Case ConferenceBlock 8B Class 2011

Sylim, Tabula, Taldtad, Taleon

Tampo, Tanyu, Tiongson, Torio

OUTLINE

Clinical Case

Acetaminophen Toxicity

Management

CLINICAL CASE

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• 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

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

Procedures

• 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

ACETAMINOPHEN TOXICITY

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

Pathophysiology

Acetaminophen

Glucoronide moiety

Sulfate moiety

conjugation

Cytochrome P450 (CYP2E1)

nontoxic nontoxic

N-acetyl-benzoquinone-imine (NAPQI)

toxicN-acetylcysteine

Glutathione

Hepatic necrosis

Mercapturic acid

Harmless water-soluble renally excreted

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

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.

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.

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

• 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

MANAGEMENT

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

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

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)

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)

ED Care

• Assess for evidence of other life-threatening co-ingestions

• Assess risk for hepatotoxicity using Rumack-Matthew Nomogram.

Risk Assessment

• The Rumack-Matthew nomogram

• defines the risk for acetaminophen toxicity

• treatment can be stopped if risk of liver damage is low

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

Referrals

• Toxicology

• Psychiatry

• General Medicine