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1248 SECTION 15: Toxicology  SALVIA Salvia divinorum (“salvia,” “Sally,” “magic mint”) is a perennial herb in the mint family.91 Salvia is sold as seeds, plant cuttings, whole plants, fresh and dried leaves, and liquid extracts purported to contain the active ingredient salvinorin A. Although salvia and salvinorin A are not currently regulated under the U.S. Controlled Substances Act, a number of states have placed controls on the plant and extract. When chewed, the leaf mass and juice are retained within the mouth, and absorption of the active ingredient is rapid, causing clinical effects within 5 to 10 minutes. Dried leaves, as well as extract-enhanced leaves, can be smoked. Smoking pure salvinorin A at a dose of 200 to 500 micrograms results in effects that begin within 30 seconds and last up to 30 minutes. Desired effects include perceptions of bright lights, vivid colors and shapes, body movements, and object distortions. 79,92,93 Adverse effects may include dysphoria, incoordination, dizziness, and slurred speech. 94 Treatment is supportive.  BUFOTOXINS Bufotoxins (bufotenine and 5-methoxy-dimethyltryptamine) are hal lucinogenic tryptamines found in the venom, skin, and eggs of many toads (e.g., Bufo alvarius, Bufo marinus). 95 Toad venom has also been used as an aphrodisiac (“love stone” or “rock hard”) and in some traditional Chinese medicines (chan su and kyushin). Venom can be obtained by “milking” the toad’s parotid glands and drying the liquid venom to form an extract. 5-Methoxy-dimethyltryptamine is a powerful psyche delic, whereas bufotenine has weaker effects. In addition to psychoac tive substances, the venom contains cardioactive steroids (bufagins or bufadienolides), catecholamines (epinephrine and norepinephrine), and noncardiac sterols (e.g., cholesterol). Bufagins are cardioactive steroids that can cause cardiac toxicity similar to digoxin. 96 Toxicity from toad venom varies considerably depending on the toad species and its geo graphic location. Symptoms of toad venom poisoning occur almost immediately. Effects may be restricted to local GI irritation, with copious salivation, nausea, vomiting, and abdominal discomfort persisting for hours. Sys temic toxicity may develop due to sympathomimetic effects. Cardiac toxicity is similar to acute digoxin poisoning, with hyperkalemia, bra dycardia, atrioventricular conduction block, ventricular tachycardia, ventricular fibrillation, and cardiac arrest. 97,98 Serum digoxin immunoassay often yields a positive result. Bradyar rhythmias are initially treated with atropine and may require pace maker placement. Antiarrhythmic drugs should be used for ventricular arrhythmias. Digoxin-specific Fab antibody treatment has been effective in animal models and human cases. 99,100  MORNING GLORY SEEDS AND IPOMOEA SPECIES Morning glory seeds (Ipomoea violacea , Ipomoea tricolor, and others) contain lysergic acid amide (ergine), a compound closely related to LSD. The seeds can be ingested for their hallucinogenic effects; typically, several hundred seeds are ingested as one “dose. ” Physical and psychological manifestations closely resemble the effects of LSD, and patients are managed similarly.  MYRISTICIN Nutmeg is the dried seed from the tropical Myristica fragrans tree. Accidental or intentional ingestion of large amounts of nutmeg can cause delirium with hallucinations.

