01Approach to the Critical Patient/attcp50

Immediate Stabilization

›Airway protection priorities

›Obtunded patient with GCS < 13

›Immediate airway assessment

›Rapid sequence intubation preparation

›Aspiration risk in altered mental status

›Position lateral decubitus if vomiting

›Suction available at bedside

›Oxygen delivery

›Target SpO2 >= 94%

›Supplemental O2 if aspirating or hypoxic

›Circulatory targets

›IV access x2 large bore

›Normal saline resuscitation for volume depletion

›Target MAP >= 65 mmHg

›Cardiac monitoring

›Continuous ECG for dysrhythmia detection

›QTc monitoring every 4 hours

›Hemodynamic instability triggers

›SBP < 90 mmHg: fluid bolus 1 L NS

›Persistent hypotension: vasopressor support

Critical Decision Points

›Severity stratification on arrival

›Mild: serum lithium 1.5–2.5 mEq/L with nausea, tremor, lethargy

›IV hydration, monitoring, serial levels

›No dialysis if clinically stable and renal function preserved

›Moderate: serum lithium 2.5–3.5 mEq/L with coarse tremor, ataxia, confusion

›Nephrology consult for dialysis consideration

02History/hx74

Ingestion Pattern

›Type of toxicity exposure

›Acute: intentional or accidental single large ingestion in lithium-naive patient

›Formulation: immediate-release vs. extended-release (ER)

›ER tablets: prolonged absorption, delayed peak level

›Chronic: gradual accumulation from impaired elimination

›Most common and most dangerous pattern

›Often triggered by precipitating factor

›Acute-on-chronic: additional dose in patient on chronic lithium

›Combines high tissue burden with rising serum level

›Timing and dose

›Time since ingestion or last dose

›Estimated number of tablets ingested

›Recent dose changes or missed doses with catch-up dosing

Symptoms

›Gastrointestinal (earliest symptoms)

›Nausea and vomiting

›Diarrhea

›Abdominal discomfort

›Neurological progression

›Fine tremor (early)

›Progresses to coarse tremor (moderate)

›Myoclonus and clonus (severe)

›Confusion or altered consciousness

›Ataxia and unsteady gait

›Slurred speech

›Visual disturbances

›Seizure or loss of consciousness (severe)

03Physical Exam/exam41

Vital Signs

›Hemodynamic assessment

›Blood pressure: hypotension in severe toxicity

›Heart rate: bradycardia from sinus node dysfunction

›Temperature: fever worsens prognosis and predicts SILENT syndrome

›SpO2: respiratory compromise in obtunded patients

›Respiratory rate: aspiration risk assessment

Neurological Examination

›Mental status (most critical system)

›Level of consciousness: alert, confused, obtunded, coma

›GCS score documentation

›Orientation to person, place, time

›Motor findings by severity

›Mild: fine tremor, hyperreflexia

›Bilateral hand tremor

›Brisk deep tendon reflexes

›Moderate: coarse tremor, ataxia, fasciculations, nystagmus

›Finger-to-nose testing impaired

›Tandem gait abnormal

›Severe: clonus, rigidity, myoclonus, seizures

›Ankle clonus beats

›Decorticate or decerebrate posturing

›Cerebellar signs

›Dysarthria (slurred speech)

›Dysdiadochokinesia

›Intention tremor

Cardiovascular Examination

›Cardiac rhythm assessment

04Differential Diagnosis/ddx57

Neurological Mimics

›Serotonin syndrome

›ICD-10: T43.216A

›Differentiating features: hyperthermia, clonus, agitation, hyperreflexia

›Overlap risk when serotonergic drugs co-administered with lithium

›Hunter Criteria positive in serotonin syndrome

›Neuroleptic malignant syndrome

›ICD-10: G21.0

›Differentiating features: lead-pipe rigidity, fever, autonomic instability, bradykinesia

