medical grandrounds mary antoniette m. tan, m.d. first year resident

MEDICAL MEDICAL GRANDROUNDSGRANDROUNDS

Mary Antoniette M. Tan, M.D.Mary Antoniette M. Tan, M.D.

First Year ResidentFirst Year Resident

ObjectivesObjectives

To present a case of lithium toxicityTo present a case of lithium toxicity

To discuss the use of lithium in mood To discuss the use of lithium in mood disorder and its adverse effectsdisorder and its adverse effects

To discuss the management of lithium To discuss the management of lithium toxicitytoxicity

Identifying DataIdentifying Data

CFCF

77 years old77 years old

FemaleFemale

FilipinoFilipino

SeparatedSeparated

Education GraduateEducation Graduate

HomeboundHomebound

Chief Complaint Chief Complaint

Decreased sensoriumDecreased sensorium

History of Present IllnessHistory of Present Illness

Patient is a known case of bipolar mood Patient is a known case of bipolar mood disorder since 1981, maintained on lithium 900 disorder since 1981, maintained on lithium 900 mg per day.mg per day.

1 year PTA ------ apparently well 1 year PTA ------ apparently well free from medications for free from medications for

5 months 5 months (+) paranoia, irritability (+) paranoia, irritability no consult, no meds no consult, no meds


1 month PTA ----- persistence of paranoia 1 month PTA ----- persistence of paranoia and irritability and irritability

(+) poor appetite (+) poor appetite

(+) sleeping problems (+) sleeping problems

consult with a private consult with a private psychiatrist, advised psychiatrist, advised

admission admission


1 month PTA ----- maintained on 1 month PTA ----- maintained on Olanzapine 10mg OD Olanzapine 10mg OD

and lithium carbonate and lithium carbonate

1350 mg per day 1350 mg per day along with Valsartan, along with Valsartan,

ISMN and CentrumISMN and Centrum


4 days PTA ----- (+) right hand tremors4 days PTA ----- (+) right hand tremors

more withdrawnmore withdrawn

3 days PTA ----- tremors more generalized 3 days PTA ----- tremors more generalized and pronounced and pronounced

(+) episodes of passing (+) episodes of passing out loose to watery stools out loose to watery stools

(+) very poor oral intake(+) very poor oral intake


1 day PTA ------ tremors persistent, involved the 1 day PTA ------ tremors persistent, involved the lips lips

(+) decreased SBP: 70mmHg (+) decreased SBP: 70mmHg (+) decreased sensorium, (+) decreased sensorium, aroused only by painful aroused only by painful

stimulusstimulus

Patient rushed to a local hospital – IV Patient rushed to a local hospital – IV hydration done, serum electrolytes hydration done, serum electrolytes unremarkable. Relatives opted transfer to our unremarkable. Relatives opted transfer to our institution.institution.

Past Medical HistoryPast Medical History

(+) HPN x 15 years on Valsartan 40mg (+) HPN x 15 years on Valsartan 40mg OD and ISMN 30mg ODOD and ISMN 30mg OD

(-) DM, asthma(-) DM, asthma

Personal/Social HistoryPersonal/Social History

(-) smoking(-) smoking (-) alcoholic beverage drinking(-) alcoholic beverage drinking

Family HistoryFamily History

(-) Hypertension, DM, asthma, cancer(-) Hypertension, DM, asthma, cancer (-) Psychiatric illness(-) Psychiatric illness

Review of SystemsReview of Systems

(-) headache, (-) dizziness, (-) BOV, (-) nausea, (-) headache, (-) dizziness, (-) BOV, (-) nausea, (-) vomiting(-) vomiting

(-) fever, (-) cough and colds, (-) nasal (-) fever, (-) cough and colds, (-) nasal congestion, (-) dyspneacongestion, (-) dyspnea

(-) chest pain, (-) palpitations, (-) orthopnea, (-) (-) chest pain, (-) palpitations, (-) orthopnea, (-) PND, (-) edemaPND, (-) edema

(-) abdominal pain, (-) hematemesis, (-) (-) abdominal pain, (-) hematemesis, (-) hematochezia, (-) melena, (-) weight losshematochezia, (-) melena, (-) weight loss

(-) hematuria, (-) dysuria, (-) polyuria(-) hematuria, (-) dysuria, (-) polyuria (-) joint pains, (-) skin lesions(-) joint pains, (-) skin lesions

