Tintinalli's Emergency Medicine - Just the Facts, 3ed.

104. PSYCHOPHARMACOLOGIC AGENTS

C. Crawford Mechem

CYCLIC ANTIDEPRESSANTS

EPIDEMIOLOGY

images Cyclic antidepressants are the most common antide-pressants to cause overdose-related deaths. In 2008, 11,000 exposures were reported to US poison control centers.

PATHOPHYSIOLOGY

images Cyclic antidepressants are first-generation antidepressants. They have a low therapeutic index, troublesome side effects, and the potential to produce severe toxicity in overdose.

images Pharmacologic effects include antagonism of histamine and α-adrenergic receptors, inhibition of norepine-phrine and serotonin reuptake, and inhibition of sodium and potassium channels.

CLINICAL FEATURES

images Toxicity can occur both at therapeutic doses and in overdose. Manifestations range from mild antimus-carinic symptoms (dry mouth, sinus tachycardia) to severe cardiotoxicity.

images Altered mental status is the most common symptom of toxicity.

images Sinus tachycardia is the most frequent dysrhythmia.

images Serious toxicity is almost always seen within 6 hours of ingestion and consists of coma, cardiac conduction delays, supraventricular tachycardia, hypotension, respiratory depression, premature ventricular beats, ventricular tachycardia, and seizures.

DIAGNOSIS AND DIFFERENTIAL

images ECG abnormalities develop within 6 hours of ingestion and identify patients at increased risk for seizures and ventricular dysrhythmias. However, life-threatening complications can occur in the absence of significant ECG abnormalities.

images Classic findings are sinus tachycardia, right axis deviation of the terminal 40 milliseconds (positive terminal R wave in aVR, negative S wave in lead I), and prolongation of the PR, QRS, and QT intervals. Less common findings are right-bundle branch block and the Brugada pattern.

EMERGENCY DEPARTMENT CARE AND DISPOSITION

images Obtain IV or IO access, initiate continuous cardiac monitoring, and perform an ECG on all patients.

images Suggested laboratory studies include serum electrolytes, creatinine, glucose, an ABG, and quantitative serum acetaminophen and aspirin levels.

images Patients may require urinary catheterization, and an NG tube may be needed to relieve urinary retention and ileus.

images Administer 1 gram/kg of activated charcoal PO/NG. Consider gastric lavage followed by activated charcoal in patients presenting within an hour of ingestion.

images Treat hypotension with IV/IO isotonic crystalloids in increments of 20 mL/kg. Administer sodium bicarbonate if no response. Treat persistent hypotension with an infusion of norepinephrine starting at 1 microgram/min, and titrating to effect, up to 30 micrograms/min.

images Administer sodium bicarbonate to patients with hypotension refractory to IV fluids, cardiac conduction abnormalities (prolonged QRS duration or Brugada pattern), and ventricular dysrhythmias. Give an initial IV bolus of 1 to 2 mEq/kg, and repeat until the patient improves or blood pH equals 7.50 to 7.55; after the bolus, begin a continuous infusion (150 mEq added to 1 L of 5% dextrose in water, or 100 mEq added to 5% dextrose in 0.45% saline) at 2 to 3 mL/kg/h, to maintain alkalemia. Anticipate and treat associated hypokalemia as needed.

images Treat agitation with reassurance, a quiet environment, and benzodiazepines.

images Treat seizures with lorazepam or diazepam, followed by IV phenobarbital, 15 milligrams/kg in refractory cases. Anticipate hypotension. Consider paralysis with a neuromuscular blocking agent followed by continued anticonvulsant therapy for refractory seizures; ongoing electroencephalographic monitoring is required in these cases.

images No therapy is required for asymptomatic patients with sinus tachycardia, isolated PR prolongation, or first-degree AV block; however, consider sodium bicarbonate in asymptomatic or minimally toxic patients if the QRS duration is >100 milliseconds.

images Treat ventricular dysrhythmias with sodium bicarbonate. Lidocaine is a second-line agent. Synchronized cardioversion is appropriate for unstable tachy dysrhythmias.

images Treat torsades de pointes with 2 grams (50 milligrams/kg in children) of IV magnesium sulfate.

images Patients who remain asymptomatic after 6 hours of observation do not require hospital admission for toxicologic reasons. Admit all symptomatic patients to a monitored bed, and those with signs of moderate to severe toxicity to the ICU.

