in the Emergency Department Acetaminophen and Salicylate Ingestions
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Transcript of in the Emergency Department Acetaminophen and Salicylate Ingestions
in the Emergency Department
Acetaminophen and Salicylate Ingestions
Thomas J. Sugarman, MD, FACEP
December 2007
Outline
• 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 anti-
depressants most common--50% of deaths
Patient Characteristics
• 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
• 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– Possible tricyclic ingestions
Tests
• 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
• 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 – Hypotension– Hypoxia – Dysrhythmia
Gut Decontamination
• Options– 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 – 1-5 years 15cc– 6 mos-5 years 10cc
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– 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 – Small ions (Li, Fe, K)– Alcohols – Caustics– Hydrocarbons – Solvents
• Repeated dose charcoal– Theophylline – Barbiturates– Carbamazepine – Phenytoin– Tricyclics – Aspirin
Charcoal vs. Gastric Emptying• Charcoal
– Decreased drug absorption– Works in small intestine
• Gastric emptying is generally not helpful except– 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– 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
• Stage IV: 3-5 days post ingestion– Hepatic regeneration
Or
Acetaminophen Range of Toxicity
• >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 IngestionApproach
• 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 IngestionApproach
• 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 ToxicitySources 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 PhysiologyAcid-Base Disturbances
• HyperventilationRespiratory Alkalosis– Respiratory acidosis may develop late if severe
• Oxidative phosphorylation becomes uncoupledMetabolic 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
• Tinnitus• Hearing disturbance• Mild hyperventilation
Mild
• Severe hyperventilation• Lethargy• Nausea/vomiting• Anion gap acidosis• Dehydration• Hypokalemia
Moderate
Salicylate OD Presentation
• Hypoglycemia• Hyperthermia• Pulmonary Edema• Severe metabolic
acidosis
Severe
• Cerebral Edema• Coma• Seizures• GI bleeding• Platelet dysfunction
Acute Salicylate Range of Toxicity
• < 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
Based on Ingested Amount
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/dltherapeutic, non toxic
• 30-100 mg/dltoxic
• >100 mg/dl very severe
• Should be checked 4-6 hours post ingestion
• Beware of increasing levels from delayed absorption
Salicylate Levels
• Done Nomagram– 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
• 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
• 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