1. Intranasal Drug Delivery – Advantages of use in Rural and Remote practice

2. Lecture outline Why use intranasal medications?
Intranasal drugs indications with clinical cases and personal insights:
• Pain Control
• Sedation
• Seizures
• Opiate overdose
Drug doses and optimizing absorption
Resources

3. Why nasal drugs in rural practice?
Ease of use and convenience
Saves time / reduces human resource utilization
Rapidly effective - onset within 2-10 minutes
Safe – No high peak serum levels yet rapidly therapeutic
No special training is required to deliver the medication
No injection is needed
Painless
No needle stick risk
Extensive literature support
Patients (& Parents & clinicians) really like this approach
Faster care and discharge 3

4. Intranasal Medication Cases
Pain Control

5. Case: Pediatric Hand burn
A 5 year old burned her hand with boiling water
Clinical Needs: Pain control, debride, clean and dress the wound.
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
15 minutes later the patient easily tolerates cleansing of the burn and dressing application.
She is discharged with an oral pain
killer less than one hour after arrival. 5

6. Case: Injured ankle A 25 year old injured his ankle and has
significant ankle swelling, bruising and pain.
Clinical Needs: Pain control, x-ray, splint.
Treatment: 0.5 mcg/kg of intranasal sufentanil (45 mcg – 0.9 ml of generic “IV” sufentanil)
5-10 minutes later the pain is gone and he is calm
He is taken off to x-ray for diagnostic evaluation of his ankle, followed by a splint, crutches and referral to followup.
He leaves with very little pain, pleased with the timely care

7. Literature to support these cases – long bone fractures in pediatrics
Nasal
Intravenous
Borland, Ann Emerg Med 2007 7

8. Literature to support these cases – extremity trauma in adults
Steenblik, Am J Emerg Med 2012 8

9. But - are nasal drugs safe?

10. Pain control – Literature support
Over a decade of EMS 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
20-30 min vs minutes to drug delivered
Equivalency to IV morphine (even if they have an IV)
Superior to IM morphine
Care givers are more likely to treat pediatric severe pain
Highly satisfied patients and providers
Safe

11. IN opiates for Pain control – My insights
This is the most common use of IN drugs in my practice - daily.
Generic concentrations available in U.S. work fine and are
inexpensive ($1-4/vial)
Great patient and parent satisfier: Rapid pain resolution with no
need for a painful injection.
Efficacy: Very effective – and it can be titrated.
Use a pulse oximeter with sufentanil:
Sufentanil is especially potent and must be treated with
respect.
Fentanyl seems fine and can safely be given with minimal
risk
Give an oral pain killer as well: It kicks in as IN drug wears off

12. Nasal
The Doubters: Surely IN drugs can’t be as good as an injection for pain control!
Intravenous
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 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 12

13. Intranasal Medication Cases
Sedation

14. Case: CT scan child
A 5-year old boy requires a CT scan (computed tomography) of his head due to head injury.
He does not have an IV in place and is mildly agitated.
He will not remain still enough to obtain quality images.
The clinician administers topical lidocaine followed by 0.5 mg/kg of IN midazolam (or 2 ug/kg dexmedetomidine if longer duration of sedation is needed for MRI) and 10 minutes later he is dozing off and remains calm and still for the CT scan. 14

15. Case: Abscess Drainage
A 21 year old autistic male complains of redness, swelling and pain on his thigh. Exam reveals a large pus filled abscess, terrified patient.
Clinical Needs: Pain control, sedation, incision and drainage of the abscess
Treatment:
40 mcg of IN sufentanil then 5 mg intranasal midazolam
15 minutes later he is asleep, mildly sedated
The abscess is incised, drained and patient is discharged when awake.

16. Literature to support these cases - pediatrics
Klein, Ann Emerg Med 2011 16

17. Sedation – Literature support
Hundreds of articles dating back into the 1980’s. Most used midazolam.
Effective only if adequate dose is given (0.4 to 0.5 mg/kg)
Burns upon application – pretreat with lignocaine
Effective in children and adults (even exited delirium in EMS)
Safe – no reports of respiratory depression

18. Intranasal Medication Cases
Seizure Control

19. Case: Seizing child
The ambulance is transporting a 4 y.o. girl suffering a grand mal seizure.
Despite trying, no IV can be successfully established.
Rectal diazepam is unsuccessful at controlling the seizure.
IV attempts in the clinic / hospital are also unsuccessful.
However, on patient arrival a dose of 0.2 mg/kg of nasal midazolam (Versed, Dormicum) is given and within 3 minutes of drug delivery the child stops seizing. 19