›Can co-occur with lithium toxicity when antipsychotics co-prescribed

›Wernicke encephalopathy

›ICD-10: E51.2

›Triad: ophthalmoplegia, ataxia, confusion

›Thiamine deficiency often in alcoholic patients

Metabolic Encephalopathy

›Hyponatremia

›ICD-10: E87.1

›Serum sodium < 130 mmol/L with neurological signs

›Lithium toxicity precipitated by low-sodium state

›Hypercalcemia

›ICD-10: E83.52

›Lithium-associated hyperparathyroidism can cause calcium elevation

›Serum calcium > 3.0 mmol/L

›Uremic encephalopathy

›ICD-10: N18.9

›Creatinine markedly elevated, asterixis

›Renal failure both cause and consequence of lithium toxicity

›Hepatic encephalopathy

05Laboratory Tests/lt52

Lithium Level

›Serum lithium concentration (cornerstone of diagnosis)

›Therapeutic range: 0.6–1.2 mEq/L

›Mild toxicity: 1.5–2.5 mEq/L

›Moderate toxicity: 2.5–3.5 mEq/L

›Severe/life-threatening: >3.5 mEq/L

›Serial levels required

›Repeat every 2–4 hours in acute ingestions

›Levels may continue to rise, especially with ER formulations

›Peak may be delayed 6–12 hours post-ingestion

›Repeat 6–8 hours after hemodialysis

›Rebound elevation from tissue redistribution is common

›Additional dialysis sessions may be required

›Level-clinical correlation pitfall

›Chronic toxicity: severe symptoms at lower serum levels

›Tissue (CNS) stores already saturated in chronic users

›Do not use serum level alone to exclude toxicity

Renal and Electrolyte Panel

›Basic metabolic panel (BMP)

›Sodium: low-sodium state precipitates and worsens toxicity

›Target correction in hypernatremia from nephrogenic DI

›Avoid overcorrection of hyponatremia

›Potassium: hypokalemia potentiates QTc prolongation

›BUN and creatinine: renal function is primary determinant of clearance

›Estimated GFR guides dialysis decision

›Creatinine rise indicates impaired lithium elimination

›Glucose: rule out hypoglycemia as AMS contributor

›Calcium: lithium-associated hypercalcemia (hyperparathyroidism)

06Diagnostic Tests/dt100

Scoring Systems

›Severity classification (clinical + level-based)

›Mild: serum lithium 1.5–2.5 mEq/L

›Clinical: nausea, vomiting, diarrhea, fine tremor, lethargy

›Management: IV hydration, monitoring, serial levels

›Moderate: serum lithium 2.5–3.5 mEq/L

›Clinical: coarse tremor, ataxia, slurred speech, confusion, hyperreflexia, fasciculations

›Management: nephrology consult, dialysis consideration

›Severe: serum lithium >3.5 mEq/L or major CNS/cardiac findings at any level

›Clinical: seizures, coma, cardiovascular collapse, renal failure

›Management: emergent hemodialysis, ICU

›EXTRIP Workgroup hemodialysis criteria (2015)

›Recommended dialysis indications

›Renal impairment AND serum lithium >4.0 mEq/L

›Decreased level of consciousness (any lithium level)

›Seizures (any lithium level)

›Life-threatening dysrhythmias (any lithium level)

›Suggested dialysis indications

›Serum lithium >5.0 mEq/L regardless of symptoms

›Significant confusion

›Expected time to reduce lithium below 1.0 mEq/L exceeds 36 hours

›Dialysis endpoint

›Continue HD until clinical improvement OR lithium < 1.0 mEq/L

›Minimum 6 hours if level not readily available

›SILENT syndrome criteria

›Syndrome of Irreversible Lithium-Effectuated Neurotoxicity

›Persistent neurological dysfunction lasting >2 months after exposure

›Cerebellar sequelae in approximately 79% of cases

›May occur even at levels below 2.5 mEq/L

›Risk factors for SILENT

›Concurrent fever at time of toxicity (48% of SILENT cases)

