In a patient taking lithium who develops gastrointestinal, neurologic, cardiac, or renal symptoms, how is lithium toxicity diagnosed (including serum lithium level thresholds) and managed, and when is emergent hemodialysis indicated?

Lithium Toxicity: Diagnosis and Management

Immediate Diagnostic Approach

In patients on lithium presenting with gastrointestinal, neurologic, cardiac, or renal symptoms, obtain a serum lithium level immediately and assess for toxicity based on clinical presentation rather than relying solely on the level, as chronic toxicity produces severe symptoms even at lower concentrations than acute overdose. 1, 2

Critical Diagnostic Considerations

Distinguish between three patterns of toxicity, as they have different clinical implications:

• Acute toxicity (single overdose in lithium-naive patients): Often produces mild symptoms despite potentially lethal levels (>3.5 mEq/L), as lithium has not yet distributed into tissues 1
• Acute-on-chronic toxicity (overdose in patients on maintenance therapy): Intermediate severity 3
• Chronic toxicity (accumulation during maintenance therapy): Most common pattern, produces the most severe neurologic symptoms at lower serum levels because intracellular lithium is elevated 1, 2, 3

Serum Lithium Level Thresholds

The FDA establishes that toxicity risk begins at 1.5 mEq/L, with serious toxicity occurring at >2.0 mEq/L, though these thresholds apply primarily to acute toxicity. 4

• Therapeutic range: 0.6-1.2 mEq/L (acute treatment); 0.2-0.6 mEq/L (augmentation therapy) 4
• Toxicity threshold: ≥1.5 mEq/L 4
• Severe toxicity: >2.0 mEq/L 4
• Potentially lethal: ≥3.5 mEq/L 1

Critical pitfall: In chronic toxicity, serum levels correlate poorly with clinical severity—patients may have severe neurologic toxicity with levels only modestly elevated above therapeutic range. 1, 2

Avoid collection error: Blood must not be collected in lithium heparin tubes, which artificially elevate levels. 5

Clinical Manifestations by System

Neurologic Symptoms (Primary Site of Toxicity)

• Confusion, altered mental status, agitation 6, 3, 7
• Ataxia, tremor, myoclonic jerks 6, 3
• Seizures 3
• Coma in severe cases 3
• Can mimic stroke presentation 6

Gastrointestinal Symptoms

• Nausea, vomiting 8
• Diarrhea 3

Cardiovascular Symptoms

• Arrhythmias 1, 3
• ECG changes 3

Renal Manifestations

• Acute kidney injury (often precipitating factor) 3, 7
• Nephrogenic diabetes insipidus (may cause volume depletion leading to toxicity) 3

Management Algorithm

Step 1: Stabilize and Support

• Ensure airway, breathing, circulation 3
• Obtain IV access and initiate fluid resuscitation if volume depleted 2, 3
• Monitor cardiac rhythm 3
• Check renal function, electrolytes, and serial lithium levels 2, 3

Step 2: Discontinue Lithium and Identify Precipitants

• Stop lithium immediately 3
• Identify causes of chronic toxicity: volume depletion, renal impairment, drug interactions (especially NSAIDs), intercurrent illness 4, 3

Step 3: Determine Need for Enhanced Elimination

Base the decision on clinical toxicity severity, exposure pattern, and serial lithium levels—not a single spot level. 2, 3

Indications for Emergent Hemodialysis

Hemodialysis is indicated for patients with severe clinical toxicity (altered mental status, seizures, life-threatening arrhythmias) combined with elevated lithium levels, particularly in chronic or acute-on-chronic toxicity. 1, 2, 3

Specific Hemodialysis Criteria:

Perform emergent hemodialysis when:

• Severe neurologic symptoms (confusion, seizures, coma) with any lithium level above therapeutic range in chronic toxicity 1, 2
• Lithium level >4.0 mEq/L regardless of symptoms 3
• Renal failure preventing lithium elimination 3, 7
• Deteriorating clinical status despite supportive care 3

Consider hemodialysis when:

• Lithium level 2.5-4.0 mEq/L with moderate symptoms 3
• Acute-on-chronic toxicity with levels >3.5 mEq/L 1

Hemodialysis may NOT be necessary when:

• Acute toxicity (single overdose) with mild symptoms, even if level >3.5 mEq/L, as these patients often recover with supportive care alone 1
• In one series, 5 patients with acute toxicity and levels of 4.7-5.7 mEq/L recovered without dialysis or permanent sequelae 1

Hemodialysis Technical Considerations:

• Lithium is readily dialyzable 3
• Continuous veno-venous hemodialysis (CVVHD) effectively removes lithium and may be preferred in hemodynamically unstable patients 7
• Monitor for rebound elevation in lithium levels post-dialysis due to redistribution from tissues; serial levels and repeat dialysis may be necessary 2, 3

Key Clinical Pitfalls

The most dangerous error is relying on serum lithium levels alone in chronic toxicity—clinical symptoms are paramount. 1, 2 Patients on chronic therapy develop severe neurotoxicity at lower serum levels because intracellular concentrations are elevated 2, 3

Do not withhold dialysis in symptomatic chronic toxicity based solely on a "not high enough" lithium level. 1, 2

Conversely, avoid unnecessary dialysis in acute overdose patients with high levels but minimal symptoms, as they typically recover with supportive care. 1