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General Management of Poisoned Patients Shaun Greene INTRODUCTION Poisoning is a worldwide problem that consumes substantial healthcare resources and causes many premature deaths. The burden of serious poisoning is carried by the developing world 1,2; however, poisoningrelated morbidity and mortality are also a significant public health concern in the developed world.3-7 Unintentional poisoning deaths in the United States are increasing, especially as a result of prescription analgesics. This increase has been ascribed to increasing prescription rates and aging of the baby-boom population. 8-10 Prevention is the key to reducing unintentional poisoning deaths. Pharmacists can ensure that medications are labeled cor rectly, anticipate potential drug interactions, and educate patients to use medications safely. Parents have the responsibility to ensure that poisons are placed in childproof, labeled containers stored in adultonly accessible nonfood storage areas to reduce pediatric exposures. Teachers and healthcare providers can provide age-appropriate education to children about the dangers of poisons. After an exposure, poison control centers staffed by highly trained individuals can pro vide customized advice to healthcare providers and the public. Poison control centers also participate in prevention, education, and toxicosurveillance activities. Exposures occur most commonly by ingestion; other routes include inhalation, insufflation, cutaneous and mucous membrane exposure, and injection. 10 Some exposures have minimal risk. The criteria used to determine whether the exposure is nontoxic are as follows: (1) an unintentional exposure to a clearly identified single substance, (2) an estimate of the dose is known, and (3) a recognized information source (e.g., a poison control center) confirms the substance as nontoxic in the reported dose. Asymptomatic patients with nontoxic exposures may be discharged after a short period of observation, providing they have access to further consultation and a safe discharge destination. Serious clinical effects occur in <5% of acutely poisoned patients presenting to developed-world hospitals, and in-hospital mortality rates are <1%. RESUSCITATION Resuscitation is the first priority in any poisoned patient. After resuscitation, a structured risk assessment is used to identify patients who may benefit from an antidote, decontamination, or enhanced elimination techniques. Most patients only require provision of good supportive care during a period of observation in an appropriate environment. Treatment of cardiac arrest in poisoned patients follows Advanced Cardiac Life Support guidelines with the addition of interventions potentially beneficial in toxin-induced cardiac arrest ( Table 176-1). Prolonged resuscitation is generally indicated, as patients are often young with minimal preexisting organ dysfunction. Utilization of extracorporeal cardiac and respiratory assist devices until organ toxicity resolves may be lifesaving. Stabilization of airway, breathing, and circulation represents initial priorities. Compromised airway patency or reduced respiratory drive may lead to inadequate ventilation; provision of a mechanical airway and assisted ventilation is vital in these circumstances. IV crystalloid bolus (10 to 20 mL/kg) is first-line treatment of hypotension. Since most patients without toxin-induced fluid loss are generally not fluid depleted, avoid administration of excess fluid.

to inadequate ventilation; provision of a mechanical airway and assisted ventilation is vital in these circumstances. IV crystalloid bolus (10 to 20 mL/kg) is first-line treatment of hypotension. Since most patients without toxin-induced fluid loss are generally not fluid depleted, avoid administration of excess fluid. Persisting hypotension despite an adequate volume infusion may respond to a specific antidote. Otherwise, cautious administration of an inotropic agent is indicated. Inotrope choice is guided by knowledge of the toxin’s toxicodynamic properties and assessment of circulatory status (e.g., cardiac pump failure vs. vasodilatory shock). Extracorporeal membrane oxygenation should be considered for cases of cardiovascular failure refractory to other treatment modalities.  ANTIDOTES Stabilization of airway, breathing, and circulation allows further assess ment of blood glucose concentration, temperature, and conscious state. Although the proper use of antidotes (Table 176-2) is important, only a few are indicated before cardiopulmonary stabilization (e.g., naloxone for opiate toxicity, cyanide antidotes for cyanide toxicity, and atropine for organophosphate poisoning).  HYPOGLYCEMIA Treat hypoglycemia with IV dextrose (glucose). Patients at risk of Wernicke’s encephalopathy also require thiamine, but do not require that it be administered before the dextrose. 