1. Management of Acute Overdose By: Peter Rempel March 27 th, 2013

2. Presentation Outline  Introduction and Statistics  General management strategy  Identification of Toxidromes  Management of overdose for specific medications  Role of pharmacist

3. Introduction - Overdose  Definition: The use of a substance in quantities greater than recommended.  Accidental vs. Intentional misuse

4. Epidemiology - Overdose  Approximately 2.3 million cases reported (US)  50% caused by pharmaceutics  41,592 deaths occurred in the US (2009)  76% were unintentional  91% caused by medications  Prevalence higher in males during the early years (0-12y)  Rates in females surpass males in older populations

5. Epidemiology (Continued) Most common pharmaceutics:  Analgesics (Opioids)  Sedative/hypnotic/antipsychotics  Antidepressants  Antihistamines  Cardiovascular drugs  Vitamins, cough and cold products  Rates of unintentional overdose has been steadily increasing

6. General Management Strategy 1) ABC management (vital signs) 2) Call Poison Control 3) Obtain best possible medical history 4) Order Labs 5) Prevent absorption of toxin 6) Enhance elimination (antidote)

7. General management strategy 1) ABC management Airway patency - head-tilt and chin-lift, removal of obstructions Breathing - assisted ventilation Circulation - colour change, sweating, decreased LOC - EKG, saline infusion, vasopressers

8. General Management Strategy 2) Call Poison Control  Available 24/7 to provide poison treatment information  Help guide treatment strategy  Prevent unnecessary use of health care resources  http://www.capcc.ca/provcentres/on/on.html http://www.capcc.ca/provcentres/on/on.html

9. General Management Strategy 3) Obtain accurate history  Determine the causative agent  Dose  Time since exposure  Route  Demographics (age, weight)  Symptoms*  Physical Examination

10. What if you don’t know what medication/poison was ingested?

11. Identification of Toxidromes

12. What is a Toxidrome?  Characteristic symptoms that are associated with a specific group of medications.  These group of symptoms are known as a “Toxidrome”

13. Identification of Toxidromes Cholinergic Toxidrome  “SLUDGE”  Salivation, Lacrimation, Urination, Defecation, GI upset, Emesis  Miosis, diaphoresis, bradycardia  Causative Agents: Physostigmine, Organophosphates, Carbamate

14. Identification of Toxidromes Anticholinergic Toxidrome  Hot as a Hare - fever  Red as a Beet - flushing  Mad as a Hatter – confusion, delirium  Dry as a bone – dry skin/mucus membranes  Mydriasis, tachycardia, urinary retention  Causative Agents: Antihistamines, TCA`s, Anti- parkinson medications

15. Identification of Toxidromes Sympathomimetic Toxidrome  Anxiety, Delusions, Sweating, Piloerrection, Seizures, Hyperreflexia, Mydriasis  Causative Agents: cocaine, salbutamol,, amphetamines, ephedrine, pseudoephedrine, methamphetamine

16. Identification of Toxidromes Sedative/Hypnotic/Opiate Toxidrome  Slurred speech, confusion, stupor, coma, apnoea, respiratory depression  Hypotension, bradycardia, miosis  Causative agents: opioids, anticonvulsants, antipyschotics, barbiturates, benzodiazepines, ethanol

17. Back to the Management Strategy

18. General Management Strategy 4) Order lab tests  Confirm offending agent(s)  Predict prognosis  Direct therapy/monitoring Includes: Toxicology screen, anion gap, osmol gap, CBC, BUN, SCr, blood glucose, electrolytes, EKG monitoring

19. General Management Strategy 5) Prevent absorption  *Activated Charcoal- first line therapy in most emergency departments  Whole Bowel Irrigations- clears the GI tract using high volumes of PEG  Orogastric Lavage- No benefit over the use of activated charcoal  Syrup of Ipecac- NO LONGER RECOMMENDED http://www.freepatentsonline.com /7077825.html

20. General Management Strategy Activated Charcoal  Ability to adsorb substances due to its high surface area  Offending agent(s) become trapped by the charcoal and are excreted in the feces Dosing: 1g/kg po OR by NG tube (usually given multiple times) AE: aspiration pneumonia, GI obstruction Contraindications: presence of ileus

21. General Management Strategy Activated Charcoal  Does not adsorb the following compounds:  Iron  Lithium  Lead  Cyanide  Alcohol

