Can substantial or prolonged bismuth exposure cause neurotoxicity and encephalopathy?

Bismuth-related encephalopathy is uncommon but clinically important because it is potentially reversible. The evidence supports the claim that substantial or prolonged exposure can produce a neurotoxic syndrome, and that impaired elimination—especially renal impairment—can increase systemic accumulation and susceptibility.

Clinical evidence

• Historical case reports and a 45-patient bismuth-subnitrate series describe confusion/delirium, cognitive and behavioral changes, reduced alertness, myoclonus, ataxia, tremor, dysarthria, hallucinations, seizures, and encephalopathy after substantial exposure.
• In that series, blood bismuth concentrations were 150–1,600 µg/L and urinary concentrations 200–9,600 µg/L. All patients recovered within 3–12 weeks of stopping bismuth, although memory or behavioral deficits sometimes persisted longer.
• A chronic bismuth-subsalicylate case after approximately 20 years of use documented confusion, instability, myoclonus, and impaired alertness with elevated serum, urine, and CSF bismuth. Clinical recovery followed discontinuation and supportive care.

Elimination and mechanism

• Bismuth undergoes urinary and biliary elimination and has prolonged multicompartment kinetics: reported intermediate half-lives are 5–11 days and terminal half-lives 21–72 days.
• Reduced creatinine clearance is associated with approximately 3–5-fold higher trough plasma bismuth concentrations, with urinary concentrations remaining elevated for weeks. Thus, renal dysfunction can convert repeated exposure into sustained body burden.
• A patient with severe CKD (creatinine clearance 15 mL/min) developed hallucinations, ataxia, confusion, and EEG abnormalities after two months of high-dose exposure; cognition improved as bismuth levels declined after cessation.

Clinical interpretation

• No validated blood, urine, or CSF bismuth threshold confirms toxicity; concentrations should support, not replace, assessment for metabolic, infectious, structural, seizure-related, medication-related, and other toxic causes.

Bottom line

• Substantial or prolonged bismuth exposure can cause reversible confusion, cognitive change, and encephalopathy, with reduced renal elimination materially increasing concern for accumulation and neurotoxicity.