Clinical Presentation

Young children often present to the emergency department without symptoms, so it is important to differentiate an exposure (e.g., found in an area with pills available) from an actual ingestion, which in this age group usually involves a single medication or household product. With liquids, the parents may report that the child ingested a single or multiple swallows of a substance before spitting it out. In adolescents, the ingestion may be impulsive, whether stemming from recreational use or psychiatric disorders (mood disorders, schizophrenia, substance abuse), and the history may be unclear at the time of presentation. These ingestions can involve multiple medications, illicit drugs and alcohol, and frequently result in symptoms. If the ingestant is known, assess the likelihood of toxicity. Most household products and plants are nontoxic, although some common plants are toxic. A continuously updated reference, which includes a listing of poisonous and non-poisonous plants and household products, can be found on the National Capital Poison Center website: www.poison.org. Several medications can be fatal to infants in very small amounts (Table 14.1) and certain medications may cause delayed toxicity (Table 14.2).

Symptoms can also develop from toxins that are ingested, inhaled, or absorbed through the skin. This is especially important when evaluating neonates or infants due to their relatively large body surface area to mass ratio.

Diagnosis

In most instances, the diagnosis can be made based on history. Estimate the volume of a swallow to be approximately 0.25 mL/kg. In adolescents, and occasionally in toddlers, the parent or child may intentionally conceal the ingestant or it may not be known. Consider an ingestion in any previously well child with a change in mental status, lethargy, hallucinations, delirium, seizures, dysrhythmia, or coma.

In the critically ill child, the first priority is the ABCs, including, intravenous/intraosseous (IV/IO) access and monitoring. Empiric therapy for common disorders, such as dextrose for hypoglycemia and naloxone for opioid toxicity, can then be considered. After assessment of vital signs and initiation of therapy, the specific toxin may be determined by history, physical findings, and/or laboratory data, and specific care may be rendered.

In less acute situations, or after stabilization, a thorough physical examination focusing on vital signs, mental status, pupillary responses, bowel sounds, and skin and mucosal findings may lead to identification of a specific exposure.

The Unconscious Patient

1. 
   

   1. Assess the airway, breathing and circulation (ABCs), provide continuous cardiorespiratory monitoring, and secure (IV) or (IO) access.

   
   
2. 
   

   2. If there are clinical signs of hypoperfusion (delayed capillary refill, poor pulse quality, pallor, cool extremities), give a rapid bolus (20 mL/kg) of normal saline or Ringer’s lactate (may be repeated twice), and if possible place the patient in the Trendelenburg position.

   
   
3. 
   

   3. Obtain an ECG.

   
   
4. 
   

   4. Assess the level of alertness, pupillary responses, gag reflex, muscle tone, deep tendon reflexes, and examine the head and neck carefully for evidence of injury while maintaining the cervical spine in neutral position.

   
   
5. 
   

   5. Remove the patient’s clothing to facilitate the examination, to look for signs of trauma, and to search for pills and other substances.

   
   
6. 
   

   6. Measure the temperature and, if possible, weigh the patient.

   
   
7. 
   

   7. Obtain an ABG to assess the adequacy of ventilation and the acid–base status.

   
   
8. 
   

   8. Obtain blood specimens for rapid blood glucose, CBC, liver function tests, serum electrolytes, carboxyhemoglobin (if CO poisoning cannot be ruled out by history), and methemoglobin (if cyanosis is present). Also, draw and hold tubes for type and screen and further serum tests as indicated.

   
   
9. 
   

   9. Give 0.5 g/kg of glucose to any unresponsive patient either empirically or in response to a low bedside measured glucose.

   
   
10. 
    

    10. Give naloxone 0.1 mg/kg, maximum 2.0 mg (preferably IV, but can be given IM, SC, or ET) either empirically or to correct respiratory depression of opioid toxicity. If there is no response within 1–2 minutes, give a second dose. A positive response may last only 30 minutes, so if resedation occurs either give repeated doses or start a continuous IV infusion at two-thirds the effective dose, infused every hour (e.g., if a total of 0.6 mg was initially required, start the infusion at 0.4 mg/h). If habitual use is suspected in an adolescent, lower the initial dose to 0.05–0.1 mg, increasing to 0.4 mg, and then to 2.0 mg, in order to avoid acute withdrawal. Separate repeated dosing of IV naloxone by 1–2 minutes, as the onset of action for naloxone administered IV is 1–2 minutes.

