Transcript in the Emergency Department Acetaminophen and Salicylate

in the
Emergency Department
Acetaminophen and Salicylate Ingestions
Thomas J. Sugarman, MD, FACEP
December 2007
Outline
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Overview of the poisoned patient
Charcoal vs. gastric emptying
Acetaminophen ingestions
Salicylate ingestions
Scope of Problem
• 4-5 million poisonings per year
– 2 million reported
• Death is rare--0.04% of reported poisonings
• 60% of poisonings in children < 6 years old
– Iron ingestion most common cause of death
• 87% of fatalities occur in adults,
– Analgesic (salicylate/acetaminophen) and antidepressants most common--50% of deaths
Patient Characteristics
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Intentional vs. Unintentional
Chronic vs. Acute
Adult vs. Pediatric
Unclear presentation
Toxidromes--characteristic constellation of
signs and symptoms
History
• Time of Ingestion
• Quantity
• Substance
– Over the counter medicines
• Hints
– Examine pill bottles
– Search patient and clothing
– Talk to family, friends, witnesses, ambulance
personnel
Exam
• Characteristic odor
– Wintergreen--methyl salicylate
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Vital Signs including accurate temperature
Mental Status
Skin signs
Ability to protect airway
Pupils
Assess for Other Conditions
• Suicidal potential
• Trauma
Tests
• Glucose check
– Possible salicylate ingestions--especially
children
– Altered sensorium, including alcohol
intoxication
• EKG or monitor
– Tachycardia or bradycardia
– All patients with altered sensorium and possible
overdose
Tests
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Pulse oximetry
Toxicology screen generally not helpful
Electrolytes
CPK
Urine
– Crystals
– Heme positive may suggest rhabdomyolysis
Drug Levels
• Acetaminophen
– Order as screening exam unless sure not
acetaminophen ingestion
• Salicylate
– Controversial if needed as a screen
• Toxicology screen generally not useful
– Not sensitive
– Slow--does not effect clinical decision making
Approach to the Poisoned Patient
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Treat the patient, not the toxin
Supportive care
Prevent absorption
Enhance elimination
Specific antidotes
Consult poison control or Poisindex
www.emedicine.com
Supportive Care
• ABC’s--basic life support
• Glucose, thiamine
• Prevent aspiration
– Left lateral decubitus position
– Readily available suction
• Treat other conditions
– Seizures
– Hypoxia
– Hypotension
– Dysrhythmia
Gut Decontamination
• Options
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Syrup of ipecac
Gastric lavage
Charcoal
Charcoal + gastric lavage
Whole bowel irrigation
• Generally charcoal alone is preferred
Syrup of Ipecac
• Advantages
– Given at home
– Tastes good so easy to get kids to take
– Causes vomiting within 30-60 minutes
• Disadvantages
– Vomiting with risk of aspiration
– May increase absorption in small bowel
– Interferes with oral medications
• N-acetyl cysteine
• Charcoal
Syrup of Ipecac
• Contraindications
– Caustic ingestions, hydrocarbons
– Altered mental status or potential for AMS
• Coma
• Seizures
– Infants < 6 months old
• Dosage (follow with water)
– Adults 30cc
– 6 mos-5 years  10cc
– 1-5 years  15cc
Gastric lavage
• Advantages
– Can be done in uncooperative patient
• Disadvantages
– Aspiration
– Stomach or esophageal perforation
– Risk of complications increases in
uncooperative patient
Gastric lavage
• Left lateral decubitus position with head
down to decrease risk of aspiration
• Must use large tube 30-40 French in adult
– Pills are bigger than small holes in NG tube
• Consider intubation
• Nothing in literature suggests using lavage
to “teach a lesson”
– Cruel, dangerous
– Unethical without medical indication
Charcoal
• Advantages
– Works immediately
– Can be given by small bore NG tube in
uncooperative patient
• Disadvantages
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Aspiration
Makes intubation difficult
Constipation