Physical ExaminationPhysical ExaminationGeneral General SurveySurvey

Drowsy, lethargic, uttering incomprehensible sounds, not Drowsy, lethargic, uttering incomprehensible sounds, not in respiratory distress in respiratory distress

Vital SignsVital Signs BP = 130/80 BP = 130/80 mmHgmmHg

HR = 64 bpmHR = 64 bpm RR = 20 cpmRR = 20 cpm Temp = 36.8CTemp = 36.8C

HEENTHEENT Anicteric sclerae, pink palpebral conjunctivae, no Anicteric sclerae, pink palpebral conjunctivae, no tonsillophrayngeal congestion, no cervical tonsillophrayngeal congestion, no cervical lypmhadenopathies, neck veins not distendedlypmhadenopathies, neck veins not distended

Chest / Chest / LungsLungs

Symmetric chest expansion, no retractions, clear breath Symmetric chest expansion, no retractions, clear breath sounds, no rales or wheezessounds, no rales or wheezes

CVSCVS Adynamic precordium, normal rate, regular rhythm, Adynamic precordium, normal rate, regular rhythm, distinct S1 and S2, no murmursdistinct S1 and S2, no murmurs

AbdomenAbdomen Flabby, soft, normoactive bowel sounds, no masses or Flabby, soft, normoactive bowel sounds, no masses or tendernesstenderness

ExtremitiesExtremities Full and equal pulsesFull and equal pulses, n, no cyanosis, no edema, no o cyanosis, no edema, no clubbingclubbing

Neurologic ExaminationNeurologic Examination Fairly kempt and groomedFairly kempt and groomed Lethargic, responded to vigorous sternal rubbing, uttering Lethargic, responded to vigorous sternal rubbing, uttering

incomprehensible soundsincomprehensible sounds Cranial NervesCranial Nerves

Pupils 2-3mm equally briskly reactive to lightPupils 2-3mm equally briskly reactive to lightEOMS full and equalEOMS full and equalAble to localize soundAble to localize soundTongue at midline on protrusionTongue at midline on protrusion

Motor : able to move all extremities spontaneously and to Motor : able to move all extremities spontaneously and to withdraw to painwithdraw to pain

Sensory : responds to vigorous sternal rubbing, withdraws to Sensory : responds to vigorous sternal rubbing, withdraws to painpain

Meningeal : (-) nuchal rigidityMeningeal : (-) nuchal rigidity Pathologic : (-) Babinski sign, (-) ankle clonusPathologic : (-) Babinski sign, (-) ankle clonus

Diagnostics done at the ER

CBC, Na, K, Ca, Mg : NormalCBC, Na, K, Ca, Mg : Normal

BUN = 27, creatinine = 2.0BUN = 27, creatinine = 2.0

Chest xray : clear lung fields, left ventricular Chest xray : clear lung fields, left ventricular enlargement, atherosclerotic aortaenlargement, atherosclerotic aorta

12-L ECG : Bifascicular block (first degree AV 12-L ECG : Bifascicular block (first degree AV block and left anterior hemiblock)block and left anterior hemiblock)

Diagnostics done at the ER

Arterial blood gas : slight metabolic acidosis - Arterial blood gas : slight metabolic acidosis - pO2 98.0, pH 7.33, PCO2 39.8, HCO3 20.6, pO2 98.0, pH 7.33, PCO2 39.8, HCO3 20.6, O2sat 97.1%, BE -4.9, total CO2 21.8O2sat 97.1%, BE -4.9, total CO2 21.8

Urinalysis : leukocyte esterase +2, blood +3, Urinalysis : leukocyte esterase +2, blood +3, RBC 32.1, WBC 6.3RBC 32.1, WBC 6.3 Obtained via foley catheterization; initial output = Obtained via foley catheterization; initial output =

130cc in 8 hrs130cc in 8 hrs

Serum lithium : 2.57 mmol/L (NV 0.5-1.5)Serum lithium : 2.57 mmol/L (NV 0.5-1.5)

Salient FeaturesSalient Features

77 years old77 years old

FemaleFemale

Known to have bipolar mood disorderKnown to have bipolar mood disorder

Maintained on lithium carbonate 1350 mg/day Maintained on lithium carbonate 1350 mg/day

tremors, altered sensorium, anorexia, diarrheatremors, altered sensorium, anorexia, diarrhea

