss of lung volume.^{32,138,167,215} IV injection of illicit xenobiotics that have particulate contaminants, such as talc, causes a chronic interstitial lung disease known as talcosis.^1,55,212

Pleural Disorders.

Asbestos-related calcified pleural plaques develop many years after asbestos exposure (Fig. 5–20). These lesions do not cause clinical symptoms and have only a minor association with malignancy and interstitial lung disease. Asbestos-related pleural plaques should not be called asbestosis because that term refers specifically to the interstitial lung disease caused by asbestos. Pleural plaques must be distinguished from mesotheliomas, which are not calcified, enlarge at a rapid rate, and erode into nearby structures such as the ribs.

Pleural effusions occur with drug-induced systemic lupus erythematosus (SLE).¹⁴⁰ The medications most frequently implicated are procainamide, hydralazine, isoniazid, and methyldopa. The patient presents with fever as well as other symptoms of SLE.

Pneumothorax and pneumomediastinum are associated with illicit drug use. These complications are related to the route of administration rather than to the particular drug. Barotrauma associated with the ­Valsalva maneuver or intense inhalation with breath holding during the smoking of “crack” cocaine or marijuana results in pneumomediastinum (Fig. 5–21A).^20,50,75,150 Pneumomediastinum is one cause of cocaine-related chest pain that can be diagnosed by chest radiography. Forceful vomiting after ingestion of syrup of ipecac or alcohol may produce a Mallory-Weiss syndrome, pneumomediastinum, and mediastinitis (Boerhaave syndrome).²²⁰ IV drug users who attempt to inject into the subclavian and internal jugular veins may cause a pneumothorax.⁴⁶

Lymphadenopathy.

Phenytoin may cause drug-induced lymphoid hyperplasia with hilar lymphadenopathy.¹⁴⁰ Chronic beryllium exposure results in hilar lymphadenopathy that mimics sarcoidosis, with granulomatous changes in the lung parenchyma. Silicosis is associated with “eggshell” calcification of hilar lymph nodes.

Cardiovascular Abnormalities.

Dilated cardiomyopathy occurs in chronic alcoholism and exposure to cardiotoxic medications such as doxorubicin (Adriamycin). Enlargement of the cardiac silhouette may also be caused by a pericardial effusion, which may accompany drug-induced SLE. Aortic dissection is associated with use of cocaine and amphetamines.^{66,75,114,152,162} The chest radiograph may show an enlarged or indistinct aortic knob and an ascending or descending aorta (Figs. 5–21B to D).

Abdominal Problems

Abdominal imaging modalities include conventional radiography, CT, GI contrast studies, and angiography.⁶⁸ Conventional radiography is limited in its ability to detect most intraabdominal pathology because most pathologic processes involve soft tissue structures that are not well seen. Plain radiography readily visualizes gas in the abdomen and is therefore usable to diagnose pneumoperitoneum (free intraperitoneal air) and bowel distension caused by mechanical obstruction or diminished gut motility (adynamic ileus). Other abnormal gas collections, such as intramural gas associated with intestinal infarction, are seen infrequently (Table 5–4).^{73,120,128,137,186}

Pneumoperitoneum.

GI perforation is diagnosed by seeing free intraperitoneal air under the diaphragm on an upright chest radiograph. Peptic ulcer perforation is associated with crack cocaine use.^2,29,107 Esophageal or gastric perforation (or tear) can be a complication of forceful emesis induced by syrup of ipecac or alcohol intoxication or attempted placement of a large-bore orogastric tube (Fig. 5–22).²²⁰ Esophageal and gastric perforation may also occur after the ingestion of caustics such as iron, alkali, or acid.¹⁰³ Esophageal perforation causes pneumomediastinum and ­mediastinitis.

Obstruction and Ileus.

Both mechanical bowel obstruction and adynamic ileus (diminished gut motility) cause bowel distension. With mechanical obstruction, there is a greater amount of intestinal distension proximal to the obstruction and a relative paucity of gas and intestinal collapse distal to the obstruction. In adynamic ileus, the bowel distension is relatively uniform throughout the entire intestinal tract. On the upright abdominal radiograph, both mechanical obstruction and adynamic ileus show air-fluid levels. In mechanical obstruction, air-fluid levels are seen at different heights and produce a “stepladder” appearance.

Mechanical bowel obstruction may be caused by large intraluminal foreign bodies such as a body packer’s packets or a medication bezoar.^64,197 Adynamic ileus may result from the use of opioids, anticholinergics, and tricyclic antidepressants (Fig. 5–23).^15,68 Because adynamic ileus occurs in many diseases, the radiographic finding of an ileus is not helpful diagnostically. When the distinction between obstruction and adynamic ileus cannot be made based on the abdominal radiographs, abdominal CT can clarify the diagnosis.¹³⁵

Mesenteric Ischemia.