22. General Management Strategy 6) Enhance Elimination  Hemodialysis/Hemoperfusion  Administer Antidote

23. General Management Strategy Administer Antidote: *See my website for a more exhaustive list www.ODmanagement.weebly.com Offending AgentAntidote TylenolN-acetylcysteine AnticholinergicsPhysostigmine BenzodiazepinesFlumazenil CCBGlucagon, Calcium Beta BlockersGlucagon OpioidsNaloxone

24. Opioid Overdose Managment

25. Opioid Overdose Management  Signs and Symptoms?  Hint: Remember the toxidrome!

26. Opioid Overdose Management  Signs and Symptoms?  Hint: Remember the toxidrome!  Decreased LOC, RR, GI motility  Hypotension, bradycardia, miosis

27. Naloxone  Reverses effects from opioid overdose  Pure opioid receptor antagonist  Duration of action 30-120 minutes  0.4-2mg (IV,IM,SC); repeat q2-3 minutes until reversal of symptoms  Use continuous IV infusion for exposure to long-acting opioids or SR formulations

28. Acetaminophen Overdose

29. Hamm J. Acute acetaminophen overdose in adolescents and adults.Critical Care Nurse; Jun 2000; 20(3) 69-74

31. N-acetylcysteine  Indicated for the reversal of Acetaminophen toxicity  Hepatoprotective agent  Restores hepatic glutathione and acts as a glutathione substitute  Prevents the production of the toxic by-product of acetaminophen

32. N-acetylcysteine Dosing  21 hour IV dosing regimen (3 doses)  LD: 150 mg/kg (Max 15g) over 1 hour  2 nd dose: 50 mg/kg (max 5g) over 4 hours  3 rd dose: 100 mg/kg (max 10g) over 16 hours  Oral dosing regimen also available (72 hours)  Therapy is guided by the Matthew-Rumack Nomogram

33. Matthew-Rumack Nomogram The Merck Manual for Health Professionals. Acetaminophen Poisoning. http://www.merckmanuals.com/professional/injuries_poisoning/poisoning/acetaminophen_poisoning.html

34. Anaesthetic Overdose/Refractory Cases

35. Lipids 20%- Intralipid®  Used in anaesthetic overdose and refractory cases (unlabelled use)  Mechanism unknown  Effective for lipophilic medication overdose  Suggested Dose:  1.5 mL/kg bolus infused over 1 minute (may repeat up to 2 times)  Followed by 0.25 mL/kg/minute continuous infusion http://www.lipidrescue.org/

36. Role of the Pharmacist  Role in both the community and hospital setting  Educating patients on the dangers of drug misuse  Identifying potential at risk patients  Identifying inappropriate medication regimens  Medication Reconciliation

37. Highlights  Majority of overdoses are accidental  Rates of accidental overdose is steadily increasing  Identifying Toxidromes plays a vital role in the management of overdose  Activated charcoal and whole bowel irrigation are effective at lowering absorption  Pharmacists can play a role in both the prevention and treatment of an overdose

38. References 1) Clinical Practice Guidelines. Management of Drug Overdose & Poisoning. Ministry of Health, Singapore. May 2000. 2) Green SL, Dargan PI, Jones AL. Acute poisoning: understanding 90% of cases in a nutshell. Postgrad Med J. 2005;81:204-216. 3) Tenenbein M et al. Efficacy of ipecac-induced emesis, orogastric lavage, and activated charcoal for acute drug overdose. Annals of Emergency Medicine; 16(8): 838-841 4) Lab Tests Online. Emergency and Overdose Drug Tests. http://labtestsonline.org/understanding/analytes/emergenc y/tab/test: Accessed March 22, 2013 http://labtestsonline.org/understanding/analytes/emergenc y/tab/test 5) Thim T, Niels HV, et al. Initial assessment and treatment with the Airway, Breathing, Circulation, Disability, Exposure (ABCDE) approach. International Journal of General Medicine; 2012:5 117-121

39. References 6)Centers for disease control and prevention. Home and Recreational Safety. Unintentional Poisoning Data and Statistics. Retrieved from http://www.cdc.gov/HomeandRecreationalSafety/Poiso ning/data.html ; accessed March 3, 2013 http://www.cdc.gov/HomeandRecreationalSafety/Poiso ning/data.html 7)Hodgman MJ et al. A review of Acetaminophen Toxicity. Crit Care Clin. 28 (2012) 499-516 8)G Cave et al. Intravenous Lipid Emulsion as Antidote Beyond Local Anesthetic Toxicity: A Systematic Review. Academic Emergency Medicine: 2009; 16:815-824 9)Boyer EW. Management of Opioid Analgesic Overdose.. N Engl J Med: 367;2 146-155

40. Thank you for listening ANY QUESTIONS? www.odmanagement.weebly.com