SIGNS AND SYMPTOMS
- Acute toxicity:
- Less common/serious than chronic toxicity
- Neurologic (mild):
- Weakness
- Fine tremor
- Lightheadedness
- Neurologic (moderate):
- Ataxia
- Slurred speech
- Blurred vision
- Tinnitus
- Weakness
- Coarse tremor
- Fasciculations
- Hyper-reflexia
- Apathy
- Neurologic (severe):
- Confusion
- Coma
- Seizure
- Clonus
- Extrapyramidal symptoms
- GI:
- Very common
- Nausea/vomiting
- Diarrhea
- Abdominal pain
- Cardiac:
- Prolonged QT, ST depression
- T-wave flattening
most common
ECG abnormality
- U-waves
- Serious dysrhythmias (rare)
- Chronic toxicity:
- Neurologic:
- Most common
- Same symptoms as acute
- Severe toxicity includes parkinsonism, psychosis, and memory deficits
- Renal:
- Nephrogenic diabetes insipidus
- Interstitial nephritis
- Distal tubular acidosis
- Direct cellular damage
- Dermatologic:
- Dermatitis
- Ulcers
- Localized edema
- Endocrine:
- Hematologic:
- Leukocytosis
- Aplastic anemia
History
- Time of last dose ingested
- Ingestion history:
- Acute (1-time overdose)
- Chronic (scheduled dosing)
- Acute on chronic (overdose in patients who regularly take lithium)
Physical-Exam
Perform complete neurologic exam
ESSENTIAL WORKUP
- Lithium level: Goal = postdistribution:
- Because of prolonged distribution, repeat every 2 hr to ensure trend
- Stratify patient into 1 of 3 categories of toxicity to interpret level and predict toxicity: Acute, acute on chronic, chronic:
- Acute toxicity:
- Intentional overdose in patient not previously taking lithium
- Poor correlation between lithium level and symptoms because intracellular distribution has not yet occurred
- Toxic levels may appear in asymptomatic patients
- Lithium level >4 mEq/L may result in toxic sequelae because of slowed clearance
- Acute on chronic toxicity:
- Intentional or accidental overdose in patient on lithium therapy
- Lithium level >3 mEq/L usually associated with symptoms
- Chronic toxicity:
- Patients on lithium therapy who progressively develop toxicity secondary to factors other than acute ingestion
- Stronger correlation between lithium level and symptoms
- Lithium level >1.5 mEq/L may correlate with toxicity
DIAGNOSIS TESTS & NTERPRETATION
Lab
- Electrolytes, BUN, creatinine, and glucose levels to determine electrolyte disturbances/renal function
- Aspirin and/or acetaminophen levels as indicated by history
- Urinalysis:
DIFFERENTIAL DIAGNOSIS
- Consider lithium toxicity with altered mental status and fasciculations
- Endocrine:
- Toxicologic:
- Cholinergic substances
- Heavy-metal poisoning
- Neuroleptic overdose
- Black widow/scorpion envenomation
- Strychnine poisoning
TREATMENT
PRE HOSPITAL
- Transport all appropriate pill bottles to the hospital
- IV access, oxygen, and cardiac monitoring
INITIAL STABILIZATION/THERAPY
- ABCs
- Secure IV access with 0.9% NS
- Cardiac monitor
- Naloxone, thiamine, dextrose (or Accu-Chek) if altered mental status
- Benzodiazepines for seizures
ADDITIONAL TREATMENT
General Measures
- Correct electrolyte abnormalities
- Maintain well-hydrated state
- Continuous cardiac monitoring
- Observe for neurologic changes
- Prevent absorption:
- Consider gastric lavage only if patient presents within 1 hr of acute life-threatening ingestion and has protected airway
- Activated charcoal:
- Lithium is not adsorbed by charcoal
- Administer 1 dose of activated charcoal if possible coingestants
- Whole-bowel irrigation:
- Polyethylene glycol (PEG) solution (GoLytely)
- Sustained-release lithium products
- Flushes lithium through gut
- Administer (2 L/hr per nasogastric tube) until rectal effluent is clear
