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1292 SECTION 15: Toxicology There is uncertainty regarding the duration of deferoxamine therapy.3,16,23 Clinical recovery of the patient is the most important factor guiding the decision to terminate deferoxamine therapy because measured iron levels are artificially depressed by the presence of deferoxamine and urine color change can be unreliable. Continue deferoxamine therapy in patients who continue to exhibit severe iron toxicity after 24 hours of treatment, using a decreased rate to avoid the associated risks mentioned earlier.  OTHER THERAPIES Oral iron chelators— deferiprone and deferasirox —reduce iron absorption when administered simultaneously or within 1 hour of iron ingestion. 27 However, there is no evidence of benefit in human overdoses, and oral chelation therapy would theoretically be of use only when taken promptly after the iron ingestion; thus, their use is limited by the time to presentation for treatment and the significant vomiting expected with clinical iron toxicity. Oral iron chelating agents should not replace IV deferoxamine when chelation is indicated in clinical iron toxicity. Although hemodialysis and hemofiltration do not remove iron, such treatment may be necessary to remove the deferoxamine–iron complex in patients with renal failure who are unable to excrete the complex in their urine. 16,28,29 Severe iron poisoning can be treated with exchange transfusion in addition to deferoxamine therapy.30 In patients with rapidly rising liver transaminases, coagulopathy, and acute kidney injury, there should be timely assessment for liver trans plantation. Progression to fulminant hepatic failure may be precipitous, and with delay, there is increased risk of clinical deterioration precluding liver transplant. Asymptomatic History of ingestion <20 mg/kg >60 mg/kg 20–60 mg/kg or unknown Obtain an abdominal radiograph, and define the need for lavage and WBI Asymptomatic at 6–8 h postingestion <500 mcg/dL or unavailable, AND asymptomatic with normal acid-base status Discharge Obtain serum [Fe] 4 h postingestion >500 mcg/dL, or metabolic acidosis, or symptoms develop or persist Stop deferoxamine Clinically stable? Yes Yes Send serum [Fe] Obtain baseline urine; start deferoxamine therapy Urine color alteration Continue deferoxamine for a maximum of 24 h Systemic toxicity (acidosis, altered mental status, or hemodynamic instability) Obtain abdominal radiograph and acid-base status and define the need for lavage and WBI Only GI symptoms present Iron ingested Obtain abdominal radiograph and acid-base status and define the need for lavage and WBI FIGURE 198-2. Algorithm for clinical management of iron salt ingestion. Fe = iron; mcg = microgram. [Reproduced with permission from Nelson LS, Howland MA, Lewin NA, et al: Goldfrank’s Toxicologic Emergencies, 11th ed. New York, NY: McGraw-Hill Education; 2019. Figure 45-3, Pg 673.] DISPOSITION AND FOLLOW-UP Patients who have not ingested a potentially toxic amount of iron, who remain asymptomatic (other than transient vomiting from the gastric irritant effects of iron), and who have normal findings on physical and laboratory evaluation for a period of 4 to 6 hours can be safely discharged or transferred for appropriate mental health evaluation. Patients who receive deferoxamine therapy should be admitted. The regional poison control center or a medical toxicologist should be contacted for assistance with management.