Elevated serum BUN and creatinineElevated serum BUN and creatinine

Elevated serum lithium Elevated serum lithium

Known hypertensive x 15 yearsKnown hypertensive x 15 years

ADMITTING IMPRESSIONADMITTING IMPRESSION

1.1. Lithium ToxicityLithium Toxicity

2.2. ARF prerenal, sec to volume depletion, ARF prerenal, sec to volume depletion, on top of CRI sec to Hypertensive on top of CRI sec to Hypertensive NephrosclerosisNephrosclerosis

3.3. Bipolar Mood DisorderBipolar Mood Disorder

4.4. Hypertensive Atherosclerotic Hypertensive Atherosclerotic Cardiovascular DiseaseCardiovascular Disease

Problem #1: Tremors, altered sensorium, Problem #1: Tremors, altered sensorium, anorexia, diarrhea anorexia, diarrhea

(elevated serum lithium level + CRI) (elevated serum lithium level + CRI) lithium level: 2.57 mmol/L (NV 0.5-1.5)lithium level: 2.57 mmol/L (NV 0.5-1.5)

referral to Nephrologyreferral to Nephrology

hydration with PNSS at 150cc/hourhydration with PNSS at 150cc/hour

Problem #1: Tremors, altered sensorium, Problem #1: Tremors, altered sensorium, anorexia, diarrhea anorexia, diarrhea

(elevated serum lithium level + CRI) (elevated serum lithium level + CRI)

stat hemodialysis : extended hemodialysis (8 hours) stat hemodialysis : extended hemodialysis (8 hours) done (indication: increased lithium level > 2.5 + CRI, done (indication: increased lithium level > 2.5 + CRI, presence of neurologic symptoms) and tolerated presence of neurologic symptoms) and tolerated

serum lithium level post dialysis : 0.35 mmol/Lserum lithium level post dialysis : 0.35 mmol/L

marked clinical improvement post dialysis : more marked clinical improvement post dialysis : more awake, (-) tremors and fasciculations, adequate awake, (-) tremors and fasciculations, adequate verbal outputverbal output

4/9/074/9/07 4/10/074/10/07

post-HDpost-HD

(10am)(10am)

4/10/07 4/10/07 (4pm)(4pm)

4/11/074/11/07

Serum lithium Serum lithium (NV 0.5-1.5 mmol/L)(NV 0.5-1.5 mmol/L)

2.572.57 0.35 0.35 0.64 0.64 0.590.59

4/9/07 4/9/07 4/10/07 4/10/07 (post-(post-HD)HD)

4/11/07 4/11/07 4/12/07 4/12/07 4/14/07 4/14/07 4/16/07 4/16/07

NaNa 140140 138138 138138 141141 138138 141141

KK 4.14.1 4.14.1 4.04.0 4.44.4 3.93.9 4.04.0

BUNBUN 2727 7.07.0 1818

CreaCrea 2.02.0 1.11.1 1.41.4 1.21.2 1.31.3 1.41.4

CaCa 8.98.9

MgMg 1.81.8 1.71.7 1.81.8

Problem #2: Restlessness and Problem #2: Restlessness and agitation agitation

attributed to patient’s bipolar mood disorderattributed to patient’s bipolar mood disorder

Haloperidol 1.25mg slow IV push PRN for Haloperidol 1.25mg slow IV push PRN for anxiety and aggressionanxiety and aggression

cranial CT scan with contrast planned to rule cranial CT scan with contrast planned to rule out any neurologic problem; plain CT scan out any neurologic problem; plain CT scan suggested due to moderate risk for contrast suggested due to moderate risk for contrast nephropathy (CRI and age)nephropathy (CRI and age)


Urine osmolality requested for plans of Urine osmolality requested for plans of resuming lithium and other psych meds resuming lithium and other psych meds

= normal at 399mOsm/kg H20= normal at 399mOsm/kg H20

Divalproex sodium (Depakote) Divalproex sodium (Depakote) 500mg/tab 1tab BID started on the 3500mg/tab 1tab BID started on the 3rdrd HD HD


MRI with gadolinium suggested instead; no MRI with gadolinium suggested instead; no further behavioral changes noted on the 4further behavioral changes noted on the 4thth HDHD cranial CT scan eventually deferred cranial CT scan eventually deferred

Serum valproic acid level = 79.23ug/ml Serum valproic acid level = 79.23ug/ml (optimum therapeutic level: 50-100 ug/ml) on (optimum therapeutic level: 50-100 ug/ml) on the 9the 9thth HD HD Depakote 500mg/tab 1tab PO Depakote 500mg/tab 1tab PO BID continued BID continued

