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tox.lithium-toxicity.core.v1PRODUCTION
tox.lithium-toxicity.core.v1

Lithium toxicity

toxicologyacutechronicadultgeriatric
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12/12 authored

Canonical 12-phase frame with authored status for this dossier.

Current phase

Frame

Detailed

Classify exposure pattern up front: acute (GI-predominant, high levels tolerated, late neuro) vs chronic (neurotoxicity at LOW levels — tremor/ataxia/encephalopathy/seizure, SILENT risk) vs acute-on-chronic (worst — high level + tissue-loaded) (EXTRIP 2015)

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Acute / chronic / acute-on-chronic pattern assigned

Patient inputs (13)

Elderly clear lithium poorly (reduced GFR), present with chronic neurotoxicity at lower levels, and are SILENT-prone (Baird-Gunning 2017)

Acute vs chronic vs acute-on-chronic dictates level interpretation and HD threshold (EXTRIP 2015)

Acute SR ingestion peaks late and erratically — a single early level under-estimates burden (Baird-Gunning 2017)

Sustained-release → delayed peak + whole-bowel irrigation candidacy; charcoal does NOT bind lithium (AACT/EAPCCT)

NSAIDs, ACEi/ARB, thiazide diuretics, and metronidazole reduce renal lithium clearance and precipitate chronic toxicity (Baird-Gunning 2017)

Volume depletion, low-sodium diet, vomiting/diarrhea, AKI, and febrile illness are the dominant chronic precipitants

EXTRIP 2015 HD criterion anchor; must be serial (q2–4h) given redistribution + SR delayed peak

Impaired renal function / inability to clear is itself an EXTRIP HD criterion at level >2.5 mEq/L

Hyponatremia and nephrogenic DI (hypernatremia) both alter lithium handling; low sodium reduces clearance

Decreased consciousness is an EXTRIP HD criterion at level >2.5 mEq/L (decker 2015)

Chronic lithium causes hypothyroidism and may contribute to encephalopathy mimicry; baseline before discharge

Electrolyte derangement with vomiting/diarrhea; arrhythmia substrate

Lithium causes T-wave flattening, QT prolongation, sinus node dysfunction/bradyarrhythmia — arrhythmia is an EXTRIP HD criterion

* = hard-required. Engine cannot meaningfully run until these are filled.

Severity triggers (7)

7 need judgement
  • informationallife_threateningextrip_hd_level_over_4
    Serum lithium >4.0 mEq/L in ANY exposure pattern [EXTRIP 2015 hemodialysis criterion]
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationallife_threateningextrip_hd_level_over_2_5_with_organ_dysfunction
    Serum lithium >2.5 mEq/L WITH decreased consciousness, seizure, life-threatening arrhythmia, OR impaired renal function / inability to clear [EXTRIP 2015]
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationallife_threateningsilent_irreversible_neurotoxicity
    Persistent cerebellar/extrapyramidal deficits or encephalopathy after the lithium level has normalized — Syndrome of Irreversible Lithium-Effectuated NeuroToxicity [Baird-Gunning 2017]
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationallife_threateninglithium_arrhythmia
    Life-threatening bradyarrhythmia / sinus node dysfunction / significant QT prolongation in lithium toxicity [EXTRIP 2015]
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseverechronic_neurotoxicity_low_level
    Tremor, ataxia, dysarthria, encephalopathy, or myoclonus in chronic lithium use even at a near-therapeutic level (1.5–2.5 mEq/L) [Baird-Gunning 2017]
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseveresustained_release_rising_levels
    Sustained-release ingestion with rising serial lithium levels despite supportive care [AACT/EAPCCT; EXTRIP 2015]
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseverepost_hd_rebound_recrosses_threshold
    Post-HD rebound lithium level (6–12h) re-crosses an EXTRIP threshold due to intracellular → plasma redistribution [EXTRIP 2015]
    Trigger could not be auto-evaluated — needs clinician judgement.