    
    
11. 
    

    11. Obtain urine by catheter for dipstick examination, urine toxicology, and, in adolescent females, a pregnancy test.

    
    
12. 
    

    12. Consider gastrointestinal decontamination as indicated if the airway is maintainable and bowel sounds are present (see pp. 451–452).

If the ingestion was witnessed, determine the specific substance, amount, and time of the ingestion. It may be important to contact someone at the home to check information on pharmaceuticals, or to contact the pharmacy where prescriptions are typically filled. Refer to Table 14.3 for information to include in the history.

Table 14.3 Important history

Where was the patient found?

Who has the patient visited recently?

Who has visited the patient’s home recently?

Is anyone in the home taking any medications or herbals?

Is anyone else in the home suffering from headaches, seizures, fevers, or other illnesses?

Are there any pills, pill bottles, or other open containers in the house (including the garbage), or were any unusual odors noticed?

Does anyone in the house use any unusual chemicals for work or hobbies?

Was a suspect substance or pharmaceutical in the original container, or was it transferred into another one?

Was there more than one suspect substance in a container?

Was the patient given milk, clear liquids, syrup of ipecac, or food prior to arrival?

Has the patient vomited since the suspected ingestion?

Perform a thorough physical examination (Table 14.4), including assessment of the pupils, mucosal membranes, heart, lungs, abdomen, skin, and a thorough neurologic examination (level of consciousness, pupils, motor, reflexes, and gag reflex). Certain poisons manifest consistent and unique sets of vital signs and physical examination findings, grouped into “toxidromes” (Table 14.5).

Table 14.4 Physical examination findings

Finding	Drugs/toxins
Vital signs
Hyperthermia	Amphetamines, anticholinergics, cocaine, phencyclidine salicylates, theophylline, tricyclics
Hypothermia	Barbiturates, ethanol, gamma-hydroxybutyric acid, opioids, phenothiazines
	Hypotension
Tachycardia	Amphetamines, anticholinergics, caffeine, cannabis, cocaine, ethanol, iron, opioid withdrawal, phenothiazines, theophylline
	Hypoglycemia or hypotension
Bradycardia	Barbiturates, β-blockers, calcium channel blockers, clonidine, digoxin, gamma-hydroxybutyric acid, opioids
	Hypoglycemia or hypotension
	Increased intracranial pressure
Tachypnea	Amphetamines, salicylates, theophylline
	Metabolic acidosis,
Depressed respirations	Botulism, clonidine (early)
	CNS depressants (ethanol, barbiturates, opioids, sedative-hypnotics)
Hypotension	Barbiturates, β-blockers, calcium channel blockers, cardiac glycosides, clonidine, ethanol, iron, opioids, tricyclic antidepressants
Hypertension	Clonidine, MAO inhibitors, SSRIs
	Anticholinergics (antihistamines, atropine, phenothiazines, scopolamine, tricyclic antidepressants)
	Sympathomimetics (amphetamines, cocaine, phencyclidine, theophylline)
Skin
Cyanosis	Methemoglobinemia
	Hypoxia
Flushing	Amphetamines, anticholinergics
Diaphoresis	Amphetamines, anticholinesterase pesticides, cocaine, salicylates
Hot, dry skin	Anticholinergics
Piloerection	Opioid withdrawal
Bullae	Barbiturates, carbon monoxide,
Pruritus	Vitamin A
Eyes
Miosis	Clonidine, ethanol, opioids, organophosphates, phenothiazines, sedative-hypnotics
Mydriasis	Amphetamines, anticholinergics, antihistamines, cannabis, cocaine, dextromethorphan, ethanol, LSD, opioid withdrawal, phenylephrine, phencyclidine, psilocybin
	Hypoglycemia
Conjunctival injection	Cannabis, direct irritants
Nystagmus	Alcohols, carbamazepine, ketamine, phencyclidine, phenytoin
Visual disturbances	Botulism, digitalis, methanol, parathion, vitamin A
Neck
Rigidity	Phencyclidine, strychnine
	Dystonia from phenothiazines and haloperidol
Breath sounds
Rhonchi, wheezes	β-blockers, cholinesterase-inhibitor pesticides, petroleum distillate aspiration, toxic inhalants
Abdomen
Distention, ↓bowel sounds	Anticholinergics, CNS depressants (many), tricyclics
↑ Bowel sounds	Amphetamines, cholinesterase-inhibitor pesticides, cocaine, drug withdrawal
	Food poisoning
Tenderness	Acetaminophen, alcoholic gastritis, corrosives, iron, salicylates
Distended bladder	Anticholinergics, tricyclics
Neurologic
Ataxia	Alcohols, benzodiazepines, carbon monoxide, phenytoin, sedative-hypnotics, solvents
Coma	Anticholinergics, alcohols, anticonvulsants, antipsychotics, carbon monoxide, clonidine, opioids, organophosphates, salicylates
Delirium	Anticholinergics, drugs of abuse, heavy metals, phenothiazines, sympathomimetics,
Focal signs	Alcohols
	Hypoglycemia
	Increased intracranial pressure due to a mass lesion
Tremor	Arsenic, carbon monoxide, ethanol, lithium, mercury, parathion, phenothiazines, solvents