In most patients with intestinal ischemia, plain abdominal radiographs show only a nonspecific or adynamic ileus pattern. In a small proportion of patients with ischemic bowel (5%), intramural gas is seen.¹⁵ Rarely, gas is also seen in the hepatic portal venous system. CT is better able to detect signs of mesenteric ischemia, particularly bowel wall thickening (Fig. 5–24).¹⁴

Intestinal ischemia and infarction may be caused by use of cocaine; other sympathomimetics; and the ergot alkaloids, all of which induce mesenteric vasoconstriction.^79,110,130 Calcium channel blocker overdoses cause splanchnic vasodilation and hypotension that may result in intestinal ischemia. Superior mesenteric vein thrombosis may be caused by hypercoagulability associated with chronic oral contraceptive use.

Gastrointestinal Hemorrhage and Hepatotoxicity.

Radiography is not usually helpful in the diagnosis of such common abdominal complications as GI bleeding and hepatotoxicity.

The now obsolete radiocontrast agent thorium dioxide (Thorotrast; thorium, atomic number 90) provides a unique example of pharmaceutical-induced hepatotoxicity. It was used as an angiographic contrast agent until 1947, when it was found to cause hepatic malignancies. The radioactive isotope of thorium has a half-life of 400 years. It accumulates within the reticuloendothelial system and remains there for the life of the patient. It had a characteristic radiographic appearance, with multiple punctate opacities in the liver, spleen, and lymph nodes (Fig. 5–25). Patients who received thorium before its removal from the market may still present with hepatic malignancies.^18,204

Contrast Esophagram and Upper Gastrointestinal Series.

Ingestion of a caustic may cause severe damage to the mucosal lining of the esophagus. This can be demonstrated by a contrast esophagram. However, in the acute setting, upper endoscopy should be performed rather than an esophagram because it provides more information about the extent of injury and ­prognosis.¹¹¹ In addition, administration of barium will coat the mucosa, making endoscopy difficult. For later evaluation, a contrast esophagram identifies mucosal defects, scarring, and stricture formation (Figs. 5–26 and 106–4).¹²⁹

The choice of radiographic contrast agent (barium or water-soluble material) depends on the clinical situation. If the esophagus is severely strictured and there is a risk of aspiration, barium should be used because water-soluble contrast material is damaging to the pulmonary parenchyma. If, on the other hand, esophageal or gastric perforation is suspected, water-soluble contrast is safer because extravasated barium is highly irritating to mediastinal and peritoneal tissues, but extravasated water-soluble contrast is gradually absorbed into the circulation.

Ingested foreign bodies may cause esophageal and gastric outlet obstruction. Esophageal obstruction caused by a drug packet can be demonstrated by a contrast esophagram. Concretions of ingested material in the stomach may cause gastric outlet obstruction. This has been reported with potassium chloride tablets and enteric-coated aspirin.^11,185

Abdominal Computed Tomography.

CT provides great anatomic definition of intraabdominal organs and plays an important role in the diagnosis of a wide variety of abdominal disorders. In most cases, both oral and IV contrast are administered. Oral contrast delineates the intestinal lumen. IV contrast is needed to reliably detect lesions in hepatic and splenic parenchyma, the kidneys, and the bowel wall.

Certain abdominal complications of poisonings are amenable to CT diagnosis. Intestinal ischemia causes bowel wall thickening; intramural hemorrhage; and at a later stage, intramural gas and hepatic portal venous gas (Fig. 5–24).¹⁴ Hepatic portal venous gas can also be seen after ingestion of 3% hydrogen peroxide. Splenic infarction and splenic and psoas abscesses are complications of IV drug use that may be diagnosed on CT.¹⁵ Radiopaque foreign substances such as intravenously injected elemental mercury may be detected and accurately localized by CT.¹²⁶ Radiolucent foreign bodies, such as a body packer’s packets, may be detected by using enteric contrast.^83,85

Vascular Lesions.