›Delayed treatment and prolonged high lithium exposure

›Chronic toxicity pattern with tissue saturation

MRI

›MRI brain indications in lithium toxicity

›Persistent neurological deficits after level normalization

›Suspected SILENT syndrome

›Ataxia, nystagmus, dysarthria persisting >2 months

›Differentiate structural from toxic etiology

›Stroke, PRES, encephalitis

›When focal deficits disproportionate to lithium level

›MRI findings in SILENT syndrome

›Cerebellar atrophy

›Vermis and hemispheres affected

›Correlates with persistent ataxia

›Diffuse gliosis on FLAIR sequences

›Subcortical white matter changes on diffusion tensor imaging

›Tractography disruption in severe cases

›MRI timing

›Acute phase: MRI rarely indicated unless stroke excluded

›Subacute/chronic: preferred over CT for posterior fossa assessment

›Superior cerebellar detail compared to CT

›No radiation

CT

›CT head indications

›Altered mental status with focal neurological signs

›Exclude hemorrhagic stroke before lumbar puncture

›Exclude mass lesion

›Seizure in lithium-toxic patient

›Rule out intracranial pathology

›Standard pre-LP evaluation

›Head trauma in obtunded patient (fall risk)

›Abdominal X-ray / KUB (alternative to CT)

›Lithium tablets may be radiopaque on plain film

›Helps estimate pill burden in large acute ingestions

›Guides decision for whole bowel irrigation

›Particularly useful for extended-release formulations

›Serial KUB to assess tablet clearance with WBI

›CT limitations in lithium toxicity

›CT normal in toxic encephalopathy

›Poor sensitivity for posterior fossa pathology versus MRI

›Cerebellar changes of SILENT better seen on MRI

Ultrasound

›Renal ultrasound indications

›Bilateral hydronephrosis assessment (obstruction mimicking oliguria)

›Renal size and echogenicity in chronic lithium nephropathy

›Small echogenic kidneys in chronic lithium-induced CKD

›Microcysts in medullary regions (characteristic of lithium nephropathy)

›Bladder volume if urinary retention suspected

›Point-of-care ultrasound (POCUS)

›Inferior vena cava collapsibility index for volume status

›Guides aggressiveness of saline resuscitation

›IVC < 1.5 cm with >50% collapsibility: volume-depleted

›Left ventricular function assessment

›Hyperdynamic vs. depressed function

›Guides vasopressor choice in hemodynamic instability

›Pulmonary edema assessment

›B-lines in pulmonary fields post aggressive hydration

ECG

›ECG: mandatory in all cases of lithium toxicity

›T-wave changes (most common ECG finding)

›T-wave flattening or inversion

›ST-segment depression or elevation

›QTc prolongation

›Present in approximately 24% of intoxication episodes

›QTc >500 ms in 54% of those with QTc prolongation

›Risk of torsades de pointes at QTc >500 ms

›Sinus bradycardia

›Lithium causes sinus node dysfunction

›Symptomatic bradycardia may require pacing

›AV block

›First-degree or higher

›Progressive AV block in severe toxicity

›Premature ventricular beats

›Rare: myocarditis pattern

07Disposition/dispo41

ICU Admission

›ICU indications (Class I)

›Severe neurological manifestations

›Seizures

›Coma or GCS < 13

›Significant altered mental status

›Hemodialysis requirement

›Continuous monitoring during and after dialysis

›Post-dialysis rebound lithium monitoring

›Hemodynamic instability

›Persistent hypotension requiring vasopressors

›Symptomatic dysrhythmias

›Aspiration or respiratory compromise

›Intubation or high-flow oxygen requirement

Monitored Ward Admission

›Step-down or telemetry indications

›Moderate toxicity (lithium 2.5–3.5 mEq/L with moderate symptoms)