Table 14.5 Toxidromes

Sympathomimetic

Findings: Hyperthermia, tachycardia, hypertension, mydriasis (reactive), warm/moist skin, agitated/delirium

Causes: Amphetamines, cocaine, phencyclidine, theophylline, ethanol withdrawal

Anticholinergic

Findings: hyperthermia, tachycardia, hypertension, hot/red/dry skin, mydriasis (unreactive), urinary retention, absent bowel sounds, confusion/hallucinations

Causes: Antihistamines, atropine, phenothiazines, scopolamine, tricyclic antidepressants

Cholinergic

Findings: SLUDGE (Salivation, Lacrimation, Urinary incontinence, Diarrhea/Diaphoresis, GI upset/hyperactive bowel sounds, Emesis), miosis, bradycardia, bronchial secretions, seizures, altered mental status, paralysis

Causes: Carbamates, chemical warfare agents (VX, Soman, Sarin), organophosphates, pilocarpine eye drops

Opioid (narcotic)

Findings: Miosis, respiratory depression, depressed mental status, hypothermia, bradycardia, hypotension

Distinctive odors may also help make the diagnosis (Table 14.6).

Table 14.6 Odors

Odor	Toxin
Acetone	Aspirin, chloroform, isopropanol, ketoacidosis, methanol
Bitter almonds	Cyanide (silver polish)
Eggs (rotten)	Disulfiram, hydrogen sulfide, mercaptans
Fish or raw liver (musty)	Hepatic failure, zinc phosphide
Fruit-like	Amyl nitrite, ethanol, isopropanol, ketoacidosis
Garlic	Arsenic, dimethylsulfoxide (DMSO), organophosphates, phosphorus, selenium, thallium
Mothballs	Camphor
Peanuts	N-pyridylmethylurea (Vacor), other rodenticides
Pear-like (acrid)	Chloral hydrate, paraldehyde
Petroleum	Petroleum distillates
Shoe polish	Chlorinated hydrocarbons, nitrobenzene
Violets (urine)	Turpentine
Wintergreen	Methylsalicylate

Routine urine or blood toxicology screens are rarely helpful in the poisoned patient and each institution’s screen detects different drugs. Specific levels are available for several medications and may assist in making treatment decisions (Table 14.7). Obtain an acetaminophen level after an oral ingestion or if the patient is comatose, as it is a common co-ingestant.

Table 14.7 Important drug levels

Drug	Level	Intervention
Acetaminophen	Nomogram	N-acetylcysteine
Carbamazepine	40 mg/L	Activated charcoal + hemodialysis
Carboxyhemoglobin	25% (any if pregnant)	Hyperbaric oxygen
Digoxin	15 ng/mL1	Digoxin-specific Fab fragments
Ethanol	Low level	Necessitates search for other toxins
Ethylene glycol	25 mg/dL	Ethanol or fomepizole or hemodialysis
Iron	500 mcg/dL	Deferoxamine
Lithium	4 mEq/L2 (acute)	Hemodialysis
Methanol	25 mg/dL	Ethanol or fomepizole or hemodialysis
Methemoglobin	25%	Methylene blue
Phenobarbital	100 mcg/mL	Hemodialysis ± activated charcoal
Salicylate	100 mg/dL (acute)	Bicarbonate, hemodialysis
Theophylline	100 mg/L	Activated charcoal + hemodialysis
Valproic acid	1000 mg/L	Hemodialysis

¹ Treatment with digoxin-specific Fab fragments is based on symptoms and an elevated potassium (>5.0 mEq/L). However, if the digoxin level is >10 ng/mL in an overdose, give Fab fragments, regardless of symptoms.