Problem #3: Catheter-related urinary tract Problem #3: Catheter-related urinary tract

infection infection (+) dysuria on the 10(+) dysuria on the 10thth hospital day hospital day

urinalysis : protein +1, leukocyte esterase urinalysis : protein +1, leukocyte esterase +1, blood +1, RBC 8.6, WBC 58.1, +1, blood +1, RBC 8.6, WBC 58.1, epithelial cells 3.2, bacteria 457.0epithelial cells 3.2, bacteria 457.0

Cefuroxime (Zinnat) 250mg/tab BID to Cefuroxime (Zinnat) 250mg/tab BID to

complete 10dayscomplete 10days

Hospital CourseHospital Course

11th hospital day11th hospital day

discharged improved and clinically discharged improved and clinically stablestable

Final DiagnosisFinal Diagnosis

1.1. Lithium Toxicity, S/P Hemodialysis Lithium Toxicity, S/P Hemodialysis (4/10/07)(4/10/07)

2.2. ARF prerenal, sec to volume depletion, ARF prerenal, sec to volume depletion, resolved, on top of CRI sec to resolved, on top of CRI sec to Hypertensive NephrosclerosisHypertensive Nephrosclerosis

3.3. Bipolar Mood Disorder Bipolar Mood Disorder 4.4. Urinary Tract Infection, catheter-relatedUrinary Tract Infection, catheter-related5.5. Hypertensive Atherosclerotic Hypertensive Atherosclerotic

Cardiovascular DiseaseCardiovascular Disease

DISCUSSIONDISCUSSION

Lithium carbonateLithium carbonate

““anti-manic” druganti-manic” drug

““mood-stabilizing” agent - mainstay of mood-stabilizing” agent - mainstay of treatment in patients with bipolar treatment in patients with bipolar affective (manic-depressive) disorderaffective (manic-depressive) disorder

Pharmacokinetics of lithiumPharmacokinetics of lithiumAbsorptionAbsorption Virtually complete within 6-8 hours; peak Virtually complete within 6-8 hours; peak

plasma levels in 30 minutes to 2 hours.plasma levels in 30 minutes to 2 hours.

DistributionDistribution In total body water; slow entry into In total body water; slow entry into intracellular compartment. Initial volume intracellular compartment. Initial volume of distribution 0.5L/kg, rising to of distribution 0.5L/kg, rising to 0.7-0.9L/kg; some sequestration in bone. 0.7-0.9L/kg; some sequestration in bone. No protein binding.No protein binding.

MetabolismMetabolism NoneNone

ExcretionExcretion Virtually entirely in urine. Lithium Virtually entirely in urine. Lithium clearance clearance 20% of creatinine. Most of 20% of creatinine. Most of the filtered lithium is reabsorbed in the the filtered lithium is reabsorbed in the proximal tubule.proximal tubule.

Pharmacokinetics of lithiumPharmacokinetics of lithium

Steady-state plasma levels : 5 days at the Steady-state plasma levels : 5 days at the oral dose of 1200 to 1800 mg/dayoral dose of 1200 to 1800 mg/day

Plasma half-life for lithium : Plasma half-life for lithium :

young adults - 18 hours young adults - 18 hours

elderly - 36 hourselderly - 36 hours

Pharmacodynamics of lithiumPharmacodynamics of lithium

Mode of action (major possibilities)Mode of action (major possibilities)(1) Effects on electrolytes and ion transport (1) Effects on electrolytes and ion transport

closely related to Na in its properties, can closely related to Na in its properties, can

substitute for it in generating action potentials substitute for it in generating action potentials (in Na-Na exchange across membranes)(in Na-Na exchange across membranes)

it inhibits the latter process, i.e., Li-Na it inhibits the latter process, i.e., Li-Na exchange is gradually slowed after lithium is exchange is gradually slowed after lithium is introduced into the body. introduced into the body.


at therapeutic concentration (around 1 at therapeutic concentration (around 1 mmol/L), it does not significantly affect the mmol/L), it does not significantly affect the Na/Ca exchange process or the Na/K Na/Ca exchange process or the Na/K ATPase pump.ATPase pump.