Interferes with oral drugs except n-acetyl
cysteine
Charcoal
• Dosage
– 1 gram/kg (50-100 grams in adult)
– 10 grams charcoal/1 mg drug
• Use without cathartic–or for first dose only
– Magnesium Citrate 4ml/kg (one bottle for
adults)
– Sorbitol (70%) 1 gram/kg (50-150 ml)
– Mag Sulfate (10%) 250 mg/kg (15-30 g)
• Use nasal-gastric tube if patient will not
drink
Charcoal
• Charcoal ineffective for
– Heavy Metals
– Alcohols
– Hydrocarbons
– Small ions (Li, Fe, K)
– Caustics
– Solvents
• Repeated dose charcoal
– Theophylline
– Carbamazepine
– Tricyclics
– Barbiturates
– Phenytoin
– Aspirin
Charcoal vs. Gastric Emptying
• Charcoal
– Decreased drug absorption
– Works in small intestine
• Gastric emptying is generally not helpful
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Within first hour in obtunded patients
Ingestions with delayed gastric emptying
Ingestions that slow motility
Massive ingestions
Charcoal vs. Gastric Emptying
• Kulig 1985--592 patients
– Lavage/ipecac + charcoal vs. Charcoal only
– Only difference was in obtunded patients seen
in first hour
– 2 complications
• Pond 1995--876 patients
– Similar designs
– No differences between groups
• Conclusion do not empty stomach routinely
Charcoal vs. Gastric Emptying
• Most of the time charcoal alone is best
choice
• In asymptomatic, late presenting patients,
no decontamination is a reasonable option
Whole Bowel Irrigation
• Polyethylene glycol by NG/oral until rectal
effluent is clear
– 25 ml/kg/hour children –1.5-2 l/hr adults
• Indications
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Drugs not absorbed by charcoal
Sustained release or enteric coated pills
Aspirin concretions
Body packers
Acetaminophen
• 70 minutes to peak level
• 4 hour peak with delayed gastric emptying
• Glucuronide and sulfate conjugation to non
toxic metabolites
• p450 metabolizes it to NAPQI--toxic
• NAPQI is metabolized by glutathione
dependent reaction
• Glutathione depletion toxicity
Acetaminophen OD Presentation
• Few signs and symptoms early
• Stage I: 7-14 hours post ingestion
– Anorexia, nausea, vomiting, diaphoresis
• Stage II: 24-48 hours post ingestion
– Stage I symptoms improve
– Right upper quadrant pain, hepatomegaly,
elevated transaminases and prothrombin time
– Renal damage in up to 25%
Acetaminophen OD Presentation
• Stage III: 3-5 days post ingestion
– Hepatic failure
– Death
Or
• Stage IV: 3-5 days post ingestion
– Hepatic regeneration
Acetaminophen Range of
Toxicity
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>150 mg/kg ingested
> 7 grams ingested in adult
Alcoholics at greater risk
Rumack-Matthew nomagram
– 4 hour level > 150 ug/ml
– Only valid for single acute ingestion
– Extended release needs later levels and trends
Acetaminophen OD--Antidote
• N-acetylcysteine (NAC), Mucomyst
– Increases glutathione
• 100% effective if given in first 8 hours
• Decreasing effectiveness for next 16 hours
N-acetyl cysteine dosing
• Oral dose
– Load 140 mg/kg
– Maintenance 70 mg/kg for 17 doses
– Do not need to adjust dose for charcoal
• Dilute 1:3 if given orally, or use NG
– Repeat dose if vomit within 1 hour
– Can use anti-emetics
– Does not effect acetaminophen levels
N-acetylcysteine IV dosing
• Acute within 8 hours—21 hour treatment
– Load 150 mg/kg over 1 hour (250 ml D5W)
– 50 mg/kg over 4 hours (500 ml D5W)
– 100 mg/kg over next 16 hours (1 liter D5W)
OR
• Late or chronic presentation—48 hour
– Load 140 mg/kg over 1 hour (500 ml D5W)
– 70 mg/kg over 1 hour (250 ml D5W) give 12
doses
Acetaminophen Ingestion
Approach
• 4 hour level on all overdose patients
– May be asymptomatic until hepatic damage
– Repeat level if below but near toxic range
• Use charcoal if early
• Start NAC within 8 hours of ingestion or as
soon as possible
• Continue if in toxic range
• Alcoholics at higher risk, treat at lower
levels
Acetaminophen Ingestion
Approach
• Supportive care
• Consider co-ingestions, extended release
capsules, and chronic ingestion
• Caution with:
– Pregnant patients consider IV NAC
