10. Lithium Toxicity

Pharmacokinetics

  • Lithium is a small, positively charged ion.
  • Narrow therapeutic index (0.8-1.2 mEq/L); many patients on lithium for long periods of time will endure a toxic event at least once during their treatment. 
  • Absorbed by the gastrointestinal tract. Peak blood levels 1-2 hours post-ingestion for immediate release formulation, and 4-6 hours post-ingestion for sustained release formulation. Acute, large volume overdose may lead to delay in peak levels up to 12 hours.
  • Excreted by the kidneys. Volume depletion will lead to increased lithium absorption, similar to sodium.

At Risk Populations

Lithium toxicity generally fall into two categories:

  • Acute toxicity: high dose lithium ingestion (usually intentional) in a patient with normal renal function. These patients tend to have a misleadingly high level, particularly if checked within the first 6-8 hours before it has fully distributed to tissues.
  • Chronic toxicity: chronic lithium therapy in a patient with sudden decrease in renal function. Causes for decreased GFR can include dehydration, recent illness, diuretics, NSAIDS, ACE inhibitors, and heart failure. Elderly patients are particularly at risk for toxicity given decreased GFR and total body water.

Signs and Symptoms

Acute toxicity:

  • GI: nausea, vomiting, diarrhea are all very common, and can exacerbate toxicity due to subsequent dehydration.
  • Cardiac: QT prolongation, bradycardia, T wave inversions. Life-threatening arrhythmias are rare.
  • Neurology: sluggishness, ataxia, delirium, agitation, tremors, ataxia, rigidity, fasciculations, myoclonic jerks. Severe toxicity can lead to seizures, nonconvulsive status epilepticus, and encephalopathy. Neurologic symptoms are usually late findings, as lithium takes time to be absorbed and cross blood brain barrier.

Chronic toxicity:

  • Neuro: same as above, though in contrast to acute toxicity, in chronic toxicity the neurologic symptoms develop gradually and are often part of presenting complaint. 
  • Cardiac: same as above.
  • Renal: nephrogenic diabetes insipidus with volume depletion secondary to urinary water loss.

Evaluation

  • Obtain lithium level on presentation, though note that peak levels may occur hours afterwards, especially in acute ingestions of sustained-release formulations. One normal level should not be reassuring in high-risk patients. Continue checking lithium level for every 2-4 hours to ensure improvement after therapy has been initiated.
  • Note that lithium level is NOT an accurate predictor of toxicity. For patients with chronic ingestion, even a slight elevation in level can lead to toxicity.
  • Must check lithium in lithium-free tube. Otherwise, can have a false positive up to 6-8 mEq/L!
  • Elimination half-life increases with chronicity of use, so long-term users may require longer monitoring.
  • Check BMP, with attention to sodium and creatinine levels to assess for prerenal AKI and nephrogenic diabetes insipidus. Continue checking sodium every 4-6 hours for first 24-48 hours, even as treatment is initiated.
  • Check ECG to look for cardiac toxicity.
  • Check CBC; note that lithium increases WBC, even in the absence of infection.
  • Any acid-base disturbance should prompt consideration of co-ingestion.

Management

  • Hydration:
    • IV hydration with isotonic saline, roughly 2-3L if possible.
    • Check serum sodium every 4-6 hours in patients with lithium-induced nephrogenic diabetes insipidus.
    • Can switch to ½NS after initial resuscitation to decrease risk of hypernatremia with diabetes insipidus.
    • Monitor UOP closely.
  • Gastrointestinal decontamination:
    • Whole bowel irrigation: can administer polyethylene glycol via NG tube in patients who present within 2-3 hours after acute ingestion for more than 10-15 tablets of sustained-release formulation. Only appropriate for awake, asymptomatic patients; otherwise, it is contraindicated. Not useful in immediate-release formulation or in chronic toxicity.
    • Activated charcoal does not bind to lithium and is not useful in management of lithium toxicity. Can still be used if co-ingestion is suspected.
  • Hemodialysis:
    • Treatment of choice for severe toxicity. Consult nephrology early if any concern for need for dialysis. Indications remain controversial.
    • Hemodialysis is recommended:
      • Any patient with decreased level of consciousness, seizures, or life-threatening complications, regardless of lithium level.
      • Serum lithium >4 mEq/L with impaired kidney function.
    • Hemodialysis is suggested:
      • Serum lithium >5 mEq/L.
      • Confusion is present.
      • Expected time to obtain Li <1 mEq/L with optimal management is >36 hours.

Key Points

  • Lithium level correlates poorly with degree of toxicity. May be falsely elevated soon after acute ingestion, or just slightly elevated in chronic toxicity.
  • Monitor closely for development of nephrogenic diabetes insipidus.
  • Consider dialysis for severe toxicity.

 

Baird-Gunning J, Lea-Henry T, Hoegberg LCG, Gosselin S, Roberts DM. Lithium Poisoning. J Intensive Care Med. 2017;32(4):249‐263.

Decker BS, Goldfarb DS, Dargan PI, et al. Extracorporeal Treatment for Lithium Poisoning: Systematic Review and Recommendations from the EXTRIP Workgroup. Clin J Am Soc Nephrol. 2015;10(5):875‐887.

Okusa MD, Crystal LJ. Clinical manifestations and management of acute lithium intoxication. Am J Med. 1994;97(4):383-9.