Signs of Lithium Toxicity
Lithium toxicity presents with gastrointestinal and neurological symptoms that progress in severity as serum levels rise, with early signs including diarrhea, vomiting, drowsiness, muscular weakness, and lack of coordination appearing even at levels below 2.0 mEq/L. 1
Early Warning Signs (Levels < 2.0 mEq/L)
The FDA emphasizes that early manifestations of lithium toxicity can occur at therapeutic or near-therapeutic levels and include: 1
- Gastrointestinal symptoms: Diarrhea, nausea, vomiting, and anorexia 1
- Neuromuscular signs: Drowsiness, muscular weakness, lack of coordination, and fine hand tremor 1
- Dehydration-related symptoms: Fatigue, reduced urine output, dizziness, muscle weakness, excessive sweating—these indicate decreased lithium clearance and heightened toxicity risk requiring immediate medical evaluation 2
Moderate Toxicity Signs (Levels 1.5-2.5 mEq/L)
As toxicity progresses, the FDA notes additional neurological manifestations emerge: 1
- Ataxia (loss of coordination) and giddiness 1
- Blurred vision and tinnitus 1
- Large output of dilute urine (polyuria) 1
- Slurred speech and confusion 1, 3
- Tremor progression: From fine hand tremor to coarse tremor and muscle hyperirritability (fasciculations, twitching, clonic movements) 1
A critical caveat: The American Heart Association warns that lithium toxicity can mimic stroke with confusion, ataxia, and altered consciousness, making medication history and lithium levels essential in any patient presenting with acute neurological changes 3. Additionally, patients may exhibit clinical toxicity even with "normal" serum lithium levels, particularly in chronic toxicity scenarios 4.
Severe Toxicity Signs (Levels > 2.5-3.0 mEq/L)
The FDA describes a complex clinical picture involving multiple organ systems at higher levels: 1
- Central nervous system: Seizures, stupor, coma, somnolence, psychomotor retardation, restlessness, blackout spells, incontinence of urine or feces, downbeat nystagmus 1
- Cardiovascular complications: Cardiac arrhythmias, hypotension, peripheral circulatory collapse, severe bradycardia with sinus node dysfunction (potentially causing syncope) 2, 1, 5
- Neurological: Choreo-athetotic movements, hyperactive deep tendon reflexes, acute dystonia 1
Additional Clinical Manifestations
Beyond the dose-related effects, the FDA notes other important signs: 1
- Renal: Polyuria, oliguria, albuminuria, glycosuria 1
- Thyroid: Euthyroid goiter, hypothyroidism with myxedema 1
- Dermatologic: Drying and thinning of hair, skin anesthesia 1
- Autonomic: Dry mouth, blurred vision 1
- Cardiac rhythm changes: Reversible T-wave flattening, isoelectricity, or inversion 1
Critical Monitoring Points
The FDA emphasizes that toxicity risk begins at 1.5 mEq/L, with serious toxicity at levels >2.0 mEq/L, though sensitive patients may exhibit toxic signs below 1.5 mEq/L 2, 1. During acute treatment, serum levels should not exceed 2.0 mEq/L and require twice-weekly monitoring until stabilized 2, 6.
Important pitfall: Blood collected in lithium heparin tubes can produce artificially elevated levels, potentially leading to misdiagnosis 7. Always treat the clinical presentation, not just the numbers, as chronic toxicity can manifest with normal serum levels due to intracellular lithium accumulation 4.