Lab Rounds

1
Lab Rounds

• Juliette Sacks
• CCFP-EM
• August 10, 2006

2
Case

• L.W. 49 y.o. Female
• 3-4 day hx of
• disorientation
• dysarthria
• progressing ataxia
• dysphagia
• no vomiting
• acute on chronic diarrhea
• no hx of trauma, seizures or LOC
• no drug or EtOH abuse

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Case contd

• FHx adopted
• Collateral Hx from pts daughter who is primary
  caregiver
• NKDA
• Meds
• Lithium 120mg qhs
• Zyprexa 10mg at noon and 20mg qhs
• Zopiclone 22.5mg qhs
• Propanolol 40mg at noon and 40mg qhs

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Case contd

• PMHx/Sx
• Bipolar disorder
• Chronic diarrhea
• Multiple laparotomies with ileostomy
• Px
• 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

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Results

• 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

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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

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Lithium Dosing

• Therapeutic 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

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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

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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

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Factors predisposing to Li Toxicity(courtesy of
Tintinalli)

• Renal failure
• Volume depletion
• Hyperthermia/NMS
• Infection
• CHF
• Diabetes mellitus
• Gastroenteritis
• Surgery
• Cirrhosis
• Decreased Na intake

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Drug interactions with Li(courtesy of Tintinalli)

• Major Haloperidol
• Moderate
• ACEI - Methyldopa
• Anorexiants - Metronidazole
• Benzodiazepines - NSAIDs
• Caffeine - Phenytoin
• CCB - Tetracyclines
• Carbamazepine - Theophyllines
• Clozapine - Thiazide diuretics
• Fluoxetine - Urea
• Iodide salts - Succinylcholine
• Loop diuretics - Nondepolarizing muscle
  paralytics
• Phenothiazines - TCAs
• Minor Carbonic anhydrase inhibitors,
  sympathomimetics

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Clinical Manifestations

• GI
• Nausea and vomiting
• Diarrhea
• CNS
• Weakness and fatigue
• Lethargy and confusion
• Tremor (coarse, irregular)
• Ataxia
• Seizures
• Neuromuscular excitability/fascicular twitching
• Stupor
• Coma

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Clinical Manifestations 2

• Renal
• May cause acute renal failure
• Decreased CrCl
• Nephrogenic diabetes insipidus
• With polyuria and polydipsia
• CV
• 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

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Clinical Manifestations 3

• Neurological sequelae
• 10 risk of permanent damage
• Truncal and gait ataxia
• Nystagmus
• Short term memory deficits
• Dementia

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Lithium Toxicity(chronic ingestion)
Level sLi mEq/L Clinical Features Treatment
Grade 1 1.5-2.5 Nausea Vomiting Tremor Hyperreflexia Ataxia Agitation Muscular Weakness Hydration (x 4-6h) Kayexalate
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Level sLi mEq/L Clinical Manifestations Treatment
Grade 2 2.5-3.5 Stupor Rigidity Hypertonia Hypotension Hydration, Kayexalate, /- dialysis
Grade 3 gt3.5 Coma Seizures Myoclonus Collapse Hemodialysis
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Treatment

• 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

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Treatment contd

• 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
• If given within 1h of ingestion may remove 60 of
  drug

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Hemodialysis

• For severe lithium toxicity
• When?
• sLi gt4.0 mEq/L regardless of clinical status
• sLi gt2.5 mEq/L with symptoms with renal
  insufficiency or other factor(s) that limit Li
  excretion
• sLi 2.5-4.0 mEq/L asymptomatic patient but who
  is not expected to have sLi lt1.0mEq/L w/i 36h

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• Goal decrease sLi levels to lt1 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

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Adjuncts

• Consult renal service
• Consult psychiatric service
• Consult poison control/toxicology service

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What about L.W.?

• 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 gt1 course of dialysis
• Persistent neurological deficits despite sLi of
  1.0-1.1 mEq/L
• Lithium discontinued replaced by olanzepine

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