in the Emergency Department Acetaminophen and Salicylate Ingestions

1. The Oral Overdose Patient in the Emergency DepartmentAcetaminophen and Salicylate Ingestions Thomas J. Sugarman, MD, FACEP December 2007

2. Outline • Overview of the poisoned patient • Charcoal vs. gastric emptying • Acetaminophen ingestions • Salicylate ingestions

3. 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

4. Patient Characteristics • Intentional vs. Unintentional • Chronic vs. Acute • Adult vs. Pediatric • Unclear presentation • Toxidromes--characteristic constellation of signs and symptoms

5. 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

6. Exam • Characteristic odor • Wintergreen--methyl salicylate • Vital Signs including accurate temperature • Mental Status • Skin signs • Ability to protect airway • Pupils

7. Assess for Other Conditions • Suicidal potential • Trauma

8. 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

9. Tests • Pulse oximetry • Toxicology screen generally not helpful • Electrolytes • CPK • Urine • Crystals • Heme positive may suggest rhabdomyolysis

10. 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

11. 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

12. 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

13. Gut Decontamination • Options • Syrup of ipecac • Gastric lavage • Charcoal • Charcoal + gastric lavage • Whole bowel irrigation • Generally charcoal alone is preferred

14. 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

15. 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

16. Gastric lavage • Advantages • Can be done in uncooperative patient • Disadvantages • Aspiration • Stomach or esophageal perforation • Risk of complications increases in uncooperative patient

17. 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

18. 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

19. 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

20. Charcoal • Charcoal ineffective for • Heavy Metals – Small ions (Li, Fe, K) • Alcohols – Caustics • Hydrocarbons – Solvents • Repeated dose charcoal • Theophylline – Barbiturates • Carbamazepine – Phenytoin • Tricyclics – Aspirin

21. 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

22. 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

23. Charcoal vs. Gastric Emptying • Most of the time charcoal alone is best choice • In asymptomatic, late presenting patients, no decontamination is a reasonable option

24. 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

25. 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

26. 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%

27. Acetaminophen OD Presentation • Stage III: 3-5 days post ingestion • Hepatic failure • Death • Stage IV: 3-5 days post ingestion • Hepatic regeneration Or

28. 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

29. Acetaminophen OD--Antidote • N-acetylcysteine (NAC), Mucomyst • Increases glutathione • 100% effective if given in first 8 hours • Decreasing effectiveness for next 16 hours

30. 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

31. 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

32. 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

33. 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

34. Salicylate ToxicitySources of Salicylate • Aspirin • Oil of Wintergreen (methyl salicylate) • 1 teaspoon can be fatal for a child • Over the counter preparations • Topical preparations

35. 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

36. Salicylate PhysiologyAcid-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

37. 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

38. Tinnitus Hearing disturbance Mild hyperventilation Salicylate OD Presentation Mild Moderate • Severe hyperventilation • Lethargy • Nausea/vomiting • Anion gap acidosis • Dehydration • Hypokalemia

39. Hypoglycemia Hyperthermia Pulmonary Edema Severe metabolic acidosis Salicylate OD Presentation Severe • Cerebral Edema • Coma • Seizures • GI bleeding • Platelet dysfunction

40. 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

41. 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

42. 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

43. 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

44. GI Decontamination • Repeated Dose Charcoal • Consider lavage if early--remember need big tube • Whole bowel irrigation

45. Hypoglycemia • Check glucose • IV fluid should have glucose

46. 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

47. 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

48. Dialysis Indications • Renal Failure • Congestive heart failure or pulmonary edema • Unresponsive to other therapy • Levels > 100-120 mg/dl may require dialysis

49. Chronic Ingestions • Common in elderly • 25% mortality • Consider with non cardiogenic pulmonary edema • Done Nomagram irrelevant • Lower threshold for dialysis • Levels > 60 mg/dl

50. 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