(2) Effects on neurotransmitters(2) Effects on neurotransmitters

enhance some of the actions of serotoninenhance some of the actions of serotonin

decreases norepinephrine and dopamine decreases norepinephrine and dopamine turnover: antimanic actionturnover: antimanic action


block the development of dopamine block the development of dopamine receptor supersensitivityreceptor supersensitivity

augment the synthesis of acetylcholine augment the synthesis of acetylcholine by increasing choline uptake into nerve by increasing choline uptake into nerve terminals: mitigate mania terminals: mitigate mania


(3) Effects on second messengers(3) Effects on second messengers

lithium inhibits several enzymes in the lithium inhibits several enzymes in the

recycling of membrane phosphoinositides recycling of membrane phosphoinositides depletion of PIP2, the membrane depletion of PIP2, the membrane precursor of IP3 and DAG (important precursor of IP3 and DAG (important second messengers for second messengers for -adrenergic and -adrenergic and muscarinic neurons)muscarinic neurons)


also inhibits norepinephrine-sensitive also inhibits norepinephrine-sensitive adenylyl cyclase: antimanic and adenylyl cyclase: antimanic and antidepressant effectsantidepressant effects

affects G proteins such as their uncoupling affects G proteins such as their uncoupling with vasopressin and TSH receptors: with vasopressin and TSH receptors: polyuria and subclinical hypothyroidismpolyuria and subclinical hypothyroidism

Lithium IntoxicationLithium Intoxication

Lithium has a low therapeutic index Lithium has a low therapeutic index Mortality rate Mortality rate 25% with acute overdose 25% with acute overdose

9% in patients 9% in patients intoxicated intoxicated during during maintenance therapy maintenance therapy (10% (10% in this group suffer in this group suffer permanent permanent neurologic neurologic damage) damage) 11

1 Hansen, HE, Amdisen, A. Lithium intoxication. Report of 23 cases and review of 100 cases from the literature. Q J Med 1978; 47:123.


The recommended therapeutic serum lithium The recommended therapeutic serum lithium concentration: concentration:

(1) 0.6 to 1.2 meq/L - prophylactic control of (1) 0.6 to 1.2 meq/L - prophylactic control of mania mania

(2) 1.0 to 1.5 meq/L - treatment of acute mania (2) 1.0 to 1.5 meq/L - treatment of acute mania

*Blood drawn to monitor the serum lithium *Blood drawn to monitor the serum lithium concentration should be obtained 12 hours after concentration should be obtained 12 hours after the last dose. the last dose.


Serum lithium levels in lithium toxicity:Serum lithium levels in lithium toxicity:

(1)(1) Mild - 1.5 to 2.5 mEq/LMild - 1.5 to 2.5 mEq/L

(2)(2) Moderate - 2.5 to 3.5 mEq/LModerate - 2.5 to 3.5 mEq/L

(3)(3) Severe - above 3.5 mEq/L Severe - above 3.5 mEq/L


Adverse Effects and ComplicationsAdverse Effects and Complications

A. Neurologic and Psychiatric: A. Neurologic and Psychiatric:

tremor (most common) dysarthriatremor (most common) dysarthria

choreoathetosischoreoathetosis aphasia aphasia

ataxia ataxia hyperactivityhyperactivity

marked mental confusion marked mental confusion



B. Thyroid Function: B. Thyroid Function:

hypothyroidism hypothyroidism

frank thyroid enlargement (reversible, frank thyroid enlargement (reversible, non-progressive)non-progressive)



C. Renal: C. Renal:

polydipsia polydipsia

polyuriapolyuria

nephrogenic diabetes insipidus (resistant to nephrogenic diabetes insipidus (resistant to vasopressin but responsive to amiloride)vasopressin but responsive to amiloride) chronic interstitial nephritischronic interstitial nephritis

minimal change nephropathy with nephrotic minimal change nephropathy with nephrotic syndrome (chronic lithium therapy)syndrome (chronic lithium therapy)



D. Edema: D. Edema:

due to sodium retention (a frequent adverse due to sodium retention (a frequent adverse effect)effect)

E. Cardiac: E. Cardiac:

bradyarrhythmias (depresses the sinus node)bradyarrhythmias (depresses the sinus node)

T wave flattening often observed on ECGT wave flattening often observed on ECG

hypotensionhypotension


Adverse Effects and ComplicationsAdverse Effects and ComplicationsF. Gastrointestinal: F. Gastrointestinal:

nauseanauseavomitingvomitingdiarrheadiarrhea

G. Miscellaneous: G. Miscellaneous: acne erruptionsacne erruptionsfolliculitisfolliculitisleukocytosisleukocytosis


PreventionPrevention Monitor serum levels periodicallyMonitor serum levels periodically