13 Altered mental status when hypoglycemia cannot be excluded is an indication for IV dex trose. Supplemental oxygen, thiamine, glucose, and naloxone are often administered empirically as a cocktail in cases of altered mental status. Although relatively safe and affordable in the developed world, this approach may not be cost effective in developing countries. The decision to administer an antidote should be made after a rapid collat eral history is obtained and targeted examination completed. Altered mental status not responding to an antidote or not consistent with exposure history requires further investigation. Metabolic, infective, and surgical (e.g., intracranial injury) causes of altered mental status should be considered.  CARDIAC ARRHYTHMIAS In general, antidysrhythmic drugs are not first-line treatment for toxin-induced dysrhythmias, as most antidysrhythmic drugs have prodysrhythmic and negative inotropic properties. Most toxin-induced dysrhythmias respond to correction of hypoxia, metabolic/acid-base abnormalities, and administration of an antidote (e.g., digoxin Fab). Sodium bicarbonate is administered for sodium channel–blocker toxicity with cardiovascular complications, such as wide QRS complex tachydysrhythmias. Ventricular tachydysrhythmias may respond to overdrive pacing.  SEIZURES Drug-induced seizures are treated with titrated doses of IV benzodiazepines, with the exception that isoniazid-induced seizures require pyri doxine. Metabolic disorders, such as hypoglycemia and hyponatremia, can also produce seizures and should be rapidly excluded. Propofol and barbiturates are second-line agents for benzodiazepine-resistant seizures (once isoniazid-induced seizures are excluded). 14 A small study provided evidence for the safety of levetiracetam for treatment of toxin-induced CHAPTER SECTION 15Toxicology Tintinalli_Sec15_p1187-1332.indd 1187 8/2/19 8:39 PM

uded. Propofol and barbiturates are second-line agents for benzodiazepine-resistant seizures (once isoniazid-induced seizures are excluded). 14 A small study provided evidence for the safety of levetiracetam for treatment of toxin-induced CHAPTER SECTION 15Toxicology Tintinalli_Sec15_p1187-1332.indd 1187 8/2/19 8:39 PM 1188 SECTION 15: Toxicology seizures; however, larger studies are required to evaluate efficacy. 15 There is no role for phenytoin in the treatment of toxin-induced seizures; it has neither theoretical nor proven efficacy, and it may worsen toxicity.  AGITATION Agitation is treated with titrated doses of benzodiazepines. See Figure 287-1, Acute Agitation. Large doses may be required and are appropriate in monitored settings where advanced airway interventions are available if required. Although antipsychotic agents are often used as second-line agents for toxin-induced agitation, they have theoretical disadvantages, including anticholinergic and extrapyramidal effects. 17,18 First generation antipsychotics, such as haloperidol have been associated with QTinterval prolongation and cardiac dysrhythmias; however, the incidence of adverse effects appears to be very low.  HYPERTHERMIA AND HYPOTHERMIA Patients with core temperatures of >39°C (>102.2°F) require aggres sive active cooling measures to prevent complications such as TABLE 176-1 Potential Interventions in Toxin-Induced Cardiac Arrest11 Toxin or Toxin/Drug Class Intervention Toxins with a specific antidote (examples) Digoxin Organophosphates Envenomation Antidote Digoxin Fab Atropine Antivenom Sodium channel blocker or wide-complex tachycardia Sodium bicarbonate Calcium channel blocker or beta-blocker High-dose insulin infusion Local anesthetic agents Lipophilic cardiotoxins IV lipid emulsion Other Therapies to Consider Cardiac pacing Intra-aortic balloon pump Extracorporeal membrane oxygenation TABLE 176-2 Common Antidotes Used in Resuscitation of the Acutely Poisoned Patient Antidote Initial Pediatric Dose* Initial Adult Dose* Indication Calcium chloride 10% 27.2 milligrams/mL elemental Ca 0.15 mL/kg IV 10 mL IV Calcium channel blockers Calcium gluconate 10% 9 milligrams/mL elemental Ca 0.5–0.45 mL/kg IV 10–30 mL IV Hypermagnesemia Calcium channel blockers Cyanide antidote kit Amyl nitrite Not typically used Crack vial and inhale over 30 seconds, or place in chamber of ventilation bag and use 30 s on/30 s off Cyanide Sodium nitrite (3% solution) Dosed according to hemoglobin level.

ams/mL elemental Ca 0.5–0.45 mL/kg IV 10–30 mL IV Hypermagnesemia Calcium channel blockers Cyanide antidote kit Amyl nitrite Not typically used Crack vial and inhale over 30 seconds, or place in chamber of ventilation bag and use 30 s on/30 s off Cyanide Sodium nitrite (3% solution) Dosed according to hemoglobin level. If unknown, assume hemoglobin level is 12 g/dL (120 g/L) and dose with 0.33 mL/kg IV 10 mL IV Cyanide Hydrogen sulfide (use only sodium nitrite) Sodium thiosulfate (25% solution) 1.65 mL/kg IV 50 mL IV Cyanide Dextrose (glucose) 0.5–1.09 gram/kg IV 1 gram/kg IV Insulin Oral hypoglycemics Digoxin Fab Acute toxicity 5–10 vials IV 10 vials Digoxin and other cardioactive steroids Flumazenil 0.01 milligram/kg IV 0.2 milligram IV Benzodiazepines Glucagon 30 micrograms/kg IV over 1–2 min for CCB toxicity and 30–150 micrograms/kg IV over 1–2 min for BB