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