Diagnostic imaging plays 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 8–1).²¹⁹

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 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 is often seen on an abdominal radiograph as described in detail in this chapter. Injected radiopaque xenobiotics are also visualized by radiography. If the toxic material itself is available for examination, it can be radiographed outside of the body to detect its radiopacity or any radiopaque contents (Fig. 102–2).⁹²

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.⁴⁰ Solid pills within the fluid-filled stomach infrequently 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.⁸ 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. In a well-controlled trial comparing participants who ingested 50 enteric-coated placebo tablets with control participants, ultrasonography of the stomach had a sensitivity of only 62.5% at the time of ingestion and 20.8% after 1 hour and a specificity of 58.3% and 79%, respectively.²³⁴ Ultrasonography, therefore, has limited clinical practicality and is therefore not routinely recommended.

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.⁷ 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. 8–1).^1,248,266 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.⁶ 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. 8–2).^214,225

Several investigators evaluated the radiopacity of various medications.^{61,70,97,103,114,173,211,228,238} These investigators used an in vitro water-bath model to simulate the radiopacity of abdominal soft tissues.²¹¹ 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.²¹¹ 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.^173,211 For example, whereas trifluoperazine (containing fluorine; atomic number 9) is radiopaque in vitro, chlorpromazine (containing chlorine; atomic number 17) is not.²¹¹ 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 once opened no longer contain active medication. Some sustained-release cardiac medications such as verapamil and nifedipine have inconsistent radiopacity.^140,227,240 Finally, this was a very old study, and many pills currently on the market have never been tested.

When a xenobiotic that is known to be radiopaque is involved in an exposure, radiography plays an important role in patient care.⁶ 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,^123,232 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. 8–3).^{60,74,118,123,172,178,181} Nonetheless, caution must be exercised in using radiography to exclude an iron ingestion. Some iron preparations are not radiographically detectable. Liquid, chewable, or encapsulated (Chap. 45) (“Spansule”) iron preparations rapidly fragment and disperse after ingestion. Even when intact, these preparations are less radiopaque than ferrous sulfate tablets.⁶¹

Metals

Metals, such as arsenic, cesium, lead, manganese, mercury, potassium, and thallium, are often detected radiographically. Examples of metal exposure include leaded ceramic glaze (Fig. 8–4),¹⁹⁹ paint chips containing lead (Fig. 93–7),^131,158 mercuric oxide and elemental mercury (Fig. 95–1),¹⁴³ thallium salts (atomic number 81),^53,159 and zinc (atomic number 30).²⁸ Arsenic (Fig. 8–5) with a lower atomic number (atomic number 33) is also radiopaque.^93,136,246

Mercury

Unintentional ingestion of elemental mercury used to occur when a glass thermometer or a long intestinal tube with a mercury-containing balloon broke. Liquid elemental mercury is 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. 8–6).^{32,47,148,169}

Lead

Ingested lead is detected only by abdominal radiography, such as in a child with lead poisoning who has ingested paint chips (Fig. 93–7). 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 significant absorption often occurs. Over many years, mechanical and chemical action within the joint causes the bullet to fragment and gradually dissolve.^{52,54,62,231,236} Radiography confirms the source of lead poisoning by revealing metallic material in the joint or CSF (Fig. 8–7).

Xenobiotics in Containers

In some circumstances, ingested xenobiotics are seen even though they are of similar radiopacity to surrounding soft tissues. If a xenobiotic is ingested in a container, the container itself will be visible (Special Considerations: SC5).

Body Packers

“Body packers” are individuals who smuggle large quantities of illicit drugs across international borders in securely sealed packets.^{4,18,20,31,43,65,69,111,129,146,157,184,220,223,243} The uniformly shaped, oblong packets are 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. 8–8). In some cases, a “rosette” representing the knot at the end of the packet is seen. Intraabdominal calcifications (pancreatic calcifications and bladder stones) have occasionally been misinterpreted as drug-containing packets.^244,261

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.²⁰⁴ Ultrasonography is used to rapidly detect packets, although it also should not be relied on to exclude such a life-threatening ingestion.^39,94,161 Computed tomography without oral contrast is more sensitive than radiography and ultrasonography (Figs. SC5-1 and SC5-2).^{15,16,27,33,69,147,185,218,220} After intestinal decontamination, an upper GI series with oral contrast or CT without enteric contrast usually reveals any remaining packets (Fig. SC5–1).^{96,107,152,174}