² Treatment with hemodialysis is based on symptoms (severely altered mental status, seizures, arrhythmias). However, a lithium level >4 mEq/L is indicative of severe toxicity and hemodialysis is indicated.

Acid–base status can be determined from arterial blood gas and chemistry panels. The mnemonic “MUDPILES CAT” represents the list of toxins that produce an elevated anion gap with a metabolic acidosis (Table 14.8). The anion gap is calculated by: [Na⁺] – ([HCO3⁻] + [Cl⁻])

Table 14.8 Causes of increased anion gap metabolic acidosis (Mudpiles CAT)

Methanol or metformin	Cyanide
Uremia	Alcohols or acids (valproic)
Diabetic ketoacidosis	Toluene or bheophylline
Paraldehyde or phenformin
Iron, isoniazid, or ibuprofen
Lactic acidosis
Ethylene glycol
Salicylates

The normal anion gap is typically <12, but use the upper limit of normal set by each laboratory, since this reflects differences in the methods used to calculate the electrolytes.

Order a serum osmolality in cases of suspected poisoning due to ethylene glycol, methanol, or isopropanol. To calculate the osmolar gap, subtract the calculated osmolality from the measured osmolality:

Osmol gap=measured osmolality–calculated osmolalityCalculated osmolality=(2×Na+)+(BUN/2.8)+(glucose/18)+(ethanol/4.6)

Including ethanol in the calculated gap increases the likelihood of correctly identifying gaps attributable to methanol, ethylene glycol, or isopropanol. A normal osmol gap is ±10, while an elevated osmol gap (>40 mOsm/L) is consistent with the presence of a toxic alcohol ingestion. However, a normal osmol gap cannot be used to exclude the diagnosis of a toxic alcohol ingestion.

Assess ECG for conduction delays, as they may precede significant rhythm disturbances. Additionally, as is the case with tricyclic antidepressant ingestions, abnormalities on the ECG may predict the development of seizures or other toxic effects.

Radiographic evaluation of the poisoned patient is generally unnecessary; however, the mnemonic CHIPES refers to tablets that may be seen on abdominal x-ray: chloral hydrate, heavy metals (lead, iron, arsenic), iodides, phenothiazines, enteric-coated medications, and sodium and other elements (calcium, potassium, bismuth). In practice, only the heavy metals are readily visible on abdominal x-rays. “Body packers” who are intentionally transporting illicit drugs wrapped in packages in their intestines will often have visible oblong densities on x-ray. A chest x-ray, including the upper airway, is indicated if there is possibility of aspiration or if the patient ingested a button battery or mini-magnets.

Clinical Presentation

In the first hours after an ingestion of acetaminophen, symptoms may be absent or mild and may include nausea, vomiting, and anorexia, but these are not predictive of the subsequent course. Liver function tests (LFTs) are normal during this stage. Between 24 and 48 hours after ingestion, subclinical hepatotoxicity occurs and is evidenced by mild right upper quadrant (RUQ) abdominal pain, nausea, and vomiting, with elevations of AST (SGOT), ALT (SGPT), bilirubin, and prothrombin time. Over the next several days, fulminant hepatic failure may develop with jaundice, renal failure, cerebral edema, and hypotension. A patient who survives the stage of maximum hepatotoxicity will recover due to hepatic regeneration.

Diagnosis

The potential for an acetaminophen ingestion to cause hepatotoxicity may be predicted by obtaining a serum level four or more hours after the ingestion. Plot the serum level on the acetaminophen nomogram (Figure 14.1). If the level appears above the “possible hepatotoxicity” line, treat with NAC. A patient whose level falls below this line does not need treatment, including those who ingested a sustained-release product.

Figure 14.1 Acetaminophen nomogram.