physical and laboratory evaluation for a period of 4 to 6 hours can be safely discharged or transferred for appropriate mental health evaluation. Patients who receive deferoxamine therapy should be admitted. The regional poison control center or a medical toxicologist should be contacted for assistance with management. REFERENCES The complete reference list is available online at www.TintinalliEM.com. Hydrocarbons and Volatile Substances C. William Heise Frank LoVecchio INTRODUCTION Hydrocarbons are a diverse group of organic compounds consisting primarily of carbon and hydrogen atoms. The two basic forms of hydrocarbons are aliphatic (straight- or branched-chain carbon arrangement) CHAPTER Tintinalli_Sec15_p1187-1332.indd 1292 8/2/19 8:40 PM

ubstances C. William Heise Frank LoVecchio INTRODUCTION Hydrocarbons are a diverse group of organic compounds consisting primarily of carbon and hydrogen atoms. The two basic forms of hydrocarbons are aliphatic (straight- or branched-chain carbon arrangement) CHAPTER Tintinalli_Sec15_p1187-1332.indd 1292 8/2/19 8:40 PM CHAPTER 199: Hydrocarbons and Volatile Substances 1293 different methods: (1) in “huffing, ” the individual soaks a rag with the inhalant and then places it over the mouth and nose; (2) in “bagging, ” the individual puts the hydrocarbon in a bag (usually a plastic bag) and repeatedly inhales deeply from the bag; and (3) in “sniffing, ” the hydrocarbon is directly inhaled via the nostrils. 10 In addition to causing deaths, abuse of volatile agents is associated with crimes such as homicide, sexual assault, and child abuse. 11 The most commonly abused volatile hydro carbons are paints, solvents, and gasoline. PATHOPHYSIOLOGY The toxic potential of hydrocarbons depends on their physical charac teristics (viscosity, surface tension, and volatility), chemical character istics (aliphatic, aromatic, or halogenated), presence of toxic additives (pesticides or heavy metals), routes of exposure, concentration, and dose. The physical characteristics contribute the most to aspiration risk. Viscosity refers to the general “thickness” of a liquid; fluids with a lower viscosity flow more easily than ones with high viscosity. Viscosity is measured in Saybolt universal seconds (SUS); fluids such as gasoline, kerosene, mineral seal oil, and turpentine have low viscosity (<60 SUS), whereas diesel fuel, grease, mineral oil, paraffin wax, and petroleum jelly have high viscosity (>100 SUS). 12 Surface tension refers to the property where liquid molecules tend to cohere to each other. Liquids with high surface tension in contact with a solid surface tend to ball up, creating the smallest surface area rather than spreading out. Volatility refers to the ability of the liquid or solid to vaporize and is inversely related to the boiling point; highly volatile liquids have a low boiling point. Ingestion of liquids with low viscosity and surface tension and high volatility increases the risk for aspiration because these substances flow eas ily, spreading out widely on the oral mucosa, and vaporize at body temperature. Inhalation of aromatic hydrocarbons or halogenated hydrocarbons can result in systemic absorption and the potential for significant toxicity. CLINICAL FEATURES Ingestion or aspiration of hydrocarbons mainly impairs the pulmonary system, but depending on the specific compound, the central nervous, peripheral nervous, GI, cardiovascular, renal, hepatic, dermal, and/or hematologic systems may be affected (Table 199-3). 13,14  PULMONARY TOXICITY Hydrocarbon aspiration causes chemical pneumonitis by direct toxicity to the pulmonary parenchyma and alteration of surfactant function.

fic compound, the central nervous, peripheral nervous, GI, cardiovascular, renal, hepatic, dermal, and/or hematologic systems may be affected (Table 199-3). 