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Case Conference

Case Conference. Block 8B Class 2011 Sylim, Tabula, Taldtad, Taleon Tampo, Tanyu, Tiongson, Torio. Clinical Case Acetaminophen Toxicity Management. outline. Clinical case. Primary Survey. MB, 19 year old female student from Cavite Acetaminophen ingestion BP = 110/70 HR = 90 RR = 20

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Case Conference

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  1. Case Conference Block 8B Class 2011 Sylim, Tabula, Taldtad, Taleon Tampo, Tanyu, Tiongson, Torio

  2. Clinical Case Acetaminophen Toxicity Management outline

  3. Clinical case

  4. Primary Survey • MB, 19 year old female student from Cavite • Acetaminophen ingestion • BP = 110/70 • HR = 90 • RR = 20 • GCS 15

  5. History of Present Illness • Four hours prior to consult, the patient intentionally took in 18 tablets of acetaminophen 500 mg per tablet after repeated arguments with her mother over her allowance. • Patient then experienced nausea, 1 episode of vomiting, and headache.

  6. History of Present Illness • There were no seizures, diaphoresis, loss of consciousness, nor headache. • Patient appeared flushed and had clammy extremities. • She was rushed to a private hospita; and referred to PGH.

  7. Review of Systems • (+) epigastric pain • (-) headache • (-) loss of consciousness • (-) bleeding • (-) jaundince • (-) urinary changes

  8. Past Medical History • Non-asthmatic, no known allergies • No previous hospitalizations • No previous surgeries

  9. Family Medical History • (+) hypertension – mother, father • (+) kidney problem – mother • (+) heart problem – mother, father

  10. OB History • G0 • LMP: January 13, 2010 • Menarche at 11 • 5-6 days duration, 3 ppd, regular monthly intervals • Denies OCP use

  11. Personal and Social History • Smoker for 5 years consuming 5 sticks per day; note of increased frequency and number of sticks consumed wihin the month • Occasional alcohol drinker; history of alchol binge 1 day PTA consuming beer, gin, and vodka • Denies illicit drug use

  12. Physical Examination • Awake, conversant • BP 110/70, HR 88, RR 20 • Anicteric sclerae, pink palpebral conjuctivae, no NVE, no ANM • ECE, CBS • AP, DHS, NRRR, no murmurs • Flabby, soft, NABS, (+) direct tenderness epigastric area • FEP, PNB. No edema, no cyanosis

  13. Initial Assessment • Acetaminophen ingestion, non-accidental, mild • t/c adjustment disorder

  14. Initial Diagnostics • CBC • RBS, Crea, Na, K, Cl • PT/PTT • Urinalysis • Pregnancy test • ABG • 12 lead ECG • Chest x-ray

  15. Therapeutics • O2 6 lpm via nasal cannula • Diet: NPO • IVF: D5NSS 1 L x 8 hours • Famotidine 40 mg IV • N-acetylcysteine antidote

  16. Procedures • NGT inserted for gastric lavage

  17. Referrals • Toxicology • Psychiatry • General Medicine

  18. Treatment • For gastric lavage with activated charcoal 100 mg in 200 mL water then NaSO4 15 g in 100 mL water • For serum paracetamol assay • Urine tox screening for paracetamol

  19. Treatment • NAC 200 mg/dL • Phase 1 150 mg/kg in 200 mL D5W x 1 hour (7.5 g) • Phase 2 50 mg/kg in 500 mL D5W x 4 hours (2-5 g) • Phase 3 100 mg in 1000 mL D5W x 16 hours (5 g)

  20. Laboratory Results (1/15) • PT 11.9/11.3/>1.0/1.09 • PTT 36.2/37/0 • ABG: pH 7.394, pCO2 34.8, pO2 116.3, HCO3 21.2, O2 sat 98.1, BE -2.4 mmol/L, TCO2 22.3, SBC 22.5 • CBC: Hgb 130, Hct 0.359, WBC 6.1, PC 379, neut 0.487, lymph 0.36, mono 0.138, eosino 0.009, baso 0.006

  21. Laboratory Results (1/15) • Glucose 6.09, BUN 2.51, Crea 73, Na 137, K 3.7, Cl 103

  22. acetaminophen toxicity

  23. Introduction • Acetaminophen is a direct toxin that can cause severe centrilobular hepatic necrosis when ingested in large amounts • Maximum therapeutic dose: • 4g in adults • 90 mg/kg in children

