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Lithium Poisoning, Emergency Medicine

Basics

Description

- 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

- Acute toxicity: - Less common/serious than chronic toxicity - Neurologic (mild): - Weakness - Fine tremor - Lightheadedness

- 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

- 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

- 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

- Kayexalate (sodium polystyrene sulfonate): - Animal and human studies indicate some efficacy - Complications may include hypokalemia, hyperkalemia, fluid overload, and dysrhythmias

  • GI absorption is rapid:Regular release: Peak serum levels 2 " 4 hrSustained 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 metabolizedRenal excretion (unchanged)Reabsorbed in the proximal tubules by sodium transport mechanismElimination 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 intracellularNarrow toxic-to-therapeutic ratioTherapeutic 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)OverdoseChronic conditions:HypertensionDiabetes mellitusRenal failureCongestive heart failureAdvanced ageDose changeDrug interactionsLithium therapyLow-salt dietThe following may result in increased serum lithium levels due to decreased renal clearance or exacerbated effects:NSAIDsThiazide diureticsACE inhibitorsPhenytoinTricyclic antidepressantsPhenothiazines

Etiology

  • Acute or chronic conditions affecting lithium clearance
  • Overdose

Diagnosis

Signs and Symptoms

  • Acute toxicity:Less common/serious than chronic toxicityNeurologic (mild):WeaknessFine tremorLightheadednessNeurologic (moderate):AtaxiaSlurred speechBlurred visionTinnitusWeaknessCoarse tremorFasciculationsHyper-reflexiaApathyNeurologic (severe):ConfusionComaSeizureClonusExtrapyramidal symptomsGI:Very commonNausea/vomitingDiarrheaAbdominal painCardiac:Prolonged QT, ST depressionT-wave flattening most common ECG abnormalityU-wavesSerious dysrhythmias (rare)
  • Chronic toxicity:Neurologic:Most commonSame symptoms as acuteSevere toxicity includes parkinsonism, psychosis, and memory deficitsRenal:Nephrogenic diabetes insipidusInterstitial nephritisDistal tubular acidosisDirect cellular damageDermatologic:DermatitisUlcersLocalized edemaEndocrine:Hematologic:LeukocytosisAplastic 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 lithiumPoor correlation between lithium level and symptoms because intracellular distribution has not yet occurredToxic levels may appear in asymptomatic patientsLithium level >4 mEq/L may result in toxic sequelae because of slowed clearanceAcute on chronic toxicity:Intentional or accidental overdose in patient on lithium therapyLithium level >3 mEq/L usually associated with symptomsChronic toxicity:Patients on lithium therapy who progressively develop toxicity secondary to factors other than acute ingestionStronger correlation between lithium level and symptomsLithium 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:

Differential Diagnosis

  • Consider lithium toxicity with altered mental status and fasciculations
  • Endocrine:
  • Toxicologic:Cholinergic substancesHeavy-metal poisoningNeuroleptic overdoseBlack widow/scorpion envenomationStrychnine 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 airwayActivated charcoal:Lithium is not adsorbed by charcoalAdminister 1 dose of activated charcoal if possible coingestantsWhole-bowel irrigation:Polyethylene glycol (PEG) solution (GoLytely)Sustained-release lithium productsFlushes lithium through gutAdminister (2 L/hr per nasogastric tube) until rectal effluent is clearContraindications 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 lithiumMaintain urine output, 1 " 2 mL/kg/hrLimited value once glomerular filtration rate maximizedSodium bicarbonate offers no additional advantageLoop, thiazide, and osmotic diuretics not recommended:Dehydration may result in worsening toxicityNo direct effect on renal reabsorption because lithium is reabsorbed in proximal tubulesKayexalate (sodium polystyrene sulfonate):Animal and human studies indicate some efficacyComplications may include hypokalemia, hyperkalemia, fluid overload, and dysrhythmiasDialysis:Peritoneal dialysis is not recommendedHemodialysis 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 abnormalitiesRenal insufficiencyAltered mental status (e.g., placidly tolerating a rectal tube for GI effects would be considered substantial obtundation)Ventricular dysrhythmia/cardiogenic shockHistory of congestive heart failure or pulmonary edemaAcute ingestions with levels >4 " 5 mEq/LChronic ingestions with levels >2.5 " 3 mEq/LEndpoint is lithium level <1 mEq/LRepeat lithium level 6 hr after dialysis checking for evidence of redistributionMay 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:

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