13,14  PULMONARY TOXICITY Hydrocarbon aspiration causes chemical pneumonitis by direct toxicity to the pulmonary parenchyma and alteration of surfactant function. TABLE 199-1 Common Products That Contain Hydrocarbons Hydrocarbon and State at Room Temperature Commercial Use Aliphatic–linear structure, toxicity varies depending on volatility Gasoline (petrol)–liquid Motor fuel Kerosene (paraffin)–liquid Stove and lamp fuel Mineral seal oil–liquid Furniture polish Petroleum ether–liquid Industrial solvent Diesel fuel–liquid Motor fuel n-Hexane–liquid Plastic cement, rubber cement Methane, butane, propane, and ethane–gas Fuel Mineral spirits (white spirits)–liquid Solvent, paint thinner Turpentine–liquid Solvent, paint thinner Mineral oil (liquid paraffin)–liquid Lubricant, laxative Paraffin wax–solid Industrial uses, candles Petroleum jelly (petrolatum or soft paraffin)–solid Skin lotion Aromatic–ring structure, high toxicity Benzene–liquid Chemical intermediate, gasoline (small amount, 0.8% on average) Toluene–liquid Airplane glue, plastic cement, acrylic paint Xylene–liquid Solvent, cleaning agent, degreaser Halogenated–high toxicity Carbon tetrachloride–liquid Solvent, refrigerant, aerosol propellant Chloroform–liquid Solvent, chemical intermediate Methylene chloride–liquid Paint stripper, varnish remover, aerosol paint, degreaser Trichloroethylene–liquid Spot remover, degreaser, typewriter correction fluid Trichloroethane–liquid Spot remover, degreaser, typewriter correction fluid Tetrachloroethylene (perchloroethylene)–liquid Dry cleaning agent, degreaser TABLE 199-2 Commonly Abused Volatile Substances Product Volatile Agent Acrylic spray paint Toluene Adhesives, glue Toluene, trichloroethylene Aerosol propellants Propellants and butane Cigarette lighter refills Butane Degreasing agents Trichloroethylene Dry cleaning agents Tetrachloroethylene Fire extinguishers Bromochlorodifluoromethane Inhalational anesthetics Nitrous oxide, halothane Lighter fluid Naphtha Motor fuel Gasoline (petrol) Nitrites (“poppers”) Isobutyl nitrite, amyl nitrite Paint stripper Methylene chloride Plastic modeling cement Methyl ethyl ketone, toluene Spot removers Trichloroethylene, trichloroethane Typewriter correction fluid Trichloroethane, trichloroethylene or aromatic (carbon arranged in a ring). Hydrocarbons are in many household and occupational products ( Table 199-1). While all hydrocarbons can be toxic, aromatic and halogenated hydrocarbons are associated with the most severe systemic toxicity. Volatile agents are associated with the highest aspiration risk. Identification of the specific hydrocarbon or class can help anticipate specific potential toxicity and guide management. Chain length and branching determine the phase of the hydrocar bon at room temperature. Short-chain aliphatic compounds (up to 4 carbons), such as methane, ethane, propane, and butane, are gases; intermediate-chain aliphatic compounds (5 to 19 carbons), such as solvents, lamp oil, lighter fluid, and gasoline, are liquid; and long-chain aliphatic compounds (>19 carbons), such as waxes, are solids. Liquid hydrocarbons account for most exposures seen in the ED. Most hydrocarbon exposures occur as liquid ingestions or inhala tions and usually have a benign clinical course. 1,2 Serious toxicity and deaths associated with hydrocarbon exposure are usually due to inges tions rather than inhalation. Symptoms and signs of pulmonary injury develop in up to 50% of children who ingest hydrocarbons, 3,4 and hydrocarbon aspiration can produce acute respiratory distress syndrome.

gn clinical course. 1,2 Serious toxicity and deaths associated with hydrocarbon exposure are usually due to inges tions rather than inhalation. Symptoms and signs of pulmonary injury develop in up to 50% of children who ingest hydrocarbons, 3,4 and hydrocarbon aspiration can produce acute respiratory distress syndrome. 5 Suicidal injection of gasoline or kerosene with severe multiorgan toxicity has been reported. 6,7 Volatile substances, usually hydrocarbon solvents contained in household or commercial products, can be inhaled for their euphoric effects (Table 199-2). 8 Abusers are typically teenagers and younger adults, especially those in lower socioeconomic groups.9 Inhalation occurs by three Tintinalli_Sec15_p1187-1332.indd 1293 8/2/19 8:40 PM

ces, usually hydrocarbon solvents contained in household or commercial products, can be inhaled for their euphoric effects (Table 199-2). 