TOXICOLOGY■ Most patients will not require further therapy.
■ Antidote = sodium nitrite (if prolonged symptoms).
■ Induces methemoglobinemia
■ Methemoglobin binds H 2 S, producing sulfmethemglobin.
A 30-year-old male on chronic lithium therapy for bipolar disorder is
brought to the ED by his mother for mental-status changes. She reports
he has had a flulike illness over the past few days with vomiting and
diarrhea. On examination the patient appears dehydrated, lethargic, and con-
fused, but has normal VS. His lithium level returns at 1.5 (upper level of nor-
mal). What is the single most important therapeutic intervention for this
patient with presumed lithium toxicity?
This patient likely has chronic lithium toxicity related to a decreased GFR
from dehydration. In chronic toxicity, CNS effects predominate. The single most
important therapy for this patient is to reestablish GFR with IV hydration.LITHIUMLithium is a mood stabilizer used to treat bipolar disorder. It has a narrow
therapeutic window.
MECHANISM/TOXICITY
■ Lithium is a cation and behaves like Na+or K+. It is thought to affect cate-
cholamine and serotonergic neurotransmission.
■ CNS uptake andelimination are slow, therefore serum lithium levels do
NOT correlate with CNS effects.
■ Lithium elimination is glomerular filtration rate (GFR) dependent.
■ Precursors to chronic toxicity:
■ ↑Therapeutic dose
■ ↑Renal reabsorption in dehydration
■ ↑GFR (renal insufficiency, use of NSAIDs, ACE–I)
■ Drug-drug interactions with SSRIs and antipsychotic agents
SYMPTOMS/EXAM
The expected effects from lithium intoxication depend on whether the inges-
tion is acute or chronic.
Acute ingestion
■ Occurs in patients who do not normally take lithium but acutely ingest a
large quantity
■ GI toxicity >> CNS toxicity (no time for CNS uptake).
■ GI toxicity = nausea/vomiting/diarrhea.
■ CNS findings are typically mild.
■ Severe ingestion: hyperreflexia, clonus, agitation, AMS, seizures
■ Chronic ingestion
■ Patient on chronic lithium therapy with toxicity due to:
■ CNS toxicity >> GI toxicity
■ CNS effects may range from lethargy and confusion to coma and
seizures.
■ ECG changes are common, including prolonged PR, QRS, qTc,
nonspecific ST-T changes, bradycardia.
Acute lithium ingestion →
high serum levels, minimal
CNS effects.
Chronic lithium toxicity →
lower serum levels, significant
CNS effects.A decrease in GRF (↓drug
clearance) is a common
precursor to chronic lithium
toxicity.