ested as one “dose. ” Physical and psychological manifestations closely resemble the effects of LSD, and patients are managed similarly.  MYRISTICIN Nutmeg is the dried seed from the tropical Myristica fragrans tree. Accidental or intentional ingestion of large amounts of nutmeg can cause delirium with hallucinations. 101 Misuse of nutmeg is more com monly encountered among college students, adolescents, and prisoners, often when ethanol or other recreational drugs are not available. 102 The hallucinogenic properties of nutmeg may be due to the component myristicin, but the mechanism is not well understood. Ingestion of one to three nutmeg seeds (or 5 to 15 grams of the ground spice) produces psychological effects that begin 3 to 6 hours later and last for 6 to 24 hours. Symptoms include tachycardia, flushing, dry mouth, nausea, and abdominal pain. Signs and symptoms may resemble anticholinergic poisoning, but pupils are usually small or midsized. Management is supportive care.  DATURA SPECIES Jimson weed ( Datura stramonium ) and angel’s trumpet ( Datura candida) are plants that originated in the United States and Mexico but have spread worldwide throughout areas with warm and temperate climates. All Datura species contain the anticholinergic alkaloids atropine, scopolamine, and hyoscyamine. Seeds or other parts of the plant can be ingested or smoked and produce delirium, hallucinations, and sei zures along with other classic anticholinergic effects, such as mydriasis, tachycardia, dry mouth and skin, blurred vision, urinary retention, and hyperthermia (see Chapter 202, “ Anticholinergics”). 103,104 Gastric emptying is often delayed, and the small, plentiful seeds can become trapped among the GI folds after ingestion; thus, GI decontamination can be considered in select cases. Whole-bowel irrigation is recommended for patients who have ingested a large number of seeds. Medications with anticholinergic properties, such as phenothiazines, should be avoided. Physostigmine, a reversible acetylcholinesterase antagonist, is a poten tial treatment for severe anticholinergic poisoning. 104 For further discussion, see Chapter 202, “ Anticholinergics. ”  KETAMINE AND DEXTROMETHORPHAN Ketamine and dextromethorphan are chemically related to PCP . Ketamine and PCP are described as dissociative drugs because they distort per ceptions of sight and sound and produce feelings of detachment from the environment and self. 56,105 Ketamine, known by the street names “vitamin K” and “special K, ” can be abused by SC or IM injection, nasal insufflation of the dried powder, or smoking of the dried power admixed with marijuana or tobacco. 106 Ketamine abusers may come to the ED because of anxiety, palpitations, and chest pain. 107 Ketamine is thought to be psychologically addictive. Chronic abuse can cause GI toxicity including epigastric pain, hepatic dysfunction, and impaired gallbladder activity; urinary tract effects include ketamine cystitis. Dextromethorphan, available in over-the-counter cough suppres sants, has become popular among adolescents. 109,110 A large quantity must be ingested for the user to experience hallucinogenic effects. Abuse among youths has prompted many states to enact restrictions regarding the buyer age and the maximum amount that can be purchased; most retailers and pharmacists keep dextromethorphan-containing cough medicines behind the counter. Since dextromethorphan-containing symptomatic relief products often contain other ingredients (e.g., antihistamines, acetaminophen), investigate for toxic amounts of a co-ingestant in any patient who has ingested hallucinogenic doses of dextromethorphan. Medical care is primarily supportive with treatment as outlined earlier in the general approach section.

omatic relief products often contain other ingredients (e.g., antihistamines, acetaminophen), investigate for toxic amounts of a co-ingestant in any patient who has ingested hallucinogenic doses of dextromethorphan. Medical care is primarily supportive with treatment as outlined earlier in the general approach section. REFERENCES The complete reference list is available online at www.TintinalliEM.com. Salicylates Rachel Levitan Frank LoVecchio INTRODUCTION The widespread availability of aspirin or acetylsalicylic acid in prescription and over-the-counter preparations can lead to both accidental and intentional toxicity. Morbidity and mortality increase significantly when the condition is not rapidly identified, if there is a delay to starting treatment, or if poisoned patients are not treated aggressively. CHAPTER Tintinalli_Sec15_p1187-1332.indd 1248 8/2/19 8:39 PM

er preparations can lead to both accidental and intentional toxicity. Morbidity and mortality increase significantly when the condition is not rapidly identified, if there is a delay to starting treatment, or if poisoned patients are not treated aggressively. CHAPTER Tintinalli_Sec15_p1187-1332.indd 1248 8/2/19 8:39 PM CHAPTER 189: Salicylates 1249 late and ominous finding. Decreased ventilation can also be related to co-ingestions or iatrogenic medication. Salicylate affects both central and peripheral glucose homeostasis. Although salicylate causes mobilization of glycogen stores, resulting in hyperglycemia, it is also a potent inhibitor of gluconeogenesis. There fore, normoglycemia is the most common finding in toxicity; hyperglycemia can be seen occasionally, and hypoglycemia is a rare finding. 11,12 Salicylate can cause corrosive injury of the GI tract with abdominal pain, nausea, and vomiting with occasional hematemesis. These GI manifestations can lead to volume loss, metabolic alkalosis, and hypo kalemia. Gastric perforation has been reported after a significant acute aspirin ingestion. 