Body Stuffers

A “body stuffer” is an individual who, in an attempt to avoid imminent arrest, hurriedly ingests contraband in insecure packaging.²⁰¹ The risk of leakage from such haphazardly constructed containers is high. Unfortunately, radiographic studies cannot reliably confirm or exclude such ingestions.²²⁶

Occasionally, a radiograph will demonstrate the ingested container (Fig. 8–9). If the drug is in a glass or in a hard-plastic crack vial, the container is frequently seen.¹⁰⁶ 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.^{44,57,99,101,125,186}

Halogenated Hydrocarbons

Some halogenated hydrocarbons are visualized radiographically.^38,45 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 is 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.²⁵⁹

Moth Repellants

Some types of moth repellants (mothballs) can be visualized by radiography. Whereas relatively common and nontoxic paradichlorobenzene moth repellants (containing chlorine; atomic number 17) are moderately radiopaque, more toxic naphthalene moth repellants are faintly radiopaque.²³³ If the patient is known to have ingested a moth repellant but the nature of the moth repellant is unknown, the difference in radiopacity helps determine the type. Radiographs of the moth repellant outside of the patient can distinguish these two types (Fig. 102–2).

Radiolucent Xenobiotics

A radiolucent xenobiotic is often 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. 8–10).¹⁷⁶

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.^21,42,63,200 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.²⁵¹ 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 participants and is therefore controversial. Various strategies are 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 is recommended to lower the incidence of ulceration. 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. 8–11).⁴²

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 are 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. Radiography will demonstrate xenobiotic 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).⁹⁵

Skeletal Changes Caused by Xenobiotics

A number of xenobiotics affect bone mineralization. Toxicologic effects on bone result in either increased or decreased density (Table 8–2). Some xenobiotics produce characteristic radiographic images, although exact diagnoses usually depend on correlation with the clinical scenario.^11,171 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 suggests the diagnosis of chronic lead poisoning in children 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. 8–12).^{25,189,191,209} 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 mcg/dL, lead lines usually occur in children between the ages of 2 and 9 years.²⁵ In most children, it takes several weeks for lead lines to appear, although in very young infants (2–4 months old), lead lines develop within days of exposure.²⁶⁵ After exposure ceases, lead lines diminish and eventually disappear in some children.

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.^25,56 Other xenobiotics that cause metaphyseal bands are yellow phosphorus (Chap. 112), bismuth (Chap. 87), and vitamin D (Chap. 44).

Fluorosis

Fluoride poisoning causes a diffuse increase in bone mineralization. Endemic fluorosis occurs where drinking water contains very high concentrations 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. 8–13). Fluorosis primarily affects the axial skeleton, especially the vertebral column and pelvis. Thickening of the vertebral column causes compression of the spinal cord and nerve roots. Without a history of fluoride exposure, the clinical and radiographic findings are mistaken for osteoblastic skeletal metastases. The diagnosis of fluorosis is confirmed by histologic examination of the bone and measurement of fluoride concentrations in the bone and urine (Figs. 81–1 and 81–2).^26,120,253

Bisphosphonates

Bisphosphonates such as alendronate 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. 8–14).^{89,137,215-217,260}

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.¹⁴⁹ 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. 8–15A).

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.¹⁹²

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. 8–15B and C).^90,95 Back pain or neck pain in injection drug users warrants careful consideration. Spinal epidural abscesses causing spinal cord compression accompany vertebral osteomyelitis. Radiographic findings are negative early in the disease course before skeletal changes are visible, and the diagnosis is confirmed by MRI or CT (Fig. 8–15D).

Soft Tissue Changes

Certain abnormalities in soft tissues, that occur predominantly as a consequence of infectious complications of injection drug use, are amenable to radiographic diagnosis.^{90,95,116,239} 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 is recognized in a necrotizing soft tissue infection such as necrotizing fasciitis. Computed tomography is more sensitive at detecting soft tissue gas than is conventional radiography. Computed tomography and ultrasonography 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 will be detected on chest radiographs.^{10,30,58,76,105,144,165,195,203,230,262,263} The lungs are most often affected, resulting in dyspnea or cough, but the pleura, hila, heart, and great vessels are also involved. Patients with chest pain need to be evaluated for pneumothorax, pneumomediastinum, or aortic dissection. Patients with fever, with or without respiratory symptoms, can have focal infiltrates, pleural effusions, or hilar lymphadenopathy.

Chest radiographic findings 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 can initially be misdiagnosed as having pneumonia or another disorder that is more common than xenobiotic-mediated lung disease. 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 accumulates 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 8–3). Most xenobiotics are widely distributed throughout the lungs and produce diffuse rather than focal radiographic abnormalities.