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Anna Lee & Charles Gomersall
Updated June 2006
Mode
of poisoning
- most
cases due to unintentional overdose during chronic therapy
- often
precipitated by volume depletion and renal inufficiency
- acute
intentional overdose also common
Pharmacokinetics
- rapidly
absorbed from GI tract
- virtually
no protein binding and low volume of distribution
(0.7-1 l/kg)
- small molecule (molecular weight 74 daltons)
- eliminated
by glomerular filtration but 80% reabsorbed in tubules, even more if
patient dehydrated
- elimination
half-life ~18 h
- prolonged
in elderly and patients on chronic therapy
Clinical
features
- clinical
features varied and many. Severe poisoning may result in
permanent neurological damage in 10% of patients. Serum levels following acute ingestion correlate
poorly with intracellular concentrations and clinical symptoms. Closer
correlation in chronic and acute on chronic toxicity. Severe toxicity may
occur at a lower serum concentration in chronic ingestion than in acute
overdose
- mild
intoxication (serum lithium 1.5-2.5 mmol/l)
- tremor,
ataxia
- nystagmus
- choreoathetosis
- photophobia
- lethargy
- moderate
intoxication (serum lithium 2.5-3.5 mmol/l)
- agitation
- fascicular
twitching
- confusion
- nausea,
vomiting, diarrhoea
- cerebellar
signs
- severe
toxicity (>3.5 mmol/l)
- seizures,
coma
- cardiovascular
instability
- sinus
bradycardia
- hypotension
- decreased
anion gap (<6 mEq/l)
- chronic
toxicity includes nephrogenic DI,
renal failure, hypothyroidism and leukocytosis
Treatment
- gastric
lavage
- poorly
adsorbed by activated charcoal which is not indicated in absence of
co-ingestion of other drugs
- majority of patients respond to general supportive measures
- haemodialysis
or haemofiltration for:
- serum
levels >3.5 mmol/l in acute ingestion
- serum
level >2.5 mmol/l in chronic ingestion, symptomatic patients or
patients with renal insufficiency
- serum
level <2.5 but following large ingestion so that rising levels
expected
-
serum level 1.5-2.5 mmol/l in any patients
with renal insufficiency, severe neurological symptoms or unstable
hemodyanmics
-
serum level < 1.5 mmol/l in patients with end-stage
renal failure, or following large ingestion so that rising levels
expected
Hemodialysis is more effective than hemofiltration.
Problems of rebound toxicity after discontinuation of HD due to tissue
redistribution, which can be prevented by either extending the dialysis
therapy to 8-12 hours, or initiating CVVH
©Anna Lee & Charles Gomersall, June 2006 |
