Diferencia entre revisiones de «Lithium toxicity»

(Text replacement - "==Treatment==" to "==Management==")
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==Background==
==Background==
*Mechanism of action is poorly understood.
*Lithium remains the most effective treatment for [[bipolar disorder]] despite availability of newer agents
*Despite availability of newer drugs, Lithium remains most effective tx for bipolar disorder, and it is still in use
*Mechanism of action poorly understood; modulates neurotransmitter signaling
*Lithium initially distributes in extracellular fluid, then gradually redistributes to other areas including the brain (takes up to 24 hours after absorption)
*Narrow therapeutic index (therapeutic level: 0.6-1.2 mEq/L)
*95% renal excretion
*Pharmacokinetics:
**NSAIDs, Diuretics, ACE-inhibitors → ↑ Lithium serum concentration by ↓ lithium excretion
**Rapidly absorbed (peak 1-2h for immediate release; 4-12h for sustained release)
*Lithium toxicity rarely fatal (only 3 deaths in 2009)<ref>Bronstein AC, et al: 2009 Annual Report of the American Association of Poison Control Centers’ National Poison Data System (NPDS). Clin Toxicol (Phila) 2010; 48:979.</ref>
**Initially distributes in extracellular fluid → gradually redistributes to CNS (up to 24 hours)
**95% renally excreted; handled like sodium by proximal tubule
*Lithium toxicity rarely fatal (only 11 deaths out of 6815 reported toxic exposures in 2012)<ref>Mowry JB, et al. 2012 annual report of the AAPCC NPDS. ''Clin Toxicol (Phila)''. 2013;51:949-1229. PMID 24359283</ref>
 
===Common Precipitants===
*Volume depletion: vomiting, diarrhea, diaphoresis, decreased PO intake
*Medications that decrease lithium excretion:
**[[NSAIDs]], [[ACE inhibitors]]/ARBs, [[thiazide diuretics]]
*[[Acute kidney injury]] or chronic kidney disease
*Intentional overdose
*[[Hyperthermia]], [[CHF]], [[sepsis]]
*Nephrogenic [[diabetes insipidus]] (caused by chronic lithium use) → dehydration → ↑ lithium levels


==Clinical Features==
==Clinical Features==
''Three recognized patterns of Lithium toxicity - "Acute", "Acute-on-chronic", and "Chronic".<ref>Waring WS, Laing WJ, Good AM, Bateman DN. Pattern of lithium exposure predicts poisoning severity: evaluation of referrals to a regional poisons unit. QJM. 2007 May;100(5):271-6. Epub 2007 Apr 5.</ref>''
Three recognized patterns of toxicity<ref>Waring WS, et al. Pattern of lithium exposure predicts poisoning severity. ''QJM''. 2007;100(5):271-6. PMID 17410291</ref>:
 
===Acute===
Occurs in patients not previously receiving lithium (i.e. with no current body stores)
 
Serum concentrations can fall rapidly as lithium redistributes to tissues, and serum level does not correlate with degree of toxicity. GI symptoms predominate.


*GI - nausea, vomiting, diarrhea, abdominal pain
===Acute Ingestion===
**Earliest and most common symptoms
*Patient not previously on lithium (no body stores)
*Cardiac effects - bradycardia, QT prolongation, T-wave flattening or inversion<ref>Canan F, Kaya A, Bulur S, Albayrak ES, Ordu S, Ataoglu A. Lithium intoxication related multiple temporary ecg changes: A case report. Cases Journal. 2008;1:156. doi:10.1186/1757-1626-1-156.</ref>
*GI symptoms predominate: nausea, vomiting, diarrhea, abdominal pain (earliest/most common)
**Can also cause Brugada-like ECG pattern
*Cardiac: [[bradycardia]], QT prolongation, T-wave flattening/inversion, Brugada-like pattern<ref>Canan F, et al. Lithium intoxication related multiple temporary ECG changes. ''Cases Journal''. 2008;1:156. PMID 18801176</ref>
*CNS Depression - late finding (takes time for lithium to distribute to CNS), indicates progression of toxicity
*CNS depression is a late finding (takes time for lithium to redistribute to brain)
*Serum levels may be very high but '''do not correlate with clinical toxicity'''


