1. Region 6 Protocol Update 2014 Pharmacology Presence Regional EMS

2. Intranasal Drug Delivery – Clinical Implications for Pre-hospital care

3. Educational Web site:  www.intranasal.net www.intranasal.net

4. Topics  Why use intranasal medications?  Intranasal drug delivery: General concepts  Intranasal drugs indications with clinical cases and personal insights: Pain Control Opiate overdose  Drug doses  Resources

5. Why is nasal drug delivery important in prehospital care? Efficacy, speed and ease of delivery  No delivery delays (no IV)  Can deliver to anyone with an exposed nose  Rapid onset of action  As effective and fast as IV drugs in most situations Safety  No needle stick risk  Lower risk of respiratory depression (compared to IV) Easier to proceed with additional care  Start IV in children or agitated adult  Calm the agitated patient

6. Understanding IN delivery: General principles  First pass metabolism  Nose brain pathway  Bioavailability / Drug absorption  Safety vs IV drugs

7. First pass metabolism Nasal Mucosa: No first pass metabolism Gut mucosa: Subject to first pass metabolism

8. Nose brain pathway  The olfactory mucosa (smelling area in nose) is in direct contact with the brain and CSF.  Medications absorbed across the olfactory mucosa directly enter the CSF.  Offers a rapid, direct route for drug delivery to the brain (skipping the blood brain barrier). Olfactory mucosa, nerve Brain CSF Highly vascular nasal mucosa

9. Bioavailability/ Drug absorption How much of the administered medication actually ends up in the blood stream. Examples:  IV medications are 100% bioavailable.  Most oral medications are about 5%-10% bioavailable due to destruction in the gut and liver.  Nasal medications vary depending on molecule, pH, etc  Fentanyl 80+%  Naloxone 90+%

10. Optimizing Bioavailability of IN drugs  Minimize volume - Maximize concentration  0.2 to 0.3 ml per nostril ideal, 1 ml is maximum  Most potent (highly concentrated) drug should be used  Maximize total absorptive mucosal surface area  Use BOTH nostrils (doubles your absorptive surface area)  Use a delivery system that maximizes mucosal coverage and minimizes run-off.  Atomized particles across broad surface area  Beware of abnormal nasal mucosal characteristics  Mucous, blood and vasoconstrictors may reduce absorption  Suction nose or consider alternate delivery route if present Critical Concept

11. Dropper vs Atomizer Absorption  Drops = runs down to pharynx and swallowed  Atomizer = sticks to broad mucosal surface and absorbs Usability / acceptance  Drops = Minutes to give, cooperative patient, head position required  Atomizer = seconds to deliver, better accepted

12. Region 6 Protocols  Intranasal medications must be administered through an atomizer

13. IN Administration 1.Aspirate the proper volume of medication required. Remember – use a filtered needle for aspirating from an ampule. 2.Remove the needle from the syringe and attach the MAD Nasal™ Device to the syringe. 3.Using your free hand to hold the crown of the head stable, place the tip of the atomizer snugly against the nostril aiming slightly up and outward toward the top of the ear. 4.Briskly compress the syringe plunger to deliver approximately half of the medication into the nostril. 5.Move the device over to the opposite nostril and administer the remaining medication.

14. What IN medications can we use in prehospital care?

15. Region 6 Protocol – IN Medications ScenarioDrug and DoseProtocols Pain Control: Adult and Pediatrics Fentanyl: 1 mcg/kg 1 ml per nostril Max dose 50 mcg; May repeat x 1 after 5 minutes at 0.5 mcg/kg Adult and Pediatrics: Amputation Burns Painful Swollen and Deformed Extremity Opiate Overdose: Adult and Pediatrics Naloxone: 1 mg/ml per nostril (1 ml per nostril maximum; 2 mg total dose) May repeat every 2-3 minutes to a maximum dose of 4 mg Adult and Pediatrics: Altered LOC Poisoning / Overdose

16. Intranasal Medication Cases Pain Control

17. Case: Pediatric Hand burn A 5 year old burned her hand on the stove  Clinical Needs: Pain control, Transport for wound care  Treatment: 2.0 mcg/kg of intranasal fentanyl (40 mcg – 0.8 ml of generic “IV” fentanyl)  Within 3-5 minutes her pain is improved  She is transported to a nearby medical facility  15 minutes later the patient easily tolerates cleansing of the burn and dressing application.