Angiography may detect such complications of injection drug use as venous thrombosis and arterial laceration causing pseudoaneurysm formation (Figs. 5–27 and 5–28). IV injection of amphetamine, cocaine, or ergotamine causes necrotizing angiitis that is associated with microaneurysms, segmental stenosis, and arterial thrombosis. These lesions are seen in the kidneys, small bowel, liver, pancreas, and cerebral circulation (Fig. 5–29).^34,161 Complications include aneurysm rupture and visceral infarction. Renal lesions cause severe hypertension and acute ­kidney injury.¹⁷⁵

Neurologic Problems

Diagnostic imaging studies have revolutionized the management of CNS disorders.^57,71 Both acute brain lesions and chronic degenerative changes can be detected (Table 5–5).¹¹⁸ Some xenobiotics have a direct toxic effect on the CNS; others indirectly cause neurologic injury by causing hypoxia, hypotension, hypertension, cerebral vasoconstriction, head trauma, or infection.

Imaging Modalities.

CT can directly visualize brain tissue and many intracranial lesions.⁷⁰ CT is the imaging study of choice in the emergency setting because it readily detects acute intracranial hemorrhage as well as parenchymal lesions that are causing mass effect. CT is fast, is widely available on an emergency basis, and can accommodate critical support and monitoring devices. Infusion of IV contrast further delineates intracerebral mass lesions such as tumors and abscesses.

MRI has largely supplanted CT in nonemergency neurodiagnosis. It offers better anatomic discrimination of brain tissues and areas of cerebral edema and demyelination. However, MRI is no better than CT in detecting acute blood collections or mass lesions. In the emergency setting, the disadvantages of MRI outweigh its strengths. MRI is usually not readily available on an emergency basis, image acquisition time is long, and critical care supportive and monitoring devices are often incompatible with MR scanning machines.¹²¹

Nuclear scintigraphy that uses CT technology (SPECT and PET) is being used as a tool to elucidate functional characteristics of the CNS. Examples include both immediate and long-term effects of various xenobiotics on regional brain metabolism, blood flow, and neurotransmitter function.^115,154,207

Emergency Head Computed Tomography Scanning.

An emergency noncontrast head CT scan is obtained to detect acute intracranial hemorrhage and focal brain lesions causing cerebral edema and mass effect. Patients with these lesions present with focal neurologic deficits, seizures, headache, or altered mental status. Toxicologic causes of intraparenchymal and subarachnoid hemorrhage include cocaine and other sympathomimetics (Fig. 5–30).^113,117 Cocaine-induced vasospasm may cause ischemic infarction, although this is not well seen by CT until 6 to 24 or more hours after onset of the neurologic deficit (Fig. 5–31). Drug-induced CNS depression, most commonly ethanol intoxication, predisposes the patient to head trauma, which may result in a subdural hematoma or cerebral contusion (Fig. 5–32). Toxicologic causes of intracerebral mass lesions include septic emboli complicating injection drug use and HIV-associated CNS toxoplasmosis and lymphoma (Fig. 5–33).^19,74,79,149 On a contrast CT, such tumors and focal infections exhibit a pattern of “ring enhancement.”

Xenobiotic-Mediated Neurodegenerative Disorders.

A number of xenobiotics directly damage brain tissue, producing morphologic changes that may be detectable using CT and MRI. Such changes include generalized atrophy, focal areas of neuronal loss, demyelinization, and cerebral edema. Imaging abnormalities may help establish a diagnosis or predict prognosis in a patient with neurologic dysfunction after a xenobiotic exposure. In some cases, the imaging abnormality will suggest a toxicologic diagnosis in a patient with a neurologic disorder in whom a xenobiotic exposure was not suspected clinically.^{4,13,57,100,104,155,165,214}

Atrophy.

Ethanol is the most widely used neurotoxin. With long-term ethanol use, there is a widespread loss of neurons and resultant atrophy. In some individuals with alcoholism, the loss of brain tissue is especially prominent in the cerebellum. However, the amount of cerebral or cerebellar atrophy does not always correlate with the extent of cognitive impairment or gait disturbance.^{42,67,84,86,106,209,211} Chronic solvent exposure, such as to toluene (occupational and illicit use), also causes diffuse cerebral atrophy.^93,171

Focal Degenerative Lesions.

Carbon monoxide poisoning produces focal degenerative lesions in the brain. In about half of patients with severe neurologic dysfunction after carbon monoxide poisoning, CT scans show bilateral symmetric lucencies in the basal ganglia, particularly the globus pallidus (Figs. 5–34 and 125–1).^{27,94,100,141,155,158,159,177,178,182,200,206} The basal ganglia are especially sensitive to hypoxic damage because of their limited blood supply and high metabolic requirements. Subcortical white matter lesions also occur after carbon monoxide poisoning. Although less frequent than lesions of the basal ganglia, white matter lesions are more clearly associated with a poor neurologic outcome. MRI is more sensitive than CT at detecting these white matter abnormalities.^{27,57,104,159,200}

Basal ganglion lucencies, white matter lesions, and atrophy are caused by other xenobiotics such as methanol,^{12,41,69,82,142,173} ethylene glycol, cyanide,^58,139 hydrogen sulfide, inorganic and organic mercury,¹³¹ manganese,^13,190 heroin,^104,108 barbiturates, chemotherapeutic agents, solvents such as toluene,^{57,93,171,50,83,156} and podophyllin.^28,144 Nontoxicologic disorders may cause similar imaging abnormalities, including hypoxia, hypoglycemia, and infectious encephalitis.^82,88

Nuclear Scintigraphy.