13 Salicylate-induced acute lung injury (noncardiogenic pulmonary edema) has been observed in humans. Although antiplatelet activity is a well-known, often desired effect of aspirin (but not other salicylate products), hemorrhage is a rare complication of acute (even massive) overdose. Large doses of all salicylates may cause significant hypoprothrombinemia resulting from inhibition of vitamin K–dependent functions. Salicylate ototoxicity is common, and tinnitus often occurs with levels in the therapeutic range (20 milligrams/dL [1.5 mmol/L]). Although classically described as tinnitus or “ringing in the ears, ” in practice, most patients will describe decreased sounds or that their hearing is “muffled. ” The exact mechanism causing this is unknown, and hearing effects are not permanent. Cardiac arrhythmias are a rare complication of salicylate poisoning. CLINICAL FEATURES Clinical manifestations of salicylate toxicity depend on the dose ingested, duration of exposure, and age and comorbidities of the patient. 8,16 In children and the elderly, end-organ toxicity can be seen with smaller doses and lower serum levels following an acute overdose. Chronic toxicity can produce insidious and severe neurologic changes that do not correlate well with dose or serum salicylate level. Patients with even a mild toxicity can become critically and severely ill if acidemia or dehydration develops.  INTOXICATION IN CHILDREN In general, when the duration of salicylate intoxication is between 12 and 24 hours, metabolic acidosis and acidemia (pH <7.35) occur pri marily in children <4 years old, and nearly all children <1 year old have acidosis. Y oung children can have a respiratory alkalosis, but this is often transient and missed because of their smaller ventilatory reserves. 17 In older children (>4 years old), the acid-base disturbance is usually a mixed disturbance with respiratory alkalosis, increased anion gap metabolic acidosis, and alkalemia (pH >7.45). Chronic or “therapeutic” (repeated dose) pediatric salicylate poison ings are more serious and are associated with a higher mortality than acute salicylism. 8,16,18 Often, several days may elapse between the initial salicylate administration and the onset of symptoms. There is frequently a concurrent illness that prompted salicylate administration, and chil dren usually appear more ill than those with acute intoxication.

iated with a higher mortality than acute salicylism. 8,16,18 Often, several days may elapse between the initial salicylate administration and the onset of symptoms. There is frequently a concurrent illness that prompted salicylate administration, and chil dren usually appear more ill than those with acute intoxication. The TABLE 189-1 Pathophysiology of Salicylate Toxicity •  Local  gastric irritation •  Reversible  ototoxicity •  Stimulation  of the chemoreceptor zone •  Stimulation  of medullary respiratory center •  Stimulation  of skeletal muscle metabolism •  Uncoupling  of oxidative phosphorylation •  Enhancement  of lipolysis •  Inhibition  of Krebs cycle •  Increased  vascular permeability •  Mobilization  of glycogen stores •  Inhibition  of gluconeogenesis In additional to aspirin oral preparations, numerous forms of salicy late are available as karyolitic agents, liniments, flavoring agents, and combination products. These products may contain salicylate, methyl salicylate, or acetylsalicylic acid, but regardless of the product, all formulations are rapidly converted to salicylate once ingested. 1 Five milliliters of oil of wintergreen contain 7 grams of aspirin and can be deadly to a toddler. Liniments and products used in hot vaporizers have high concentrations of methyl salicylate, and an ingestion of 5 to 10 mL can be lethal for an infant or a toddler. 2 Even though salicylate is poorly absorbed after ingestion of bismuth subsalicylate (Pepto-Bismol ® ), significant exposures can occur from massive ingestions, such as in patients with human immunodeficiency virus/acquired immunodeficiency syndrome taking this medication for chronic diarrhea. PATHOPHYSIOLOGY After ingestion of therapeutic doses in standard tablet formulation, absorption is variable and dependent on dosage form, presence of food, and gastric pH, with peak salicylate levels usually occurring in 1 to 2 hours. In overdose, peak serum salicylate concentrations may not be reached for hours. Enteric-coated aspirin exhibits erratic absorption in therapeutic doses, and peak levels may also be delayed for hours after an overdose. 4 Salicylate itself impairs gastric emptying, which can result in delayed absorption.5 There is potential for formation of gastric bezoars that can serve as a source of ongoing absorption. 6 Ingestion of methyl salicylate or other liquid formulations may have much more rapid absorption and achieve peak levels more rapidly. Limited information on powder forms of salicylates (common in the southeastern United States and the Middle East) suggests these forms follow the liquid salicylate pattern of low risk of prolonged absorption. After absorption, aspirin is hydrolyzed to salicylic acid (salicylate) and is distributed throughout body tissues, with 50% to 80% being bound to serum proteins. As salicylate concentrations increase and saturate protein-binding sites, free (unbound) concentrations of salicylate increase. In solution, salicylate exists in equilibrium between the ionized and nonionized state; only the unbound, nonionized salicylate can readily cross cell membranes. At physiologic pH (7.40), almost all salicylate is ionized, but acidemia will increase the nonionized fraction, enabling more salicylate to cross cell membranes and, importantly, substantially increase brain salicylate concentration. 8 Patients with identical total salicylate serum concentrations may vary greatly in their degree of toxicity depending on their tissue burden, plasma protein concentrations, pH, and other factors. Salicylate undergoes hepatic metabolism in a process that rapidly becomes saturated even within the drug’s therapeutic range.