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RISK_STRATIFICATIONrequiredDrives severity classification
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Recommended regimen

Lithium toxicity — stop drug + saline → WBI (SR) → hemodialysis (EXTRIP 2015) → rebound recheck → supportive
axis: lithium_decontam_elimination_ladderstep 1 - Step 1 — Stop lithium + all clearance-reducing drugs; aggressive isotonic saline
Selected step "Step 1 — Stop lithium + all clearance-reducing drugs; aggressive isotonic saline" — Any confirmed/suspected lithium toxicity (acute, chronic, or acute-on-chronic)
  • discontinue lithium + offending nephrotoxic/clearance-reducing meds
    first line
    exposure_removal
    triggers: lithium_toxicity_confirmed_or_suspected, nsaid_acei_arb_thiazide_metronidazole_on_med_list
    EXTRIP 2015 / Baird-Gunning 2017 — removing the source and stopping NSAID/ACEi/ARB/thiazide/metronidazole restores renal lithium clearance; foundational in every pattern
  • isotonic 0.9% sodium chloride resuscitation
    first line
    crystalloid_volume_expansion
    10–20 mL/kg bolus then maintenance titrated to euvolemia + UOP ≥1 mL/kg/h • IV • continuous
    triggers: volume_depletion, chronic_toxicity_with_dehydration, awaiting_renal_clearance
    Volume repletion + normal saline restores GFR and renal lithium excretion; avoid hypotonic fluids and avoid forced diuresis/diuretics (worsen clearance)

ed playbook — drug actions (4)

  1. 1. discontinue lithium + offending drugs
    Stop lithium; hold NSAID/ACEi/ARB/thiazide/metronidazole • n/a • immediate
    trigger: Any suspected lithium toxicity
    Restores renal clearance (Baird-Gunning 2017)
  2. 2. isotonic 0.9% saline
    10–20 mL/kg bolus then maintenance to euvolemia, UOP ≥1 mL/kg/h • IV • continuous
    trigger: Volume depletion / restore clearance
    GFR + renal lithium excretion; no forced diuresis (Baird-Gunning 2017)
  3. 3. whole-bowel irrigation (PEG-ELS)
    1.5–2 L/h PO/NG until clear effluent • PO/NG • continuous
    trigger: SR formulation or large acute ingestion, airway protected
    Charcoal does NOT bind lithium (AACT/EAPCCT)
  4. 4. benzodiazepine (seizure)
    Lorazepam per status protocol • IV • PRN seizure
    trigger: Seizure activity
    Benzodiazepine-first; seizure is an EXTRIP HD criterion at level >2.5

Auto-drafted A&P note

ed

Subjective

- Possible entry pathways: Reported acute lithium ingestion (intentional/accidental) — known lithium-treated patient or pill bottle (EXTRIP 2015); Tremor, ataxia, dysarthria, confusion, myoclonus, or seizure in a patient on chronic lithium (EXTRIP 2015); Serum lithium >1.5 mEq/L (therapeutic 0.6–1.2) on a routine or screening draw (EXTRIP 2015).

Objective

- No vitals, labs, or imaging entered for this encounter.

Assessment

**Lithium toxicity** (tox.lithium-toxicity.core.v1).
Phenotype framing: Distinguish lithium neurotoxicity from serotonin syndrome / NMS (clonus + autonomic + recent serotonergic vs lead-pipe rigidity + neuroleptic), from non-dialysable tox, and from primary CNS/metabolic encephalopathy; lithium tremor + ataxia + nephrogenic DI is the signature (Baird-Gunning 2017)
Scope: Classify exposure pattern up front: acute (GI-predominant, high levels tolerated, late neuro) vs chronic (neurotoxicity at LOW levels — tremor/ataxia/encephalopathy/seizure, SILENT risk) vs acute-on-chronic (worst — high level + tissue-loaded) (EXTRIP 2015)

No severity triggers fired against current inputs.