ATYPICAL ANTIDEPRESSANTS, SEROTONIN REUPTAKE INHIBITORS, AND SEROTONIN SYNDROME

EPIDEMIOLOGY

images These newer antidepressants comprise a heterogeneous group that are more selective in their pharmacologic activity and have a different presentation in overdose than monoamine oxidase inhibitors (MAOIs) and cyclic antidepressants. They are associated with less toxicity and fewer fatalities.

PATHOPHYSIOLOGY

images The mechanism of action of atypical antidepressants most likely involves inhibition of neurotransmitter reuptake or interruption of negative feedback loops.

images Almost all agents have serotoninergic activity and can produce serotonin syndrome, particularly when combined with other serotoninergic drugs (Table 104-1).

images Atypical antidepressants are less likely to cause the ECG conduction abnormalities and cardiotoxicity seen with cyclic antidepressants.

images Newer antidepressants (except bupropion) have a higher safety margin than the MAOIs and cyclic antidepressants. However, they can still cause fatalities.

TABLE 104-1 Serotoninergic Drugs

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TRAZODONE

CLINICAL FEATURES

images Adverse effects include orthostatic hypotension, sedation, priapism, and liver toxicity.

images Cardiac dysrhythmias include sinus arrest, sinus bradycardia, AV blocks, complete heart block, atrial fibrillation, premature ventricular beats, and torsades de pointes.

images ECG findings include sinus bradycardia and tachycardia and QT prolongation.

images Serious toxicity in an average adult is not expected with acute, isolated ingestions of <2 grams.

images Following acute ingestion, the most common symptom is CNS depression. Other neurologic symptoms include ataxia, dizziness, coma, and seizures.

images Commonly reported GI complaints include nausea, vomiting, and nonspecific abdominal pain.

EMERGENCY DEPARTMENT CARE AND DISPOSITION

images Obtain a 12-lead ECG and initiate cardiac monitoring for all patients.

images Administer single-dose activated charcoal. Consider gastric lavage followed by activated charcoal in patients presenting within 1 hour of ingesting >2 grams of trazodone or those with toxic coingestions.

images Treat hypotension with isotonic IV fluids, followed by norepinephrine for refractory shock.

images Treat torsades de pointes with IV magnesium sulfate or defibrillation.

images Patients who remain asymptomatic for 6 hours can be discharged, provided that any necessary psychiatric evaluation has been completed.

images Admit patients with neurologic and/or cardiac symptoms persisting >6 hours after ingestion to a monitored bed.

BUPROPION

CLINICAL FEATURES

images Adverse effects include dry mouth, dizziness, agitation, nausea, headache, constipation, tremor, anxiety, confusion, blurred vision, and increased motor activity. Abrupt discontinuation may pose a theoretical risk of precipitating neuroleptic malignant syndrome.

images Bupropion has a low therapeutic index, and toxicity can occur at dosages equal to or just slightly greater than the maximum therapeutic dose of 450 milligrams/d.

images The most common symptoms in overdose are agitation, dizziness, tremor, nausea, vomiting, drowsiness, tachycardia, and hyperthermia.

images Sinus tachycardia is the most common ECG finding.

images Hypotension may develop in mixed overdoses, and hypertension may also occur.

images Coma and cardiac arrest can occur with severe overdoses.

images Seizures are more common than with other atypical anti-depressants and can develop in otherwise asymptomatic patients.

images Laboratory studies are usually normal except for occasional hypokalemia.

EMERGENCY DEPARTMENT CARE AND DISPOSITION

images Anticipate generalized seizures in all cases.

images Obtain IV access and initiate cardiac rhythm monitoring.

images Perform GI decontamination if it can be done within 1 hour of ingestion. Whole-bowel irrigation is helpful in overdoses of sustained-release products.

images Treat seizures with benzodiazepines and phenobarbital (15 milligrams/kg) if needed.

images Admit all patients with seizures, persistent sinus tachycardia, or lethargy. Asymptomatic patients who have ingested regular-release bupropion should be observed for 8 hours before discharge. Adult patients ingesting >450 milligrams of sustained-release bupropion require monitoring for longer periods up to 24 hours.

