Download Nasal Drug Delivery in EMS - Intranasal medication delivery

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?
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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)
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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 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)
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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?
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:
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Faster drug delivery (no IV start needed) so faster onset
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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
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!
Nasal
Intravenous
ACTUALLY – They are equivalent or better (in these settings)
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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
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.
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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
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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.
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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)
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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
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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 insights
Very effective, very fast: Rapid seizure resolution
without IV access.
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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 support
Intranasal naloxone literature
 Barton 02, 05; Kelly 05; Robertson 09; Kerr 09; Merlin 2010;
Doe Simkins 09; Walley 12:
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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?
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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 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
•Use concentrated formula
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
Oxymetazoline or
Phenylephrine +
Lidocaine
•Wait 3 full minutes for anesthetic effect
Optimizing absorption of IN
drugs
Critical
 Minimize volume - Maximize concentrationConcept
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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
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Use BOTH nostrils (doubles your absorptive surface area)
 Use a delivery system that maximizes mucosal
coverage and minimizes run-off.
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Atomized particles across broad surface area
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.