Lithium Poisoning, Emergency Medicine

Basics

Description

GI absorption is rapid:
- Regular release: Peak serum levels 2 " 4 hr
- Sustained release: Peak serum levels 4 " 12 hr
Half-life 24 hr
Slow distribution (at least 6 hr)
Volume of distribution 0.6 " 0.9 L/kg
Elimination:
- Not metabolized
- Renal excretion (unchanged)
- Reabsorbed in the proximal tubules by sodium transport mechanism
- Elimination half-life (therapeutic) is 20 " 24 hr and prolonged in chronic users
Therapeutic and toxic indices:
- Therapeutic and toxic effects occur only when lithium is intracellular
- Narrow toxic-to-therapeutic ratio
- Therapeutic level 0.6 " 1.2 mEq/L (postdistribution)
- Because of small size, renal handling is similar to sodium, potassium, and magnesium
Risk factors:
- Acute conditions increasing risk of toxicity:
  - Dehydration (larger percent reabsorbed)
  - Overdose
- Chronic conditions:
  - Hypertension
  - Diabetes mellitus
  - Renal failure
  - Congestive heart failure
  - Advanced age
  - Dose change
  - Drug interactions
  - Lithium therapy
  - Low-salt diet
- The following may result in increased serum lithium levels due to decreased renal clearance or exacerbated effects:
  - NSAIDs
  - Thiazide diuretics
  - ACE inhibitors
  - Phenytoin
  - Tricyclic antidepressants
  - Phenothiazines

Etiology

Acute or chronic conditions affecting lithium clearance
Overdose

Diagnosis

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:
  - Hypothyroidism
- 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 & Interpretation

Lab

Electrolytes, BUN, creatinine, and glucose levels to determine electrolyte disturbances/renal function
Aspirin and/or acetaminophen levels as indicated by history
Urinalysis:
- Specific gravity

Differential Diagnosis

Consider lithium toxicity with altered mental status and fasciculations
Endocrine:
- Hypoglycemia
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:

Psychiatry consultation

Followup 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 neurotoxicity 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

ICD10

T56.891A Toxic effect of other metals, accidental (unintentional), initial encounter
T56.892A Toxic effect of other metals, intentional self-harm, initial encounter
T56.894A Toxic effect of other metals, undetermined, init encntr

SNOMED

290802009 Lithium poisoning (disorder)
290804005 Intentional lithium poisoning
290803004 Accidental lithium poisoning
290805006 Lithium poisoning of undetermined intent

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