›Coarse tremor, ataxia, confusion not severe enough for ICU

›Rising lithium levels on serial monitoring despite treatment

›Renal insufficiency with elevated levels

›GFR impaired, slower expected clearance

›Acute ingestion of large or sustained-release formulation

›Levels may continue to rise hours after presentation

›QTc prolongation (>500 ms): telemetry mandatory

Observation

›Observation unit criteria

›Mild symptoms with lithium 1.5–2.0 mEq/L

›Normal or near-normal renal function

08Treatment/t110

Immediate Interventions

›Stop lithium

›Discontinue lithium immediately in all cases of toxicity

›Class I recommendation

›Do not resume until toxicity resolved and precipitant addressed

›Discontinue all interacting medications

›NSAIDs: switch to acetaminophen

›Diuretics: hold unless specific cardiac indication overrides

›ACEi/ARBs: hold until renal function and levels normalize

›IV access and monitoring

›Two large-bore peripheral IVs

›Continuous cardiac monitoring

›Urinary catheter for accurate urine output monitoring in severe cases

Volume Resuscitation

›Normal saline hydration

›Mechanism: volume replacement enhances renal lithium clearance

›Sodium repletion reduces tubular lithium reabsorption

›NS preferred over hypotonic solutions to avoid worsening hyponatremia

›Initial bolus: 1 L NS IV over 30–60 minutes if volume depleted

›Repeat as needed to restore euvolemia

›Monitor for fluid overload in renal failure or heart failure

›Maintenance: NS at 100–200 mL/hr to maintain urine output >0.5 mL/kg/hr

›Target urine output 1–2 mL/kg/hr in moderate-to-severe toxicity

›Monitor for hypernatremia if nephrogenic DI present

›Electrolyte correction

›Sodium: correct hyponatremia slowly (max 10–12 mmol/L per 24 hours)

›Potassium: maintain >3.5 mmol/L to reduce QTc risk

›Calcium: correct hypocalcemia

Gastrointestinal Decontamination

›Activated charcoal: CONTRAINDICATED

›Lithium is an ion and NOT adsorbed by activated charcoal

›No clinical benefit; aspiration risk in obtunded patients

›Whole bowel irrigation (WBI) for acute/acute-on-chronic ingestions

›Indications

›Large acute ingestion of IR or ER lithium tablets

›Extended-release formulation: WBI most beneficial

›Effective even when administered >4 hours post-ingestion

›Administration

›Polyethylene glycol solution (GoLYTELY) at 1,500–2,000 mL/hr in adults

›Via NG tube if patient unable to drink adequate volume

›Continue until rectal effluent clear

›Contraindications

›Ileus or bowel obstruction

›Unprotected airway in obtunded patients (intubate first)

›Hemodynamic instability

›Gastric lavage

›Considered only if very early presentation (<1–2 hours of acute ingestion)

›Not routinely recommended

›Airway protection required before lavage in altered patients

Hemodialysis

›Hemodialysis: definitive treatment for severe lithium toxicity

›EXTRIP recommended indications

›Renal impairment AND lithium >4.0 mEq/L

›Decreased level of consciousness (any level)

›Seizures (any level)

›Life-threatening dysrhythmias (any level)

›EXTRIP suggested indications

›Lithium >5.0 mEq/L regardless of symptoms

›Significant confusion not improving

›Expected time to clear below 1.0 mEq/L >36 hours with conservative management

›HD protocol

›High-flux intermittent hemodialysis preferred

›Duration: minimum 6 hours per session

›Target: serum lithium <1.0 mEq/L and clinical improvement

›Monitor levels every 2–4 hours during HD

›Post-dialysis rebound

›Lithium redistributes from CNS and tissues after HD

›Recheck level 6–8 hours after HD completion

›Repeat dialysis if rebound to >1.0 mEq/L with persistent symptoms

›CRRT alternative

›Continuous renal replacement therapy if hemodynamically unstable

›Less efficient per hour than intermittent HD but better tolerated hemodynamically

›Use CRRT when HD not feasible due to hemodynamic instability

Seizure Management

›Benzodiazepines: first-line for lithium-induced seizures

›Lorazepam 2–4 mg IV push

›Repeat every 5–10 minutes as needed

›Maximum 8 mg IV in acute setting

›Diazepam 5–10 mg IV if lorazepam unavailable

›Onset: 1–3 minutes IV

›May repeat every 5–10 minutes

›Mechanism: GABAergic inhibition reduces neuronal excitability

›Phenobarbital second-line if refractory

›20 mg/kg IV loading dose at 50–100 mg/min

›Monitor respiratory depression

›Avoid phenytoin for lithium-induced seizures

›Limited efficacy for toxic/metabolic seizures

›Does not address underlying lithium toxicity

›Definitive seizure control

›Hemodialysis to remove lithium is key treatment

›Seizures unlikely to resolve without eliminating lithium burden

Cardiac Dysrhythmia Management

›QTc prolongation management

›Correct hypokalemia and hypomagnesemia

›Magnesium sulfate 2 g IV over 15 minutes for QTc >500 ms

›Target potassium >4.0 mmol/L

›Torsades de pointes

›Magnesium sulfate 2 g IV bolus immediately

›Overdrive pacing if refractory

›Avoid antiarrhythmics that further prolong QTc (amiodarone)