20. Seizure Therapy - Literature support
Lahat 2000; Fisgin 2002; Holsti 2006; Ahmad 2006; Arya 2011; Holsti 2011; Javadzadeh 2012; Thakker 2012:
IN midazolam is superior to rectal diazepam for seizure control and is preferred by care givers
IN midazolam is superior to intramuscular injection of paraldehyde
IN midazolam/lorazepam is equivalent to intravenous delivery for stopping seizures, much faster at stopping them due to no IV start needed and it leads to less respiratory depression
IN midazolam can be delivered by family at home safely and effectively

21. Nasal vs buccal
Anderson 2011: IN vs buccal lorazepam

22. The Doubters: Surely IN drugs can’t be as good as IV for seizures!
ACTUALLY – They are equivalent or better (in these settings)
Lahat 00, Mahmoudian 04, Arya 11, Thakker 12, Javadzadeh 12 – IV and IN are equivalent for stopping seizures rapidly, but IN works faster due to no delays
Holsti 2007, Fisgin 2002 – IN is superior to rectal
Holsti 2011 – IN is safe at home with immediate results
Conclusions
IN seizure medication are just as good as IV, better than rectal
IN seizure medication are delivered much more rapidly so seizure stops sooner.
Anyone (Parents, care givers, nursing home staff, ambulance driver, etc.) can administer the medication so seizure length is shorter. 22

23. IN benzodiazepines for seizures – My insights
Very effective, very fast: Rapid seizure resolution without IV access.
Should be first line therapy in ALL prolonged acute seizures while IV access is being established (if at all)
Effective and safe at home, in EMS setting, in hospital
More effective, less expensive and preferred by providers when compared to alternative (rectal diazepam).

24. Intranasal Medication Cases
Opiate Overdose

25. Case: Methadone induced coma
A mother enters her daughters room to find her unconscious, barely breathing, blue color. Since her daughter is on methadone maintenance, the family was trained to deliver rescue naloxone (see photo of kit above).
The mother quickly delivers the naloxone intranasally.
She provides 2-3 minutes of rescue breathing until her daughter begins to arouse. She gradually awakens over 10 minutes.
The patient is transferred to the hospital for observation due to the long half life of methadone, but makes an uneventful recovery.

26. 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 efficacy to IV or IM therapy.
IN naloxone results in less agitation upon arousal
IN naloxone is lay person approved in many places. It safe and has saved many lives.

27. IN naloxone for opiate overdose – my insights
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
Every ambulance system, police agency and many clinics and families with high risk patients should be utilizing this approach.

28. Drug doses Scenario Drug and Dose Important Reminders Pain Control
Fentanyl: 2 mcg/kg
Sufentanil: 0.5 mcg/kg
Titration is possible
Sufentanil – use pulse ox
Half up each nostril
Sedation
Midazolam: 0.5 mg/kg
(combination w/ pain)
Use lidocaine to prevent burning
Use concentrated formula
Seizures
Midazolam: 0.2 mg/kg
Lorazepam 0.1 mg/kg
Support breathing while waiting
Opiate Overdose
Naloxone: 2 mg
Support breathing while awaiting onset
Epistaxis
Oxymetazoline or
Phenylephrine +
Lidocaine
Blow nose prior to application
Spray, then apply soaked cotton ball
Pinch nose for 10 minutes
Nasal Procedures
Wait 3 full minutes for anesthetic effect

29. Optimizing absorption of IN drugs
Critical
Concept
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 29

30. Dropper vs Atomizer Absorption Usability / acceptance
Drops = Oral drug via the nasal passage
Atomizer = nasal mist onto broad mucosal surface
Usability / acceptance
Drops = Minutes to give, cooperative patient, head position critical
Atomizer = seconds to deliver, better accepted

31. Dropper vs Atomizer
Merkus 2006

32. 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

33. Questions?
Educational Web site:

34. IN Benzos for sedation – my insights
Nasal Midazolam burns on application: Pretreat with lignocaine, warn the parents, this lasts seconds then dissipates
Timing: Children become sedated at about 5-10 minutes, maximal at and starts to wear off at so be ready to do prep and suture or do procedure in this time frame.
Efficacy: Sedation is not deep. OK for minor procedures, calming an agitated patient, CT/ MRI. It is not good enough for complex face laceration repair. 34