6 days are required for stabilization of the 6 days are required for stabilization of the plasma concentration after a change in plasma concentration after a change in dosagedosage


PreventionPrevention Reduce lithium dose in settings in which Reduce lithium dose in settings in which

its excretion is decreased its excretion is decreased

renal insufficiency induced by renal insufficiency induced by chronic lithium therapy, older age, or chronic lithium therapy, older age, or acutely by volume depletion, acutely by volume depletion, administration of NSAIDS or ACE administration of NSAIDS or ACE inhibitorsinhibitors


TreatmentTreatment Adequacy of renal function and the degree of Adequacy of renal function and the degree of

intoxicationintoxication

Cessation of other drugs that may have additive Cessation of other drugs that may have additive side effects (phenothiazine, haloperidol)side effects (phenothiazine, haloperidol)22

Patients with severe intoxication or significant Patients with severe intoxication or significant cardiac disease – ICU admissioncardiac disease – ICU admission

2 2 Okusa, MD, Crystal, LJ. Clinical manifestations and management of acute lithium intoxication. Am J Okusa, MD, Crystal, LJ. Clinical manifestations and management of acute lithium intoxication. Am J

Med 1994; 97:383.Med 1994; 97:383.


TreatmentTreatment

Fluid repletion — restoration of sodium Fluid repletion — restoration of sodium and water balance in hypovolemic patients and water balance in hypovolemic patients lithium clearance lithium clearance

Serum Na must be monitored in patients Serum Na must be monitored in patients

with nephrogenic diabetes insipiduswith nephrogenic diabetes insipidus


TreatmentTreatment

Combination of isotonic saline and urine Combination of isotonic saline and urine hypotonic losses hypotonic losses --- leads to hypernatremia, exacerbating --- leads to hypernatremia, exacerbating neurologic symptoms; a hypotonic solution neurologic symptoms; a hypotonic solution (half-isotonic saline) should be given(half-isotonic saline) should be given22

2 Okusa, MD, Crystal, LJ. Clinical manifestations and management of acute lithium intoxication. Am J Med 1994; 2 Okusa, MD, Crystal, LJ. Clinical manifestations and management of acute lithium intoxication. Am J Med 1994; 97:383. 97:383.

Lithium IntoxicationLithium IntoxicationTreatmentTreatment

Oral activated charcoal does not limit the Oral activated charcoal does not limit the absorption of charged particles such as absorption of charged particles such as lithiumlithium3-53-5

Whole bowel irrigation with polyethylene Whole bowel irrigation with polyethylene glycol solution may be effective after acute glycol solution may be effective after acute ingestion of sustained release lithiumingestion of sustained release lithium66

3 Favin, FD, Klein-Schwartz, W, Oderda, GM, et al. 3 Favin, FD, Klein-Schwartz, W, Oderda, GM, et al. In vitro study of lithium carbonate absorption by activated charcoal. J In vitro study of lithium carbonate absorption by activated charcoal. J Toxicol Clin Toxicol 1988; 26:443.Toxicol Clin Toxicol 1988; 26:443.

4 Linakis, JG, Lacouture, PG, Eisenberg MS, et al. 4 Linakis, JG, Lacouture, PG, Eisenberg MS, et al. Administration of activated charcoal or sodium polystyrene sulfonate Administration of activated charcoal or sodium polystyrene sulfonate (Kayexalate™) as gastric decontamination for lithium intoxication: An animal model. Pharmacol Toxicol 1989; 65:387.(Kayexalate™) as gastric decontamination for lithium intoxication: An animal model. Pharmacol Toxicol 1989; 65:387.

5 Linakis, JG, Eisenberg, MS, Lacouture, PG, et al. 5 Linakis, JG, Eisenberg, MS, Lacouture, PG, et al. Multiple-dose polystyrene sulfonate in lithium intoxication: An animal Multiple-dose polystyrene sulfonate in lithium intoxication: An animal model. Pharmacol Toxicol 1992; 70:38.model. Pharmacol Toxicol 1992; 70:38.