===Acute-on-Chronic===
===Acute-on-Chronic===
Also called "Acute-on-therapeutic", occurs in patients currently taking lithium due to acute ingestion of supra-therapeutic doses.
*Patient on chronic lithium who takes supra-therapeutic dose
*Mixed GI and CNS symptoms


*Symptoms are a mix of both acute and chronic - includes both GI and CNS effects
===Chronic Toxicity===
*Insidious onset in patients on chronic therapy
*Due to increased absorption or decreased elimination
*CNS symptoms predominate (generally more severe than acute):
**Mild: fine tremor, drowsiness, muscle weakness
**Moderate: hyperreflexia, confusion, coarse tremor, ataxia, slurred speech
**Severe: [[seizures]], myoclonus, coma, extrapyramidal symptoms
*Hypothyroidism (lithium inhibits thyroid hormone release)


===Chronic===
===SILENT Syndrome<ref>Adityanjee, et al. The syndrome of irreversible lithium-effectuated neurotoxicity. ''Clin Neuropharmacol''. 2005;28(1):38-49. PMID 15681811</ref>===
Occurs insidiously in patients on chronic lithium therapy. Toxicity is secondary to increased absorption or decreased elimination. CNS symptoms predominate.
*Syndrome of Irreversible Lithium-Effectuated Neurotoxicity
*Neurologic dysfunction persisting >2 months after cessation of lithium
*Cerebellar dysfunction (dysarthria, ataxia, gait instability), peripheral neuropathy, dementia


Chronic lithium therapy is associated with nephrogenic diabetes insipidus, which → hyponatremia, fluid loss → ↑ lithium levels (can precipitate toxicity)
==Differential Diagnosis==
*[[Serotonin syndrome]]
*[[Neuroleptic malignant syndrome]]
*[[Thyroid storm]] / [[hypothyroidism]]
*[[Alcohol]] or sedative-hypnotic intoxication
*Structural CNS lesion
*Other [[heavy metals]] toxicity
*[[Uremia]]


*Neurotoxicity is major finding, and is generally more profound than that seen in acute toxicity
{{Heavy metals DDX}}
**Mild symptoms include tremor, drowsiness
**Progressive symptoms include hyperreflexia, confusion, ataxia, seizures, extrapyramidal signs, coma
*Hypothyroidism (lithium inhibits thyroid hormone release)


===Syndrome of Irreversible Lithium-Effectuated Neurotoxicity (SILENT)<ref>Adityanjee, Munshi KR, Thampy A. The syndrome of irreversible lithium-effectuated neurotoxicity. Clin Neuropharmacol. 2005 Jan-Feb;28(1):38-49.</ref>===
==Evaluation==
Persistent sequelae of lithium toxicity. Defined as neurologic dysfunction persisting more than 2 months after cessation of lithium therapy. Exact mechanism unknown (possibly related to CNS demyelination).
*Lithium level:
**Therapeutic: 0.6-1.2 mEq/L
**Levels >1.5 mEq/L may be associated with toxicity (chronic > acute for same level)
**'''Do NOT use green top (lithium heparin) tube''' — falsely elevates level
**Serum levels '''do not predict CNS levels''' and only roughly correlate with clinical symptoms
**Serial levels every 2-4 hours (especially after overdose or post-HD)
*BMP: creatinine, sodium (often hyponatremic or hypernatremic), calcium
*TSH (chronic use → hypothyroidism)
*ECG: QT prolongation, T-wave changes, bradycardia, Brugada pattern
*Acetaminophen and salicylate levels (possible coingestants)
*Urinalysis (urine specific gravity to evaluate concentrating ability)