Patients with identical total salicylate serum concentrations may vary greatly in their degree of toxicity depending on their tissue burden, plasma protein concentrations, pH, and other factors. Salicylate undergoes hepatic metabolism in a process that rapidly becomes saturated even within the drug’s therapeutic range. Thus, salicylate metabolism in the overdose situation follows zero-order kinetics (i.e., a set amount of salicylate is eliminated per unit of time). Increased fraction of unbound salicylate also enhances renal clearance, making the kidney the major route of elimination during toxicity. Serum alkalinization can be used to keep salicylate in the plasma compartment and out of tissues, and urinary alkalinization can be used to enhance renal elimination. If the urine pH is above 7.5, more salicylate molecules in the urine will be ionized compared with the renal tubular cell pH of 7.4, and reabsorption across the urinary tubule will be reduced. This pH difference will also enhance secretion of nonionized salicylate down the concentration gradient. Salicylate toxicity affects many physiologic systems (Table 189-1). Salicylate directly stimulates the medullary respiratory center to produce tachypnea, hyperpnea, and respiratory alkalosis. 10 As toxicity worsens, inhibition of metabolism produces an acidosis that overwhelms the alkalosis. Classically, the acid-base disturbance associated with salicylate poisoning is mixed: early respiratory alkalosis, followed by an elevated anion gap metabolic acidosis, and possibly late respira tory acidosis. This respiratory alkalosis and metabolic acidosis are commonly mistaken for sepsis syndromes. Co-ingestion or administration of CNS depressants may blunt this initial respiratory stimulation. Salicylate stimulates skeletal muscle metabolism, which causes an increase in oxygen consumption and carbon dioxide production. Neurologic toxicity may impair ventilation so that it is unable to keep pace with increased carbon dioxide production, leading to respiratory acidosis—usually a Tintinalli_Sec15_p1187-1332.indd 1249 8/2/19 8:39 PM

skeletal muscle metabolism, which causes an increase in oxygen consumption and carbon dioxide production. Neurologic toxicity may impair ventilation so that it is unable to keep pace with increased carbon dioxide production, leading to respiratory acidosis—usually a Tintinalli_Sec15_p1187-1332.indd 1249 8/2/19 8:39 PM 1250 SECTION 15: Toxicology presenting features are usually fever, hyperventilation, and altered mental status with volume depletion, acidosis, and severe hypokalemia. 16 Y oung children are prone to hyperpyrexia, which indicates a worse prognosis.18 Renal failure may be a significant complication, but pulmonary edema is unusual in the pediatric population. 16,18 Chronic salicylism is often mistaken for an infectious process, and the resultant delay in diagnosis may account for the more severe clinical picture. The diagnosis can be particularly difficult due to the proscription against aspirin use for fever in children (Reye’s syndrome risk). Aspirin may have been given by family members rather than by a physician. The diagnosis may be delayed if a history of salicylate ingestion is not available. The differential diagnosis includes diabetic ketoacidosis, sepsis, iron intoxication, and toxic alcohol poisoning.  INTOXICATION IN ADULTS Acute salicylate intoxication in adults is often due to intentional inges tion. The typical clinical presentation includes nausea, vomiting, tinnitus, hearing loss, sweating, and hyperventilation. Patients with tinnitus or hearing loss following an acute ingestion usually have an elevated serum salicylate value. Most adult patients with acute salicylate overdose have a mixed acidbase disturbance of alkalemia with respiratory alkalosis and metabolic acidosis. As toxicity progresses, acidosis worsens. CNS dysfunction manifests as agitation, lethargy, confusion, seizure, or coma. CNS dys function leading to cerebral edema is an ominous development and a sign of severe toxicity, requiring rapid and aggressive treatment. 8,20 Despite treatment and decreasing serum salicylate levels, patients may worsen and die from progressive neurologic impairment, possibly because of increasing CNS salicylate levels. Salicylate-induced vomiting can produce a metabolic alkalosis. Other rare complications of salicylate toxicity include rhabdomyolysis, gastric perforation, and GI hemorrhage. Poor prognostic factors for acute salicylate toxicity include coma, fever, respiratory acidosis, seizure, and cardiac dysrhythmias. In adults with acute salicylate poisoning, independent predictors of severe outcome were older age, tachypnea, and initial lactate concentration. Initial salicylate concentration alone was not predictive. Chronic salicylate intoxication (from repeated excessive dosing) in adults often presents with neurologic abnormalities such as lethargy, altered mental status, irritability, and hallucinations, particularly in the elderly. 