Background

Mechanism of action is poorly understood.

Despite availability of newer drugs, Lithium remains most effective treatment for bipolar disorder, and it is still in use

Lithium initially distributes in extracellular fluid, then gradually redistributes to other areas including the brain (takes up to 24 hours after absorption)

95% renal excretion NSAIDs, diuretics, ACE-inhibitors → ↑ Lithium serum concentration by ↓ lithium excretion

Lithium toxicity rarely fatal (only 11 deaths out of 6815 reported toxic exposures in 2012)[1]

Common Precipitants

Clinical Features

Three recognized patterns of Lithium toxicity - "Acute", "Acute-on-chronic", and "Chronic".[2]

Acute

Occurs in patients not previously receiving lithium (i.e. with no current body stores)

Serum concentrations can fall rapidly as lithium redistributes to tissues, and serum level does not correlate with degree of toxicity. GI symptoms predominate.

GI - nausea/vomiting, diarrhea, abdominal pain Earliest and most common symptoms

Cardiac effects - bradycardia, QT prolongation, T-wave flattening or inversion [3] Can also cause Brugada-like ECG pattern

CNS Depression - late finding (takes time for lithium to distribute to CNS), indicates progression of toxicity

Acute-on-Chronic

Also called "Acute-on-therapeutic", occurs in patients currently taking lithium due to acute ingestion of supra-therapeutic doses.

Symptoms are a mix of both acute and chronic - includes both GI and CNS effects

Chronic

Occurs insidiously in patients on chronic lithium therapy. Toxicity is secondary to increased absorption or decreased elimination. CNS symptoms predominate.

Chronic lithium therapy is associated with nephrogenic diabetes insipidus, which → hyponatremia, fluid loss → ↑ lithium levels (can precipitate toxicity)

Neurotoxicity is major finding, and is generally more profound than that seen in acute toxicity Mild symptoms include tremor, drowsiness Progressive symptoms include hyperreflexia, confusion, ataxia, seizures, extrapyramidal symptoms, coma

Hypothyroidism (lithium inhibits thyroid hormone release)

[4] Syndrome of Irreversible Lithium-Effectuated Neurotoxicity (SILENT)

Persistent sequelae of lithium toxicity

Defined as neurologic dysfunction persisting > 2 months after cessation of lithium therapy

Exact mechanism unknown (possibly related to CNS demyelination).

Symptoms Cerebellar dysfunction (dysarthria, ataxia, tremor, gait instability) Peripheral neuropathy Extrapyramidal symptoms

Brainstem dysfunction

Dementia

Differential Diagnosis

Evaluation

Lithium level Therapeutic level = 0.6-1.2 meq/L Serum level may be falsely elevated if placed in a green top tube due to the heparin lithium interaction Serum levels do not predict CNS levels and only roughly correlate with clinical symptoms

Metabolic Panel

TSH

ECG

Acetaminophen and Salicylate Levels (possible coingestants)

Management

GI decontamination

Whole bowel irrigation (only for extended release tablets)

Gastric lavage and activated charcoal not effective and potentially harmful

Average patient has Na/volume deficit; giving fluid helps reestablish normal renal Lithium excretion

Give 2L NS bolus, then start 200mL/hr or 2x maintenance rate

Most effective method of removal. Must follow serial lithium levels - levels will likely rise after HD due to redistribution from tissues; additional HD may be required. Indications:

Kidney function is impaired and the [Li+] >4.0 mEq/L (1D recommendation) [5]

Clinical deterioration

In the presence of a decreased level of consciousness, seizures, or life-threatening dysrhythmias irrespective of [Li+] (1D) [5]

[Li+].>5.0 mEq/L (2D suggestion)

If the expected time to obtain a [Li+]<1.0 mEq/L with optimal management is >36 h (2D suggestion) [5]

Baseline renal failure

Contraindication to aggressive fluid resuscitation (CHF, etc)

Disposition

Consider discharge for patients who are asymptomatic after 4-6hr obs, 2 downtrending lithium levels, and no worsening of renal function

Admit all patients with Li level >1.5

Admit all patients with ingestion of sustained-release preparation (regardless of Li level)

See Also

References