8 Abusers are typically teenagers and younger adults, especially those in lower socioeconomic groups.9 Inhalation occurs by three Tintinalli_Sec15_p1187-1332.indd 1293 8/2/19 8:40 PM 1294 SECTION 15: Toxicology FIGURE 199-1. Two chest radiographs of a child who aspirated lamp oil and developed aspiration pneumonitis. A. Day 1: intubated, left lower lobe infiltrates. B. Day 3: intubated, worsening perihilar and bibasilar patchy infiltrates and new right small pleural effusion. TABLE 199-3 Clinical Manifestations of Hydrocarbon Exposure System Clinical Manifestations Pulmonary Tachypnea, grunting respirations, wheezing, retractions Cardiac Ventricular dysrhythmias (may occur after exposure to halogenated hydrocarbons and aromatic hydrocarbons) Central nervous Slurred speech, ataxia, lethargy, coma Peripheral nervous Numbness and paresthesias in the extremities GI and hepatic Nausea, vomiting, abdominal pain, hepatotoxicity, loss of appetite (mostly with halogenated hydrocarbons) Renal and metabolic Muscle weakness or paralysis secondary to hypokalemia in patients who abuse toluene Hematologic Lethargy (anemia), shortness of breath (anemia), neurologic depression/syncope (carbon monoxide from methylene chloride), cyanosis (methemoglobinemia from aminecontaining hydrocarbons) Dermal Local erythema, papules, vesicles, generalized scarlatiniform eruption, exfoliative dermatitis, “huffer’s rash,” cellulitis Destruction of alveolar and capillary membranes results in increased vascular permeability and edema. The clinical manifestations of pulmonary aspiration are usually apparent soon after exposure from irritation of the oral mucosa and tracheobronchial tree. Symptoms include coughing, choking, gasping, dyspnea, and burning of the mouth. Patients with these symptoms should be assumed to have aspirated. Signs include tachypnea, grunting respirations, wheezing, or retrac tions depending on the severity of aspiration. An odor of the hydro carbon may be noted on the patient’s breath. Hyperthermia of ≥39°C (≥102.2°F) is likely and may occur initially or 6 to 8 hours after expo sure. The fever is usually an inflammatory response due to pneumonitis. Necrotizing pneumonitis and hemorrhagic pulmonary edema may develop within minutes to hours in patients with severe aspiration. In most fatalities, these complications occur rapidly. With less severe damage, symptoms usually subside within 2 to 5 days, except in the case of pneumatoceles and lipoid pneumonias, the symptoms of which may persist for weeks to months. In most patients with clinically significant aspiration, chest radiogra phy results are eventually abnormal, but the time course of radiographic changes varies and correlation with physical examination findings may be poor. Changes may be seen as early as 30 minutes after aspiration, but the initial radiograph in a symptomatic patient may be deceptively clear. Conversely, an asymptomatic patient can still have abnormal chest radiographic findings. Radiographic changes usually appear by 2 to 6 hours; if they are going to occur, they are almost always present by 24 hours ( Figure 199-1). The most common radiologic finding is bilateral infiltrates at the bases. Multilobar involvement is more com mon than single-lobe involvement, and right-sided involvement is more common than left-sided involvement. 15-17 Hydrocarbon-induced aspiration pneumonitis can lead to lung necrosis and the creation of a pneumatocele.  CARDIAC TOXICITY Life-threatening dysrhythmias, such as ventricular tachycardia and ventricular fibrillation, may occur with systemic absorption.

sided involvement is more common than left-sided involvement. 15-17 Hydrocarbon-induced aspiration pneumonitis can lead to lung necrosis and the creation of a pneumatocele.  CARDIAC TOXICITY Life-threatening dysrhythmias, such as ventricular tachycardia and ventricular fibrillation, may occur with systemic absorption. Dysrhythmias occur most commonly after exposure to halogenated hydrocarbons and aromatic hydrocarbons. Exposure to short-chain aliphatic hydrocarbons occasionally causes dysrhythmias (mainly ventricular fibrillation). 10 The most worrisome acute complication found in solvent abusers is “sudden sniffing death syndrome,” which occurs within minutes of exposure. The mechanism of toxicity is believed to be catecholamine sensitization of the heart by hydrocarbons (especially halogenated hydrocarbons), resulting in ventricular dysrhythmias. 8,10,19 Other mechanisms for sudden death include simple asphyxia, respiratory depression, and vagal inhibition. Ventricular akinesia and polymorphic ventricular dysrhyth mias have also been described after overdose of chloral hydrate (a halo genated aliphatic hydrocarbon).  CNS TOXICITY CNS effects, primarily depression of consciousness, result from a com bination of: (1) direct toxic response to the systemic absorption of the hydrocarbon, (2) indirect result of severe hypoxia secondary to aspira tion, (3) simple asphyxiation due to the displacement of oxygen by the volatile hydrocarbon, or (4) volatile substance abuse with a plastic bag that prevents adequate oxygenation. Systemic effects occur through GI absorption, the inhalation of highly volatile petroleum distillates, or direct dermal penetration. Signs of neurologic toxicity include slurred speech, ataxia, lethargy, and coma. 13 Although hydrocarbons are central neurologic depressants, they often have an initial excitatory effect manifested as hallucinations, tremor, agitation, and convulsions. Individuals who abuse volatile Tintinalli_Sec15_p1187-1332.indd 1294 8/2/19 8:40 PM

