CRACKCast E160 – Lithium

In CRACKCast, Podcast by Adam ThomasLeave a Comment

This episode of CRACKCast covers Rosen’s Chapter 154, Lithium. You will have a solid approach to lithium overdose after listening to this episode!

Shownotes – PDF HERE

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Rosen’s In Perspective:

Lithium was approved for the treatment of bipolar disorder in 1970, and it remains one of the most effective agents for both depressive and manic symptoms.

Lithium largely has no effect when given in therapeutic doses to patients without mood disorders.

[1] How does lithium work? 

From Rosen’s:  

 “In spite of long-term therapeutic use, the mechanism by which lithium acts is still not fully understood. Its efficacy in the treatment of psychiatric illnesses is thought to be due to the modulation of neurotransmitters, which has downstream effects through cell signaling and molecular mechanisms.”

[2] What is the clinical presentation of lithium toxicity?

Acute toxicity  = GI symptoms predominate

Chronic toxicity = neurologic symptoms predominate

  • an increase in serum levels of lithium in a patient who is regularly taking lithium. This can either be from reduced excretion, renal insufficiency, or dose adjustment (either by a clinician or by the patient). Chronic lithium toxicity causes predominantly neurological symptoms.
  • “Acute-on-chronic toxicity occurs when a patient with a stable steady-state lithium level takes a substantial additional amount of lithium, whether intentional or accidental. These patients present with a combination of both acute and chronic toxicity signs and symptoms. Either acute or chronic toxicity can result in cardiac conduction abnormalities or bradycardia.” 

 

Table 154.1: Clinical Features of Lithium Toxicity

 

CLINICAL FEATURESTYPE OF TOXICITY
ACUTECHRONIC
GastrointestinalNausea
Vomiting
Diarrhea		Mild or nonexistent
NeurologicalSimilar to chronic toxicity, occurs several hours after lithium distribution to the brainTremors
Clonus
Hyperreflexia
Somnolence
Extrapyramidal symptoms
Coma
Seizures
CardiacSinus node dysfunction
AV blockade
Brugada pattern on ECG
Ischemic changes on ECG
QTc prolongation
AV, Atrioventricular; ECG, electrocardiogram.

Mnemonic time:

  • Leukostasis
  • Insipidus
  • Tremor / teratogen
  • Hypothyroidism
  • Increased weight
  • Vomiting ? nausea
  • Myocardium = ecg changes
  • Serotonin syndrome / nms like effect

[3] List risk factors for toxicity in the setting of chronic lithium use.

  • Nephrogenic DI
  • Renal impairment
  • Acute illness
  • Diuretic use, NSAIDS, ACE/ARB drugs
  • Dementia
  • Increased age
  • SILENT: cerebellar findings with pseudodementia

[4] List 4 factors which impair renal filtration of Lithium

  • Volume depletion
  • Kidney injury
  • Nephrogenic DI
  • Diuretic use

[5] List 2 disease states caused by Lithium

Here’s a bunch:

  • nephrogenic diabetes insipidus
  • Hypothyroidism (and hyperthyroidism)
    • Both of these conditions are reversible with discontinuation of the medication and respond well to conventional management.
  • Hypercalcemia and hyperparathyroidism also can occur and reverse upon discontinuation of lithium.
  • Patients chronically taking lithium can develop the syndrome of irreversible lithium-effectuated neurotoxicity (SILENT). Patients with SILENT will often have persistent cerebellar and brainstem dysfunction, dementia, and extrapyramidal signs even after lithium use has been discontinued for more than 2 months.

[6] Describe the management of lithium toxicity.

R/O differential diagnoses and co-ingestants (ASA, iron, acetaminophen, substance withdrawal, serotonin syndrome).

Box 154.1: Diagnostic Testing For Lithium:

  • Serum lithium level
  • Serum electrolytes
  • Electrocardiogram (ECG)
  • If the clinical picture dictates:
    • Acetaminophen/salicylate levels
    • Thyroid function tests

General Points

  • No antidote
  • No activated charcoal (does not bind)
  • Supportive care and enhanced elimination.
  • Early crystalloid to enhance renal elimination (initial 1L bolus then 150% of maintenance if fluid tolerant – no CHF, etc.)
  • Diuretics are contraindicated (can worsen dehydration and elimination of lithium)
  • Correct electrolyte abnormalities
  • WBI (whole bowel irrigation): not recommended by Rosen’s

[7] What are the indications for dialysis in a patient with lithium toxicity?

Dialysis can remove lithium at a rate five to seven times the rate of typical renal elimination.

Box 154.2: Indications For Dialysis in Lithium Poisoned Patients

  1. Severely symptomatic patients
  2. Unable to tolerate fluid hydration
  3. Renal impairment
  4. Acute toxicity: Levels above 4 mEq/L
  5. Chronic toxicity: Levels above 2.5 mEq/L
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Wisecracks

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 [1] List 4 common clinical scenarios for Li toxicity and describe the clinical syndromes

  • Acute toxicity
    • a recent ingestion in a patient who is not therapeutically taking lithium.
    • Acute toxicity typically manifests with gastrointestinal symptoms such as vomiting and diarrhea and can mimic many other disease states.
    • Neurologic consequences of an acute lithium overdose (such as, altered mental status and seizures) occur several hours later after lithium redistributes to the brain, but in some cases where lithium has delayed-release properties, this can occur even 12 or more hours after ingestion.
    • May have cardiac toxicity
  • Acute on chronic toxicity
    • Overlap of GI, Neuro, and cardiotoxicity (AV blockade, qtc prolonged, ischemic changes)
  • Chronic toxicity (reduced excretion, renal insufficiency, dose adjustment (either by a clinician or by the patient).
    • predominantly neurological symptoms = ataxia, EPS, tremors, seizures, coma/somnolence.
  • Lithium has also been implicated in serotonin syndrome when combined with other drugs, such as monoamine oxidase (MAO) inhibitors, selective serotonin reuptake inhibitor (SSRIs), dextromethorphan, and meperidine 

 Any changes in renal excretion due to conditions such as dehydration, hyponatremia, or renal dysfunction will lead to increases in serum lithium levels.

[2] List the ECG changes potentially seen in lithium toxicity

These are usually seen in acute overdose 

  • Bradycardia
  • Junctional rhythm / AV blockade
  • ST changes
  • QT prolongation
  • Flattened or inverted T-waves
  • Brugada pattern on ECG
  • Ischemic changes on ECG
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This post was edited and uploaded by Owen Scheirer.

 

Adam Thomas

CRACKCast Co-founder and newly minted FRCPC emergency physician from the University of British Columbia. Currently spending his days between a fellowship in critical care and making sure his toddler survives past age 5.

Chris Lipp

Chris Lipp is one of the founding Fathers for CrackCast. He currently divides his time as an EM Physician in Calgary (SHC/FMC) and in Sports Medicine (Innovative Sport Medicine Calgary). His interests are in paediatrics, endurance sports, exercise as medicine, and wilderness medical education. When he isn’t outdoors with his family, he's brewing a coffee or dreaming up an adventure…..