LITHIUM OVERDOSE
Charcoal ineffective
Pathophysiology
Therapeutic dose: 300 – 2700mg/day
Therapeutic levels: 0.6-1.2mmol/L; peak in 2-4hrs (6-8hrs if SR)
Acute toxic dose: if normal renal function and Na, acute OD usually tolerated quite well; toxicity determined by rate of rise of serum levels
>2500mg (>40mg/kg)  GI Sx, but rarely neuro Sx
Chronic toxic dose: more severe Sx at lower levels
>1.5mmol/L = toxicity
Drug properties: Low therapeutic index; renal clearance (small deterioration in renal function  large effect on Li elimination); elimination half life 1227hrs; suitable for dialysis (small molecular size, high water solubility, lack of metabolites, little protein binding)
Causes: usually due to decr GFR (eg. thiazides, NSAIDs, ACEi, SSRI, sepsis, hypotension, dehydration, CCF); hypoNa ( incr Li reabsorption)
Drug interactions: haloperidol + phenothiazides ( NMS like effect), methyldopa ( Parkinsonian), NM blockers ( prolonged DOA)
Effects of chronic use: alters urinary concentrating ability  nephrogenic DI; competes with Na + K for reabsorption; blunts response of thirst centre to
dehydration; causes hypothyroidism
Toxicity
Acute: mimics gastro / flu; Sx may have 3-5/7 delay in onset
GI Sx more common (N+D+AP, polydipsia, polyuria)  significant fluid loss; GI Sx correlate well with levels (unlike in Fe)
CV Sx (HB, prolonged QTc; usually not assoc with significant CV effects)
Neuro Sx uncommon (but more likely if severe / delayed presentation / renal failure / dehydrated)
Chronic: occurs following change in dose
Neurotoxicity more common; may be permanent
GI Sx uncommon
Assessment
Mng
= N+V, fine intention tremor (most common and earliest); lethargy, memory and conc probs
Grade 1 (mild):
<1.5mmol/L
Grade 2 (mod):
1.5-2.5mmol/L = hyperreflexia / hypertonia, coarse resting tremor, ataxia / dysarthria, weakness, visual probs,
agitation / confusion, fasciculations
2.5-3.5mmol/L = rigidity / myoclonus, incr / decr tone, choreoathetosis, nystagmus, stupor, decr BP
Grade 3 Isevere): >3.5mmol/L
= seizures, flaccid paralysis, coma, ARF
Consider in any patient on lithium who presents unwell / with neuro Sx; look for precipitating illness
Differential diagnosis: non-convulsive status, SS, NMS, electrolyte abnormality, CNS pathology
Investigations: Li level (less helpful in acute poisoning, used to make diagnosis only; guide to trt in chronic), U+E (decr K, low AG, decr/incr Na,
acidosis), FBC (chronic Li use  neutrophilia, WBC 10-15); ECG (chronic Li use  T wave flattening and inversion; toxicity  long PR, QRS, QTc); AXR
Indications for GI decontamination: acute overdose +
>40mg/kg ingested /
tablets on AXR
+ within 1-2hrs ingestion
Use PEG; resonium may incr rate of Li elimination
>6mmol/L (acute) / >2.5mmol/L (chronic)
Indications for dialysis: Li level
Severe clinical Sx (esp neuro Sx: coma / seizures) with high level
ARF even if lower level
Decr BP not responding to fluids
Mostly used in chronic / delayed presentation acute; will need to be prolonged as slow equilibration time between intraC and extraC; may get rebound
incr level on stopping; serial Li levels helpful; no evidence that haemodialysis improves outcome
May increase effect of sux and vec
Prognosis
Other trt: in acute – give IVF (aim UO >1ml/kg/hr) to help Li diuresis, decr intracellular Li levels; stop interacting drugs
Disposition: discharge if: acute ingestion + asymptomatic + peak level <1.5mmol/L
Prolonged observation if: SR
If treated, discharge once: level <2
Good prognosis: GI Sx only
Notes from: Dunn, Cameron, Tox Book