18. Over a decade of prehospital and ER literature exists for burn, orthopedic trauma and visceral pain in both adults and children showing the following:  Faster drug delivery (no IV start needed) so faster onset  Equivalent to IV morphine  Superior to IM morphine  Care givers are more likely to treat pediatric severe pain  Highly satisfied patients and providers  Safe Pain control – Literature support

19. The Doubters: Surely IN drugs can’t be as good as an injection for pain control! ACTUALLY – They are equivalent or better (in these settings)  Borland 2007 – IN fentanyl onset of action and quality of pain control was identical to IV morphine in patients with broken legs and arms  Borland 2008, Holdgate 2010, Crellin 2010 - time to delivery of IN opiates was half that of IV and more patients get treated  Kendal 2001 – IN opiate superior to IM opiate for pain control  Conclusions  IN opiates are just as good as IV  IN opiates are delivered in half the waiting time as IV  IN opiate are preferred by patients, providers and parents over injections Nasal Intravenous

20. Intranasal Medication Cases Opiate Overdose

21. Case: Heroin Overdose The ambulance responds to an unconscious, barely breathing patient with obvious intravenous drug needle marks on both arms – consistent with heroin overdose  After an IV is established, naloxone (Narcan  ) is administered and the patient is successfully resuscitated.  Unfortunately, the medic suffers a contaminated needle stick while establishing the IV.  The patient admits to being infected with both HIV and hepatitis C. He remains alert for 2 hours with no further therapy in the ED (i.e.- no need for an IV) and is discharged.

22. Case: Heroin Overdose  The medic now needs treatment - HIV prophylaxis  The next few months will be difficult for him:  Side effects that accompany HIV medications  Personal life is in turmoil due to issues of safe sex with his spouse  Mental anguish of waiting to see if he develops HIV or hepatitis C.  He wonders why his system is not using MAD nasal to deliver naloxone on all these patients.

23. Opiate overdose – Literature support Intranasal naloxone literature  Barton 02, 05; Kelly 05; Robertson 09; Kerr 09; Merlin 2010 ; Doe Simkins 09; Walley 12:  IN naloxone is at least 80-90% effective at reversing opiate overdose  When compared directly it is equivalent in time of onset and in efficacy to IV or IM therapy.  IN naloxone results in less agitation upon arousal  IN naloxone is lay person approved in many places. It is safe, has saved many lives and reduces medical resource consumption

24. IN naloxone for opiate overdose Why not? Is there a downside?  High risk population for HIV, HCV, HBV  Difficult IV to establish due to scarring of veins  Elimination of needle eliminates needle stick risk  They awaken more gently than with IV naloxone  New epidemiology shows prescription drugs (methadone, etc) are causing many deaths that naloxone at home could reverse.  Simple enough that lay public can administer and not even call ambulance

25. Intranasal Medications Summary  Another tool for drug delivery to supplement standard IV, IM, PO– very useful when appropriate  Supported by extensive literature  Inexpensive  Speeds up care in many situations  Safe

26. Intramuscular Injections  Preferred sites:  Deltoid  Thigh  Hip

27. How much can the muscle hold? Preferred siteGeneral volumeMaximum volume Deltoid< 0.5 ml1.0 ml Thigh< 1.0 ml2.0 ml Buttocks / Hip< 2.5 ml5.0 ml

28. Amiodarone  Ventricular Ectopy  Tachyarrhythmia – Stable No longer need to mix with D5W Dose: 150 mg IVP; may repeat q 5 – 10 minutes; maximum dose 450 mg