Plan

Regimen axis: **Lithium toxicity — stop drug + saline → WBI (SR) → hemodialysis (EXTRIP 2015) → rebound recheck → supportive** — step "Step 1 — Stop lithium + all clearance-reducing drugs; aggressive isotonic saline".
1. discontinue lithium + offending nephrotoxic/clearance-reducing meds (exposure_removal, first line) — EXTRIP 2015 / Baird-Gunning 2017 — removing the source and stopping NSAID/ACEi/ARB/thiazide/metronidazole restores renal lithium clearance; foundational in every pattern
2. isotonic 0.9% sodium chloride resuscitation 10–20 mL/kg bolus then maintenance titrated to euvolemia + UOP ≥1 mL/kg/h IV continuous (crystalloid_volume_expansion, first line) — Volume repletion + normal saline restores GFR and renal lithium excretion; avoid hypotonic fluids and avoid forced diuresis/diuretics (worsen clearance)

Setting playbook (ed) — Classify acute vs chronic vs acute-on-chronic, stop lithium + offending drugs, start isotonic saline, send serial levels, WBI for SR, engage nephrology for EXTRIP HD (EXTRIP 2015)
3. discontinue lithium + offending drugs Stop lithium; hold NSAID/ACEi/ARB/thiazide/metronidazole n/a immediate — Any suspected lithium toxicity (Restores renal clearance (Baird-Gunning 2017))
4. isotonic 0.9% saline 10–20 mL/kg bolus then maintenance to euvolemia, UOP ≥1 mL/kg/h IV continuous — Volume depletion / restore clearance (GFR + renal lithium excretion; no forced diuresis (Baird-Gunning 2017))
5. whole-bowel irrigation (PEG-ELS) 1.5–2 L/h PO/NG until clear effluent PO/NG continuous — SR formulation or large acute ingestion, airway protected (Charcoal does NOT bind lithium (AACT/EAPCCT))
6. benzodiazepine (seizure) Lorazepam per status protocol IV PRN seizure — Seizure activity (Benzodiazepine-first; seizure is an EXTRIP HD criterion at level >2.5)

Non-pharmacologic actions:
- Notify nephrology — emergent intermittent HD if EXTRIP criteria met
- Continuous cardiac + SpO2 monitoring (bradyarrhythmia, QT)
- IV access × 2, strict I/O + Foley for UOP
- NPO if HD/airway concern; airway watch if declining GCS
- Contact regional poison center / toxicology
- Psychiatry hold/eval if intentional ingestion

AVOID / contraindication checks:
- Activated_charcoal_does_not_bind_lithium_use_WBI (AACT/EAPCCT WBI position)
- No_forced_diuresis_or_thiazide_loop_diuretics_worsen_clearance (Baird Gunning 2017)
- Avoid_hypotonic_fluids_use_isotonic_saline (Baird Gunning 2017)
- Stop_NSAID_ACEi_ARB_thiazide_metronidazole_reduce_renal_clearance (Baird Gunning 2017)
- Mandatory_post_HD_rebound_recheck_before_disposition (EXTRIP 2015)
- Intermittent_HD_preferred_over_CRRT_for_clearance (EXTRIP 2015)

Monitoring

Regimen monitoring:
- serum lithium q2-4h until clearly falling then q6-12h (EXTRIP 2015)
- mandatory post HD rebound level 6-12h after each session (EXTRIP 2015)
- creatinine and BMP q6h for AKI and clearance (Baird-Gunning 2017)
- sodium trend for nephrogenic DI (Baird-Gunning 2017)
- continuous telemetry for bradyarrhythmia QT (Baird-Gunning 2017)
- q1h neuro exam GCS for SILENT progression (Baird-Gunning 2017)
- strict IO UOP target 1mL kg h (Baird-Gunning 2017)

Setting (ed) monitoring:
- Serum lithium q2–4h (SR delayed/erratic peak) (EXTRIP 2015)
- q2h electrolytes + creatinine (Baird-Gunning 2017)
- q1h neuro exam + GCS (Baird-Gunning 2017)
- Continuous telemetry (Baird-Gunning 2017)
- Hourly UOP (Baird-Gunning 2017)

