DESCRIPTION

Lithium is an oral medication used in the treatment of a variety of psychiatric disorders.

FORMS AND USES

Substances include lithium carbonate (Eskalith, Lithotabs, Lithonate, Eskalith, Lithobid) and lithium citrate.

Therapeutic Uses and Dosage

• Lithium is used for treatment of bipolar affective disorder.
• It is less often used for schizoaffective disorder, attention deficit disorder, aggressive disorders, alcoholism, cluster headaches, anorexia nervosa, and induction of leukocytosis.
• It is generally not used in children under 12 years of age.
• Typical adult dose is 900 to 1,200 mg/day orally.

TOXIC DOSE

• Due to variable absorption, the ingested dose is not a reliable indicator of toxicity. A serum lithium level above 2.0 mEq/L is often associated with toxic effects.
• Toxicity is based on clinical manifestations.

PATHOPHYSIOLOGY

• The mechanism of toxicity is poorly understood.
• Lithium may alter cell membrane conductivity, decrease neurotransmitter levels, and inhibit adenylate cyclase activity.
• Lithium is filtered and reabsorbed in the proximal tubule, much like sodium.
• Chronic intoxication during therapeutic dosing may occur if renal resorption of sodium is increased (e.g., by dehydration or drug interactions).

EPIDEMIOLOGY

• Poisoning is common.
• Toxic effects following acute overdose are typically mild to moderate.
• Death is rare.

CAUSES

• Acute intoxication is usually intentional.
• Chronic intoxication is usually due to intercurrent illness.
• The possibility of child neglect should be considered in patients under 1 year of age; suicide attempt in patients over 6 years of age.

RISK FACTORS

Elderly patients or those with dehydration, renal insufficiency, hyponatremia, low sodium diet, metabolic stress, or infection are at risk for chronic intoxication.

DRUG AND DISEASE INTERACTIONS

• Concurrent neuroleptic use may increase risk of toxic effects or neuroleptic malignant syndrome.
• Calcium channel blockers increase the risk of lithium neurotoxicity.
• Drugs that decrease lithium excretion include diuretics (especially thiazides and spironolactone), nonsteroidal antiinflammatory drugs, angiotensin-converting enzyme inhibitors, and metronidazole.

PREGNANCY AND LACTATION

• US FDA Pregnancy Category D. Positive evidence of human fetal risk exists, but benefits in certain situations (e.g., life-threatening situations or serious diseases) may make use of the drug acceptable despite its risks.
• Maternal use is associated with cardiac abnormalities in the infant.
• Infants born to mothers with lithium toxicity may have increased lithium levels and clinical toxicity.

Section Outline:

• DESCRIPTION
• FORMS AND USES
  • Therapeutic Uses and Dosage
• TOXIC DOSE
• PATHOPHYSIOLOGY
• EPIDEMIOLOGY
• CAUSES
• RISK FACTORS
• DRUG AND DISEASE INTERACTIONS
• PREGNANCY AND LACTATION

DIFFERENTIAL DIAGNOSIS

• Toxic causes of altered mental status, tremors, and movement disorders include sympathomimetic drugs, and withdrawal from ethanol, sedative-hypnotic agents.
• Nontoxic causes include thyrotoxicosis and catecholamine excess.

SIGNS AND SYMPTOMS

• Acute overdose generally causes nausea and vomiting.
• CNS effects (tremor, hyperreflexia, altered mental status) may develop over hours or days if a large ingestion has occurred.
• In chronic overdose, CNS effects predominate: confusion, hyperreflexia, cogwheeling, tremor, nystagmus, seizures, and coma.
• Hypotension and dysrhythmias occur in exceptional cases.

Vital Signs

Hypotension occurs in severe cases.

HEENT

Nystagmus and extraocular muscle abnormalities may develop.

Cardiovascular

ECG changes (primarily T-wave flattening or inversion) and dysrhythmias (conduction delays, sinus node dysfunction) occur in more severe cases.

Pulmonary

Respiratory failure and adult respiratory distress syndrome occur with severe intoxication.

Gastrointestinal

Nausea, vomiting, and diarrhea are common.

Renal

Diabetes insipidus may develop.

Fluids and Electrolytes

• Dehydration is a common precipitant of chronic intoxication.
• Hypernatremia may develop with diabetes insipidus.
• Decreased anion gap is common.