MIRTAZAPINE

CLINICAL FEATURES

images Mirtazapine has limited toxicity in overdose. Signs and symptoms include sedation, confusion, sinus tachycardia, and mild hypertension.

images The risk of coma and respiratory depression is greatest at larger doses or when mirtazapine is combined with other sedative drugs.

EMERGENCY DEPARTMENT CARE AND DISPOSITION

images Isolated mirtazapine overdoses are generally managed with supportive care.

images Administer activated charcoal, 1 gram/kg, and consider gastric lavage if performed early after large overdoses or with significant coingestions.

images Admit symptomatic patients to a monitored bed, although life-threatening cardiac toxicity is rare. Asymptomatic patients can be discharged after 8 hours of observation.

SELECTIVE SEROTONIN REUPTAKE INHIBITORS

EPIDEMIOLOGY

images Selective serotonin reuptake inhibitors (SSRIs) currently available in the United States are fluoxetine, sertraline, paroxetine, fluvoxamine, citalopram, and escitalopram, which, as a group, have a high therapeutic-to-toxic ratio.

CLINICAL FEATURES

images The most serious adverse effect is serotonin syndrome.

images Other adverse effects include headache, sedation, insomnia, dizziness, weakness or fatigue, tremor, nervousness, nausea, vomiting, diarrhea, constipation, and anorexia. Dystonic reactions, akathisia, dyskinesia, hypokinesia, and parkinsonian symptoms can develop.

images Most patients remain asymptomatic following overdose, but may develop nausea, vomiting, sedation, tremor, and sinus tachycardia. Sinus bradycardia is more commonly observed with fluvoxamine overdoses. QRS and QT prolongation have been reported with citalopram ingestions. In most cases, ECG abnormalities gradually resolve over 24 hours.

images Life-threatening complications are uncommon. Patients at higher risk include those with underlying seizure disorders, symptoms of serotonin syndrome, or mixed-drug overdoses.

EMERGENCY DEPARTMENT CARE AND DISPOSITION

images Supportive care is generally all that is required for SSRI overdoses.

images For symptomatic patients, obtain vascular access and initiate cardiac monitoring.

images Administer single-dose activated charcoal for most ingestions.

images Treat seizures with benzodiazepines.

images Observe patients for at least 6 hours. Patients with persistent tachycardia or lethargy and those with ECG conduction abnormalities 6 hours after ingestion require admission.

SEROTONIN/NOREPINEPHRINE REUPTAKE INHIBITORS

EPIDEMIOLOGY

images Serotonin/norepinephrine reuptake inhibitors available in the United States include venlafaxine, desvenlafax-ine, and duloxetine. Adverse effects are similar to those of the SSRIs.

CLINICAL FEATURES

images Venlafaxine can produce hypertension. Duloxetine may cause nausea, dizziness, and vomiting.

images In acute overdose, all three medications can cause tachycardia, hypertension, diaphoresis, tremor, and mydriasis. Altered mental status is common. Generalized seizures are more frequent in overdose with these medications than with SSRIs and can occur shortly after ingestion.

images ECG abnormalities include sinus tachycardia, QRS widening, and QT prolongation.

EMERGENCY DEPARTMENT CARE AND DISPOSITION

images Experience with overdoses of these agents is limited. Toxic effects may appear precipitously.

images Obtain vascular access andinitiate cardiac monitoring.

images Administer single-dose activated charcoal and consider gastric lavage with early presentation after large ingestions. Consider whole-bowel irrigation in the case of a massive ingestion of sustained-release preparations.

images Treat seizures with benzodiazepines.

images Treat hypotension with isotonic crystalloid and direct-acting α-agonists for refractory cases.

images Observe all patients for at least 6 hours and longer for those with extended-release ingestions. Admit all symptomatic patients to a monitored bed.