Adapted from Rumack BH, Matthew H. Acetaminophen poisoning and toxicity. Pediatrics 1975;55:871–876

Toxicity may be predicted less reliably by calculating whether the ingested dose is greater than 150 mg/kg. Toxicity is less common in toddlers since they generally ingest smaller quantities and have a larger relative liver size as compared with adults. In addition, young children can metabolize via the sulfation pathway at a faster rate, limiting the production of NAPQI, and they may have greater glutathione stores. Toxicity is unlikely in a child under six years of age unless >200 mg/kg was ingested.

ED Management

Immediately administer 1 g/kg of activated charcoal if the ingestion was less than two hours prior to arrival. Although charcoal does adsorb some acetaminophen, it is not the treatment of choice, so in a case of an isolated acetaminophen ingestion, do not force the patient to accept a nasogastric tube simply to instill charcoal.

NAC is indicated if the serum level is on or above the “possibly hepatotoxic” line on the nomogram. It is 100% effective in preventing hepatotoxicity if given within eight hours of ingestion. Both oral and intravenous routes are approved for use and are equally efficacious and available in the United States. IV administration has more side effects, including a risk of an anaphylactoid reaction, but it is preferred if the patient presents with fulminant hepatic failure or is unable to tolerate the oral formulation.

The oral loading dose is 140 mg/kg, followed by 70 mg/kg q 4h for 17 more doses. Oral NAC is foul-smelling and often causes emesis, so dilute it 1:4 in juice to increase its palatability. In addition, give an antiemetic, such as metoclopramide (1–2 mg/kg/dose IV, IM, PO) or ondansetron (8–15 kg: 2 mg PO; 15–30 kg: 4 mg PO; >30 kg: 8 mg PO). Giving IV NAC decreases the treatment time to 21 hours versus 72 hours for oral NAC. Give a 150 mg/kg IV loading dose over 60 minutes, followed by 50 mg/kg over the next four hours, then 100 mg/kg over the final 16 hours.

If the acetaminophen level will not be available until more than eight hours after ingestion, give a single oral loading dose of NAC while waiting for the result. Treat a patient who arrives for care >24 hours post-ingestion, or one in whom the time of ingestion cannot be determined, with a course of NAC if the acetaminophen level is detectable or the AST is elevated.

Obtain a CBC, electrolytes, creatinine, liver function tests, and PT and INR in a patient who meets criteria for treatment.

Indications for Admission

• 
  

  Possible acetaminophen toxicity requiring antidotal therapy

  
  
• 
  

  Evidence of hepatotoxicity

  
  
• 
  

  Suicide attempt or gesture without psychiatric clearance and appropriate follow-up arranged

Clinical Presentation

Amphetamine and other stimulant toxicity consist of a typical sympathomimetic toxidrome (hyperthermia, tachycardia, hypertension, dilated but reactive pupils, and diaphoresis). Clonidine toxicity resembles an opioid overdose and includes miosis, sedation, coma, hypothermia, hypotension, respiratory depression, and bradycardia. Paradoxical hypertension may develop because, early in overdose, these medications have a preponderance of peripheral alpha stimulation, prior to entry of the drug into the central nervous system. This paradoxical hypertension is then followed by hypotension. Bupropion toxicity can cause a hyperadrenergic state with agitation and seizures, although seizures can occur with normal therapeutic doses.

Diagnosis

Diagnosis is generally made by history as well as by identifying the signs and symptoms consistent with the appropriate toxidrome.

ED Management

Assess the ABCs and vital signs. Check the glucose level and obtain an ECG. Administer activated charcoal (1 g/kg PO) to a patient who arrives in the ED within two hours of ingestion. Treat agitation quickly with benzodiazepines such as midazolam (0.1–0.3 mg/kg IV, 0.2–0.4 mg/kg IM, or 0.4–0.9 mg/kg PO), as it may lead to acidosis, hyperthermia, and rhabdomyolysis. Aggressively treat severe hyperthermia (>40 °C; 104 °F) by covering the patient with a wet sheet and applying ice packs to the groin and axillae. The cardiovascular manifestations generally respond to benzodiazepines; also use benzodiazepines for seizures. Treat sustained tachycardia and hypertension, despite adequate sedation and cooling, with phentolamine (0.02–0.1 mg/kg IV q 10 min).