Neurologic

• Lethargy, confusion, tremor, ataxia, slurred speech, hyperreflexia, clonus, choreoathetosis, dystonia, cogwheel rigidity, and fasciculations may develop.
• Coma and seizures may occur with severe toxicity.
• Sensory-motor peripheral neuropathy and neuroleptic malignant syndrome occur rarely.
• Permanent neurologic effects may include ataxia, cerebellar atrophy, basal ganglia degeneration, parkinsonism, and altered mental status.

Endocrine

• Therapeutic use is associated with hypothyroidism.
• Diabetes insipidus may develop with acute or chronic intoxication.

Hematologic

Leukocytosis is common.

PROCEDURES AND LABORATORY TESTS

Essential Tests

• Serum electrolytes, BUN, and creatinine should be determined; dehydration or renal insufficiency suggests etiology of chronic intoxication.
• Serum lithium levels should be determined every 2 to 4 hours until levels decline and symptoms improve. The normal range is typically 0.6 to 1.2 mEq/L.
  • Patients with chronic or acute-on-chronic (supratherapeutic ingestion while on therapy with lithium) intoxication may have neurologic effects at levels only slightly above or within the therapeutic range.
  • Patients with high levels following acute overdose may be initially asymptomatic only to become toxic over the next 12 to 24 hours.
  • Peak levels may be delayed more than 8 hours with sustained-release products.

Recommended Tests

• Serum creatine kinase should be determined in patients with seizure or persistent fasciculation to assess muscle injury.
• ECG, serum acetaminophen and aspirin levels are measured in overdose setting to detect occult ingestion.
• CT, lumbar puncture, cultures, and other tests may be performed as needed to rule out other causes of altered mental status.
• Tablets may be visible on plain abdominal radiographs or abdominal radiographs, but the absence of radiopacity does not rule out lithium ingestion.

Drugs and Disorders that May Alter Laboratory Results

Green-top Vacutainer tubes contain lithium heparin, resulting in spuriously elevated lithium levels.

Section Outline:

• DIFFERENTIAL DIAGNOSIS
• SIGNS AND SYMPTOMS
  • Vital Signs
  • HEENT
  • Cardiovascular
  • Pulmonary
  • Gastrointestinal
  • Renal
  • Fluids and Electrolytes
  • Neurologic
  • Endocrine
  • Hematologic
• PROCEDURES AND LABORATORY TESTS
  • Essential Tests
  • Recommended Tests
  • Drugs and Disorders that May Alter Laboratory Results

• Treatment should focus on decontamination, hydration, and initiating hemodialysis if appropriate.
• Dose and time of exposure should be determined for substances involved.

DIRECTING PATIENT COURSE

The health-care provider should call the poison control center when:

• Altered mental status, seizure, or other severe effects are present.
• Hemodialysis is being considered.
• Toxic effects are not consistent with lithium poisoning.
• Coingestant, drug interaction, or underlying disease presents unusual problems.

The patient should be referred to a health-care facility when:

• Attempted suicide or homicide is possible.
• Patient or caregiver seems unreliable.
• Any toxic effects are present.
• Coingestant, drug interaction, or underlying disease presents unusual problems.

Admission Considerations

Inpatient treatment is warranted when the patient has signs of toxicity (other than mild gastrointestinal upset), the serum lithium level is rising, or a sustained-release preparation was ingested.

DECONTAMINATION

Out of Hospital

Emesis should be induced with ipecac within 1 hour of single ingestion for alert pediatric or adult patients if health care evaluation will be delayed.

In Hospital

• Emesis should be induced with ipecac within 1 hour of ingestion for the pediatric patient who is too small to have effective gastric lavage due to orogastric tube size constraints.
• Gastric lavage should be performed in pediatric (tube size 24-32 French) or adult (tube size 36-42 French) patients presenting within 1 hour of a large ingestion or if serious effects are present.
• Activated charcoal does not bind lithium efficiently, but is used if a coingestant is possible.
• Whole-bowel irrigation should be considered for large ingestion or ingestion of a sustained-release preparation (see SECTION III, Whole-Bowel Irrigation chapter, for details).

ANTIDOTES

There is no specific antidote for lithium intoxication.