SEROTONIN SYNDROME

PATHOPHYSIOLOGY

images Serotonin syndrome is a potentially fatal adverse drug reaction to serotoninergic medications, characterized by cognitive impairment and autonomic and neuromuscular dysfunction.

images Serotonin syndrome can be caused by any drug or combination of drugs that increase serotonin transmission.

CLINICAL FEATURES

images Cognitive and behavioral findings include confusion, agitation, coma, anxiety, hypomania, lethargy, seizures, insomnia, hallucinations, and dizziness.

images Autonomic signs include hyperthermia, diaphoresis, sinus tachycardia, hypertension or hypotension, tachypnea, dilated or unreactive pupils, flushed skin, diarrhea, and salivation.

images Neuromuscular findings include myoclonus, hyper-reflexia, muscle rigidity, tremor, hyperactivity, ataxia, shivering, Babinski sign, nystagmus, opisthotonus, and trismus.

DIAGNOSIS AND DIFFERENTIAL

images The diagnosis is made on clinical grounds after exclusion of other psychiatric and medical conditions. There are no confirmatory laboratory tests.

EMERGENCY DEPARTMENT CARE AND DISPOSITION

images Therapy involves discontinuing all serotoninergic agents and providing supportive care.

images Consider administration of antiserotonergic agents such as cyproheptadine, 4 to 12 milligrams PO, repeated in 2 hours if no response, to a maximum of 32 milligrams. Patients who respond are given 4 milligrams PO every 6 hours for 48 hours. Chlorpromazine may also be used.

images Administer benzodiazepines to relieve muscle rigidity and discomfort.

images Monitor all patients with muscle rigidity, seizures, or hyperthermia for development of rhabdomyolysis and/or metabolic acidosis.

images Admit all patients with serotonin syndrome to the hospital.

MONOAMINE OXIDASE INHIBITORS

EPIDEMIOLOGY

images Monoamine oxidase inhibitors (MAOIs) were the first class of antidepressants. Their use is now limited to treating atypical and refractory cases of depression, and some cases of Parkinson’s disease.

images MAOIs have a low therapeutic index, and can cause tyramine reactions, serotonin syndrome, and potentially fatal drug interactions.

PATHOPHYSIOLOGY

images Monoamine oxidase is an intracellular enzyme that inactivates norepinephrine, dopamine, serotonin, and tyramine.

images Inhibition leads to accumulation of neurotransmitters in presynaptic nerve terminals and increased systemic availability of dietary amines.

images Toxicity results from ingestion of foods containing tyramine, drug interactions, or overdose.

CLINICAL FEATURES

images Tyramine reactions develop within 15 to 90 minutes of ingestion of dietary tyramine, which is found in foods such as aged meats and cheeses. Symptoms include severe headache, hypertension, diaphoresis, mydriasis, neck stiffness, pallor, neuromuscular excitation, palpitations, and chest pain. Fatalities have been reported.

images Drug interactions involving MAOIs can result in a hyperadrenergic state or the serotonin syndrome. Physicians should exercise caution when administering medications to patients who have taken MAOIs within the past 2 weeks.

images Appearance of toxicity is often delayed 6 to 12 hours after ingestion, and as long as 24 hours.

images Initial symptoms of overdose include headache, agitation, irritability, nausea, palpitations, and tremor.

images Signs of toxicity include sinus tachycardia, hyper-reflexia, hyperactivity, fasciculations, mydriasis, hyperventilation, nystagmus, and generalized flushing.

images In more severe cases, muscle rigidity, diaphoresis, chest pain, hypertension, diarrhea, hallucinations, combativeness, confusion, hyperthermia, and trismus may be noted.

images Severe toxicity is accompanied by coma, seizures, bradycardia, hypoxia, worsening hyperthermia, and hypotension. Death usually results from multiorgan failure.

