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Lab Rounds

Lab Rounds. Juliette Sacks CCFP-EM August 10, 2006. 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. Case cont’d. FHx: adopted

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Lab Rounds

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  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

  3. Case cont’d • FHx: adopted • Collateral Hx: from pt’s 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

  4. Case cont’d: • 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

  5. 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

  6. 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

  7. 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

  8. 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 • Lireabsorption follows Na reabsorption but may be reabsorped preferentially to counter Na losses in volume depleted pts

  9. 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

  10. Factors predisposing to Li Toxicity(courtesy of Tintinalli) • Renal failure • Volume depletion • Hyperthermia/NMS • Infection • CHF • Diabetes mellitus • Gastroenteritis • Surgery • Cirrhosis • Decreased Na intake

  11. 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

  12. 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

  13. 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

  14. Clinical Manifestations 3 • Neurological sequelae: • 10% risk of permanent damage • Truncal and gait ataxia • Nystagmus • Short term memory deficits • Dementia

  15. Lithium Toxicity(chronic ingestion)

  16. 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

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

  18. Hemodialysis • For severe lithium toxicity • When? • 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

  19. 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

  20. Adjuncts • Consult renal service • Consult psychiatric service • Consult poison control/toxicology service

  21. 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 >1 course of dialysis • Persistent neurological deficits despite s[Li] of 1.0-1.1 mEq/L • Lithium discontinued; replaced by olanzepine

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