Whereas both CT and MRI display cerebral anatomy, nuclear medicine studies provide functional information about the brain. Nuclear scintigraphy uses radioactive isotopes that are bound to carrier molecules (ligands). The choice of ligand depends on the biologic function being studied. Brain cells take up the radiolabeled ligand in proportion to their physiologic activity or the regional blood flow. The radioactive emission from the isotope is detected by a scintigraphic camera, which produces an image showing the quantity and distribution of tracer. Better anatomic detail is provided by using CT techniques to generate cross-sectional images. There are two such technologies: SPECT and PET. These imaging modalities are used in the research and clinical settings to study the neurologic effects of particular xenobiotics and the mechanisms of xenobiotic-induced neurologic dysfunction.

SPECT uses conventional isotopes such as technetium-99m and iodine-123.¹¹⁵ These isotopes are bound to ligands that are taken up in the brain in proportion to regional blood flow, reflecting the local metabolic rate.

PET uses radioactive isotopes of biologic elements such as carbon-11, oxygen-15, nitrogen-13, and fluoride-18 (a substitute for hydrogen).¹⁵⁴ These radioisotopes have very short half-lives so that PET scanning requires an onsite cyclotron to produce the isotope. The isotopes are incorporated into molecules such as glucose, oxygen, water, various neurotransmitters, and drugs. Labeled glucose is taken up in proportion to the local metabolic rate for glucose. Uptake of labeled oxygen demonstrates the local metabolic rate for oxygen. Labeled neurotransmitters generate images reflecting their concentration and distribution within the brain.

Both PET and SPECT have been used to study the effects of various xenobiotics on cerebral function. For example, although both CT and MRI can detect cerebellar atrophy in individuals with chronic alcoholism, there is a poor correlation between the magnitude of cerebellar atrophy and the clinical signs of cerebellar dysfunction. PET scans may demonstrate diminished cerebellar metabolic rate for glucose, which correlates more accurately with the patient’s clinical status.^72,209

In patients with severe neurologic dysfunction after carbon monoxide poisoning, SPECT regional blood flow measurements show diffuse hypometabolism in the frontal cortex.³⁰ In one patient, severe perfusion abnormalities improved slightly over several months in proportion to the patient’s gradual clinical improvement.⁹⁸ In another patient treated with hyperbaric oxygen, a SPECT scan revealed increased blood flow in the frontal lobes, although the blood flow still remained significantly less than normal.¹²⁴

In patients who chronically use cocaine, SPECT blood flow scintigraphy demonstrates focal cortical perfusion defects. The extent of these perfusion defects correlates with the frequency of drug use. Focal perfusion defects probably represent local vasculitis or small areas of infarction.^92,202 PET scanning has been used to demonstrate the effects of cocaine on cerebral blood flow and regional glucose metabolism. PET neurotransmitter studies show promise in elucidating potential mechanisms of action of cocaine. Using radiolabeled dopamine analogs, downregulation of dopamine (D₂) receptors has been noted after a cocaine binge. This finding may be responsible for cocaine craving that occurs during cocaine withdrawal. Using¹¹ C-labeled cocaine, uptake of cocaine can be demonstrated in the basal ganglia, a region rich in dopamine receptors.²⁰⁷

Much has been learned about these imaging modalities, and initial applications can be applied to patient care. These imaging modalities are capable of demonstrating abnormalities in many patients with xenobiotic exposures, although other patients with significant cerebral dysfunction have normal study findings.

This chapter has highlighted a variety of situations in which diagnostic imaging studies are useful in toxicologic emergencies.

• Imaging can be an important tool in establishing a diagnosis, assisting in the treatment of patients, and detecting complications of a toxicologic emergency.

• The imaging modalities include plain radiography, CT, enteric and intravascular contrast studies, nuclear scintigraphy, and ultrasonography.

• However, effective use of a diagnostic test requires a precise understanding of the clinical situations in which each test can be useful, knowledge of the capabilities and limitations of the tests, and how the results should be applied to the care of an individual patient.

References