What are the cardiac effects of lithium therapy?

Cardiac Effects of Lithium Therapy

Lithium produces reversible T wave changes on ECG at therapeutic levels and can cause serious cardiac complications including sinus node dysfunction, bradyarrhythmias, and rarely cardiomyopathy, particularly at toxic levels or in patients with pre-existing cardiac disease. 1, 2

ECG Monitoring Requirements

ECG monitoring is indicated before initiating lithium therapy and during treatment, particularly in patients over 50 years or those with cardiac disease. 3, 4

• Baseline ECG should be obtained before starting lithium therapy 3
• Serial ECGs are warranted after initiation of lithium therapy, after dose changes, and when adding interacting medications 3
• More frequent ECG monitoring is recommended for patients over age 50 or with known cardiac disease 4
• Regular monitoring of serum lithium levels (twice weekly during acute phase until stabilized, then every 3-6 months) helps prevent toxicity-related cardiac effects 5, 6

Common Cardiac Effects at Therapeutic Levels

Electrocardiographic Changes

T wave flattening and inversion are the most frequently reported ECG findings with lithium, occurring even at therapeutic doses and are generally reversible. 1, 7, 2

• T wave changes (flattening, isoelectricity, or inversion) are the most common ECG abnormality 1, 2
• These changes are reversible and not directly related to serum lithium levels 1
• Diffuse slowing and widening of frequency spectrum may occur on EEG 1

Arrhythmias at Therapeutic Levels

Lithium may precipitate or aggravate ventricular arrhythmias even at therapeutic levels 8:

• Premature ventricular contractions may increase in frequency 8
• Sinus node dysfunction can occur, though rarely 7, 4
• Atrial arrhythmias may actually improve during lithium therapy in some patients 8
• Cardiovascular performance as measured by exercise testing remains unchanged 8

Cardiac Effects in Lithium Toxicity

Severe cardiac complications occur primarily with lithium toxicity (levels >1.5 mEq/L), with cardiovascular collapse typically following prolonged neurologic toxicity. 1, 9

Toxicity-Related Cardiac Manifestations

Lithium intoxication causes significant cardiovascular effects including arrhythmias, ECG alterations, hypotension, and myocardial dysfunction 9:

• Cardiac arrhythmias and sinus node dysfunction with severe bradycardia (potentially causing syncope) 1
• Hypotension and peripheral circulatory collapse 1
• Symptomatic bradycardia and advanced AV block 9
• Cardiomyopathy with left ventricular systolic dysfunction 10
• Junctional escape rhythms with bundle branch morphology 10

Severity Correlation

The severity of cardiac symptoms does not always correlate with serum lithium levels, particularly in chronic versus acute intoxication 9:

• Toxic signs may appear at levels below 1.5 mEq/L in sensitive patients 1
• Levels above 3 mEq/L produce complex multi-organ toxicity 1
• Cardiovascular collapse invariably follows days of coma in severe toxicity 7

Management of Cardiac Complications

Treatment of Toxicity-Related Arrhythmias

For arrhythmias related to lithium toxicity, correct electrolytes (especially potassium and magnesium) and initiate hemodialysis as primary treatments. 9

• Avoid antiarrhythmic drugs that prolong QT interval (amiodarone, sotalol) if QT prolongation is already present 9
• Atropine may be used for symptomatic bradycardia 10
• Transvenous pacing is reserved for severe hemodynamic compromise unresponsive to medical management 10

Hemodialysis Indications

Hemodialysis is indicated urgently for severe lithium intoxication with serum levels ≥3.5 mEq/L and significant symptoms, or at any level with significant cardiovascular compromise. 9

Specific cardiovascular indications for urgent hemodialysis include 9:

• Symptomatic bradycardia
• Advanced AV block
• Refractory hypotension despite vasopressor support

Continue hemodialysis until lithium level <1.0 mEq/L after redistribution (generally 6-8 hours, with measurement 4-6 hours post-dialysis to evaluate rebound) 9

Hypotension Management

For lithium-induced hypotension 9:

• Administer intravenous fluids as first-line therapy
• Use vasopressors (norepinephrine) if hypotension persists
• Initiate urgent hemodialysis if hypotension remains refractory despite support

Prevention Strategies

Temporarily suspend lithium during intercurrent illness, planned IV radiocontrast administration, bowel preparation, or prior to major surgery. 9, 5

Additional preventive measures include 9, 5:

• Avoid concomitant NSAIDs, which increase lithium levels
• Maintain adequate hydration, especially during illness
• Monitor for dehydration, medication interactions, and renal impairment
• Regular monitoring of lithium levels, electrolytes, and renal function

Special Populations

Patients with Pre-existing Cardiac Disease

Lithium may be used safely in patients with cardiac disease if doses are adjusted to renal clearance and serum levels are monitored carefully. 7

Critical considerations for cardiac patients 7, 8:

• Recognize factors interfering with renal lithium clearance (heart failure, salt restriction, long-term diuretic therapy)
• Adjust doses accordingly based on renal function
• Frequent ECG monitoring is advised when used in patients with ventricular arrhythmias
• Careful pulse monitoring in all patients taking lithium 4

Elderly Patients

Patients over age 50 require more intensive cardiac monitoring due to higher risk of sinus node dysfunction 4

Common Pitfalls

• Failing to recognize that cardiovascular collapse in lithium toxicity typically follows prolonged neurologic symptoms - monitor for neurologic signs (drowsiness, confusion, tremor) as early warning 1, 7
• Assuming cardiac symptoms correlate directly with serum levels - chronic toxicity may cause severe cardiac effects at lower levels than acute toxicity 9
• Continuing lithium during intercurrent illness - dehydration and acute kidney injury dramatically increase toxicity risk 9, 10
• Using QT-prolonging antiarrhythmics when lithium has already caused QT changes - this compounds the risk of torsades de pointes 9