21 Toxicity can develop even with small increases in doses due to saturable kinetics. Clinical features of chronic intoxication include hyperventilation, tremor, papilledema, agitation, paranoia, bizarre behavior, memory deficits, confusion, and stupor. Nausea and vomiting are less common than in acute salicylate toxicity, whereas increased liver function tests and increased prothrombin time are more common. Neurologic abnormalities in chronic salicylate poisoning may be non specific and may often mislead physicians. Chronic salicylism should be considered in a patient with unexplained neurologic or behavioral dysfunction, especially in the presence of a mixed acid-base disturbance, tachypnea, dyspnea, or unexplained pulmonary edema.

abnormalities in chronic salicylate poisoning may be non specific and may often mislead physicians. Chronic salicylism should be considered in a patient with unexplained neurologic or behavioral dysfunction, especially in the presence of a mixed acid-base disturbance, tachypnea, dyspnea, or unexplained pulmonary edema. 22 Compared with acute toxicity, adults with chronic salicylate toxicity have a higher tissue burden of salicylate, leading to more significant toxicity at a lower serum concentration. The distinction between acute and chronic salicylate toxicity may not always be clear. A patient may present many hours after an acute severe salicylate overdose, when altered mental status, acidosis, elevated prothrombin time, and a “therapeutic” serum salicylate concentration appear more consistent with a chronically poisoned patient. Signifi cant toxicity may be evident despite declining or “therapeutic” serum salicylate concentrations. In these situations, the patient’s clinical status is most important when assessing the severity of toxicity ( Table 189-2). Chronic salicylism may develop in patients taking carbonic anhydrase inhibitors for treatment of glaucoma. The normal anion gap (hyperchloremic) metabolic acidosis produced by carbonic anhydrase inhibitors increases the volume of distribution for salicylate and facilitates its entry into the CNS, causing toxicity at a “therapeutic” serum salicylate concentration. The differential diagnosis of a triple-mixed acid-base disturbance of increased anion gap acidosis, metabolic alkalosis, and respiratory alka losis seen in salicylate toxicity is limited. Salicylates uncouple oxidative phosphorylation, which results in abnormal cellular energy production, and patients become dependent on anaerobic metabolism, resulting in accumulation of lactate. Thus, a significant salicylate poisoning will lead to an elevated serum lactate concentration, further broadening the differential diagnosis. In clinical practice or at early stages of toxicity, this classic three-part acid-base disturbance may be difficult to appreciate. The differential is broad and includes (but is not limited to) sepsis, diabetic ketoacidosis, renal and hepatic failure, alcoholic ketoacidosis, and poisoning by iron, theophylline, caffeine, methanol, or ethylene glycol. DIAGNOSIS Diagnosis of salicylate toxicity is made by correlating a careful history, physical examination, and thoughtful ancillary testing. Supportive laboratory findings include an anion gap metabolic acidosis and elevated serum salicylate levels. The Done nomogram is misleading and can grossly underestimate toxicity; it should not be used.  TOXICOLOGIC TESTING A pitfall in treating salicylate toxicity is reliance on a single serum level. 23 Significant toxicity has been reported to develop even in cases in which salicylates were undetectable on an initial assay approximately 4 hours after ingestion.24 Salicylate toxicity can evolve rapidly. In patients with moderate or severe poisoning, it is prudent to obtain serial serum salicylate concentrations approximately every 1 to 2 hours, until the concentrations are declining and the patient’s clinical status stabi lizes. 25,26 Enteric-coated or modified-release preparations are formulated to remain intact in the acidic gastric environment, dissolving in the alkaline intestinal fluids. Drug release is therefore primarily a function of gastric emptying, and peak levels may not be reached until up to 60 hours after ingestion in an overdose. Commercially available tests for serum salicylate concentration are very accurate; the only reported significant interference has been with diflunisal (a NSAID), which produces false-positive results for sig nificantly high serum salicylate concentrations.