toxicity 5 milligrams IV Calcium channel blockers Beta-blockers Hydroxocobalamin 70 milligrams/kg (maximum 5 grams) IV over 15 min 5 grams IV over 15 min Cyanide Nitroprusside IV lipid emulsion 20% 1.5 mL/kg IV bolus over 1 min (may be repeated 2 times at 5-min intervals), followed by 0.25 mL/kg per min IV infusion for 20 min 100-mL IV bolus over 1 min (may be repeated 2 times at 5-min intervals), fol lowed by 18 mL/min IV infusion for 20 min Local anesthetic systemic toxicity Rescue therapy for lipophilic cardiotoxins Methylene blue 1 milligram/kg IV Neonates: 0.3–1.0 milligram/kg IV 1 milligram/kg IV Oxidizing toxins (e.g., nitrites, benzocaine, sulfonamides) Naloxone As much as required Start: 0.01 milligram IV As much as required Start: 0.1–0.4 milligram IV Opioids Clonidine Pyridoxine Gram for gram if amount of isoniazid ingested is known, otherwise: Isoniazid 70 milligrams/kg IV (maximum 5 grams) 5 grams IV Sodium bicarbonate 1–2 mEq/kg IV over 1–2 min followed by 0.3 mEq/kg per hour IV infusion Sodium channel blockers Urinary alkalinization Thiamine 5–10 milligrams IV 100 milligrams IV Wernicke’s syndrome Wet beriberi *See specific chapter for details regarding use. Abbreviations: BB = beta-blockers; CCB = calcium channel blocker. Tintinalli_Sec15_p1187-1332.indd 1188 8/2/19 8:39 PM

Eq/kg per hour IV infusion Sodium channel blockers Urinary alkalinization Thiamine 5–10 milligrams IV 100 milligrams IV Wernicke’s syndrome Wet beriberi *See specific chapter for details regarding use. Abbreviations: BB = beta-blockers; CCB = calcium channel blocker. Tintinalli_Sec15_p1187-1332.indd 1188 8/2/19 8:39 PM CHAPTER 176: General Management of Poisoned Patients 1189 rhabdomyolysis, organ failure, and disseminated intravascular coagulation. Sedation, neuromuscular paralysis, and intubation are required if active measures are ineffective. Several toxidromes associated with hyperthermia are treated with specific pharmaceutical agents: sym pathomimetic (benzodiazepines), serotonin (cyproheptadine 19), and neuromuscular malignant syndrome (bromocriptine20). Drug-induced coma with subsequent immobility and environmental exposure or inherent drug toxicity (opioids, phenothiazines, ethanol) may produce hypothermia. A core temperature <32°C (<90°F) is an indication for active rewarming.  NALOXONE Naloxone is a nontoxic, diagnostic, and therapeutic antidote. It is a competitive opioid antagonist administered IV , IM, or intranasally 21 to reverse opioid-induced deleterious hypoventilation. Naloxone can be used as a diagnostic agent when history and/or examination findings (respiratory rate of <12 breaths/min is a predictor of response to nal oxone) suggest possible opioid exposure. Naloxone is titrated to clinical effect using bolus doses, typically 0.1 to 0.4 milligram. Large initial bolus doses may precipitate vomiting and aspiration, acute opioid withdrawal, or an uncooperative, agitated patient. Miosis is an unreliable indicator of naloxone’s adequate clinical effect, as some opioids do not affect pupil size. Doses are titrated to achieve desirable ventilation and conscious state (adequate respiratory rate, normal arterial oxygen saturations on room air, and verbal or motor response to voice). Although naloxone may reverse the effects of opioids for 20 to 60 minutes, the effect of many opioids will outlast this time frame with possible return of respiratory depression. Patients should be observed for 2 to 3 hours after adminis tration of IV naloxone.  IV LIPID EMULSION IV lipid emulsion has been postulated to provide an intravascular “lipid sink, ” sequestrating lipophilic toxins and preventing target receptor interaction. IV lipid emulsion should be used as part of management of cardiac arrest in bupivacaine toxicity. 22 Current evidence does not sup port IV lipid emulsion as first-line treatment of life-threatening toxicity associated with other drugs, including amitriptyline, calcium chan nel antagonists, non–lipid-soluble beta-receptor antagonists, cocaine, diphenhydramine, lamotrigine, bupropion, malathion, and cocaine. IV lipid emulsion therapy may affect common laboratory analyses, which may potentially lead to unintentional treatment errors. 23 IV lipid emulsion therapy may cause fat deposition in extracorporeal membrane oxygenation circuits and increase blood clot formation. 24 Currently, IV lipid emulsion can be considered as a potential rescue therapy in lifethreatening cardiotoxicity caused by lipophilic cardiotoxins that is resistant to conventional therapies. ASSESSMENT Following initial resuscitation and stabilization, a risk assessment is performed to predict course of clinical toxicity, interventions required, and patient disposition. Risk assessment is formulated using history, examination, and ancillary test results. Acute poisoning is a dynamic process; therefore, risk assessment may change with time and requires ongoing review.  HISTORY Patients may not provide a clear history due to psychiatric illness, clini cal effects of exposure, and fear of arrest or repercussions from family or friends.