Symptoms
==Management==
*Cerebellar dysfunction
===GI Decontamination===
*Peripheral neuropathy
*Whole bowel irrigation (WBI): only for sustained-release tablet ingestion
*Extrapyramidal symptoms
**PEG solution via NG at 1-2 L/hr (adults)
*Brainstem dysfunction
*Activated charcoal is NOT effective (lithium is not adsorbed)
*Dementia
*Gastric lavage generally not effective and potentially harmful


==Differential Diagnosis==
===Fluid Resuscitation===
===Common Precipitants===
*Most important initial intervention — most patients have volume/sodium deficit
*Overdose
*NS is preferred (restores sodium, promotes renal lithium excretion)
*Renal failure
*Give 2L NS bolus, then 200 mL/hr (or 2× maintenance)
*Volume depletion
*Target UOP 1-2 mL/kg/hr
**Diuretic use, [[vomiting]], [[diarrhea]], diaphoresis, decreased oral intake
*Avoid forced diuresis with loop diuretics (may worsen lithium toxicity)
*[[Hyperthermia]]
*Infection
*[[CHF]]
*Surgery
*Cirrhosis


==Diagnosis==
===Hemodialysis===
*Lithium level
*Most effective method of lithium removal
**Therapeutic level = 0.6-1.2 meq/L
*Must follow '''serial lithium levels post-HD''' — levels will rebound due to tissue redistribution
**''level may be falsely elevated if placed in a green top tube due to the heparin lithium interaction''
*May require multiple sessions
*Metabolic Panel
*EXTRIP Workgroup Indications<ref>Decker BS, et al. Extracorporeal treatment for lithium poisoning: systematic review and recommendations from the EXTRIP Workgroup. ''Clin J Am Soc Nephrol''. 2015;10(5):875-887. PMID 25583293</ref>:
*TSH
**Recommended (1D): impaired kidney function AND Li >4.0 mEq/L
*ECG
**'''Recommended (1D)''': clinical deterioration (decreased LOC, seizures, life-threatening dysrhythmias) regardless of level
*Acetaminophen and Salicylate Levels (possible coingestants)
**Suggested (2D): Li >5.0 mEq/L
**Suggested (2D): expected time to Li <1.0 mEq/L with optimal management >36 hours
*Contraindication to aggressive fluids ([[CHF]]) lowers threshold for HD
*Consult toxicology and nephrology — complex decision


==Management==
===Endpoint of Dialysis===
===GI decontamination===
*Continue HD until lithium level <1.0 mEq/L
*[[Whole bowel irrigation]] (only for extended release tablets)
*Recheck level 6-8 hours post-HD for rebound
*[[Gastric lavage]] and [[activated charcoal]] not effective and potentially harmful
===[[Fluid resuscitation]]===
*Average patient has Na/volume deficit; giving fluid helps reestablish normal renal Lithium excretion
*Give 2L NS bolus, then start 200mL/hr or 2x maintenance rate
===Dialysis===
''Most effective method of removal. Must follow serial lithium levels - levels will likely rise after HD due to redistribution from tissues; additional HD may be required.''
'''Indications:'''
*Kidney function is impaired and the [Li+] >4.0 mEq/L (1D recommendation)<ref name="extra">Extracorporeal Treatment for Lithium Poisoning: Systematic Review and Recommendations from the EXTRIP Workgroup. Decker BS et al. Clin J Am Soc Nephrol 2015 Jan 12 [http://www.extrip-workgroup.org/#!recommendations/cy1f Extrip Recs]</ref>
*Clinical deterioration
*In the presence of a decreased level of consciousness, seizures, or life-threatening dysrhythmias irrespective of [Li+] (1D)<ref name="extra"></ref>
* [Li+].>5.0 mEq/L (2D suggestion)
*If the expected time to obtain a [Li+]<1.0 mEq/L with optimal management is >36 h (2D suggestion)<ref name="extra"></ref>
*Baseline renal failure
*Contraindication to aggressive fluid resuscitation (CHF, etc)


