How do I assess chronic lithium toxicity, including history, physical examination, and laboratory evaluation?

Assessment of Chronic Lithium Toxicity

Chronic lithium toxicity assessment requires a systematic evaluation focusing on neurological symptoms, renal function, and serum lithium levels, recognizing that toxicity can occur even at therapeutic levels in patients with impaired renal function or medication interactions. 1, 2

Clinical History: Key Elements to Identify

Duration and dosing history:

• Document current lithium dose, duration of therapy, and any recent dose changes 1
• Identify if toxicity developed during stable maintenance therapy (most common presentation in chronic toxicity) 3
• Review medication adherence patterns 4

Precipitating factors:

• Renal impairment is the most critical predisposing factor—assess for any decline in kidney function 3, 5
• Concomitant medications: NSAIDs, ACE inhibitors, ARBs, and thiazide diuretics significantly increase lithium levels and toxicity risk 1, 6
• Dehydration/water loss: Impaired renal concentrating ability leading to water loss is a major precipitating factor 3, 7
• Recent intercurrent illness, vomiting, diarrhea, or fever 6
• Recent IV radiocontrast administration or bowel preparation 6

Symptom assessment:

• Early/mild signs: Tremor (especially fine hand tremor), nausea, diarrhea, polyuria-polydipsia, vomiting, drowsiness, muscular weakness, lack of coordination 6, 2
• Moderate severity: Confusion, slurred speech, ataxia, giddiness, blurred vision, tinnitus, large output of dilute urine 2
• Severe toxicity: Stupor, coma, seizures, severe tremor, muscle fasciculations/twitching, hyperactive deep tendon reflexes, incontinence 2
• Chronic-specific symptoms: Tremor and dysarthria occur more frequently in chronic (not overdose-related) toxicity 5

Physical Examination: Focused Assessment

Neurological examination (most critical):

• Mental status: Assess for confusion, somnolence, stupor, or coma 2
• Motor function: Fine tremor, coarse tremor, muscle fasciculations, twitching, clonic movements, ataxia, choreo-athetotic movements 2
• Deep tendon reflexes: Hyperactive reflexes suggest toxicity 2
• Coordination testing: Ataxia is a key finding 2
• Cranial nerves: Assess for nystagmus (particularly downbeat nystagmus), slurred speech 2

Cardiovascular examination:

• Vital signs: Hypotension, bradycardia (sinus node dysfunction can cause severe bradycardia and syncope) 2
• Cardiac rhythm assessment for arrhythmias 2

Volume status assessment:

• Signs of dehydration: Dry mucous membranes, poor skin turgor, orthostatic hypotension 3, 7
• Urine output: Polyuria or oliguria 2

Other systems:

• Thyroid examination: Goiter (hypothyroidism occurs in 20-30% of long-term lithium patients) 1

Laboratory Evaluation: Essential Tests

Immediate priority tests:

• Serum lithium level: Draw 12 hours post-dose for accurate interpretation; levels >1.5 mEq/L carry greater toxicity risk, though sensitive patients may show toxicity below 1.5 mEq/L 2
• Serum creatinine and eGFR: Creatinine clearance <50 mL/min is a significant predictor of chronic lithium toxicity 5
• Serum electrolytes: Sodium, potassium (potassium >5.5 mmol/L requires dose review) 1
• Blood urea nitrogen (BUN) 1

Additional baseline/monitoring tests:

• Complete blood count with differential 1
• Thyroid function tests (TSH, free T4) 1
• Serum calcium (hypercalcemia occurs in ~25% of long-term patients; check PTH if elevated) 1
• Urinalysis 1
• ECG: Assess for T-wave flattening/inversion, QT prolongation, conduction abnormalities 2

Interpretation of renal function changes:

• Up to 30% increase in creatinine from baseline is acceptable and does not require immediate intervention 1
• Creatinine increase >50% or >266 μmol/L: Review other nephrotoxic medications and consider dose reduction 1
• Creatinine increase >100% or >310 μmol/L: Discontinue lithium 1

Critical Distinctions: Acute vs. Chronic Toxicity

Chronic toxicity (during maintenance therapy) presents differently:

• More severe neurological symptoms despite lower serum levels compared to acute overdose 8, 3
• Longer duration of hospitalization required 5
• Higher risk of permanent neurological sequelae 3
• Often preceded by disorders of water and electrolyte metabolism 3

Acute overdose toxicity:

• Frequently presents with milder symptoms despite potentially lethal serum levels (≥3.5 mEq/L) 8
• May not require hemodialysis even at levels >3.5 mEq/L if symptoms are mild 8

Common Pitfalls to Avoid

• Do not rely solely on serum lithium level: Chronic toxicity severity correlates poorly with serum levels; clinical symptoms are paramount 3, 5
• Do not overlook renal function: Renal impairment is the most important predisposing factor and predictor of chronic toxicity 3, 5
• Do not miss medication interactions: Always review NSAIDs, ACE inhibitors, ARBs, and thiazides 1, 6
• Do not delay assessment in patients with "therapeutic" levels: Toxicity can occur at levels below 1.5 mEq/L in sensitive patients or those with chronic exposure 2
• Do not assume sodium loading is beneficial: Sodium chloride infusion has no specific effect on lithium excretion and can cause hypernatremia 3, 7