Opiate Overdose & Intranasal Naloxone Protocol

1. Opiate Overdose & Intranasal Naloxone Protocol Amy Gutman MD ~ EMS Medical Director prehospitalmd@gmail.com / www.TEAEMS.com

2. OBJECTIVES • Review opiate pharmacology • Review Naloxone / Narcan pharmacology • Review needlestick injuries • Review intranasal route advantages & pathophysiology Fail!

3. OPIOIDS / OPIATES • Among oldest known drugs (i.e. poppy flowers) • Analgesiceffects of medications that stimulate brains’ “mu-opiod receptors” decreasing pain perception & increasing pain tolerance • Therapeutic usage of opiods are for pain & cough suppression • Side effects are potentially lethal, including sedation, hypotension, histamine reaction, respiratory depression, & euphoria (usually assoc with poor judgment) • Dependence develops with ongoing administration, leading to a withdrawal syndrome with abrupt discontinuation (“Dope Sick”) • N/V, tremor, seizure, tachycardia, HTN, diaphoresis, agitation, anxiety • Opioid-induced hyperalgesia syndrome is paradoxically worsening pain as a result of rapidly escalating dosage (often due to dependence)

4. MORE OPIOID OD DEATHS THAN MVC DEATHS IN MA* Poisoning Deaths vs. Motor Vehicle-Related Injury Deaths, MA Residents (1997-2008) *Registry of Vital Records and Statistics, MA DPH

5. NEEDLESTICK INJURIES • CDC estimates >600,000 annual injuries involving contaminated sharps • High risk patients & high risk environments • AMS / combative • Scene control issues • Moving ambulance • OSHA’s Needlestick Safety and Prevention Act (2001) & Occupational Exposure & Bloodborne Pathogens Standard (1991) • “to reduce or eliminate hazards of occupational exposure, an employer must implement an exposure control plan…The plan must describe how an employer will use a combination of engineering & work practice controls. Engineering controls are the primary means & include use of safer medical devices” • “Employees responsible for direct patient care must have input into employer decisions about WHICH engineering controls to adopt” • Intranasal systems meet OSHA recommendations to improve occupational exposures byreducing Level III bloodborne exposures (HIV, hepatitis)by decreasing needlestick injuries

6. IN DELIVERY ADVANTAGES • Simple, rapid, convenient • Nose is easy access point • Minimal training required • Painless • Eliminates needlestick risk • Compared to oral medications: • Faster bloodstream delivery • Higher blood levels • No destruction by stomach acid & intestinal enzymes • No destruction by hepatic 1ST pass metabolism • Compared to IV medications: • Comparable blood levels • Higher brain levels if well absorbed across nasal mucosa

7. Naloxone should be made more widely available to trained laypersons in an effort to reduce deaths due to opioid overdose

8. IN EFFECTIVENESS • Olfactory mucosa in direct contact with brain • This area termed “Nose-Brain-Pathway”, providing a rapid, direct route for CNS drug delivery • Nasal mucosa has a large surface area, leading to high bioavailability • Drugs absorbed via the nasal mucosa absorbed via rich nasal vascular plexus entering directly into brain circulation & CSF giving almost immediate high drug levels

9. IN PHARMACOKINETICS • Bioavailability • How much of the administered medication actually ends up in the blood stream • Oral meds 5%-25% bioavailable due to destruction in GI tract / liver • Intravenous / intraosseous meds usually 100% bioavailable • Intranasal meds 55% -100% bioavailable • Not all drugs can be delivered via the nasal mucosa • Particle size • Volume • Concentration • Lipophilicity • pH (acidity) • Properties of the solution drug is solubilized within • Nasal mucosal characteristics

10. IN MEDICATION CHARACTERISTICS • 1st Pass Metabolism: • Molecules absorbed through GI tract into liver “portal circulation” • Liver enzymes break down drug so little “active med” enters bloodstream • IN meds avoid GI tract & 1st pass metabolism • Lipohilicity / “Lipid Loving” • Cell membranes composed of lipid layers • Lipophilic meds easily & rapidly absorbed across mucous membranes

11. IN MED CHARACTERISTICS • Low volume, high concentration • Too large a volume or too weak a concentration leads to failure as drug cannot be absorbed in high enough quantity to be effective • Volumes >1ml per nostril too dilute & result in “runoff” • If abnormal nasal mucosa drugs not absorbed effectively • Vasoconstriction from cocaine • Bloody nose, nasal congestion, mucous discharge prevent drug mucosal contact • Destruction of mucosa from surgery or injury prevent drug mucosal contact