nation, and ancillary test results. Acute poisoning is a dynamic process; therefore, risk assessment may change with time and requires ongoing review.  HISTORY Patients may not provide a clear history due to psychiatric illness, clini cal effects of exposure, and fear of arrest or repercussions from family or friends. Information including identity of substances, doses, and route of exposure is crucial in formulating a risk assessment. Obtain col lateral information from family, friends, previous medical records, and usual healthcare provider. Prehospital emergency services can provide information regarding empty medication containers or the scene envi ronment (smells, particular materials or substances present). If possible, obtain knowledge of hobbies, occupation, presence of a suicide note, and recent changes in patient behavior.  EXAMINATION A systematic physical examination can yield important clues to the nature and potential severity of an exposure (Table 176-3). Examine the skin folds, body cavities if appropriate, and clothing for retained tablets or substances.  TOXIDROMES Substances belonging to a particular pharmaceutical or chemical class often produce a cluster of symptoms and signs, or “toxidrome” (Table 176-4), enabling the identification of potential toxins when a clear history is unavailable.  DIAGNOSTIC TESTING A serum acetaminophen concentration is a routine screening test in poisoned patients because early acetaminophen poisoning is often asymptomatic and does not have a readily identifiable toxidrome at the time when antidotal treatment is most efficacious. Acetaminophen screening is especially important in patients presenting with altered TABLE 176-3 Examination of the Poisoned Patient Organ System Examination Example of Finding (Possible Significance) General Mental state and dress Signs of injury Odors Nutritional state Vital signs Unkempt (psychiatric illness) Scalp hematoma (intracranial injury) Malnourished (IV drug use, human immunodeficiency virus infection) Smell of bitter almonds (cyanide toxicity) CNS Conscious state Pupil size and reactivity Eye movements Cerebellar function/gait Miosis (opioids, organophosphates, phenothiazines, clonidine intoxication) Nystagmus/ataxia (anticonvulsant and ethanol toxicity) Cardiovascular Heart rate/blood pressure Cardiac auscultation Murmur (endocarditis/IV drug use) Respiratory Oxygen saturation Respiratory rate Chest auscultation Fever/crepitations/hypoxia (aspiration pneumonia) Bronchorrhea/crepitations/hypoxia (organophosphate toxicity) GI Oropharynx Abdomen Bladder Urinary retention (anticholinergic toxicity) Oral cavity burns (corrosive ingestion) Hypersalivation (cholinergic toxidrome) Peripheral nervous Reflexes Tone Fasciculations Tremor Clonus Tremor/fasciculations (lithium toxicity) “Lead pipe” rigidity (neuromuscular malignant syndrome) Clonus/hyperreflexia (serotonin toxicity) Dermal/peripheral Bruising Cyanosis Flushing Dry/moist skin Injection sites Bullae Bruising (coagulopathy, trauma, coma) Flushing/warm, dry skin (anticholinergic toxicity) Warm, moist skin (sympathomimetic toxicity) Bullae (prolonged coma, barbiturates) Tintinalli_Sec15_p1187-1332.indd 1189 8/2/19 8:39 PM

nin toxicity) Dermal/peripheral Bruising Cyanosis Flushing Dry/moist skin Injection sites Bullae Bruising (coagulopathy, trauma, coma) Flushing/warm, dry skin (anticholinergic toxicity) Warm, moist skin (sympathomimetic toxicity) Bullae (prolonged coma, barbiturates) Tintinalli_Sec15_p1187-1332.indd 1189 8/2/19 8:39 PM 1190 SECTION 15: Toxicology Toxicologic screening tests of urine can be done in a central laboratory or performed with point-of-care assays.26 Urine drug screens most often use enzyme-immunoassays to detect typical drugs within each class. Cross-reactivity is common and some drugs within the class may not be detected (Table 176-6). Dilute urine can make it difficult to detect low levels. Because some drugs are present in urine for an extended period of time, the positive test may not be related to the current clinical condition. Urine drug screen results seldom influence patient management in most adult overdoses and poisoning. Toxicologic screening may be appropriate for medicolegal reasons, especially in pediatric cases when inappropriate drug administration or nonaccidental injury is suspected. A positive urine drug screen for an illicit substance is an indication to involve local child protection services. DECONTAMINATION Decontamination is required for toxic exposures affecting large dermal areas. Healthcare providers wearing personal protective equipment (if  indicated) or observing universal precautions (gown, gloves, eye protection) should assist with undressing and washing the patient using copious amounts of water. Contaminated clothing is collected, bagged, and properly disposed. Decontamination ideally occurs in a separate area adjacent to the ED, minimizing cross-contamination. mental status or a self-harm ingestion, for whom an accurate history may not be available. An ECG is a useful test to detect cardiac conduction abnormalities and identify patients at increased risk of toxin-induced adverse cardiovascular events. Measurement of drug or toxin concentrations in body fluids is not required in most poisonings, but in some exposures, measurement of serum drug concentrations does influence management (Table 176-5).