Naloxone (0.1 mg/kg IV, 2 mg maximum) is variably effective in reversing the sedation caused by clonidine toxicity. Give up to 10 mg before considering the intervention ineffective.

Indications for Admission

• 
  

  Abnormal vital signs or mental status

  
  
• 
  

  Suicide attempt or gesture without psychiatric clearance and appropriate follow-up arranged

Clinical Presentation

The anticholinergic toxidrome must be diagnosed clinically since laboratory tests are typically not helpful. Symptoms result from peripheral blockade of acetylcholine at the muscarinic receptors and include dry mucous membranes, flushed dry skin, mydriatic and unreactive pupils, blurred vision (loss of accommodation), constipation, urinary retention, and tachycardia. Central muscarinic blockade causes temperature elevation, delirium, hallucinations, seizures, and coma.

Symptoms can be described by the mnemonic, “Dry as a bone, mad as a hatter, red as a beet, hot as Hades and blind as a bat.”

Diagnosis

Suspect an anticholinergic ingestion in any patient with a change in mental status, hallucinations, coma, sinus tachycardia, seizures, or a wide QRS/prolonged QTc on ECG. On examination, the pupils are usually dilated and nonreactive to light and accommodation. Absent bowel sounds, dry mucous membranes, urinary retention, and dry flushed skin also suggest the diagnosis. Obtain blood for a CBC, electrolytes, acetaminophen level (co-ingestion in many cold preparations or attempted suicides), pregnancy test (if indicated), and fingerstick glucose determination. Also order an ECG and urine toxicology if cocaine, amphetamine, or tricyclic ingestion is a possibility.

It is important to differentiate the anticholinergic toxidrome from the sympathomimetic toxidrome, as therapy is quite different. Both the anticholinergics and sympathomimetics can cause confusion, agitation, mydriasis, and tachycardia. The pupil, skin, and abdominal examination findings may differentiate these toxidromes. Sympathomimetics cause large yet reactive pupils, with normal or increased bowel sounds, and cool, diaphoretic skin.

ED Management

Initiate supportive care and cardiac monitoring. Administer activated charcoal if the ingestion is likely to have been within the previous two hours, as anticholinergics delay gastric emptying and increase the efficacy of activated charcoal. The treatment of coma is supportive. Treat seizures with lorazepam (0.05–0.1 mg/kg slow IV) or diazepam (0.1–0.3 mg/kg slow IV). If seizures recur give phenobarbital (loading dose 20 mg/kg IV), although propofol or general anesthesia may be necessary for intractable status epilepticus. Treat wide complex tachycardias with sodium bicarbonate (1–2 mEq/kg IV).

Physostigmine can be used in pure anticholinergic poisonings such as atropine, scopolamine, diphenhydramine, and jimson weed. Continued seizures, hemodynamic compromise, or severe agitation or hallucinations are indications for its use. Do not use physostigmine merely to arouse a comatose patient. Give a dose of 0.02 mg/kg slowly over five minutes (1–2 mg for adults). This may be repeated every ten minutes until a satisfactory endpoint is achieved. Rapid administration may cause seizures or bradycardia, and an overdose can precipitate a cholinergic crisis (salivation, lacrimation, bradycardia, hypotension, or asystole). Do not use physostigmine in a patient suspected of having tricyclic antidepressant toxicity (QRS >100 ms, PR >200 ms), as it may precipitate terminal cardiotoxicity. Also, in a patient with gamma-hydroxybutyrate toxicity, physostigmine may precipitate fasciculations and seizure activity. Always be prepared to give atropine (one-half the physostigmine dose) to a patient with physostigmine side effects.

Agitation may be reversed entirely with small doses of physostigmine. This reversal allows confirmation of the diagnosis as well as eliminating the need for further invasive diagnostic studies (i.e., CT and lumbar puncture). Repeated dosing of physostigmine at 30–60 minute intervals may be necessary. Sedation with benzodiazepines may be effective, although large doses are often necessary.