ADJUNCTIVE TREATMENT

Hydration

• Lithium renal elimination is increased by hydration.
• A bolus of 10 to 20 ml/kg 0.9% saline should be administered intravenously, followed by infusion at twice the maintenance rate.
• The dose is adjusted as needed to maintain urine output of 2 to 3 ml/kg/h.
• Serum electrolytes should be monitored, potassium administered as needed, and volume overload avoided.

Hemodialysis

• Hemodialysis increases lithium clearance.
• It is most effective following a single ingestion, when it can prevent further distribution of lithium into the CNS.
• Hemodialysis for chronic intoxication is controversial, but is recommended for life-threatening toxicity, rising levels despite decontamination, renal insufficiency, pulmonary edema or neurologic effects, and levels that do not fall with aggressive hydration.
• Hemodialysis should be continued until the serum lithium level is less than 0.5 mEq/L.
• Lithium levels rebound after hemodialysis due to redistribution of the agent from peripheral sites.
• Hemodialysis should be repeated if severe symptoms persist (and level is elevated).
• Peritoneal dialysis and hemofiltration increase clearance but are much slower than hemodialysis; they may be useful if hemodialysis is not available.

Diuretics

• Furosemide increases lithium elimination slightly, but is not routinely recommended.
• It also may be used in patients who are volume overloaded due to hydration therapy.
• The dose is 10 to 40 mg intravenously for patients not under chronic treatment with furosemide.

Seizures

Seizures are treated in the standard manner, starting with benzodiazepine administration (see SECTION II, Seizures chapter, for further details).

Sodium Polystyrene Sulfonate

• Sodium polystyrene sulfonate increases lithium clearance in animal models and human volunteers, but has not been shown to affect outcome after overdose.
• Its use is not routinely recommended.

Section Outline:

• DIRECTING PATIENT COURSE
  • Admission Considerations
• DECONTAMINATION
  • Out of Hospital
  • In Hospital
• ANTIDOTES
• ADJUNCTIVE TREATMENT
  • Hydration
  • Hemodialysis
  • Diuretics
  • Seizures
  • Sodium Polystyrene Sulfonate

PATIENT MONITORING

• ECG, hemodynamics, and electrolytes should be monitored serially in symptomatic patients.
• Serial lithium levels are used to help guide therapy.

EXPECTED COURSE AND PROGNOSIS

• Patients with acute ingestion generally recover over 1 to 2 days.
• Patients with chronic intoxication require days to months to recover, and permanent neurologic sequelae may develop (ataxia, cerebellar atrophy, basal ganglia degeneration, parkinsonism, and altered mental status).

DISCHARGE CRITERIA/INSTRUCTIONS

• From the emergency department. Asymptomatic patients who have ingested an immediate-release product may be discharged following gastrointestinal decontamination, 6 hours of observation, documentation of falling lithium level, and psychiatric evaluation, if needed.
• From the hospital. Patients may be discharged when serum lithium levels are falling, neurologic and renal effects are improving, and psychiatric clearance has been obtained, if needed.

Section Outline:

• PATIENT MONITORING
• EXPECTED COURSE AND PROGNOSIS
• DISCHARGE CRITERIA/INSTRUCTIONS

DIAGNOSIS

• A serum level at the upper end of the therapeutic range may produce chronic intoxication.
• Peak levels may be delayed more than 8 hours after ingestion of a sustained-release preparation.

TREATMENT

• Lithium therapy should not be resumed until all neurologic effects have resolved, even if serum levels are below the limits of detection.
• Substitution of another agent should be considered, particularly in the elderly or those with repeated chronic intoxication.

FOLLOW-UP

• Neurologic effects may require weeks or months to resolve.
• Some patients sustain permanent cerebellar or basal ganglia injury.

Section Outline:

• DIAGNOSIS
• TREATMENT
• FOLLOW-UP

Poisoning by psychotropic agents.

See Also: SECTION II, Seizures chapter; and SECTION III, Whole-Bowel Irrigation chapter.

RECOMMENDED READING

Henry GC, Osborn H, Weisman R. Lithium. In: Goldfrank's toxicologic emergencies, 6^th ed. Norwalk, CT: Appleton & Lange, 1998.

Author: Edwin K. Kuffner

Reviewer: Katherine M. Hurlbut