6 Smith, SW, Ling, LJ, Halstenson, CE. Whole-bowel irrigation as a treatment for acute lithium overdose. Ann Emerg Med 6 Smith, SW, Ling, LJ, Halstenson, CE. Whole-bowel irrigation as a treatment for acute lithium overdose. Ann Emerg Med 1991; 20:536.1991; 20:536.


TreatmentTreatment

HemodialysisHemodialysis — treatment of choice for — treatment of choice for severe lithium toxicitysevere lithium toxicity

lithiumlithium - the most dialyzable toxin known - the most dialyzable toxin known low molecular weight, negligible low molecular weight, negligible protein binding, volume of distribution protein binding, volume of distribution similar to that of watersimilar to that of water


HemodialysisHemodialysis UrineUrine Peritoneal Peritoneal DialysisDialysis

lithium lithium clearanceclearance

70 - 170 70 - 170 mL/minmL/min

10 - 40 mL/min 10 - 40 mL/min

(due to (due to extensive extensive proximal proximal

reabsorption)reabsorption)

15 mL/min 15 mL/min

(due to low (due to low blood flow)blood flow)22


TreatmentTreatment

Relatively slow lithium equilibrationRelatively slow lithium equilibration ::lithium diffusion (intracellular lithium diffusion (intracellular extracellular)extracellular)77 ----- rebound increase in ----- rebound increase in serum lithium levels after dialysisserum lithium levels after dialysis

7 Clendeninn, NJ, Pond, SM, Kaysen, G, et al. Potential pitfalls in the evaluation of the usefulness of 7 Clendeninn, NJ, Pond, SM, Kaysen, G, et al. Potential pitfalls in the evaluation of the usefulness of hemodialysis for the removal of lithium. J Toxicol Clin Toxicol 1982; 19:341. hemodialysis for the removal of lithium. J Toxicol Clin Toxicol 1982; 19:341.


TreatmentTreatment

Minimizing rebound serum lithium Minimizing rebound serum lithium increase: extended dialysis of 8-12 increase: extended dialysis of 8-12 hourshours1,21,2

Repeat dialysis : until serum lithium Repeat dialysis : until serum lithium remains less than 1 mEq/L for 6 to 8 remains less than 1 mEq/L for 6 to 8 hours after dialysishours after dialysis1,21,2


TreatmentTreatment

9 hours of hemodialysis - removes 60% of 9 hours of hemodialysis - removes 60% of the total body lithium burdenthe total body lithium burden88

Hemodialysis of 6 hours – sufficient with Hemodialysis of 6 hours – sufficient with modern high surface area hemodialyzersmodern high surface area hemodialyzers99

8 Garella, S. Extracorporeal techniques in the treatment of exogenous intoxications. Kidney Int 1988; 33:735.8 Garella, S. Extracorporeal techniques in the treatment of exogenous intoxications. Kidney Int 1988; 33:735.9 Winchester, JF. Lithium. In: Clinical Management of Poisoning and Drug Removal, 2d ed, Haddad LM, Winchester, JF (Eds), Saunders, 9 Winchester, JF. Lithium. In: Clinical Management of Poisoning and Drug Removal, 2d ed, Haddad LM, Winchester, JF (Eds), Saunders,

Philadelphia, 1990, pp 656-665. Philadelphia, 1990, pp 656-665.

Lithium IntoxicationLithium IntoxicationTreatmentTreatment Hemodialysis is indicated if one or more of the following Hemodialysis is indicated if one or more of the following

is presentis present1,2,8,91,2,8,9::(1)(1) A serum lithium level above 4 mEq/L, regardless of the A serum lithium level above 4 mEq/L, regardless of the

clinical status of the patientclinical status of the patient(2)(2) A serum lithium concentration above 2.5 mEq/L in a A serum lithium concentration above 2.5 mEq/L in a

patient who is markedly symptomatic or who has renal patient who is markedly symptomatic or who has renal insufficiency or other conditions that can limit urinary insufficiency or other conditions that can limit urinary lithium excretion (such as congestive heart failure or lithium excretion (such as congestive heart failure or cirrhosis)cirrhosis)

(3)(3) If serum lithium level is between 2.5 and 4 mEq/L in an If serum lithium level is between 2.5 and 4 mEq/L in an asymptomatic patient and is not anticipated to be less asymptomatic patient and is not anticipated to be less than 0.6 mEq/L within 36 hours. than 0.6 mEq/L within 36 hours.

Good Day!Good Day!

medical grandrounds mary antoniette m. tan, m.d. first year resident

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