LITHIUM I: THE BASICS

Author: Lily Nguyen, PharmD(c), Upper Darby, PaSection Editor: Allison A. Muller, PharmD, DABAT

Lithium is a mood-stabilizing agent most commonlyused for the prevention and treatment of affectivebipolar disorders.1,2 The pharmacology of lithium’s

therapeutic effects is still unclear.1-3 A lithium intoxicationcan be classified as acute, chronic, or acute on chronic.2,4

Acute poisoning refers to the ingestion of lithium by some-one not receiving lithium therapeutically.4 Chronic poison-ing refers to a patient receiving chronic lithium therapywhose dosage has been increased or renal function has de-creased, resulting in an elevated serum concentration.4

Acute on chronic poisoning refers to the accidental or in-tentional overdose of lithium by a patient who is receivingchronic lithium therapy; this form of poisoning usually re-sults in more severe toxicities than those associated withacute poisoning.2,4

Lithium has a narrow therapeutic index ranging from0.6 to 1.5 mEq/L.4 Risk factors for lithium intoxicationinclude drug interactions, illness, and alterations in potas-sium or sodium levels.4,5 Infection, dehydration, and lowsodium intake are the major causes of risk situations duringlithium treatment.4,5 Nephrogenic diabetes insipidus canoccur in patients receiving chronic lithium therapy andin turn can increase the risk for further lithium toxicity.Angiotensin-converting enzyme inhibitors, nonsteroidalanti-inflammatory drugs, and thiazide diuretics are amongthe drugs that can increase serum lithium levels.4,5 Lithiumtoxicity also can be exacerbated by certain pathologic con-ditions such as congestive heart failure, liver cirrhosis, ne-phrotic syndrome, or cystic fibrosis.5

Initially, in patients with acute lithium toxicity, gastro-intestinal symptoms usually develop, primarily nausea,vomiting, and diarrhea.2,3 Lightheadedness, dizziness, andorthostatic hypotension also are common.2 Electrocardio-

graphic abnormalities have been reported in a number ofcases.2,4 Neurologic toxicity develops late in acute poison-ing and is the most common finding in chronic poison-ing.2,4 Neurotoxicity is not accurately reflected in serumlithium concentrations. Clinical manifestations of neu-rotoxicity include tremor, dysarthria, nystagmus, ataxia,hyperreflexia, confusion, stupor, coma, and seizures.2-4 Inaddition, there are reports of persistent neurologic sequelaefollowing lithium intoxication. Patients with acute onchronic lithium toxicity may present with signs and symp-toms of both acute and chronic poisoning and thereforemay be more difficult to diagnose and manage.2

Initial management of lithium poisoning should in-clude supportive measures such as protecting the airway ifthe patient has altered mental status with decreased con-sciousness and fluid resuscitation if the patient is hypoten-sive.4,6 The severity of poisoning and the patient’s renalfunction must be determined by history, physical findings,a serum lithium level, and an SMA7.4,6 Note that becauseserum lithium levels do not reflect the intracellular lithiumconcentration, serum levels alone do not fully reflect thedegree of lithium intoxication. If the patient has good renalfunction, normal saline solution should be administeredintravenously to maintain adequate urine output, and elec-trolyte abnormalities should be corrected.4,6 Forced diuresisis not recommended because it has not shown additional ben-efits in clinical trials and may have adverse consequences.4

Gastric decontamination options include gastric lavageand whole bowel irrigation. Activated charcoal does notbind well to lithium ions.4,6 Gastric lavage with a large-boretube may be considered for very recent ingestions and whenthe amount of ingestion is potentially life-threatening.6

Whole-bowel irrigation using polyethylene glycol has shownpotential benefits in sustained-release lithium ingestions.4,6

In certain cases, hemodialysis should be performed tofacilitate the removal of lithium ions from the blood. Theindications for hemodialysis are not entirely clear. In gen-eral, it is indicated in patients presenting with coma, con-vulsions, respiratory failure, deteriorating mental status,and renal failure.2,4 Hemodialysis also is recommendedstrongly for patients with serum lithium levels higher than4 mEq/L or for those receiving chronic lithium therapywhose levels are higher than 2.5 mEq/L.4 In general, basedon the patient’s clinical condition and serum lithium level,

Lily Nguyen is PharmD Candidate, The University of the Sciences in Phila-delphia, Philadelphia College of Pharmacy and Science, Philadelphia, Pa.

For correspondence, write: Lily Nguyen, The University of the Sciences inPhiladelphia, 600 S 43rd St, Philadelphia, PA 19104; E-mail: lnguyen132@usip.edu.

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hemodialysis should optimally be started within the first8 to 12 hours.4 The dialysate bath should contain bicarbon-ate rather than acetate.2,4 Serum lithium levels must bemonitored frequently after initiating hemodialysis, especiallyin those who ingested sustained-release formulations, be-cause they can rise for up to 3 to 4 days after admission.4

The patient’s clinical signs and symptoms must be moni-tored frequently as well because toxicity can exist even attherapeutic serum lithium levels.

REFERENCES1. Schonwald S. Medical toxicology: a synopsis and study guide.

3rd ed. Philadelphia: Lippincott Williams & Wilkins; 2001.p. 683-6.

2. Greller HA. Lithium. In: Flomenbaum NE, Goldfrank LR,Hoffman RS, Howland MA, Lewin NA, Nelson LS. Goldfrank’stoxicologic emergencies. New York: McGraw-Hill; 2006. p. 1052-8.

3. Fankhauser MP, Benefield WH. Bipolar disorder. In: DipiroJT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM.

Pharmacotherapy: a pathophysiologic approach. 4th ed. NewYork: McGraw-Hill; 1999. p. 1161-81.

4. Timmer RT, Sands JM. Lithium intoxication. J Am Soc Nephrol1999;10:666-74.

5. Thomsen K, Schou M. Avoidance of lithium intoxication: advicebased on knowledge about the renal lithium clearance under var-ious circumstances. Pharmacopsychiatry 1999;32:83-6.

6. Lithium carbonate. In: Poisindex Managements, MICROMEDEXhealthcare series [proprietary database on the Internet]. GreenwoodVillage (CO): Thomson MICROMEDEX; c1974-2007 [cited2007 June 14].

Submissions to this column are welcomed and encouraged. Submis-sions may be sent to:Allison A. Muller, PharmD, DABATThe Children’s Hospital of Philadelphia, 34th and Civic Center Blvd,Philadelphia, PA 19104215 590-2004 • mullera@email.chop.edu

PHARM/TOX CORNER/Nguyen

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