Lithium
GENERAL PRINCIPLES
Lithium is a mood stabilizer that is used in the management of bipolar disorder and other psychiatric disorders.
Pathophysiology
• The mechanism of action of lithium is poorly understood.
Lithium is believed to enhance serotonergic signaling and has been implicated in cases of serotonin syndrome.• Lithium has a narrow therapeutic index; many cases of lithium poisoning are accidental. Lithium is exclusively renally cleared; any impairment in renal function will lead to lithium accumulation and potentially to toxicity.
• Lithium poisoning primarily affects the central nervous system.
• Lithium may also cause nephrogenic diabetes insipidus, hypothyroidism, and in rare cases cardiotoxicity.
• Lithium follows multicompartment kinetics. Chronic and acute-on-chronic lithium poisoning are generally more dangerous than acute lithium poisoning because of the accumulation of lithium in the tissue compartment. 19
DIAGNOSIS
Clinical Presentation
• Patients with an acute overdose (either acute or acute-on-chronic) of lithium will invariably present with GI upset, as lithium salts are very irritating to the mucosa of the GI tract.
î This feature will be absent in chronic lithium poisoning, which occurs without a single acute overdose.
î Profound GI volume losses may lead to hypovolemic shock.
• It is common for chronic poisoning to be provoked by a drop in the GFR due to a GI illness, decreased oral intake, or nephrotoxic medications.
• Lithium poisoning of any etiology may cause neurotoxicity; there is a wide spectrum of disease.
î Mental status changes may range from subtle cognitive impairment to coma. When delirium occurs, it is typically hypoactive.
î Signs of cerebellar dysfunction, including nystagmus, dysmetria, and ataxia, may be seen.
î Peripheral neuromuscular abnormalities, including hyperreflexia, clonus, rigidity, and tongue fasciculations, also occur.
• In acute overdose, there is usually delayed development of neurotoxicity. In chronic poisoning, neurotoxicity may be the presenting complaints.
• It is common for the resolution of the clinical signs and symptoms of lithium poisoning to lag behind the serum lithium concentration, sometimes by days.
Diagnostic Testing
LABORATORIES
• Obtain a se rum lithium conce ntration.
î The therapeutic range is approximately 0.6-1.2 mmol/L.
î Have a low threshold to check a lithium concentration in any patient taking lithium, given the narrow therapeutic index.
î In poisoned patients, the lithium concentration should be trended over time to demonstrate clearance; additionally, in acute overdose, absorption may be delayed.
î The lithium concentration must be checked on blood that has not come into contact with a lithium- containing sample tube.
• Obtain a BMP to evaluate renal function and assess for hyponatremia (which will impair lithium excretion) or hypernatremia (which should raise concern for diabetes insipidus).
î Significantly elevated lithium concentrations may produce a low anion gap, as lithium is an unmeasured cation.
ELECTROCARDIOGRAPHY
The ECG may show nonspecific T-wave flattening or inversion or QTc prolongation; however, cardiac dysfunction is unusual in this overdose.
TREATMENT
• AC does not bind to lithium. If GI decontamination is desired, WBI is the technique of choice. WBI may be appropriate in patients who present after ingestion a large amount of extended-release lithium preparations.
• The mainstay of treatment is hyperhydration to promote lithium excretion.
° Patients with clinical or laboratory evidence of hypovolemia should be appropriately resuscitated with intravenous crystalloid.
î All patients with lithium poisoning should be hydrated with normal saline at 1.5-2? maintenance rate.
#9632; Hypotonic fluids may promote lithium retention and should be avoided.
#9632; Generally, hyperhydration may be stopped when the lithium concentration is in the therapeutic range and the patient is clinically improved.
• Hemodialysis may be reasonable in cases of severe neurologic toxicity such as coma or seizures (especially in chronic poisoning), very high lithium concentrations (generally gt;5 mmol/L or gt;4 mmol/L in the presence of renal impairment), or the failure of standard measures to rapidly (lt;1 mmol/L within 36 h) reduce the lithium concentration. 20
î Local practice patterns vary considerably, and early consultation with a medical toxicologist (or poison control center) and a nephrologist is reasonable.
î If hemodialysis is performed, patients should be monitored for rebound in serum lithium concentration due to redistribution of lithium from tissue stores.