DIAGNOSIS AND DIFFERENTIAL

images MAOI overdose is diagnosed clinically.

images Laboratory tests can assist in the differential diagnosis and identify possible complications, including hypoxia, rhabdomyolysis, renal failure, hyperkale-mia, metabolic acidosis, hemolysis, and disseminated intravascular coagulation. Leukocytosis and thrombo-cytopenia are common.

images The most common ECG abnormality is sinus tachycardia; T-wave changes may also be seen.

images The differential includes other causes of a hyperadrenergic state, altered mental status, or muscle rigidity (Table 104-2).

TABLE 104-2 Differential Diagnosis of Monoamine Oxidase Inhibitor Overdose

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EMERGENCY DEPARTMENT CARE AND DISPOSITION

images ED management consists of supportive care and treatment of complications.

images Obtain IV/IO access, initiate cardiac monitoring, and provide supplemental oxygen.

images Gastric lavage is recommended for all significant exposures if it can be performed within 1 hour of ingestion. After gastric lavage, or if presentation is delayed for >1 hour, administer a single dose of activated charcoal.

images Treat hypertension with short-acting parenteral antihypertensive agents because of the potential for precipitous hypotension: consider phentolamine in 2.5-to 5.0 milligram IV boluses every 10 to 15 minutes until hypertension is controlled. Nitroprusside may be given as an alternative as a continuous infusion starting at a rate of 0.25-1.0 micrograms/kg/min, titrated to effect.

images Give nitroglycerin for relief of anginal chest pain and in patients with signs of myocardial ischemia.

images Treat hypotension with isotonic crystalloid boluses, followed by norepinephrine.

images Treat ventricular dysrhythmias with lidocaine or procainamide.

images Give atropine, isoproterenol, or dobutamine for bradycardia and consider cardiac pacing.

images Treat seizures with lorazepam or diazepam. Phenobarbital is effective but can cause hypotension. General anesthesia and muscle paralysis with a nonde-polarizing neuromuscular agent such as vecuronium may be necessary for status epilepticus. Paralyzed patients require electroencephalographic monitoring.

images Treat hyperthermia with benzodiazepines to reduce muscle hyperactivity and evaporative cooling methods or ice baths. Consider muscle paralysis for diffuse rigidity refractory to benzodiazepines. Dantrolene may be considered for hyperthermia resistant to other measures: the dose is 0.5 to 2.5 milligrams/kg IV every 6 hours.

images Admit all patients with intentional overdoses or accidental exposures of >1 milligram/kg to an ICU. Admit patients with accidental exposures of <1 milligram/kg to a monitored bed. Asymptomatic patients should be monitored for at least 24 hours.

ANTIPSYCHOTICS

EPIDEMIOLOGY

images Antipsychotics are a group of medications used to treat symptoms of psychosis, as well as nausea and vomiting, various types of headaches, hiccups, and involuntary motor disorders.

images Isolated overdose is rarely fatal, and most patients develop mild to moderate symptoms.

PATHOPHYSIOLOGY

images All antipsychotics bind to and inhibit CNS dopamine receptors. This results in decreased dopamine production and release, along with dopamine receptor blockade.

images Some antipsychotics bind to histamine, muscarinic, α-adrenergic, and serotonin receptors.

CLINICAL FEATURES

images Adverse effects can develop at therapeutic doses and include acute dystonia, akathisia, parkinsonism, tar-dive dyskinesia, and neuroleptic malignant syndrome.

images Acute dystonia is characterized by intermittent, uncoordinated, involuntary contractions of the muscles of the face, tongue, neck, trunk, or extremities.

images Akathisia is a subjective sensation of motor restlessness that typically occurs within minutes to days of initiating or increasing the dose of an antipsychotic.

images Parkinsonism is a delayed effect and is characterized by cogwheel-type muscle rigidity, pill-rolling tremor, mask facies, shuffling gait, bradykinesia or akinesia, and cognitive impairment.

images Tardive dyskinesia is a late-onset, often irreversible, extrapyramidal syndrome and is characterized by painless, stereotyped, repetitive movements of the face.

images Neuroleptic malignant syndrome is a rare but potentially fatal complication that most often occurs shortly after the start of therapy or after a dosage adjustment. It is characterized by fever, muscular rigidity, autonomic dysfunction, and altered mental status.