==Disposition==
==Disposition==
*Consider discharge for patients who are asymptomatic after 4-6hr obs, 2 downtrending lithium levels, and no worsening of renal function
*Discharge considerations (acute ingestion):
*Admit all patients w/ Li level >1.5
**Asymptomatic after 4-6 hours observation
*Admit all patients w/ ingestion of sustained-release preparation (regardless of Li level)
**Two downtrending lithium levels
**No worsening renal function
*Admit:
**All patients with Li level >1.5 mEq/L
**All sustained-release preparation ingestions (regardless of Li level)
**Any patient with neurologic symptoms
**Any patient requiring hemodialysis
*Poison control: 1-800-222-1222


==See Also==
==See Also==
*[[Toxicology (Main)]]
*[[Toxicology]]
*[[Heavy metals]]
*[[Bipolar disorder]]
*[[Serotonin syndrome]]
*[[Neuroleptic malignant syndrome]]


==References==
==References==
<references/>
<references/>
*Baird-Gunning J, et al. Lithium poisoning. ''J Intensive Care Med''. 2017;32(4):249-263. PMID 27055773
*Ott M, et al. Lithium intoxication: incidence, clinical course and renal function — a population-based retrospective cohort study. ''J Psychopharmacol''. 2016;30(10):1008-1019. PMID 27530173


[[Category:Toxicology]]
[[Category:Toxicology]]

Revisión actual - 09:30 22 mar 2026

Background

  • Lithium remains the most effective treatment for bipolar disorder despite availability of newer agents
  • Mechanism of action poorly understood; modulates neurotransmitter signaling
  • Narrow therapeutic index (therapeutic level: 0.6-1.2 mEq/L)
  • Pharmacokinetics:
    • Rapidly absorbed (peak 1-2h for immediate release; 4-12h for sustained release)
    • Initially distributes in extracellular fluid → gradually redistributes to CNS (up to 24 hours)
    • 95% renally excreted; handled like sodium by proximal tubule
  • Lithium toxicity rarely fatal (only 11 deaths out of 6815 reported toxic exposures in 2012)[1]

Common Precipitants

Clinical Features

Three recognized patterns of toxicity[2]:

Acute Ingestion

  • Patient not previously on lithium (no body stores)
  • GI symptoms predominate: nausea, vomiting, diarrhea, abdominal pain (earliest/most common)
  • Cardiac: bradycardia, QT prolongation, T-wave flattening/inversion, Brugada-like pattern[3]
  • CNS depression is a late finding (takes time for lithium to redistribute to brain)
  • Serum levels may be very high but do not correlate with clinical toxicity

Acute-on-Chronic

  • Patient on chronic lithium who takes supra-therapeutic dose
  • Mixed GI and CNS symptoms

Chronic Toxicity

  • Insidious onset in patients on chronic therapy
  • Due to increased absorption or decreased elimination
  • CNS symptoms predominate (generally more severe than acute):
    • Mild: fine tremor, drowsiness, muscle weakness
    • Moderate: hyperreflexia, confusion, coarse tremor, ataxia, slurred speech
    • Severe: seizures, myoclonus, coma, extrapyramidal symptoms
  • Hypothyroidism (lithium inhibits thyroid hormone release)

SILENT Syndrome[4]

  • Syndrome of Irreversible Lithium-Effectuated Neurotoxicity
  • Neurologic dysfunction persisting >2 months after cessation of lithium
  • Cerebellar dysfunction (dysarthria, ataxia, gait instability), peripheral neuropathy, dementia