›Symptomatic bradycardia

›Atropine 0.5 mg IV for hemodynamically significant bradycardia

›Repeat to maximum 3 mg total

›Transcutaneous pacing if atropine fails

›Temporary transvenous pacing for persistent high-degree AV block

Supportive Care

›Hypothyroidism management

›Levothyroxine for lithium-induced hypothyroidism

›1.6 mcg/kg/day orally as starting dose

›Adjust based on TSH normalization

›Myxedema coma: levothyroxine 200–500 mcg IV loading dose

›Nephrogenic DI management

›Adequate free water replacement

›Amiloride 5–20 mg/day PO: first-line for lithium-induced nephrogenic DI

›Reduces lithium entry into collecting duct principal cells

›May be started once toxicity resolved if DI persists

›Low-sodium, low-protein diet once stable

09Special Populations/sp78

Pregnancy

›Lithium and pregnancy risk

›FDA Category D: teratogenic potential

›Ebstein anomaly: tricuspid valve malformation

›Relative risk approximately 1.5–3x above baseline

›Risk highest during first trimester cardiac organogenesis

›Neonatal lithium toxicity

›Placental transfer is complete (fetal levels approach maternal)

›Neonatal hypotonia (floppy baby syndrome)

›Neonatal cyanosis, bradycardia, nephrogenic DI in neonate

›Neonatal lithium level at birth

›Management modifications in pregnancy

›Immediate obstetric consultation for any symptomatic toxicity

›Lithium level interpretation

›Increased renal clearance in pregnancy may cause apparent lower maternal levels

›Third trimester: GFR increases 50%; dose adjustments required

›Postpartum: GFR normalizes rapidly, toxicity risk increases

›Hemodialysis considerations

›HD is indicated by same EXTRIP criteria regardless of pregnancy

›Fetal monitoring during HD

›Obstetric and nephrology co-management required

›Delivery planning

›If lithium used near delivery: neonatal monitoring for 5–7 days

›Breastfeeding: lithium secreted in breast milk at 40–50% of serum level

›Generally contraindicated during breastfeeding

›If continued, infant lithium level and renal function monitoring required

Geriatric

›Increased vulnerability to lithium toxicity in elderly

›Reduced GFR with aging

›GFR declines approximately 1 mL/min/1.73m2 per year after age 40

›Reduced lithium clearance at any dose

›Polypharmacy

›Higher likelihood of NSAIDs, diuretics, ACEi/ARBs

›Drug interactions more common

›Reduced total body water

›Higher lithium concentration for same dose

›Lower thresholds for CNS toxicity

›Delirium and fall risk at levels considered borderline

›Clinical presentation differences

›Delirium may be presenting symptom without classic tremor

›Falls from ataxia leading to fractures

›Symptoms may progress more rapidly

›Management considerations

›Lower threshold for hemodialysis in elderly

›Impaired renal clearance prolongs toxic exposure

›Aggressive hydration with caution

›Congestive heart failure risk with high-volume saline

›Monitor fluid balance carefully

›Medication dose adjustment for CKD after recovery

›Lower maintenance lithium dose required

›More frequent level monitoring

›Cognitive and functional reassessment post-toxicity

›SILENT syndrome risk higher in elderly

›Neuropsychological testing for baseline comparison

Pediatrics

›Lithium toxicity in children

›Rare: lithium used in pediatric bipolar disorder (adolescents primarily)

›FDA approved for bipolar disorder age >=12 years

›Off-label use in younger children uncommon

›Accidental ingestion in young children

›Single tablet can cause significant toxicity due to weight

›Extended-release tablets pose higher risk from prolonged absorption

›Clinical presentation in pediatrics

›Gastrointestinal symptoms predominate initially

›Seizures may occur at lower absolute levels than adults

›Rapid clinical deterioration possible

›Management in pediatric patients

›Poison control consultation mandatory (1-800-222-1222)

›Weight-based volume resuscitation

›Normal saline 20 mL/kg IV bolus for volume depletion

›Titrate to clinical endpoints

›Whole bowel irrigation in large acute ingestions

›PEG solution 500 mL/hr for children age 6–12 years

›1,000 mL/hr for adolescents (>12 years)