gic toxicity include slurred speech, ataxia, lethargy, and coma. 13 Although hydrocarbons are central neurologic depressants, they often have an initial excitatory effect manifested as hallucinations, tremor, agitation, and convulsions. Individuals who abuse volatile Tintinalli_Sec15_p1187-1332.indd 1294 8/2/19 8:40 PM CHAPTER 199: Hydrocarbons and Volatile Substances 1295 solvents or workers who experience long-term hydrocarbon exposure may present to the ED complaining of recurrent headaches, ataxia, emotional lability, cognitive impairment, or psychomotor impairment.  PERIPHERAL NERVOUS SYSTEM TOXICITY Exposure to n-hexane, methyl n-butyl ketone, and other six-carbon aliphatic hydrocarbons is associated with the development of a char acteristic peripheral polyneuropathy caused by demyelinization and retrograde axonal degeneration. 20 Onset of symptoms may be delayed for weeks, and toxicity is attributed to a metabolite, 2,5-hexanedione, produced by the cytochrome P450–mediated biotransformation of the parent compounds. This neurotoxic metabolite is thought to inhibit glutaraldehyde-3-phosphate dehydrogenase, which supplies energy for axonal transport. Clinically, the patient may complain of chronic numbness and paresthesias in the extremities. The key component in making the diagnosis is a history of exposure to solvents, usually through occupations and hobbies. The compound n-hexane is found in gasoline, quick-drying glues, rubber cement, and various solvents used in the printing, shoemaking, textile, and furniture industries.  GI AND HEPATIC TOXICITIES Most hydrocarbons are GI irritants. Vomiting, which occurs in many patients with aliphatic hydrocarbon ingestions, increases the risk of pulmonary aspiration. Gastric perforation has been reported after acci dental ingestion of chlorofluorocarbons. Hepatic damage resulting from ingestion of halogenated hydrocar bons is well described. 23,24 Chlorinated hydrocarbons, such as carbon tetrachloride (CCl 4), methylene chloride, trichloroethylene, and tetrachloroethylene, are especially hepatotoxic. For example, CCl 4 causes centrilobular liver necrosis similar to acetaminophen toxicity. Free radical metabolites of these agents that cause lipid peroxidation are responsible for hepatocellular destruction. The time course of hepatic dysfunction with acute exposures appears to be similar to that of acet aminophen hepatotoxicity—within 24 to 48 hours after ingestion. Clinically, patients may come to the ED complaining of nausea, vomiting, abdominal pain, or loss of appetite. Depending on the severity, the physical examination may reveal a patient with jaundice, lethargy, and/ or abdominal tenderness, especially in the right upper quadrant. Results of serum transaminase tests and other hepatic synthetic function tests may be abnormal within 24 hours after ingestion.  RENAL AND METABOLIC TOXICITIES Solvent abuse and occupational exposure to hydrocarbons may result in renal dysfunction. Chlorinated hydrocarbons, such as chloroform, CCl 4, and trichloroethylene, are also nephrotoxic. Toluene, an aro matic hydrocarbon that is commonly abused, may cause renal tubular acidosis in patients who inhale toluene-containing substances. 8,25 The mechanism of toluene-induced renal tubular acidosis is not clear. The typical metabolic profile of renal tubular acidosis is a normal anion gap hyperchloremic acidosis with hypokalemia and a urine pH of >5.5. The metabolites of toluene (hippuric acid and benzoic acid) can be the cause of an elevated anion gap metabolic acidosis. Clinically, habitual toluene abusers may complain of muscle weak ness caused by hypokalemia. 27 The serum potassium level may be so low (<2 mEq/L) that severe weakness develops, occasionally resulting in muscle paralysis.

