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

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

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

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

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

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)

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

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 

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

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

Identification of Toxidromes

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

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

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

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

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

Back to the Management Strategy

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

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 / html

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

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

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

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

Opioid Overdose Managment

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

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

Naloxone  Reverses effects from opioid overdose  Pure opioid receptor antagonist  Duration of action 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

Acetaminophen Overdose

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

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

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

Matthew-Rumack Nomogram The Merck Manual for Health Professionals. Acetaminophen Poisoning.

Anaesthetic Overdose/Refractory Cases

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

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

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

References 1) Clinical Practice Guidelines. Management of Drug Overdose & Poisoning. Ministry of Health, Singapore. May ) Green SL, Dargan PI, Jones AL. Acute poisoning: understanding 90% of cases in a nutshell. Postgrad Med J. 2005;81: ) Tenenbein M et al. Efficacy of ipecac-induced emesis, orogastric lavage, and activated charcoal for acute drug overdose. Annals of Emergency Medicine; 16(8): ) Lab Tests Online. Emergency and Overdose Drug Tests. y/tab/test: Accessed March 22, 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:

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

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