Differential Diagnosis

Template:Heavy metals DDX

Evaluation

  • Lithium level:
    • Therapeutic: 0.6-1.2 mEq/L
    • Levels >1.5 mEq/L may be associated with toxicity (chronic > acute for same level)
    • Do NOT use green top (lithium heparin) tube — falsely elevates level
    • Serum levels do not predict CNS levels and only roughly correlate with clinical symptoms
    • Serial levels every 2-4 hours (especially after overdose or post-HD)
  • BMP: creatinine, sodium (often hyponatremic or hypernatremic), calcium
  • TSH (chronic use → hypothyroidism)
  • ECG: QT prolongation, T-wave changes, bradycardia, Brugada pattern
  • Acetaminophen and salicylate levels (possible coingestants)
  • Urinalysis (urine specific gravity to evaluate concentrating ability)

Management

GI Decontamination

  • Whole bowel irrigation (WBI): only for sustained-release tablet ingestion
    • PEG solution via NG at 1-2 L/hr (adults)
  • Activated charcoal is NOT effective (lithium is not adsorbed)
  • Gastric lavage generally not effective and potentially harmful

Fluid Resuscitation

  • Most important initial intervention — most patients have volume/sodium deficit
  • NS is preferred (restores sodium, promotes renal lithium excretion)
  • Give 2L NS bolus, then 200 mL/hr (or 2× maintenance)
  • Target UOP 1-2 mL/kg/hr
  • Avoid forced diuresis with loop diuretics (may worsen lithium toxicity)

Hemodialysis

  • Most effective method of lithium removal
  • Must follow serial lithium levels post-HD — levels will rebound due to tissue redistribution
  • May require multiple sessions
  • EXTRIP Workgroup Indications[5]:
    • Recommended (1D): impaired kidney function AND Li >4.0 mEq/L
    • Recommended (1D): clinical deterioration (decreased LOC, seizures, life-threatening dysrhythmias) regardless of level
    • Suggested (2D): Li >5.0 mEq/L
    • Suggested (2D): expected time to Li <1.0 mEq/L with optimal management >36 hours
  • Contraindication to aggressive fluids (CHF) lowers threshold for HD
  • Consult toxicology and nephrology — complex decision

Endpoint of Dialysis

  • Continue HD until lithium level <1.0 mEq/L
  • Recheck level 6-8 hours post-HD for rebound

Disposition

  • Discharge considerations (acute ingestion):
    • Asymptomatic after 4-6 hours observation
    • Two downtrending lithium levels
    • No worsening renal function
  • Admit:
    • All patients with Li level >1.5 mEq/L
    • All sustained-release preparation ingestions (regardless of Li level)
    • Any patient with neurologic symptoms
    • Any patient requiring hemodialysis
  • Poison control: 1-800-222-1222

See Also

References

  1. ↑ Mowry JB, et al. 2012 annual report of the AAPCC NPDS. Clin Toxicol (Phila). 2013;51:949-1229. PMID 24359283
  2. ↑ Waring WS, et al. Pattern of lithium exposure predicts poisoning severity. QJM. 2007;100(5):271-6. PMID 17410291
  3. ↑ Canan F, et al. Lithium intoxication related multiple temporary ECG changes. Cases Journal. 2008;1:156. PMID 18801176
  4. ↑ Adityanjee, et al. The syndrome of irreversible lithium-effectuated neurotoxicity. Clin Neuropharmacol. 2005;28(1):38-49. PMID 15681811
  5. ↑ Decker BS, et al. Extracorporeal treatment for lithium poisoning: systematic review and recommendations from the EXTRIP Workgroup. Clin J Am Soc Nephrol. 2015;10(5):875-887. PMID 25583293
  • Baird-Gunning J, et al. Lithium poisoning. J Intensive Care Med. 2017;32(4):249-263. PMID 27055773
  • Ott M, et al. Lithium intoxication: incidence, clinical course and renal function — a population-based retrospective cohort study. J Psychopharmacol. 2016;30(10):1008-1019. PMID 27530173
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