Lithium Toxicity

Aka: Lithium Toxicity, Lithium Poisoning, Lithium Intoxication

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II. Mechanism

  1. Lithium has a narrow therapeutic range
  2. Lithium concentrates most in CNS and renal tissue

III. Risk Factors: Toxicity

  1. Renal dysfunction (Low Glomerular Filtration Rate)
  2. Volume depletion (associated with greater Lithium reabsorption)
    1. Vomiting or Diarrhea
    2. Acute Heart Failure
    3. Cirrhosis
    4. Diuretics
  3. Medications
    1. Thiazide Diuretics (e.g. Hydrochlorothiazide, Chlorthalidone)
    2. ACE Inhibitors
    3. NSAIDS

IV. Findings: Gastrointestinal

  1. Nausea or Vomiting
  2. Diarrhea

V. Findings: Neurologic (late sign in acute toxicity, common in chronic toxicity)

  1. Listless or sluggish
  2. Ataxia
  3. Confusion
  4. Agitation
  5. Tremors or Myoclonic Jerks
  6. Seizures and encephalopathy (severe cases)

VI. Labs: General

  1. Complete Blood Count (CBC)
    1. White Blood Cell Count is commonly increased with Lithium Toxicity
  2. Serum chemistry (chem8)
    1. Nephrotoxicity (assoc. with chronic Lithium Toxicity)
      1. Increased Serum Creatinine, Blood Urea Nitrogen
    2. Nephrogenic Diabetes Insipidus
      1. Hyponatremia
  3. Urine Pregnancy Test
  4. Thyroid Stimulating Hormone (TSH)
    1. Hypothyroidism or Hyperthyroidism
  5. Unknown Ingestion and Altered Level of Consciousness testing
    1. Acetaminophen Level
    2. Salicylate Level
    3. Urine Drug Screen
    4. Serum Glucose

VII. Labs: Lithium Level

  1. Precautions
    1. Peak levels may not be reached for >12 hours after Overdose of sustained release Lithium
    2. For a given level, symptoms may be more mild in acute toxicity than in chronic toxicity
  2. Therapeutic Level: 0.8 to 1.2 mEq/L
  3. Mild Toxicity: 1.5 to 2.5 mEq/L
    1. Tremor
    2. Slurred Speech
    3. Listlessness
  4. Moderate Toxicity: 2.5 to 3.5 mEq/L
    1. Coarse Tremor
    2. Myoclonic Jerks
  5. Severe Toxicity: >3.5 mEq/L
    1. Encephalopathy
    2. Seizures

VIII. Diagnostics

  1. Electrocardiogram
    1. T Wave Flattening
    2. QTc Prolongation
    3. Bradycardia

IX. Differential Diagnosis

  1. See Altered Level of Consciousness
  2. See Unknown Ingestion
  3. Serotonin Syndrome
  4. Neuroleptic Malignant Syndrome
  5. Alcohol Withdrawal
  6. Benzodiazepine Withdrawal
  7. Closed Head Injury
  8. Cerebrovascular Accident

X. Management: General

  1. See ABC Management
  2. Gastric Decontamination (acute toxicity only)
    1. AVOID Activated Charcoal (no benefit)
    2. Whole Bowel Irrigation
      1. Consider in awake asymptomatic patients within 2-4 hours of large Lithium SR ingestion
      2. Give 500 to 2000 ml Polyethylene Glycol via Nasogastric Tube until rectal output clear
  3. Fluid Resuscitation
    1. First-line management of Lithium Toxicity
    2. Isotonic crystalloid (NS or LR)
      1. Administer IV hydration at twice maintenance for 2-3 Liters of crystalloid
      2. Rate of replacement should be decreased if Hyponatremia (prevent Central Pontine Myelinolysis)
  4. Altered Mental Status
    1. See Altered Level of Consciousness
    2. See Unknown Ingestion
    3. Bedside Serum Glucose (and treat Hypoglycemia)
    4. Consider Naloxone
    5. Consider Thiamine
  5. Seizures
    1. See Status Epilepticus
    2. Benzodiazepines
  6. Disposition
    1. Admit Lithium Toxicity to medical ward (severe toxicity to ICU)
    2. May discharge when patient is asymptomatic and serum Lithium <1.5 mEq/L

XI. Management: Hemodialysis Indications

  1. Serum Lithium Level >5 mEq/L
  2. Serum Lithium Level >4 mEq/L AND concurrent Serum Creatinine >2.0 mg/dl)
  3. Serum Lithium Level >2.5 mEq/L AND
    1. Neurologic symptoms (Seizures, decreased mental status) OR
    2. Conditions in which flud Resuscitation is limited (e.g. Congestive Heart Failure) OR
    3. Conditions limiting Lithium excretion (e.g. Renal Failure)
  4. Serum Lithium Level >1.5 mEq/L AND
    1. Life threatening complications attributed to Lithium Toxicity
    2. Increasing serum Lithium levels despite maximal medical therapy with fluid Resuscitation

XII. Complications: Chronic Lithium Toxicity

  1. Syndrome of Irreversible Lithium Effectuated Neurotoxicity (SILENT)
    1. Persistent neurologic and psychiatric effects despite Lithium discontinuation
    2. Effects may include Extrapyramidal Effects, Dementia, Ataxia, Brainstem or cerebellar dysfunction
  2. Nephrogenic Diabetes Insipidus
  3. Thyroid Dysfunction

XIII. References

  1. Perrone and Chatterjee (2018) UpToDate, accessed 8/20/2018
  2. Micromedex, accessed 8/20/2018
  3. Mike Avila, MD (2018), email communication, received 8/15/2018

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