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Case Conference. Block 8B Class 2011 Sylim , Tabula, Taldtad , Taleon Tampo , Tanyu, Tiongson , Torio. Primary Survey. MB, 19 year old female student from Cavite Acetaminophen ingestion BP = 110/70 HR = 90 RR = 20 GCS 15. History of Present Illness.
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Case Conference Block 8B Class 2011 Sylim, Tabula, Taldtad, Taleon Tampo, Tanyu, Tiongson, Torio
Primary Survey • MB, 19 year old female student from Cavite • Acetaminophen ingestion • BP = 110/70 • HR = 90 • RR = 20 • GCS 15
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.
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.
Review of Systems • (+) epigastric pain • (-) headache • (-) loss of consciousness • (-) bleeding • (-) jaundince • (-) urinary changes
Past Medical History • Non-asthmatic, no known allergies • No previous hospitalizations • No previous surgeries
Family Medical History • (+) hypertension – mother, father • (+) kidney problem – mother • (+) heart problem – mother, father
OB History • G0 • LMP: January 13, 2010 • Menarche at 11 • 5-6 days duration, 3 ppd, regular monthly intervals • Denies OCP use
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
Physical Examination • Awake, conversant • BP 110/70, HR 88, RR 20 • Anictericsclerae, pink palpebralconjuctivae, no NVE, no ANM • ECE, CBS • AP, DHS, NRRR, no murmurs • Flabby, soft, NABS, (+) direct tenderness epigastric area • FEP, PNB. No edema, no cyanosis
Initial Assessment • Acetaminophen ingestion, non-accidental, mild • t/c adjustment disorder
Initial Diagnostics • CBC • RBS, Crea, Na, K, Cl • PT/PTT • Urinalysis • Pregnancy test • ABG • 12 lead ECG • Chest x-ray
Therapeutics • O2 6 lpm via nasal cannula • Diet: NPO • IVF: D5NSS 1 L x 8 hours • Famotidine 40 mg IV • N-acetylcysteine antidote
Porcedures • NGT inserted for gastric lavage
Referrals • Toxicology • Psychiatry • General Medicine
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
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)
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
Laboratory Results (1/15) • Glucose 6.09, BUN 2.51, Crea 73, Na 137, K 3.7, Cl 103
Maximum therapeutic dose: - 4g in adults - 90mg/kg in children Toxicity is with single ingestion of 150 mg/kg or ~7-10 g (adult)
-Metabolism is primarily hepatic -Liver metabolizes more than 90% of dosage to sulfate and glucuronide conjugates, which are water soluble and are then eliminated in the urine -Two percent of an acetaminophen dose is excreted unchanged by the kidneys -Remaining acetaminophen is metabolized by CYP450 system to form a reactive, highly toxic metabolite known as N -acetyl-benzoquinoneimine (NAPQI)\ -Glutathione binds NAPQI, enabling the excretion of nontoxic mercapturate conjugates in the urine
-in excessive NAPQI formation, or reduction in glutathione stores, NAPQI covalently binds to the lipid bilayer of hepatocytes, causing hepatic centrilobular necrosis.
Four Clinical Stages Stage 1 (0.5-24 h postingestion) -Asymptomatic or with nonspecific signs like anorexia, nausea, vomiting, malaise, and diaphoresis. -If CNS involvement and/or severe metabolic acidosis (elevated anion gap) are present, consider co-ingestants. -Serum studies are within normal limits. About 12 hours post-ingestion, subclinical elevation of serum liver transaminases (alanine aminotransferase [ALT], aspartate aminotransferase [AST]) occurs.
Stage 2 (24-72 h postingestion) -Stage 1 symptoms less evident and/or resolved. -Present with pain and tenderness in the RUQ -Hepatomegaly can be present. Some may have oliguria -Elevated ALT and AST levels, prothrombin (PT) times, and bilirubin values. Renal function abnormalities (eg, BUN, creatinine) may also be present.
Stage 3 (72-120 h postingestion) -Stage 1 symptoms reappear along with signs of hepatic failure with jaundice, hypoglycemia, bleeding, or encephalopathy. -Severe toxicity evident on serum studies. Lactic acidosis, prolonged PT or INR, markedly elevated ALT and AST (>10,000 IU/L), elevated total bilirubin level of more than 4 mg/dL (primarily indirect) and hyperammonemia -Hepatic centrilobular necrosis is diagnosed on liver biopsy -Renal involvement from acute tubular necrosis is evident with abnormal renal function studies, proteinuria, hematuria and granular casts on urinalysis -Death is most common during this stage, with multiorganfailure as the primary cause.
Stage 4 (5-14 d postingestion) -this stage can last as long as 21 days. -either a complete recovery of liver function or death -period to normalization may take several weeks for patients who recover -Acetaminophen-induced hepatotoxicity does not cause chronic hepatic dysfunction.
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
Approach to a patient of Acetaminophen Ingestion • Initial Assessment • Gastric Decontamination • Acetylcysteine Need Assessment • Acetylcysteine Administration
Approach to a patient of Acetaminophen Ingestion • Initial Assessment • Determination of quantity and dosage form • Determination of the possibility of the ingestion of other substances or drugs • Determination of serum acetaminophen levels • If any information is unknown, serum levels should be determined and acetylcysteine should be administered
Approach to a patient of Acetaminophen Ingestion • Gastric Decontamination • Activated charcoal reduces peak serum levels, decreases 4-hour acetaminophen and lowers the need for acetylcysteine treatment • Activated charcoal may be given postingestion period, especially if multiple drugs are suspected • Data regarding efficacy of activated charcoal after 2 hours postingestion are limited
Approach to a patient of Acetaminophen Ingestion • Acetylcysteine Need Assessment • Ideally serum acetaminophen is measured 4 hours postingestion, or if 4 hours have passed, immediately thereafter • If ingestion is over a period of time, time of initial ingestion is used for Rumack-Matthew nomogram • If blood cannot be obtained, the dose is assumed to be toxic and treatment is given
Approach to a patient of Acetaminophen Ingestion • Acetylcysteine Administration • If patient presented within 4 hours postingestion, treatment is delayed until serum levels are determined (however treatment should not be delayed beyond 8 hours postingestion) • If patient presented beyond 8 hours postingestion, treatment is given immediately • If patient presented 24 hours postingestion, AST and ALT are determined(treatment is beneficial if levels are elevated; if not, treatment is unnecessary)
-Supportive therapy, including IV fluids, oxygen, cardiac monitor -Gastric decontamination (oral activated charcoal) -Administer N-acetylcysteine if indicated -early administration (within 8 hours) is ~100% hepatoprotective 1. PO: 140 mg/kg loading dose; maintenance dose of 70 mg/kg q4 x17 doses 2. Continuous IV: (total treatment time 21 h) Acute (8-10 h after ingestion) in patients >40 kg: >Loading dose: 150 mg/kg IV infused over 15 min (dilute in 200 mL D5W) follow with maintenance doses >First maintenance dose: 50 mg/kg IV infused over 4 h (dilute in 500 mL D5W), followed with second maintenance dose >Second maintenance dose: 100 mg/kg IV infused over 16 h (dilute in 1000 mL D5W)
3. Intermittent IV administration (total treatment 48 h)>Loading dose: 140 mg/kg IV infused over 1 h (dilute in 500 mL D5W), followed with maintenance dose >Maintenance dose: 70 mg/kg IV q4h for at least 12 doses (dilute each dose in 250mL of D5Wand infuse over minimum 1h) -Antiemetics -metoclopramide, ondansetron