12. IN ABSORBTION • IN naloxone absorption almost as fast as IV in animal & human models • Hussain et al, Int J Pharm, 1984 • Loimer et al, Int J Addict, 1994 • Loimer et al, J Psychiatr Res, 1992 • “Atomization” of medications with better absorption via IN route • Thorsson et al, Br J ClinPharmacol, 1999

13. IN DELIVERY SYSTEM CHARACTERISTICS • Particle size • 10-50 microns best adheres to nasal mucosa • Smaller particles pass on to the lungs • larger particles form droplets & form run-off • Atomization has higher bioavailability than either spray or drops • The Mucosal Atomization Device (MAD) is the most common commercially available atomization device on the market • 30-60 micron spray ensure excellent mucosal coverage, stay in airstream & not “drift” down to lungs • Single-use& disposable • Fits on standard syringe

14. What Meds Can Be Used IN? • FDA has approved many medications for IN use • Steroids, antibiotics, anesthetics, antihistamines • Non-FDA approved: • Many meds effective but pharmaceutical companies have not pursued FDA IN clearance • Drugs of interest to EMS systems: • Naloxone (Narcan) • Midazolam (Versed) • Glucagon

15. Naloxone / Narcan • Opioid antagonist used to counteract life-threatening CNS & respiratory depression • Extremely high affinity for CNS μ-opioid receptors as a competitive antagonist producing rapid opiate withdrawal • Most commonly injected IV for fastest action (within 1 min); SQ and IM slower & less predictable effects • Use as an IN spray is “off-label”, but with significant evidence of effectiveness • Effects last 20-45 mins; often requires re-dosing

16. NALOXONE SIDE EFFECTS • Puking, puking, puking • 2-3% develop acute pulmonary edema & respiratory arrest • Acute withdrawal may cause your unconscious patient to become violent, combative…& may require sedation (or police, or restraints….)

17. Barton et al. “Intranasal Administration of Naloxone by Paramedics” PEC, 2002 • “The Denver Experience” of 600-800 IV doses of naloxone annually • Sheathed needles not used or disposed of properly • Study purpose was to test efficacy of prehospital IN naloxone • Number of IN responders? • Time to patient response? • How many required repeat doses? • Determine % IV placements that could potentially be avoided

18. STUDY METHODS • Clinical indicators for naloxone: “Found down” (FD), “Suspected overdose” (OD), “Altered mental status” (AMS) • Patients given 2mg IN naloxone at 1st contact • 1mg via MAD into each nostril (2mg of 2mg/2ml solution) • Same dose as IV protocol • Standard protocols followed including airway management, establish IV, IV meds (naloxone, D50) if needed • Medics could discontinue protocols if patient responded • Times of initial pt contact, IN naloxone, IV placement, IV naloxone & pt response were recorded to nearest minute

19. STUDY RESULTS & CONCLUSIONS • 43/52 (83%) = “IN Naloxone Responders.” • Mean time to effect = 4 mins (range 1-11 mins) • Mean time from 1st contact = 10 mins • 12/43 (29%) no IV naloxone required • 7/43 (16%) required additional dose of IV naloxone due to recurring somnolence, slow response, leakage of medication • 9/52 (17%) = “IN Non-responders.” • 4 pts with “epistaxis,” “trauma,” or “septal abnormality” • Conclusions • IN naloxone effective route with 83% prehospital response • Inexpensive device, easy to use • Decreased prehospital blood exposures • 29% no IV required in a high risk population

20. UTILIZING IN MAD NALOXONE • Draw up solution / prefilled synringes of 2 mg/2 ml) • Expel air from syringe • Attach MAD device via luer lock • Briskly compress the syringe plunger for controlled atomization • 1 ml up each nostril in rapid succession • May require a 2nd dose (Medical Control) • Do not forget all standard AMS protocol steps, including glucose measurement, stroke scale, trauma & medical emergency evaluation

21. References • Walley A. MD, MSc Assistant Professor of Medicine, Boston University School of Medicine • Weber JM. Can nebulized naloxone be used safely and effectively by emergency medical services for suspected opioid overdose? PEC. 2012. Apr-Jun;16(2):289-92 • www.drugs.com • www.wikipedia.com • Barton ED, et al. Efficacy of intranasal naloxone as a needleless alternative for treatment of opioid overdose in the prehospital setting. J Emerg Med. 2005 Oct;29(3):265-71. • www.intranasal.net • www.lmana.com

22. SUMMARYprehospitalmd@gmail.com / www.TEAEMS.com • Immediately on decision to treat inject naloxone into nose with MAD, then begin standard AMS care • Successful awakening eliminates the need for any IV • Awakening gradual or abrupt, but adequate respiratory efforts occur rapidly • Not 100% effective so failures with IN naloxone need to be followed with IV naloxone