cardiac conduction abnormalities and identify patients at increased risk of toxin-induced adverse cardiovascular events. Measurement of drug or toxin concentrations in body fluids is not required in most poisonings, but in some exposures, measurement of serum drug concentrations does influence management (Table 176-5). TABLE 176-4 Common Toxidromes Toxidrome Examples of Agents Examination Findings (most common in bold) Anticholinergic Atropine, Datura spp., antihistamines, antipsychotics Altered mental status, mydriasis, dry flushed skin, urinary retention, decreased bowel sounds, hyperthermia, dry mucous membranes Seizures, arrhythmias, rhabdomyolysis Cholinergic Organophosphate and carbamate insecticides Chemical warfare agents (sarin, VX) Salivation, lacrimation, diaphoresis, vomiting, urination, defecation, bronchorrhea, muscle fasciculations, weakness Miosis/mydriasis, bradycardia, seizures Ethanolic Ethanol CNS depression, ataxia, dysarthria, odor of ethanol Extrapyramidal Risperidone, haloperidol, phenothiazines Dystonia, torticollis, muscle rigidity Choreoathetosis, hyperreflexia, seizures Hallucinogenic Phencyclidine Psilocybin, mescaline Lysergic acid diethylamide Hallucinations, dysphoria, anxiety Nausea, sympathomimetic signs Hypoglycemic Sulfonylureas, insulin Altered mental status, diaphoresis, tachycardia, hypertension Dysarthria, behavioral change, seizures Neuromuscular malignant Antipsychotics Lead-pipe muscle rigidity, bradyreflexia, hyperpyrexia, altered mental status Autonomic instability, diaphoresis, mutism, incontinence Opioid Codeine, heroin, morphine Miosis, respiratory depression, CNS depression Hypothermia, bradycardia Salicylate Aspirin Oil of wintergreen (methyl salicylate) Altered mental status, respiratory alkalosis, metabolic acidosis, tinnitus, tachypnea, tachycardia, diaphoresis, nausea, vomiting Hyperpyrexia (low grade) Sedative/hypnotic Benzodiazepines Barbiturates CNS depression, ataxia, dysarthria Bradycardia, respiratory depression Serotonin SSRIs MAOIs Tricyclic antidepressants Amphetamines Fentanyl St. John’s wort Altered mental status, hyperreflexia and hypertonia (>lower limbs), clonus, tachycardia, diaphoresis Hypertension, flushing, tremor Sympathomimetic Amphetamines Cocaine Cathinones Agitation, tachycardia, hypertension, hyperpyrexia, diaphoresis Seizures, acute coronary syndrome Abbreviations: MAOI = monoamine oxidase inhibitor; SSRI = selective serotonin reuptake inhibitor. TABLE 176-5 Drug Serum Measurements That May Assist Patient Assessment or Management Acetaminophen Carbamazepine Carbon monoxide Digoxin Ethanol Ethylene glycol Iron Lithium Methanol Methemoglobin Methotrexate Paraquat Phenobarbital Phenytoin Salicylate Theophylline Valproic acid Tintinalli_Sec15_p1187-1332.indd 1190 8/2/19 8:39 PM

rug Serum Measurements That May Assist Patient Assessment or Management Acetaminophen Carbamazepine Carbon monoxide Digoxin Ethanol Ethylene glycol Iron Lithium Methanol Methemoglobin Methotrexate Paraquat Phenobarbital Phenytoin Salicylate Theophylline Valproic acid Tintinalli_Sec15_p1187-1332.indd 1190 8/2/19 8:39 PM CHAPTER 176: General Management of Poisoned Patients 1191  OCULAR DECONTAMINATION Eye exposures may require local anesthetic (e.g., 0.5% tetracaine) instil lation and lid retractors to facilitate copious irrigation with crystalloid solution. Alkalis produce greater injury than acids due to deep tissue penetration via liquefaction so that prolonged irrigation (1 to 2 hours) may be required. Ten minutes after irrigation (allowing equilibration of crystalloid and conjunctival sac pH), conjunctival sac pH is tested. Irrigation continues until pH is between 7.2 and 7.4. Ophthalmologic consultation is indicated for all ocular alkali injuries.  GI DECONTAMINATION Gastric decontamination is not a routine part of poisoned patient management; there is minimal evidence demonstrating positive benefit, and there are associated complications ( Table 176-7). Gastric decontamination may be considered in individual patients after a threequestion risk-benefit analysis: (1) Is this exposure likely to cause sig nificant toxicity? (2) Is GI decontamination likely to change clinical outcome? (3) Is it possible that GI decontamination will cause more harm than good? 27,28 Emesis Traditionally, ipecac syrup was administered to induce vom iting, theoretically emptying the stomach of poisons. No published evidence supports the induction of emesis, and adverse outcomes asso ciated with emesis are documented. 29 There is no role for the induction of emesis in the ED in the poisoned patient. 30 Orogastric Lavage Once a widely practiced intervention, attempted removal of ingested toxin from the stomach by aspiration of fluid placed via an orogastric tube is now rarely indicated. No published evidence demonstrates that orogastric lavage changes outcome in the majority of poisoned patients, and the procedure has numerous complications.