be reached until up to 60 hours after ingestion in an overdose. Commercially available tests for serum salicylate concentration are very accurate; the only reported significant interference has been with diflunisal (a NSAID), which produces false-positive results for sig nificantly high serum salicylate concentrations. 27 Therapeutic salicylate concentrations are 150 to 300 micrograms/mL (or 15 to 30 milligrams/dL [1086 to 2172 micromole/L]). A pitfall is that units for measuring salicylate are not universal; measurement units can vary by institution, with the potential for patients to be mistakenly diagnosed as “salicylate toxic” if the physician mistakenly assumes the unit of measurement used.  ADDITIONAL ANCILLARY TESTING Essential laboratory tests include electrolytes, glucose, BUN, and creatinine. Blood gases, chest and abdominal radiograph, ECG, CBC, serum calcium level, and urinalysis with urine pH determination should be obtained as clinically indicated. As in any ingestion, consider testing for acetaminophen as well, especially considering the number of combination products available in the market. Some enteric-coated medications are radiopaque and may be visible on an abdominal radiograph. A normal anion gap does not exclude salicylate toxicity in patients with an unknown ingestion. Mixed ingestions that include aspirin and the timing of exposure can alter “classic” metabolic disturbances. A negative TABLE 189-2 Severity Grading of Salicylate Toxicity in Adults Mild Moderate Severe Acute ingestion (dose) <150 milligrams/kg 150–300 milligrams/kg >300 milligrams/kg End-organ toxicity Tinnitus Hearing loss Dizziness Nausea/vomiting Tachypnea Hyperpyrexia Diaphoresis Ataxia Anxiety Abnormal mental status Seizures Acute lung injury Renal failure Cardiac arrhythmias Shock Tintinalli_Sec15_p1187-1332.indd 1250 8/2/19 8:39 PM

<150 milligrams/kg 150–300 milligrams/kg >300 milligrams/kg End-organ toxicity Tinnitus Hearing loss Dizziness Nausea/vomiting Tachypnea Hyperpyrexia Diaphoresis Ataxia Anxiety Abnormal mental status Seizures Acute lung injury Renal failure Cardiac arrhythmias Shock Tintinalli_Sec15_p1187-1332.indd 1250 8/2/19 8:39 PM CHAPTER 189: Salicylates 1251 anion gap metabolic acidosis may be noted in salicylate toxicity due to aberrant reading of salicylate ions as chloride ions by analyzer electrodes.29 TREATMENT  GENERAL MEASURES Treatment priorities are (1) immediate resuscitation with stabilization of airway, breathing, and circulation; (2) correction of volume depletion and metabolic derangements; (3) GI decontamination; and (4) reduc tion in body salicylate burden. 25,26 Salicylate absorption is reduced by the administration of activated charcoal both for regular and modifiedrelease formulations. A single dose of activated charcoal, 1 to 2 grams/ kg, should be administered to appropriate patients who have ingested potentially toxic amounts of salicylate. 25,30,31 There are no convincing data to support the use of repeated or multiple doses of activated char coal in salicylate overdose.32 Patients with severe salicylate intoxication are usually significantly volume depleted, have serious acid-base disturbances, and require aggressive IV volume and electrolyte replacement. Careful assessment of a patient’s volume and electrolyte status is important, particularly in the elderly or in patients with a history of cardiac disease. Volume replace ment is initially undertaken with normal saline or lactated Ringer’s with administration of an initial bolus of 20 mL/kg. The average adult who presents several hours after ingestion is dehydrated by at least 4 to 6 L.  ALKALINIZATION Systemic and urinary alkalinization are beneficial for salicylate toxic ity, although the precise mechanism is debated. 