Follow-up plan: Psychiatry safety plan + lithium re-initiation decision (consider alternative mood stabilizer if recurrent toxicity); nephrology for nephrogenic DI / chronic interstitial nephropathy; endocrine for hypothyroidism/hyperparathyroidism; SILENT documentation (irreversible cerebellar deficits) + neurology rehab; education on volume/NSAID/sick-day rules (Baird-Gunning 2017)
- Close-out criterion: Discharge + safety plan + chronic-sequelae follow-up documented

Monitoring phase: Serial lithium q2–4h until clearly falling, then q6–12h; MANDATORY rebound level 6–12h after HD (intracellular → plasma redistribution); continuous telemetry, q1h neuro exam, strict I/O + UOP, Na trend (nephrogenic DI), repeat HD if rebound level re-crosses threshold (EXTRIP 2015)

Disposition

Current setting: ed — Classify acute vs chronic vs acute-on-chronic, stop lithium + offending drugs, start isotonic saline, send serial levels, WBI for SR, engage nephrology for EXTRIP HD (EXTRIP 2015)

Disposition criteria:
- Discharge: only mild asymptomatic ACUTE ingestion with falling levels, normal renal function, IR formulation, reliable follow-up (Baird-Gunning 2017)
- Admit ICU + nephrology: any HD candidate, level >4.0, decreased consciousness, seizure, arrhythmia, chronic toxicity (Baird-Gunning 2017)
- Admit ward + serial levels: SR ingestion or chronic mild toxicity not yet meeting HD criteria but needing serial monitoring (Baird-Gunning 2017)

Escalation triggers (move to higher acuity):
- Level >4.0 mEq/L (any pattern) → ICU + emergent HD (EXTRIP 2015)
- Level >2.5 mEq/L + decreased consciousness/seizure/arrhythmia → ICU + emergent HD (EXTRIP 2015)
- Impaired renal function / inability to clear at level >2.5 → ICU + HD (EXTRIP 2015)
- Rising serial levels despite WBI → ICU + HD planning (EXTRIP 2015)
- New seizure or declining GCS → ICU + airway prep (Baird-Gunning 2017)

Earlier-Return Triggers

Return-precaution thresholds (watch for):
- [LIFE_THREATENING] Serum lithium >4.0 mEq/L in ANY exposure pattern [EXTRIP 2015 hemodialysis criterion]
- [LIFE_THREATENING] Serum lithium >2.5 mEq/L WITH decreased consciousness, seizure, life-threatening arrhythmia, OR impaired renal function / inability to clear [EXTRIP 2015]
- [LIFE_THREATENING] Persistent cerebellar/extrapyramidal deficits or encephalopathy after the lithium level has normalized — Syndrome of Irreversible Lithium-Effectuated NeuroToxicity [Baird-Gunning 2017]

Citations

- EXTRIP 2015 Lithium Workgroup (Decker et al, Clin J Am Soc Nephrol) + 2024-2025 critical-care toxicology reviews (Baird-Gunning et al; AACT/EAPCCT whole-bowel irrigation position statement) [PMID:25583292](https://pubmed.ncbi.nlm.nih.gov/25583292/)
- Cited evidence (PMID 27307131) [PMID:27307131](https://pubmed.ncbi.nlm.nih.gov/27307131/)
- Cited evidence (PMID 15822766) [PMID:15822766](https://pubmed.ncbi.nlm.nih.gov/15822766/)
- Cited evidence (PMID 18800291) [PMID:18800291](https://pubmed.ncbi.nlm.nih.gov/18800291/)
- Cited evidence (PMID 24359000) [PMID:24359000](https://pubmed.ncbi.nlm.nih.gov/24359000/)

Last reconciled with current guidelines: 2026-05-16.
References
  • EXTRIP 2015 Lithium Workgroup (Decker et al, Clin J Am Soc Nephrol) + 2024-2025 critical-care toxicology reviews (Baird-Gunning et al; AACT/EAPCCT whole-bowel irrigation position statement) — PMID:25583292
  • Cited evidence (PMID 27307131) — PMID:27307131
  • Cited evidence (PMID 15822766) — PMID:15822766
  • Cited evidence (PMID 18800291) — PMID:18800291
  • Cited evidence (PMID 24359000) — PMID:24359000