widely practiced intervention, attempted removal of ingested toxin from the stomach by aspiration of fluid placed via an orogastric tube is now rarely indicated. No published evidence demonstrates that orogastric lavage changes outcome in the majority of poisoned patients, and the procedure has numerous complications. TABLE 176-6 Standard Enzyme-Immunoassay Urine Drug Screens Class (drugs typically tested) Drugs not in this class possibly detected (false positives) + Drugs in this class possibly not detected (false negatives) Comments Amphetamine and Methamphetamine Amantadine Bupropion Chlorpromazine Desipramine Dimethylamylamine Ephedrine Fluoxetine Isoxsuprine Labetalol Metformin Phentermine Phenylephrine Phenylpropanolamine Promethazine Pseudoephedrine Ranitidine Selegiline Thioridazine Trazodone Trimethobenzamide Trimipramine Methylenedioxymethylamphetamine [MDMA] Detectable up to 48 h after single use Barbiturates Ibuprofen Naproxen N/A Detectable up to: Short-acting: 24 h Long-acting: 21 d Benzodiazepines (oxazepam, nordiazepam) Oxaprozin Sertraline Alprazolam Clonazepam Flunitrazepam Lorazepam Triazolam Detectable up to: Short-acting: 3 days Long-acting: 30 d Cannabinoids (delta-9tetracannabinol- 9-carboxylic acid) Efavirenz Ibuprofen Naproxen Pantoprazole Promethazine Nabilone Synthetic cannabinoids (e.g., “K2” or “spice”) Detectable up to: Single use: 3 d Moderate use: 5–7 d Daily use: 10–15 d Long-term use: > 30 d Cocaine (benzoylecgonine) * * Detectable 2–4 d after single use Methadone Chlorpromazine Clomipramine Diphenhydramine Doxylamine Ibuprofen Quetiapine Thioridazine Verapamil N/A Detectable up to 3 d Opiates (morphine, 6acetylmorphine) Dextromethorphan Diphenhydramine Fluoroquinolones (ciprofloxacin, levofloxacin, ofloxacin) Poppy seed and oil Rifampin Quinine Buprenorphine Fentanyl Meperidine Methadone Oxycodone Oxymorphone Tramadol Detectable 2–4 d depending on specific drug Phencyclidine Dextroamphetamine Dextromethorphan Diphenhydramine Doxylamine Ibuprofen Ketamine Lamotrigine Meperidine Methylendioxyprovalerone Thioridazine Tramadol Venlafaxine N/A Detectable up to 8 d after single use Tricyclic Antidepressants Carbamazepine Cyclobenzaprine Cyproheptadine Diphenhydramine Hydroxyzine Oxcarbazepine Promethazine Quetiapine Thioridazine Clomipramine Detectable 2–7 days Class (drugs typically tested) Drugs not in this class possibly detected (false positives) + Drugs in this class possibly not detected (false negatives) Comments Abbreviation: N/A = not applicable. *Cocaine immunoassay is highly specific with low cross-reactivity. +Agents with strongest evidence for false-positive results noted in bold. Tintinalli_Sec15_p1187-1332.indd 1191 8/2/19 8:39 PM

d (false positives) + Drugs in this class possibly not detected (false negatives) Comments Abbreviation: N/A = not applicable. *Cocaine immunoassay is highly specific with low cross-reactivity. +Agents with strongest evidence for false-positive results noted in bold. Tintinalli_Sec15_p1187-1332.indd 1191 8/2/19 8:39 PM 1192 SECTION 15: Toxicology TABLE 176-7 Indications, Contraindications, and Complications of GI Decontamination Procedures Orogastric Lavage Indications Rarely indicated Consider for recent (<1 h) ingestion of life-threatening amount of a toxin for which there is no effective treatment once absorbed Contraindications Corrosive/hydrocarbon ingestion Supportive care/antidote likely to lead to recovery Unprotected airway Unstable, requiring further resuscitation (hypotension, seizures) Complications Aspiration pneumonia/hypoxia Water intoxication Hypothermia Laryngospasm Mechanical injury to GI tract Time consuming, resulting in delay instituting other definitive care Activated Charcoal Adults 50 grams orally, children 1 gram/kg orally Indications Ingestion within the previous hour of a toxic substance known to be adsorbed by activated charcoal, where the benefits of administration are judged to outweigh the risks Contraindications Nontoxic ingestion Toxin not adsorbed by activated charcoal Recovery will occur without administration of activated charcoal Unprotected airway Corrosive ingestion Possibility of upper GI perforation Complications Vomiting Aspiration of the activated charcoal Impaired absorption of orally administered antidotes Whole-Bowel Irrigation Polyethylene glycol 2 L/h in adults, children 25 mL/kg per hour (maximum 2 L/h) Indications (potential) Iron ingestion >60 milligrams/kg with opacities on abdominal radiograph Life-threatening ingestion of diltiazem or verapamil Body packers or stuffers Slow-release potassium ingestion Lead ingestion (including paint flakes containing lead) Symptomatic arsenic trioxide ingestion Life-threatening ingestions of lithium Contraindications Unprotected airway GI perforation, obstruction or ileus, hemorrhage Intractable vomiting Cardiovascular instability Complications Nausea, vomiting Pulmonary aspiration Time consuming; possible delay instituting other definitive care TABLE 176-8 Principles to Minimize Complications From Orogastric Lavage •   Ensure a protected airway if consciousness level is reduced. •   Use a 36F- to 40F-gauge orogastric tube (22F to 24F in children). •   Position the patient on the left side with the head down 20 degrees. •   Pass lubricated tube down the esophagus a distance equal to that between chin and xiphoid process. •   Confirm tube position by insufflation of air. •   Gently lavage with 200 mL (10 mL/kg in children) of warm tap water, allowing drainage after each aliquot. •   Continue until returned fluid is clear. •   Consider administration of activated charcoal via orogastric tube before removal. Gastric lavage may be considered in cases of ingestion of a lifethreatening amount of poison within the previous hour where institu tion of supportive care and antidotal therapy would not ensure full recovery. Adherence to best-practice principles can minimize complications from orogastric lavage (Table 176-8). Single-Dose Activated Charcoal Super-heating carbonaceous material produces activated charcoal, a highly porous substance, which is suspended in solution and given PO as a slurry. Toxins within the GI lumen are adsorbed onto the activated charcoal and carried through the GI tract, limiting absorption. 32 Activated charcoal does not effectively adsorb metals, corrosives, and alcohols. The decision to give activated charcoal requires individual patient risk assessment and is not consid ered routine management.

