What are the clinical manifestations of lithium toxicity at specific blood concentrations and their indicated therapies?

From the Guidelines

Lithium toxicity is a medical emergency that requires immediate attention, and treatment should be guided by blood concentrations, with severe toxicity (>3.5 mEq/L) necessitating hemodialysis and intensive care monitoring. Lithium toxicity severity and treatment depend on blood concentrations, and regular monitoring of GFR, electrolytes, and drug levels is crucial for individuals taking lithium, as recommended by the 2014 American Journal of Kidney Diseases study 1.

Clinical Manifestations and Therapies

• Mild toxicity (1.5-2.5 mEq/L):
  • Discontinue lithium
  • Increase fluid intake
  • Monitor serum levels closely
• Moderate toxicity (2.5-3.5 mEq/L):
  • Discontinue lithium
  • IV fluids (normal saline)
  • Consider activated charcoal if recent ingestion
  • Monitor ECG, electrolytes, and renal function
• Severe toxicity (>3.5 mEq/L):
  • Discontinue lithium
  • IV fluids (normal saline)
  • Hemodialysis
  • Intensive care monitoring For all levels, treat symptoms as needed (e.g., antiemetics for nausea) and restart lithium at a lower dose once toxicity resolves and the underlying cause is addressed.

Key Considerations

• Lithium has a narrow therapeutic index, and toxicity can occur even at therapeutic doses, emphasizing the importance of regular monitoring, as highlighted in the 2014 study 1.
• Renal function, dehydration, and drug interactions can increase lithium levels, making close monitoring crucial during treatment.
• Hemodialysis is highly effective in severe cases due to lithium's small size and lack of protein binding.

Monitoring and Treatment

Regular monitoring of serum lithium levels, renal function, and electrolytes is essential for early detection and management of lithium toxicity, as recommended by the study 1. Treatment should be tailored to the severity of toxicity, with a focus on supportive care, discontinuation of lithium, and, in severe cases, hemodialysis.

From the FDA Drug Label

The likelihood of toxicity increases with increasing serum lithium levels. Serum lithium levels greater than 1.5 mEq/l carry a greater risk than lower levels. However, patients sensitive to lithium may exhibit toxic signs at serum levels below 1.5 mEq/l. Diarrhea, vomiting, drowsiness, muscular weakness and lack of coordination may be early signs of lithium toxicity, and can occur at lithium levels below 2 mEq/l. At higher levels, giddiness, ataxia, blurred vision, tinnitus and a large output of dilute urine may be seen. Serum lithium levels above 3 mEq/l may produce a complex clinical picture involving multiple organs and organ systems Treatment: No specific antidote for lithium poisoning is known Early symptoms of lithium toxicity can usually be treated by reduction or cessation of dosage of the drug and resumption of the treatment at a lower dose after 24 to 48 hours. In severe cases of lithium poisoning, the first and foremost goal of treatment consists of elimination of this ion from the patient Treatment is essentially the same as that used in barbiturate poisoning: 1) gastric lavage, 2) correction of fluid and electrolyte imbalance and 3) regulation of kidney functioning. Urea, mannitol, and aminophylline all produce significant increases in lithium excretion. Hemodialysis is an effective and rapid means of removing the ion from the severely toxic patient

The clinical manifestations of lithium toxicity at specific blood concentrations are:

• Below 1.5 mEq/l: patients sensitive to lithium may exhibit toxic signs
• Below 2 mEq/l: early signs of lithium toxicity, such as diarrhea, vomiting, drowsiness, muscular weakness, and lack of coordination
• Above 1.5 mEq/l: increased risk of toxicity
• Above 2 mEq/l: giddiness, ataxia, blurred vision, tinnitus, and a large output of dilute urine
• Above 3 mEq/l: complex clinical picture involving multiple organs and organ systems

Indicated therapies for lithium toxicity include:

• Reduction or cessation of dosage
• Resumption of treatment at a lower dose after 24 to 48 hours
• Gastric lavage
• Correction of fluid and electrolyte imbalance
• Regulation of kidney functioning
• Urea, mannitol, and aminophylline to increase lithium excretion
• Hemodialysis for severe cases 2, 3

From the Research

Clinical Manifestations of Lithium Toxicity

• Lithium toxicity can manifest as neurotoxicity, with symptoms ranging from asymptomatic supratherapeutic drug concentrations to clinical toxicity such as confusion, ataxia, or seizures 4
• The primary site of toxicity is the central nervous system, and clinical manifestations can vary depending on the severity of the toxicity 4
• Chronic lithium poisoning can result in persistent cognitive and neurological impairment, and can require a prolonged hospital length of stay due to impaired mobility and cognition and associated nosocomial complications 4

Blood Concentrations and Indicated Therapies

• Mild lithium toxicity can often be managed successfully with minimal intervention, such as cessation or reduction of lithium doses 5
• Moderate and severe toxicity require more aggressive approaches, including initial general anti-poisoning measures such as gastric lavage, and hemodialysis or peritoneal dialysis to rapidly eliminate lithium from the body 5, 6
• Sodium administration and maintenance of high-normal sodium levels may also reduce the severity of lithium toxicity by removing the dangerous intracellular fraction of lithium from inside excitable cells 5
• Enhanced lithium clearance, such as through haemodialysis or continuous haemodiafiltration, should be considered in patients at greatest risk of severe poisoning, including those with chronic or acute-on-therapeutic toxicity, or those with serum lithium concentrations >2.5 mmol/L 6

Risk Factors for Lithium Toxicity

• Identifiable risk factors for chronic poisoning include nephrogenic diabetes insipidus, older age, abnormal thyroid function, and impaired renal function 7
• Patients aged 65 and over are at increased risk of lithium toxicity, and careful monitoring and prescribing are particularly important in this population 8
• Other risk factors for lithium toxicity include baseline endogenous creatinine clearance below normal limits, and the use of drugs that impair lithium clearance 7