ene (hippuric acid and benzoic acid) can be the cause of an elevated anion gap metabolic acidosis. Clinically, habitual toluene abusers may complain of muscle weak ness caused by hypokalemia. 27 The serum potassium level may be so low (<2 mEq/L) that severe weakness develops, occasionally resulting in muscle paralysis. Significant rhabdomyolysis may also result. 28 Toluene abuse should be considered in individuals (especially young patients) who come to the ED with symptoms similar to hypokalemic periodic paralysis. 25,27  HEMATOLOGIC TOXICITY Hydrocarbon-induced hemolysis rarely occurs after the acute inges tion of gasoline, kerosene, and tetrachloroethylene, and after inhalation of mineral spirits. Exposure to benzene (an aromatic hydrocarbon) is associated with an increased incidence of hematologic disorders, including aplastic anemia, acute myelogenous leukemia, and multiple myeloma. 29 Naphthalene exposure is associated with hemolytic anemia. Delayed methemoglobinemia is associated with occupational exposure to hydrocarbons containing amine functional groups such as aniline (see Chapter 207, “Dyshemoglobinemias”). 30 Delayed carboxyhemoglobinemia is associated with methylene chloride exposure due to its metabolism to carbon monoxide, which takes a few hours. 31 This is unlike ordinary carbon monoxide exposure from exogenous sources in which the maximum carboxyhemoglobin level occurs at the time of the exposure. Clinically, patients may come to the ED with malaise, headache, dyspnea, or cyanosis depending on the exposure and the severity of the toxicity.  DERMAL TOXICITY Dermal toxicity from exposure to hydrocarbons is most often associated with the short-chain aliphatic, aromatic, and halogenated hydrocarbons. These agents act as primary irritants and as sensitizers. Occasionally, highly permeable hydrocarbons can penetrate the skin, resulting in systemic toxicity. Skin findings can range from local erythema, papules, and vesicles to a generalized scarlatiniform eruption and an exfoliative dermatitis (Table 199-3). A “huffer’s rash” may be noted over the face of patients who habitually abuse the volatile hydrocarbons. 8 Frostbite of the face may develop during the inhalational abuse of fluorinated agents. A defatting dermatitis, similar to chronic eczematoid dermatitis, may occur. Cellulitis and sterile abscesses have been associated with the injection of hydrocarbons, and even a small amount of injected hydrocarbon can cause significant injury. 32 Hydrocarbon-induced soft tissue necrosis has recently been seen in patients using “krokodil, ” which is desomorphine synthesized from codeine using hydrocarbon solvents. 33 Dermal expo sure to heated high-viscosity, long-chain aliphatics, such as tar, asphalt, or bitumen, presents a particularly challenging problem because of their association with thermal burns, hyperthermia, and difficulty with decontamination. 34 Tar burns are discussed in the Chapter 218, “Chemical Burns. ” DIAGNOSIS Diagnosis of hydrocarbon toxicity incorporates the findings of the history, physical examination, bedside cardiac and pulmonary monitoring, laboratory tests, and chest radiography. Determine the specific hydrocarbon-containing product, because identification can help anticipate specific potential toxicity and guide management. Pulse oximetry is useful to evaluate oxygenation status, and blood gas analysis can be used to assess ventilation and acid-base status. Cardiac rhythm monitoring and an ECG are indicated in symptomatic patients and patients who ingest halogenated hydrocarbons. A chest radiograph is indicated in a symptomatic patient after hydrocarbon aspiration. Chest radiography is not required in asymptomatic patients.

used to assess ventilation and acid-base status. Cardiac rhythm monitoring and an ECG are indicated in symptomatic patients and patients who ingest halogenated hydrocarbons. A chest radiograph is indicated in a symptomatic patient after hydrocarbon aspiration. Chest radiography is not required in asymptomatic patients. There are no specific quantitative hydrocarbon tests for standard use when evaluating suspected hydrocarbon intoxication. A basic metabolic panel is indicated in patients with a history of toluene abuse or in whom electrolyte abnormalities and renal insufficiency are suspected. Obtain hepatic function studies, serum ammonia, and prothrombin time in patients who ingest or inhale halogenated hydrocarbons. A CBC is indicated if anemia, bleeding disorder, hemolysis, or leukemia is considered. Measure carboxyhemoglobin level in patients with exposure to methy lene chloride; repeat measurements may be necessary. Determination of methemoglobin level is indicated in patients with exposure to hydrocarbons containing amine functional groups. Abdominal radiographs may show evidence of ingestion of chlorinated hydrocarbons such as CCl or chloroform because of the radiopaque nature of polyhalogenated substances. TREATMENT Securing the airway and maintaining ventilation are the critical maneuvers in patients who present with respiratory depression and/or sig nificant neurologic depression ( Table 199-4). Swelling of the lips and tongue due to irritant effect or freeze injuries can complicate airway Tintinalli_Sec15_p1187-1332.indd 1295 8/2/19 8:40 PM