Lithium Toxicity Clinical Presentation

As with all toxic ingestions, it is important to determine the amount, time, co-ingestants, and reason for ingestion. Toxicity does not often correlate with the measured lithium level since clinical toxicity is affected by the type of the poisoning.

Clinical features

Three main categories of patients who are poisoned are as follows: acute, acute-on-chronic, and chronic.

Acute: These patients usually do not have a tissue body burden and symptoms are predominately GI including nausea, vomiting, cramping, and sometimes diarrhea. Progression of acute toxicity can involve neuromuscular signs such as tremulousness, dystonia, hyperreflexia, and ataxia. Cardiac dysrhythmias have been reported but rarely occur. The most common ECG finding is T-wave flattening.

Acute-on-chronic: These patients take lithium regularly and have taken a larger dose recently. These patients may display both GI and neurologic symptoms, and serum levels can be difficult to interpret. Patients should be treated according to their clinical manifestations.

Chronic: These patients typically have a large body burden of lithium and may be difficult to treat. Chronic lithium toxicity is usually precipitated with introduction of new medication that may impair renal function/excretion or cause a hypovolemic state. Symptoms are primarily neurologic. Mental status is often altered and can progress to coma and seizures if the diagnosis is unrecognized. Many severely poisoned patients can develop a syndrome of irreversible lithium-effectuated neurotoxicity (SILENT) such as cognitive impairment, sensorimotor peripheral neuropathy, and cerebellar dysfunction.

Drug interactions

Three major drug classes have been identified as potential precipitants of lithium toxicity:

• Diuretics that promote renal sodium wasting
• Angiotensin-converting enzyme (ACE) inhibitors that reduce glomerular filtration rate (GFR) and enhance the tubular reabsorption of lithium
• Nonsteroidal anti-inflammatory drugs (NSAIDs) that reduce GFR and interrupt of renal prostaglandin synthesis

Systemic effects

Renal toxicity is common with chronic lithium therapy, with nephrogenic diabetes insipidus being the most severe manifestation. Lithium inhibits the action of antidiuretic hormone (ADH) on the distal renal tubule, impairing sodium and water reabsorption. Other manifestations of lithium toxicity on the kidney include renal tubular acidosis, chronic tubulointerstitial nephritis, and nephrotic syndrome.

The most common endocrine disorder secondary to chronic toxicity is hypothyroidism. Lithium is taken up avidly by thyroid cells and blocks thyroid hormone release from thyroglobulin, which inhibits adenylate cyclase and prevents thyroid-stimulating hormone (TSH) from activating thyroid cells via the TSH receptor. It may also affect thyroid hormone synthesis. Myxedema coma has been reported as a complication of toxicity.

Acute exposure to lithium can cause leukocytosis, whereas chronic exposure can produce aplastic anemia.

Patients who are on chronic lithium therapy can develop localized edema, dermatitis, and skin ulcers.

Neurologic effects of lithium toxicity include tremors, lethargy, confusion, seizures, and coma.

GI effects of lithium toxicity include nausea, vomiting, crampy abdominal pain, and diarrhea.

Mild-to-moderate lithium toxicity is characterized by tremor, weakness, and mild confusion.

Moderate-to-severe lithium toxicity is characterized by altered mental status, muscle fasciculations, stupor, seizures, coma, hyperreflexia, and cardiovascular collapse.