images CNS depression is common and may range from lethargy, ataxia, dysarthria, and confusion to coma. Respiratory depression is more common in multidrug overdoses.

images Paradoxical agitation and delirium may occur in mixed overdoses.

images Seizures occur in 1% of overdoses and are more common with loxapine and clozapine.

images Patients may manifest anticholinergic toxicity, including tachycardia, dry mucous membranes and skin, mydriasis, decreased bowel sounds, urinary retention, delirium, and hyperthermia.

images Cardiovascular manifestations include sinus tachycardia and orthostatic hypotension.

images ECG changes include PR, QRS, and QT prolongation, ST depression, T-wave flattening, and a rightward shift of the terminal 40 milliseconds of the QRS frontal plane axis.

DIAGNOSIS AND DIFFERENTIAL

images In neuroleptic malignant syndrome, laboratory abnormalities include elevated creatine kinase, leukocytosis, elevated liver transaminases, hypernatremia or hyponatremia, metabolic acidosis, myoglobinuria, elevated BUN and creatinine, and decreased serum iron level.

images Obtain a CBC for any patient presenting with a fever while taking clozapine or chlorpromazine because of the possibility of associated leukopenia and agranu-locytosis.

images In acute overdose, routine laboratory analysis should include a CBC, basic chemistry tests, acetaminophen and aspirin levels, and a pregnancy test for women of childbearing age.

EMERGENCY DEPARTMENT CARE AND DISPOSITION

images Treat acute akathisia and acute dystonia with diphen-hydramine, 25 to 50 milligrams, or benztropine, 1 to 2 milligrams, IM or IV.

images Treat drug-induced parkinsonism by lowering the dosage, changing to a different agent, adding diphen-hydramine or benztropine, or adding amantadine.

images Treatment of neuroleptic malignant syndrome is primarily supportive. Patients with airway compromise, acidosis, hypoxia, or severe fever and rigidity should be intubated using a nondepolarizing agent for rapid sequence induction and benzodiazepines for sedation. Consider dantrolene (1.0-2.5 milligrams/kg IV load, followed by 1 milligram/kg IV every 6 hours) in severe cases.

images Following acute overdose, management is supportive.

images Obtain vascular access, initiate cardiac rhythm monitoring, and provide oxygen.

images Consider naloxone and thiamine, and serum glucose determination, for patients with altered mental status.

images Treat seizures with benzodiazepines.

images Treat hypotension with fluid resuscitation, followed by phenylephrine or norepinephrine.

images Patients with a QTc interval of >500 milliseconds are at risk for torsades de pointes and should receive magnesium sulfate, 2 to 4 grams IV over 10 minutes.

images Treat patients with QRS prolongation or ventricular arrhythmias with sodium bicarbonate, 1 to 2 mEq/kg IV bolus, followed by intermittent boluses or a continuous infusion.

images Observe patients for at least 6 hours. Patients with no mental status changes, pulse and blood pressure abnormalities, orthostatic hypotension, and normal ECG 6 hours from the time of ingestion are candidates for discharge.

images Monitor patients with thioridazine or mesoridazine ingestion for 24 hours.

images Patients with sinus tachycardia, QT prolongation, seizure, respiratory depression, hypotension, or acidosis require admission to a monitored bed; those with altered mental status, cardiotoxicity, or suspected neuroleptic malignant syndrome should be admitted to an ICU bed.

LITHIUM

EPIDEMIOLOGY

images Lithium is used for treatment of bipolar disorder and acute mania.

images Toxicity most often results from accidental or intentional overdose or from an alteration in clearance secondary to renal impairment.

images Up to 75% to 90% of patients on long-term lithium therapy will develop toxicity.

PATHOPHYSIOLOGY

images Lithium competes with sodium, potassium, magnesium, and calcium, displacing them from intracellular and extracellular sites.

images Lithium inhibits adenylate cyclase, decreasing cAMP and possibly cGMP.

images Lithium interferes with the release and reuptake of norepinephrine at nerve terminals.

images Lithium enhances serotonin release from the hippocampus.

images Acute toxicity may result from overdose or develop in those on long-term therapy. Decreased renal clearance and intravascular volume depletion are the most common causes.

images Most often, toxicity involves a drug-drug interaction. An important potential interaction is that the effect of neuromuscular blocking agents such as succinyl-choline and vecuronium may be prolonged in patients receiving long-term lithium therapy.