the GI lumen are adsorbed onto the activated charcoal and carried through the GI tract, limiting absorption. 32 Activated charcoal does not effectively adsorb metals, corrosives, and alcohols. The decision to give activated charcoal requires individual patient risk assessment and is not consid ered routine management. Activated charcoal may be effective when given >60 minutes after ingestion of substances known to slow GI motility (e.g., anticholinergics)33 or after massive ingestion of a substance associated with bezoar formation (e.g., salicylates). Activated charcoal mixed with ice cream improves palatability for children. Activated charcoal can be administered to intubated patients using an orogastric or nasogastric tube. Whole-Bowel Irrigation Polyethylene glycol is an osmotically bal anced electrolyte solution. Administration in large quantities mechani cally forces substances through the GI tract, limiting toxin absorption.34 Polyethylene glycol can be administered orally to cooperative, awake patients, but consider formal airway control if consciousness is likely to deteriorate. Minimize risk of pulmonary aspiration during wholebowel irrigation by patient positioning (head up 30 degrees), ensuring bowel sounds are present during fluid administration, 1:1 nursing with suctioning of the oral cavity during infusion, and utilization of cuffed endotracheal tubes. Evidence supporting whole-bowel irrigation is limited to volunteer studies and case reports 34 from which potential indications have been developed (Table 176-7). Nonsurgical treatment of asymptomatic body drug packers using whole-bowel irrigation is increasingly common, although no randomized clinical trials exist. 34 An antiemetic such as the prokinetic agent metoclopramide may be required to control poly ethylene glycol–induced gastric distention and vomiting. The end point of whole-bowel irrigation treatment is clear rectal effluent and imaging demonstrating absence of foreign bodies. ENHANCED ELIMINATION  MULTIDOSE ACTIVATED CHARCOAL Multidose activated charcoal increases elimination of toxins with enteroenteric, enterohepatic, or enterogastric recirculation. Lipophilic drugs with low volume of distribution, protein binding, and molecular weight may pass down a concentration gradient between intravascular space and activated charcoal in the gut lumen. Multidose activated charcoal may also adsorb residual intraluminal toxins; this is more likely for substances slowing gastric motility or forming bezoars ( Table 176-9). Although animal studies, volunteer studies, case reports, and case series demonstrate increased elimination rates (in some cases comparable to those of hemodialysis or charcoal hemoperfusion) of carbamazepine, dapsone, phenobarbital, phenytoin, quinine, and theophylline, there is limited evidence that multidose activated charcoal changes clinical outcome. Multidose activated charcoal may be administered by an orogastric or nasogastric tube to intubated patients. Regular aspiration of stomach contents helps avoid gastric distention. Multidose activated charcoal should not be given when bowel sounds are absent. Continued require ment for further multidose activated charcoal should be reviewed regu larly during therapy. Tintinalli_Sec15_p1187-1332.indd 1192 8/2/19 8:39 PM

tients. Regular aspiration of stomach contents helps avoid gastric distention. Multidose activated charcoal should not be given when bowel sounds are absent. Continued require ment for further multidose activated charcoal should be reviewed regu larly during therapy. Tintinalli_Sec15_p1187-1332.indd 1192 8/2/19 8:39 PM CHAPTER 176: General Management of Poisoned Patients 1193 TABLE 176-9 Indications, Contraindications, and Complications of Enhanced Elimination Procedures Multidose Activated Charcoal Initial dose: 50 grams (1 gram/kg children), repeat dose of 25 grams (0.5 gram/kg children) every 2 hours Indications Carbamazepine coma (reduces duration of coma) Phenobarbital coma (reduces duration of coma) Dapsone toxicity with significant methemoglobinemia Quinine overdose Theophylline overdose if hemodialysis/hemoperfusion unavailable Contraindications Unprotected airway Bowel obstruction Caution in ingestions resulting in reduced GI motility Complications Vomiting Pulmonary aspiration Constipation Charcoal bezoar, bowel obstruction/perforation Urinary Alkalinization Indications Moderate to severe salicylate toxicity not meeting criteria for hemodialysis Phenobarbital (multidose activated charcoal superior) Chlorophenoxy herbicides (2-4-dichlorophenoxyacetic acid and mecoprop): requires high urine flow rate of 600 mL/h to be effective