  24. Pathophysiology conjugation Sulfate moiety Glucoronide moiety nontoxic nontoxic Acetaminophen Cytochrome P450 (CYP2E1) N-acetyl-benzoquinone-imine (NAPQI) toxic N-acetylcysteine Mercapturic acid Glutathione Harmless water-soluble renally excreted Hepatic necrosis 

  25. Four Clinical Stages • Stage 1 (0.5-24 h postingestion) • Asymptomatic • (+) nonspecific signs: • Anorexia, nausea, vomiting, malaise, diaphoresis • If CNS involvement, metabolic acidosis, consider co-ingestants • Serum studies are within normal limits • About 12hrs post-ingestion, subclinical elevation of serum liver transaminase occurs

  26. Four Clinical Stages • Stage 2 (24-72 h post-ingestion) • Stage 1 symptoms less evident / resolved • Present with pain and tenderness in RUQ • Hepatomegaly may be present. Some may have oliguria • Elevated AST and Alt levels, PT times, and bilirubin values. Renal functino abnormalitiews may also be present.

  27. Four Clinical Stages • Stage 3 (72-120 h post-ingestion) • Stage 1 Sx reappear with signs of hepatic failure, jaundice, hypoglycemia, bleeding, or encepalopathy • Severe toxicity evident on serum studies: • Lactic acidosis, prolonged PT, ↑ AST/ALT (>10,000IU/L), elevated bilirubin (>4mg/dL), hyperammonemia • Hepatic centrilobular necrosis diagnosed on liver biopsy • Renal involvement from Acute tubular necrosis • abnormal renal fxn tests, proteinura, hematuria, granular casts • DEATH is most common in this stage, with multiorgan failure as the primary cause.

  28. Four Clinical Stages • Stage 4 (5-14 d post-ingestion) • This stage can last as long as 21 days • Either a complete recovery of liver function or DEATH • Period of normalization may take several weeks for patients who recover • Acetaminophen0induced hepatotoxicity does not cause chronic hepatic dysfunction

  29. Stage 1 (0.5-24 hr) • asymptomatic, nonspecific signs • Serum studies are within normal limits • Stage 2 (1-3 days) • Stage 1 symptoms relieved, (+) pain RUQ • Deranged liver and renal function tests • Stage 3 (3-5 days) • Stage 1 symptoms reappear • Severe toxicity, DEATH may occur • Stage 4 (5-14 days) • Complete recovery or death

  30. Management

  31. Emergency Department Care • Supportive Therapy • IV fluids • Oxygen support • Gastric Decontamination • Gastric lavage, activated charcoal • Effective only if patient presents <1hr post-ingestion, or >1hr if ingestion involves agent that delays gastric emptying

  32. ED Care • Administration of N-acetylcysteine • Early administration (<8hrs) ~100% hepatoprotective • Should be given: • while awaiting serum transaminase • If post-ingestion time is close to 8 hrs • If patient is pregnant

  33. ED Care • Administration of N-acetylcysteine • Per Orem: • LD: 140mg/kg • MD: (4hrs after LD) 70mg/kg q 4hrs for 15-20 doses • Continuous IV infusion (total treatment time 21 hrs) • For acute (8-10hrs after ingestion) • LD: 150mg/kg IV over 15 min, dilute in 200mL D5W • 1stMD: 50mg/kg IV over 4hr, dilute in 500mL D5W • 2ndMD: 100mg/kg IV over 16hr, (dilute in 1000mL D5W)

  34. ED Care • Intermittent IV infusion (total treatment time 48 hrs) • For late presenting or chronic (>10hrs after ingestion) • LD: 140mg/kg IV over 1hr, dilute in 500mL D5W • MD: 70mg/kg IV q4hr at least 12 doses (dilute each dose in 250mL D5W and infuse over minimum of 1hr)

  35. ED Care • Assess for evidence of other life-threatening co-ingestions • Assess risk for hepatotoxicity using Rumack-Matthew Nomogram.

  36. Risk Assessment • The Rumack-Matthew nomogram • defines the risk for acetaminophen toxicity • treatment can be stopped if risk of liver damage is low

  37. Work-up • Acetaminophen serum concentration • Transaminase levels • Measures of hepatic function • Electrolytes and creatinine • Beta-hcg for women childbearing age • BT and crossmatch • Urinalysis • ABG • UTZ/CT • ECG

  38. Referrals • Toxicology • Psychiatry • General Medicine

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