CLINICAL FEATURES

images The most common adverse effects are hand tremor, polyuria, and rash.

images Nephrogenic diabetes insipidus develops in up to 40% of patients on long-term lithium treatment. Incomplete distal renal tubular acidosis may also be noted.

images Neurologic effects include memory loss, decreased mental status, fatigue, ataxia, and dysarthria.

images Nausea, vomiting, and diarrhea are common at initiation of treatment.

images In acute toxicity, patients present with muscle fascicu-lations or weakness, ataxia, agitation, lethargy, or coma.

images Acute renal failure may develop, especially in the elderly and those with preexisting renal impairment, diabetes, hypertension, or dehydration.

images GI symptoms include nausea, vomiting, diarrhea, or generalized abdominal pain.

images Cardiac abnormalities include hypotension, conduction delays, and ventricular dysrhythmias. ECG changes include QT prolongation, ST-segment depression, or T-wave inversion.

DIAGNOSIS AND DIFFERENTIAL

images Acute lithium overdoses classically cause more GI toxicity and less neurologic toxicity. Serum lithium levels often do not correlate well with either symptom severity or prognosis.

images Chronic toxicity often displays earlier and greater neurologic effects associated with lower serum levels. Serum lithium levels correlate better with degree of toxicity and prognosis in chronic toxicity.

images The best guideline for therapy is generally the patient’s clinical condition.

images Monitoring of lithium serum levels is important, and serial measurements are useful to determine treatment and disposition options.

EMERGENCY DEPARTMENT CARE AND DISPOSITION

images Initial management is supportive.

images Establish vascular access and initiate cardiac monitoring and obtain an ECG.

images Administer normal saline, as most patients with significant toxicity have some sodium and total volume deficits. Typical adult dosing is a 2 L IV bolus over 30 to 60 minutes followed by a 200 mL/h continuous IV infusion.

images Treat seizures with benzodiazepines, followed by phenobarbital or general anesthesia.

images Activated charcoal does not absorb lithium but may be indicated in multidrug ingestions.

images Gastric lavage may be considered with massive ingestions (>4 grams in an adult), if it can be performed within 1 hour of exposure.

images Whole-bowel irrigation may be helpful in ingestions of sustained-release lithium products.

images Laboratory studies should include renal function tests, electrolyte levels, CBC, serum lithium levels, and serum acetaminophen and aspirin levels.

images Indications for hemodialysis include serum lithium levels of >4 mEq/L in acute overdose (3.5 mEq/L in chronic toxicity), or little change in serum level after 6 hours of IV saline. In addition, patients with renal failure, rapidly increasing serum levels, and those who have ingested sustained-release preparations should be considered for hemodialysis. The goal of treatment is to reduce the lithium level to <1 mEq/L. Serum level should be monitored for up to 8 hours following a dialysis session. If the level rises to >1 mEq/L, dialysis should be reinstituted.

images Monitor patients with acute ingestions for 4 to 6 hours, even if asymptomatic.

images Admit patients with serum lithium levels of >1.5 mEq/L following acute ingestion and all patients with ingestion of a sustained-release preparation.

images Patients with minor chronic toxicity and no additional risk factors can be managed with IV saline for 6 to 12 hours, often in an observation unit; once serum lithium levels decrease to <1.5 mEq, they can safely be discharged.


For further reading in Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 7th ed., see Chapter 171, “Cyclic Antidepressants,” by Kirk C. Mills; Chapter 172, “Atypical Antidepressants, Serotonin Reuptake Inhibitors, and Serotonin Syndrome,” by Kirk C. Mills and Keenan M. Bora; Chapter 173, “Monoamine Oxidase Inhibitors,” by Kirk C. Mills; Chapter 174, “Antipsychotics,” by Michael Levine and Frank LoVecchio; and Chapter 175, “Lithium,” by Sandra M. Schneider and Daniel J. Cobaugh.