›Hemodialysis in pediatrics

›Same EXTRIP criteria apply

›Pediatric nephrology consultation required

›Smaller HD circuits available for children

›Seizure management

›Lorazepam 0.1 mg/kg IV (maximum 4 mg per dose)

›Diazepam 0.1–0.3 mg/kg IV if lorazepam unavailable

10Background/b88

Epidemiology

›Lithium use prevalence

›Primary indication: bipolar disorder (type I and II)

›Bipolar disorder affects approximately 1–2% of the global population

›Lithium remains a first-line mood stabilizer for bipolar I disorder

›Additional indications: major depressive disorder augmentation, schizoaffective disorder

›Narrow therapeutic index: therapeutic 0.6–1.2 mEq/L, toxic >=1.5 mEq/L

›One of the narrowest therapeutic windows of any psychiatric medication

›Lithium toxicity incidence

›Most common cause of serious prescription drug toxicity in psychiatry

›Chronic toxicity most common pattern (approximately 60% of cases)

›Acute toxicity: 15–20%

›Acute-on-chronic: 25–30%

›Chronic pattern associated with highest morbidity and mortality

›Outcomes

›Mortality: approximately 1–2% in adequately treated cases

›SILENT syndrome: up to 10% of toxicity cases develop permanent neurological sequelae

›Cerebellar dysfunction predominates in 79% of SILENT cases

›Risk increases with fever at time of toxicity

Pathophysiology

›Mechanism of lithium action

›Monovalent cation transported similarly to sodium

›Enters cells via sodium channels but is not efficiently pumped out

›Accumulates intracellularly in CNS neurons with chronic use

›Inhibits inositol monophosphatase and glycogen synthase kinase-3 (GSK-3)

›Reduces inositol availability for phospholipid signaling

›GSK-3 inhibition: neuroprotective and mood-stabilizing effects

›Modulates dopamine and serotonin neurotransmission

›Renal handling of lithium

›Freely filtered at glomerulus (not protein bound)

›80% reabsorbed in proximal tubule alongside sodium

›Volume depletion increases proximal reabsorption (reduces clearance)

›Sodium depletion increases lithium reabsorption

›Low-sodium diet is a major precipitant of toxicity

›NSAIDs reduce renal blood flow: less filtration and more reabsorption

›GFR is the primary determinant of lithium clearance

›Any cause of reduced GFR increases toxicity risk

›Mechanism of CNS toxicity

›Lithium accumulates in brain tissue over days with chronic use

›Brain:serum ratio increases with duration of therapy

›Explains why chronic toxicity causes severe symptoms at lower serum levels

›Disrupts neuronal membrane stability

›Cerebellar Purkinje cells particularly vulnerable

›Loss of Purkinje cells underlies irreversible cerebellar ataxia in SILENT

›Delayed CNS distribution in acute ingestion

›Serum level peaks before CNS levels in acute overdose

›Up to 24 hours for CNS equilibration

›Mechanism of nephrotoxicity

›Nephrogenic diabetes insipidus

›Lithium blocks ADH (vasopressin) action on collecting duct V2 receptors

›Downregulates aquaporin-2 water channel expression

›Results in inability to concentrate urine

›Occurs in up to 40% of chronic lithium users

›Chronic lithium nephropathy

›Progressive tubulointerstitial fibrosis with long-term use

›Renal microcysts in medullary collecting ducts (pathognomonic)

›CKD progression: approximately 10–20% of long-term users develop CKD stage 3+

Therapeutic Considerations

›Evidence base for hemodialysis (EXTRIP 2015)

›Cochrane review (Lavonas and Buchanan, 2015): insufficient RCT evidence

›EXTRIP recommendations based on pharmacokinetic principles and case series

›Lithium highly dialyzable: protein binding 0%, molecular weight 7 daltons

›Clearance during HD approximately 100–200 mL/min

›Rebound phenomenon after HD

›Tissue reservoir releases lithium post-dialysis

›Post-HD rebound of 1–5 mEq/L possible in chronic toxicity

›Multiple HD sessions may be required

›Evidence for whole bowel irrigation

›WBI reduces lithium absorption in acute ingestions

›Effective even >4 hours post-ingestion (Berling and Isbister, 2026)