– Chronic ingestion or extended release
– Alcoholics
Salicylate Toxicity
Sources of Salicylate
• Aspirin
• Oil of Wintergreen (methyl salicylate)
– 1 teaspoon can be fatal for a child
• Over the counter preparations
• Topical preparations
Salicylate Physiology
• Rapidly absorbed from stomach
– Peak levels in 2-4 hours
– Enteric has delayed absorption
• Concretions may form in overdose
– Concretions cause delayed absorption
• Renal excretion
• In overdoses, excretion slows with 1/2 life
up to 15-30 hours
Salicylate Physiology
Acid-Base Disturbances
• HyperventilationRespiratory Alkalosis
– Respiratory acidosis may develop late if severe
• Oxidative phosphorylation becomes
uncoupledMetabolic Acidosis
• Young children tend to have metabolic
acidosis
• Adults tend to have respiratory alkalosis
Salicylate Physiology
• Salicylate is highly protein bound
– Decreased protein binding if acidotic
• Hypoglycemia, especially in children
• Hypokalemia very common
– K+ from early alkalosis
• Cerebral and/or Pulmonary Edema
– Increased capillary permeability
Salicylate OD Presentation
Mild
• Tinnitus
• Hearing disturbance
• Mild hyperventilation
Moderate
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Severe hyperventilation
Lethargy
Nausea/vomiting
Anion gap acidosis
Dehydration
Hypokalemia
Salicylate OD Presentation
Severe
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Hypoglycemia
Hyperthermia
Pulmonary Edema
Severe metabolic
acidosis
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Cerebral Edema
Coma
Seizures
GI bleeding
Platelet dysfunction
Acute Salicylate Range of
Toxicity
Based on Ingested Amount
• < 150 mg/kg
• 150 mg/kg mild to moderate
• 300-500 mg/kg serious
• Above true for single acute ingestion
• More serious in elderly and young children
Laboratory Evaluation
• Ferric Chloride test
– 1cc urine + few drops 10% ferric chloride
– brown-purple color indicates salicylate
• Anion Gap Acidosis
• Mixed Respiratory Alkalosis/Metabolic
Acidosis
• Hypokalemia/Hypoglycemia
Salicylate Levels
• < 30 mg/dltherapeutic, non toxic
• 30-100 mg/dltoxic
• >100 mg/dl very severe
• Should be checked 4-6 hours post ingestion
• Beware of increasing levels from delayed
absorption
Salicylate Levels
• Done Nomagram
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Single acute ingestion
Not for enteric aspirin
Assumes no concretions
Assumes normal renal function
Developed for and with Pediatric patients
• Limited utility
– Make treatment decisions based on other
clinical factors
GI Decontamination
• Repeated Dose Charcoal
• Consider lavage if early--remember need
big tube
• Whole bowel irrigation
Hypoglycemia
• Check glucose
• IV fluid should have glucose
Fluid Therapy
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Correct dehydration
Aim for urine output 2-3 cc/kg/hours
Correct hypokalemia
Avoid over hydration because of risk of
cerebral and pulmonary edema
• No forced diuresis
Urinary Alkalinization
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Helps excretion
Load 1-2 meq/kg Bicarb
1-2 meq/kg Bicarb every 1-2 hours
Urine pH 7.5-8.0
Do not cause systemic alkalosis-aim for
serum pH ~7.5
• Must correct hypokalemia
Dialysis Indications
• Renal Failure
• Congestive heart failure or pulmonary
edema
• Unresponsive to other therapy
• Levels > 100-120 mg/dl may require
dialysis
Chronic Ingestions
• Common in elderly
• 25% mortality
• Consider with non cardiogenic pulmonary
edema
• Done Nomagram irrelevant
• Lower threshold for dialysis
– Levels > 60 mg/dl
Disposition
• Medical clearance--non symptomatic, non
toxic level 4-6 hours post ingestion
– If borderline level consider repeating to rule
out delayed absorption
• Admit all others to medical bed
• Early transfer if dialysis is unavailable and
may be required
Salicylate Pitfalls
• Failure to consider in differential diagnosis
– Gap acidosis
– AMS in elderly
• Topical preparations in children can cause
serious toxicity
• Failure to be alert for delayed absorption
• Beware of hypoglycemia especially in
children