26,33 As initial fluid resuscitation is undertaken, patients should undergo treatment with sodium bicarbonate with a goal of a serum pH of approximately 7.5. Hypokalemia is common, and potassium should be added to the infu sion after adequate urine output has been established. Serum potassium should be maintained in the 4.0 to 4.5 mEq/L range. Urinary salicylate clearance is directly proportional to urine flow rate, but, more importantly, it is logarithmically proportional to urine pH. Urine alkalinization is more effective in enhancing salicylate elimination than forced diuresis. Urinary alkalinization also avoids the potential complication of fluid overload that is risked (particularly in those with marginal cardiac output or limited reserve) from the large IV volume given to increase urine flow. Urinary alkalinization should be considered as firstline treatment for patients with moderately severe salicylate poisoning. 25,34 Hydration and alkalinization should be initiated simultaneously in patients with severe salicylate intoxication. A common approach is to volume restore patients with normal saline or lactated Ringer’s to a target urine output of 1 to 2 mL/kg per hour. Concurrently, in a second IV line, an IV bolus of sodium bicarbonate (1 to 2 mEq/kg) is given followed by a continuous infusion (three ampules of either 44 or 50 mEq per ampule of sodium bicarbonate added to 1 L of 5% dextrose in water). Unless there is a contraindication, potassium should be added to the bicarbonate fluid as well. The infusion is run at two to three times maintenance and adjusted to maintain the urine pH >7.5 (Figure 189-1). In moderate and severe overdoses, the patient’s cardiopulmonary and neurologic status should be assessed frequently. Serum salicylate, urine pH, and electrolyte concentrations should be checked every 1 to 2 hours.

fusion is run at two to three times maintenance and adjusted to maintain the urine pH >7.5 (Figure 189-1). In moderate and severe overdoses, the patient’s cardiopulmonary and neurologic status should be assessed frequently. Serum salicylate, urine pH, and electrolyte concentrations should be checked every 1 to 2 hours. 25,26 Once the serum salicylate concentration peaks and begins to decrease on serial measurement, repeat measurement can be obtained every 4 to 6 hours.  OTHER MEASURES Patients with salicylate-induced acute lung injury (noncardiogenic pul monary edema) should be managed the same as patients with acute lung With signs of significant toxicity, increasing levels, or significant comorbidities • Continue IVF hydration • Continue bicarb drip (3 amps Na-bicarb in 1 L D 5W with potassium) at 2–3 × maintenance • Check ABG, electrolytes, and salicylate level every 1–2 hours • Monitor UOP and urine pH (goal ≥7.5) • Evaluate for need for hemodialysis • Admit to ICU Without signs of toxicity and low level • Continue IVF hydration • Continue bicarb drip (3 amps Na-bicarb in 1 L D 5W with potassium) at 2–3 × maintenance • Check VBG, electrolytes, and salicylate approximately every 2–3 hours • Monitor UOP and urine pH (goal ≥7.5) • Declining levels × 2 without symptoms or acidosis may be medically cleared from the ED History, exam, or symptoms of salicylate toxicity IV access, 20 milligrams/kg bolus isotonic fluid, 1–2 mEq/kg bicarbonate bolus Yes YesYes Send labs including CMP, PT, salicylate level, acetaminophen level, ABG or VBG, and other labs as clinically indicated Detectable salicylate level Consider consulting with a clinical toxicologist or regional poison control center for assistance. Consider alternative diagnosis Discontinue treatment FIGURE 189-1. Management of salicylate poisoning. ABG = arterial blood gas; bicarb = bicarbonate; CMP = comprehensive metabolic panel; D 5W = 5% dextrose in water; ICU = intensive care unit; IVF = intravenous fluids; PT = prothrombin time; UOP = urinary output; VBG = venous blood gas. Tintinalli_Sec15_p1187-1332.indd 1251 8/2/19 8:39 PM