Indications for Admission

• 
  

  Lethargy or persistent signs of toxicity (tachycardia, confusion, sedation)

  
  
• 
  

  Coma, arrhythmia, or seizures

  
  
• 
  

  Suicide attempt or gesture without psychiatric clearance and appropriate follow-up arranged

Clinical Presentation

Acute overdose of MAO inhibitors leads to a sympathomimetic toxidrome, consisting of tachycardia, tachypnea, hyperthermia, anxiety, flushing, tremor, hyperreflexia, diaphoresis, agitated delirium, and severe hypertension. The initial hyperadrenergic crisis may be followed by cardiovascular collapse and multisystem failure. These toxic effects may be delayed up to 24 hours after ingestion, so an asymptomatic patient is still at risk.

MAO inhibitors may lead to a hypertensive reaction when tyramine-rich foods (aged cheese, smoked or pickled meat, and red wine) are consumed, since MAO normally degrades tyramine in the intestine. Hypertensive reactions can also occur when additional sympathomimetic drugs are ingested. The hallmarks of such hypertensive reactions are extreme elevations in blood pressure and severe headaches.

The serotonin syndrome may develop in patients who ingest MAO inhibitors with other medications that increase serotonin in the synapse (e.g., SSRIs, meperidine, dextromethorphan). Serotonin syndrome is characterized by the triad of neuromuscular hyperactivity (hyperreflexia, clonus, rigidity, shivering), autonomic instability (tachycardia, hypertension, diaphoresis, mydriasis, tremor), and mental status changes (agitation, anxiety, confusion).

SSRI overdose can cause nausea, vomiting, sedation, and very rarely seizures. Citalopram and escitalopram cause delayed-onset QTc interval prolongation and seizures in a dose-related manner. The newer, atypical antidepressants also cause sedation and ataxia. Bupropion may initiate seizures and/or QRS prolongation. Overdose also causes tachycardia, agitation, and hallucinations. Trazodone may cause priapism, as well as hypotension secondary to alpha-blockade.

Diagnosis

A provisional diagnosis sufficient to initiate treatment can be made when the appropriate clinical presentation is identified.

ED Management

Assess the ABCs and vital signs and obtain an ECG. Treat severe hypertension secondary to MAO inhibitor toxicity with phentolamine (0.02–0.1 mg/kg IV bolus, repeat q 10 min) or nitroprusside. Treat hypotension with multiple fluid boluses (20 mL/kg each), followed by a norepinephrine infusion. Begin with 0.1 mcg/kg/min and increase every five minutes (add a 4 mg ampule to 1 L of D₅ W to make a 4 mcg/mL solution). Give activated charcoal (1 g/kg PO) to a patient who arrives within two hours of ingestion. Admit any patient with MAO inhibitor, citalopram/escitalopram, and bupropion ingestions to a monitored setting for 24 hours, because toxicity may be delayed.

Treat serotonin syndrome with aggressive cooling for hyperthermia and benzodiazepines for muscle rigidity and agitation.

Indications for Admission

• 
  

  Signs of severe toxicity (seizures, vital sign abnormalities)

  
  
• 
  

  All ingestions of MAO inhibitors, citalopram/escitalopram, and bupropion

  
  
• 
  

  Serotonin syndrome

  
  
• 
  

  Suicide attempt or gesture without psychiatric clearance and appropriate follow-up arranged

Clinical Presentation

Toxicity from antipsychotics is manifested in the CNS and the cardiovascular system, although tolerance to the sedating effects of antipsychotics can be seen in a patient on chronic therapy. The most common toxicity, at both therapeutic levels and in the overdose setting, is an acute dystonic reaction that includes torticollis, opisthotonos, difficulty speaking, facial grimacing, and oculogyric crisis. Onset can be delayed for up to three days after ingestion and the spasm may wax and wane. Postural hypotension and an anticholinergic toxidrome may also occur. In an overdose, antipsychotics commonly cause impaired consciousness ranging from somnolence to coma. In addition, antipsychotics may also lower the seizure threshold.

Cardiotoxicity from antipsychotics results in tachycardia (anticholinergic effect), and hypotension, especially postural (alpha-blockade). Many of the antipsychotics may also cause QTc prolongation and a rightward deviation or widening of the QRS complex.

Neuroleptic malignant syndrome is an extremely rare reaction that can be life-threatening. It is characterized by altered mental status, hyperthermia, muscular rigidity, and autonomic instability. The reaction can occur at any time following initiation of antipsychotic medications.