›Most benefit for extended-release formulations

›Thanacoody et al. position paper update (2015): WBI reasonable for large lithium ingestions

›No RCTs specific to lithium; evidence from case series and pharmacokinetic modeling

›ECG monitoring evidence

›LiSIE retrospective cohort study (Truedson et al., 2022)

›QTc prolongation in 24% of intoxication episodes

›QTc >500 ms in 54% of those with prolongation

›T-wave changes most common finding

›Cardiac effects concentration-dependent and generally reversible

›SILENT syndrome prevention

›Early dialysis reduces risk of permanent neurological injury

›Fever treatment: antipyretics and infection management reduce SILENT risk

›Fever reported in 48% of SILENT cases (Verdoux et al., 2021)

›Avoid prolonged toxic exposure

›Time from symptom onset to treatment inversely related to outcomes

›Lithium formulations and toxicity risk

›Immediate-release: faster absorption, earlier peak, faster clearance

›Extended-release: delayed peak, prolonged absorption

›Higher risk of late-presenting or escalating toxicity

›WBI more critical for ER formulations

›Serial levels for 12–24 hours recommended

11Patient Discharge Instructions/pdi38

copy discharge instructions

›Lithium toxicity — discharge instructions

›You were treated for a high lithium level in your blood

›Lithium is a medication used for bipolar disorder

›Too much lithium can harm your brain, kidneys, and heart

›Return to the emergency department immediately if you develop

›Tremor, shaking, or unsteady walking

›Confusion, slurred speech, or difficulty thinking

›Seizure or loss of consciousness

›Persistent vomiting or diarrhea that prevents drinking fluids

›Decreased urination or no urination

›Fever while taking lithium

›Palpitations or irregular heartbeat

›Medication instructions

›Do not restart lithium until your doctor tells you it is safe

›Your doctor will recheck your lithium level at follow-up

›Your dose may need to be changed

›Avoid anti-inflammatory pain medicines (ibuprofen, naproxen, Advil, Aleve)

›These raise your lithium level and can cause toxicity

›Use acetaminophen (Tylenol) for pain instead

›Tell all of your doctors and pharmacists that you take lithium before starting any new medication

›Never take extra doses to make up for missed doses

›Lifestyle instructions

›Drink adequate fluids every day — dehydration raises your lithium level

›Aim for 6–8 glasses of water or non-caffeinated fluid per day

›Drink more if you are exercising, in hot weather, or ill

›Maintain a consistent salt intake in your diet

›Low-salt diets raise your lithium level

12References/r55

Guidelines and Key Sources

›EXTRIP Workgroup hemodialysis recommendations

›Decker BS, Goldfarb DS, Dargan PI, et al.

›Extracorporeal Treatment for Lithium Poisoning: Systematic Review and Recommendations From the EXTRIP Workgroup

›Clinical Journal of the American Society of Nephrology. 2015

›PMID: 25583292

›Cochrane review on hemodialysis for lithium poisoning

›Lavonas EJ, Buchanan J

›Hemodialysis for Lithium Poisoning

›Cochrane Database of Systematic Reviews. 2015

›doi: 10.1002/14651858.CD007951.pub2

›Lithium poisoning comprehensive review

›Baird-Gunning J, Lea-Henry T, Hoegberg LCG, Gosselin S, Roberts DM

›Lithium Poisoning

›Journal of Intensive Care Medicine. 2017

›PMID: 27516079

›SILENT syndrome systematic review

›Verdoux H, Debruyne AL, Queuille E, De Leon J

›A Reappraisal of the Role of Fever in the Occurrence of Neurological Sequelae Following Lithium Intoxication

›Expert Opinion on Drug Safety. 2021

›PMID: 33789560

›SILENT syndrome cerebellar review

›Marmol S, Beltre N, Margolesky J

›Syndrome of Irreversible Lithium-Effectuated Neurotoxicity (SILENT): A Preventable Cerebellar Disorder

›Cerebellum. 2024

›PMID: 38321324

ECG and Cardiac References

›LiSIE retrospective cohort study

Evidence & Review