Chlorpropamide: supportive care/IV dextrose normally sufficient Contraindications Preexisting fluid overload Renal impairment Uncorrected hypokalemia Complications Hypokalemia Volume overload Alkalemia Hypocalcemia (usually mild) TABLE 176-10 Protocol for Urinary Alkalinization in Adults With Normal Renal Function •   Correct existing hypokalemia. •   Administer a 1 to 2 mEq/kg IV sodium bicarbonate bolus. •   Infuse 100 mEq of sodium bicarbonate mixed with 1 L of D5W at 250 mL/h. •   20 mEq of potassium chloride may be added to the solution to maintain normokalemia. •   Monitor serum potassium and bicarbonate every 2–4 h to detect hypokalemia or excessive serum alkalinization. •   Check urine pH regularly (every 15–30 min); goal is a pH of 7.5–8.5. •   A further IV bolus of 1 mEq/kg of sodium bicarbonate may be necessary if sufficient alkalinization of the urine is not achieved. Abbreviation: D5W = 5% dextrose in water. TABLE 176-11 Indications, Contraindications, and Complications of Extracorporeal Removal Techniques Hemodialysis Movement of solute down a concentration gradient across a semipermeable membrane Toxin requirements Low volume of distribution, low protein binding, low endog enous clearance, low molecular weight Indications Life-threatening poisoning by: Lithium Phenobarbital Salicylates Valproic acid Methanol/ethylene glycol Metformin-induced lactic acidosis Potassium salts Theophylline Contraindications Hemodynamic instability Infants (generally) Poor vascular access Significant coagulopathy Hemoperfusion Movement of toxin from blood, plasma, or plasma proteins onto a bed of activated charcoal (or other adsorbent) Toxin requirements Low volume of distribution, low endogenous clearance, bound by activated charcoal Indications Life-threatening poisoning caused by: Theophylline (high-flux hemodialysis is an alternative) Carbamazepine (multidose activated charcoal or highefficiency hemodialysis also effective) Paraquat (theoretical benefit only if instituted early after exposure) Contraindications Hemodynamic instability Infants (generally) Poor vascular access Significant coagulopathy Toxin not bound to activated charcoal Continuous Renal Replacement Therapies Movement of toxin and solute across a semipermeable membrane in response to hydrostatic gradient. Can be combined with dialysis.

osure) Contraindications Hemodynamic instability Infants (generally) Poor vascular access Significant coagulopathy Toxin not bound to activated charcoal Continuous Renal Replacement Therapies Movement of toxin and solute across a semipermeable membrane in response to hydrostatic gradient. Can be combined with dialysis. Indications (potential) Life-threatening ingestions of toxins when hemodialysis or hemoperfusion is indicated but is unavailable or hemodynamic instability precludes their utilization Contraindications Hemodialysis or hemoperfusion is available Poor vascular access Significant coagulopathy Complications of Extracorporeal Removal Techniques Fluid/metabolic disruption Removal of antidotes Limited availability Limited by hypotension (not continuous renal replacement therapy) Infection/bleeding at catheter site Intracranial hemorrhage secondary to anticoagulation  URINARY ALKALINIZATION Alkaline urine favors ionization of acidotic drugs within renal tubules, preventing resorption of the ionized drug back across the renal tubular epithelium and enhancing elimination through the urine. 36 Urinary alkalinization is most effective for weak acids primarily eliminated by the renal tract that are also readily filtered at the glomerulus and have small volumes of distribution. Hypokalemia will reduce the effectiveness of urinary alkalinization (Table 176-10). The primary indication for urinary alkalinization is moderate to severe salicylate toxicity when criteria for hemodialysis have not been met. Although urinary acidification can enhance the elimination of weak bases including amphetamines and phencyclidine, associated risks (e.g., rhabdomyolysis) outweigh potential benefit. Forced diuresis has no indication for any poisoning, with the exception of chlorophenoxy herbicides (see Chapter 201, “Pesticides”).  EXTRACORPOREAL REMOVAL Extracorporeal removal techniques, including hemodialysis, hemoper fusion, and continuous renal replacement therapies, have limited indications in poisoned patients (Table 176-11). These procedures require a critical care setting, are expensive and invasive, are not always available, and have complications. Extracorporeal removal techniques were used in 0.13% of cases reported to U.S. poison control centers in 2016. Tintinalli_Sec15_p1187-1332.indd 1193 8/2/19 8:39 PM