- Contraindications include bowel obstruction or perforation, ileus or hypotension, and unprotected airway in obtunded or seizing patient
- Enhance elimination:
- IV fluids:
- Rapidly correct any pre-existing fluid deficit with 0.9% NS at 150–300 mL/hr (or 2× maintenance)
- Saline hydration improves glomerular filtration and decreases proximal tubule reabsorption of lithium
- Maintain urine output, 1–2 mL/kg/hr
- Limited value once glomerular filtration rate maximized
- Sodium bicarbonate offers no additional advantage
- Loop, thiazide, and osmotic diuretics not recommended:
- Dehydration may result in worsening toxicity
- No direct effect on renal reabsorption because lithium is reabsorbed in proximal tubules
- Kayexalate (sodium polystyrene sulfonate):
- Animal and human studies indicate some efficacy
- Complications may include hypokalemia, hyperkalemia, fluid overload, and dysrhythmias
- Dialysis:
- Peritoneal dialysis is not recommended
- Hemodialysis may be recommended for augmenting elimination (see below)
- Hemodialysis is recommended for severe cases or acute ingestions with high levels indicating imminent toxicity:
- Controversial indications (validated criteria yet to be established):
- Severe and progressive neurologic abnormalities
- Renal insufficiency
- Altered mental status (e.g., placidly tolerating a rectal tube for GI effects would be considered substantial obtundation)
- Ventricular dysrhythmia/cardiogenic shock
- History of congestive heart failure or pulmonary edema
- Acute ingestions with levels >4–5 mEq/L
- Chronic ingestions with levels >2.5–3 mEq/L
- Endpoint is lithium level <1 mEq/L
- Repeat lithium level 6 hr after dialysis checking for evidence of redistribution
- May need to repeat dialysis due to rebound effect (redistribution of intracellular lithium)
- May reduce the potential for developing permanent neurologic sequelae with chronic toxicity
MEDICATION
- Dextrose: D50 1 amp: 25 g (peds: D25W 4 mL/kg) IV
- Diazepam: 5 mg (peds: 0.2–0.4 mg/kg) IV q5min until seizures controlled
- Naloxone: 2 mg (peds: 0.1 mg/kg) IV or via endotracheal tube
- PEG solution: 2 L/hr (peds: 2 mL/kg/h) via nasogastric tube
- Thiamine: 100 mg IV
FOLLOW-UP
DISPOSITION
Admission Criteria
- Symptomatic
- Requiring hemodialysis
- Lithium level unchanged, increased, or >2 mEq/L despite ED intervention
- Moderate to severe symptoms with chronic levels >4 mEq/L warrant admission to ICU
- Intentional ingestion
Discharge Criteria
Decreasing lithium levels every 2–4 hr in
asymptomatic
patient
and
serum lithium level <2 mEq/L (nonsuicidal patients)
Issues for Referral
Intentional overdose:
FOLLOW-UP RECOMMENDATIONS
Psychiatry follow-up to ensure correct dosing regimen in those with chronic poisoning
PEARLS AND PITFALLS
- Erroneously interpreting a predistribution lithium concentration as “toxic” in patients without symptoms or history of overdose
- Aggressive hydration in patients with pulmonary edema, renal insufficiency, or mental status changes
ADDITIONAL READING
- Bailey B, McGuigan M. Comparison of patients hemodialyzed for lithium poisoning and those for whom dialysis was recommended by PCC but not done: What lesson can we learn?
Clin Nephrol
. 2000;54:388–392.
- Ghannoum M, Lavergne V, Yue CS, et al. Successful treatment of lithium toxicity with sodium polystyrene sulfonate: A retrospective cohort study.
Clin Toxicol (Phila).
2010;48:34–41.
- Mesquita J, Cepa S, Silva L, et al. Lithium neurotox-icity at normal serum levels.
J Neuropsychiatry Clin Neurosci
. 2010;22:451-p.e29–451.e29.
- Waring WS. Management of lithium toxicity.
Toxicol Rev
. 2006;25:221–230.
CODES
ICD9
985.8 Toxic effect of other specified metals