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

2. OUTLINE Clinical Case Acetaminophen Toxicity Management

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

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 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 1 st MD: 50mg/kg IV over 4hr, dilute in 500mL D5W 2 nd MD: 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