Transcript Lithium Toxicity

Lab Rounds
Juliette Sacks
CCFP-EM
August 10, 2006
Case
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L.W. 49 y.o. Female
 3-4 day hx of:
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disorientation
dysarthria
progressing ataxia
dysphagia
no vomiting
acute on chronic diarrhea
no hx of trauma, seizures or LOC
no drug or EtOH abuse
Case cont’d
 FHx:
adopted
 Collateral Hx: from pt’s daughter who is
primary caregiver
 NKDA
 Meds:
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Lithium 120mg qhs
Zyprexa 10mg at noon and 20mg qhs
Zopiclone 22.5mg qhs
Propanolol 40mg at noon and 40mg qhs
Case cont’d:
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PMHx/Sx:
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Bipolar disorder
Chronic diarrhea
Multiple laparotomies with ileostomy
Px:
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Tremulous, dysarthric
118/56 61 18 36.7C 02 sats 97% on 3L by NP
Chest clear
CVS N
Abdo distended but nontender
CN intact, clonus, incr. DTRs, generalized muscle
weakness
Results
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Na 133, K 3.9
Troponin, CK, LFTs N, Cr 100
EtOH, APAP, ASA negative
Hgb 136, WBC 5.2, Plt 272
Li 3.96
EKG: Anterior T wave depression
AXR: ++ dilated loops of large bowel with air
fluid levels; no free air
CT head: N
Lithium
 Commonly
used to treat depressive and
bipolar affective disorder
 Low therapeutic index
 Intoxication seen with acute and chronic
use
 Multisystem dysfunction with intoxication
 T1/2: 29h
Lithium Dosing
 Therapeutic
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indices:
0.6 - 1.2 mEq/L (prophylactic control)
1.0 - 1.5 mEq/L (acute mania)
 Oral
administration only
 Absorbed from GIT 2-4h postingestion
 Minimally protein bound
 Steady state plasma levels achieved in 5d
Lithium Excretion
 Excreted
through the kidneys therefore
dosing is dependent on: renal function,
volume status, age
 Reabsorbed in the proximal tubule
 20% is excreted in urine
 Li reabsorption follows Na reabsorption but
may be reabsorped preferentially to
counter Na losses in volume depleted pts
More about Li…
 Lithium
alters the cation transport across
cell membranes in nerve and muscle cells
 Influences reuptake of serotonin and
epinephrine
 Inhibits second messenger systems
involving phosphatidylinositol cycle
 Inhibits postsynaptic D2 receptor
sensitivity
Factors predisposing to Li Toxicity
(courtesy of Tintinalli)
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Renal failure
Volume depletion
Hyperthermia/NMS
Infection
CHF
Diabetes mellitus
Gastroenteritis
Surgery
Cirrhosis
Decreased Na intake
Drug interactions with Li
(courtesy of Tintinalli)
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Major: Haloperidol
Moderate:
ACEI
- Methyldopa
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Anorexiants
- Metronidazole
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Benzodiazepines
- NSAIDs
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Caffeine
- Phenytoin
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CCB
- Tetracyclines
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Carbamazepine
- Theophyllines
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Clozapine
- Thiazide diuretics
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Fluoxetine
- Urea
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Iodide salts
- Succinylcholine
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Loop diuretics
- Nondepolarizing muscle paralytics
Phenothiazines
- TCAs
Minor: Carbonic anhydrase inhibitors, sympathomimetics
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Clinical Manifestations
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GI:
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Nausea and vomiting
Diarrhea
CNS:
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Weakness and fatigue
Lethargy and confusion
Tremor (coarse, irregular)
Ataxia
Seizures
Neuromuscular excitability/fascicular twitching
Stupor
Coma
Clinical Manifestations 2
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Renal:
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May cause acute renal failure
Decreased CrCl
Nephrogenic diabetes insipidus
• With polyuria and polydipsia
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CV:
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Hypotension
Sinus bradycardia
Ventricular dysrhythmias (including complete heart block)
EKG findings in chronic Li use: depressed ST segments and T
wave flattening/inversion; QTc prolongation
CV collapse and respiratory failure
Clinical Manifestations 3
 Neurological
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sequelae:
10% risk of permanent damage
Truncal and gait ataxia
Nystagmus
Short term memory deficits
Dementia
Lithium Toxicity
(chronic ingestion)
Level
s[Li]
mEq/L
Clinical
Features
Treatment
Grade 1
1.5-2.5 Nausea
Hydration
Vomiting
(x 4-6h)
Tremor
Kayexalate
Hyperreflexia
Ataxia
Agitation
Muscular
Weakness
Level
s[Li]
mEq/L
Clinical
Manifestations
Treatment
Grade 2 2.5-3.5
Stupor
Rigidity
Hypertonia
Hypotension
Hydration,
Kayexalate,
+/- dialysis
Grade 3 >3.5
Coma
Seizures
Myoclonus
Collapse
Hemodialysis
Treatment
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ABCs
iv fluids, cardiac monitoring
EKG
Identification of agents and amount ingested (get the pill
bottles if possible)
Beware sustained release preparations!
Rule out co-ingestions
Serum Li with 2nd sLi 2h later
Lytes, Cr, BUN, tox screen
Hx and Px
+/- CT head depending on neurological presentation
Treatment cont’d
 Restore
fluid volume and correct
electrolyte abnormalities
 Oral charcoal does not bind Li but may
bind other drugs taken
 Whole bowel irrigation may be considered
especially with SR preparations
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If given within 1h of ingestion may remove
60% of drug
Hemodialysis
 For
severe lithium toxicity
 When?
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s[Li] >4.0 mEq/L regardless of clinical status
s[Li] >2.5 mEq/L with symptoms; with renal
insufficiency or other factor(s) that limit Li
excretion
s[Li] 2.5-4.0 mEq/L asymptomatic patient but
who is not expected to have s[Li] <1.0mEq/L
w/i 36h
 Goal:
decrease sLi levels to <1 mEq/L
within 6-8h post dialysis
 Li clearance of 70-170 ml/min
 Use of continuous venovenous
hemofiltration reduces the post dialysis
rebound in sLi level
 Addition of bicarbonate to dialysate may
improve Li extraction
Adjuncts
 Consult
renal service
 Consult psychiatric service
 Consult poison control/toxicology service
What about L.W.?
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After 4h of fluid replacement, Li level was 3.53
but she remained symptomatic
Sent for hemodialysis
No role for gastric lavage, whole bowel irrigation
Serial Li levels and >1 course of dialysis
Persistent neurological deficits despite s[Li] of
1.0-1.1 mEq/L
Lithium discontinued; replaced by olanzepine