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

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

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

Intranasal Medication Cases

Pain Control

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.

Case: Injured ankleA 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

Literature to support these cases – long bone fractures in pediatrics

Nasal

Intravenous

Borland, Ann Emerg Med 2007

Literature to support these cases – extremity trauma in adults

Steenblik, Am J Emerg Med 2012

But - are nasal drugs safe?

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 60-70 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

Pain control – Literature support

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

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

Intranasal Medication Cases

Sedation

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.

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.

Literature to support these cases - pediatrics

Klein, Ann Emerg Med 2011

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

Intranasal Medication Cases

Seizure Control

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.

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

Nasal vs buccal

Anderson 2011: IN vs buccal lorazepam

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.

IN benzodiazepines for seizures – My insightsVery 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).

Intranasal Medication Cases

Opiate Overdose

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.

Opiate overdose – Literature supportIntranasal 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.

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.

Drug dosesScenario Drug and Dose Important Reminders

Pain Control Fentanyl: 2 mcg/kgSufentanil: 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/kgLorazepam 0.1 mg/kg

•Support breathing while waiting •Use concentrated formula

Opiate Overdose Naloxone: 2 mg •Support breathing while awaiting onset

Epistaxis Oxymetazoline orPhenylephrine +Lidocaine

•Blow nose prior to application•Spray, then apply soaked cotton ball•Pinch nose for 10 minutes

Nasal Procedures Oxymetazoline orPhenylephrine +Lidocaine

•Wait 3 full minutes for anesthetic effect

Optimizing absorption 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

Critical Concept

Dropper vs Atomizer

Absorption 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

Dropper vs Atomizer

Merkus 2006

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

Questions?

Educational Web site: www.intranasal.net

IN Benzos for sedation – my insights Nasal Midazolam burns on application: Pretreat with

lignocaine, warn the parents, this lasts 30-45 seconds then dissipates

Timing: Children become sedated at about 5-10 minutes, maximal at 10-20 and starts to wear off at 25-30 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.