EMS
81010
Intranasal Medications:
Prehospital Setting
Todd Davis, MD, EMT-B
Emergency Medicine
University of Cincinnati
Cincinnati, OH
EMS
81010
Objectives
1. Recognize the anatomy of
the intranasal route and its
implications for the
prehospital setting.
EMS
81010
Objectives
2. Identify pharmacology of
common intranasal
medications used in the
prehospital setting.
EMS
81010
Objectives
3. Indicate pharmacological
variances among
intravenous (IV), intranasal
(IN), and intramuscular
(IM) routes.
Intranasal Route
Video of needle stick
Goes Right HERE!
15-57%
The Nose
• 30 square inches of
total mucosal surface
Many Devices
(mucosal atomizer is
most common)
Many Devices
(plastic catheter)
Many Devices
(metered dose)
Contraindications
Is the dosage higher?
Yes
Does the rate of
absorption
vary?
Naloxone (Narcan)
Who gets Naloxone?
Texas and Opioids
• 922,208,500 mg of
oxycodone (Percocet)
• 3,064,043,640 mg of
hydrocodone (Vicodin)
Dosing Naloxone
• Concentration 1mg/mL
• Adult: 2mg IN (1mg per
nare)
Dosing Naloxone
• Pediatric: 0.1mg/kg
(20kg child may get up
to 2mg)
Study (Naloxone)
• Bioavailability was
100% via both routes
– peak levels of
intranasal (IN) within
3 minutes
Study (Naloxone)
– intravenous (IV) and
IN have same half-life
(t½)
Pharmacokinetic Study
(Naloxone)
• Crossover, volunteer
study with 6 healthy
males
Pharmacokinetic Study
(Naloxone)
• Levels at 5, 10, 15, 30,
45, 60, 90, 120, 180,
240 minutes
Predicted
Concentrations
• Dowling et al. Population
pharmacokinetics of
intravenous, intramuscular,
and intranasal naloxone in
human volunteers, Ther
Drug Monit, 2008;30(4):490496
Predicted
Concentrations
• .08 milligrams (mg)
Predicted
Concentrations
• 2 mg
Predicted
Concentrations
• Takes longer to peak
– intramuscular
– intranasal
Do you still treat to
effect?
Key Limitations
• Healthy volunteers
versus unconscious
patients
Key Limitations
• Low concentrations
• Small sample for study
Study
• Nasal Administration of
Naloxone for Detection
of Opiate Dependence Journal of Psychiatric
Research. 1992 Jan;
26(1):39-43
End Points
• Clinical rating scale
(CRS)
– nausea
– vomiting
– see hand out...
End Points
• Physicians’ ratings
were blinded to patient
group
End Points
• CRS measured at 0, 1,
5, 10, 15, and 30
minutes (min)
End Points
• Vital signs measured
at 0, 10 and 30 min
• Pupil measurements
taken at times 0, 10, 30
min via camera
Rating Scale Graph
• CRS revealed signs of
withdrawal by 1 minute
• No significant
difference in vital signs
Pupil Size
Naloxone
Naloxone
Before
Later
Naloxone in the
Emergency Department
• Kelly et al. Intranasal
naloxone for life
threatening opioid
overdose. Emergency
Medicine Journal 2002;
19(4):375
Naloxone in the
Emergency Department
• Dose of 0.8-2.0mg IN
• End point was time to
spontaneous
respiration
Naloxone in the
Emergency Department
• Key limitations:
– unblinded study
without control group
– unblinded reviewers
2005
Society for Academic
Emergency Medicine
(SAEM) Abstract
2005 SAEM Abstract
• Primary outcomes:
2005 SAEM Abstract
• Primary outcomes:
– time of medication
administration to
clinical response
2005 SAEM Abstract
• 154 patients
– 104 IV Naloxone
– 50 IN Naloxone
2005 SAEM Abstract
• Administration
response
– IV 8.1 min
– IN 12.9 min
2005 SAEM Abstract
• Patient contact to
response
– IV 20.3 min
– IN 20.7 min
Prospective Study
• Barton, et al. Efficacy
of intranasal naloxone
as a needleless
alternative for
treatment of opioid
overdose...
Prospective Study
...in the pre-hospital
setting. Journal of
Emergency Medicine,
2005, 29(3): 265-271
Prehospital Study
• 14 year-olds
– overdose (OD)
– found down (FD)
– altered mental status
(AMS)
Prehospital Study
• Outcomes
– number of subjects
who “responded”
– time to response
Response
• 95 cases of
administration
• 52 responders to IV or
IN
• 43 Non-responders
Response
• 43 (83%) IN
• 9 (17%) no response to
IN - required IV (5 had
nose problem)
Is a deviated septum
a contraindication?
Why did they follow
up with IV if they did
respond to IN?
Time to Response
(Administration)
• IN 4.2 min
• IV 3.7 min
Time to Response
(Initial Patient Contact)
• IN 9.9 min
• IV 12.9 min
IN
Versus
Intramuscular (IM)
Naloxone Study
IN Versus IM Study
• Kelly AM, et al.
Randomized trial of
intranasal versus
intramuscular naloxone
in the pre-hospital
treatment...
IN Versus IM Study
...for suspected opioid
overdose. The Medical
Journal Of Australia.
2005; 182(1):24-27.
IN Versus IM Study
• Primary outcome:
response time with
RR>10
IN Versus IM Study
• Secondary outcomes:
RR and Glasgow Coma
Scale (GCS) at 8
minutes, need for
rescue naloxone, and
adverse events
IN Versus IM Study
• 182 patients
IN Versus IM Study
• Final sample
– IN 84
– IM 71
IN Versus IM Study
• Mean time to
spontaneous
respiration:
IN Versus IM Study
– IM 6 min, 95%, CI 5-7
– IN 8 min, 95%, CI 7-8
– probability (p)=0.006
IN Versus IM Study
• Time to GCS>11
(p=0.27)
IN Versus IM Study
• Presence of agitation
(IM 13% versus IN 2%,
p=0.02)
Naloxone use in a
Tiered-Response
Emergency Medical
Services System
Tiered-Response EMS
• 164 received Naloxone
Tiered-Response EMS
• Tiered EMS dispatch
– 42% simultaneous
dispatch
Tiered-Response EMS
• Tiered EMS dispatch
– 24% advanced life
support (ALS)
dispatched based on
additional information
Tiered-Response EMS
• Tiered EMS dispatch
– 28% ALS dispatched
based on basic life
support (BLS)
request
Tiered-Response EMS
• Simultaneous dispatch
– BLS 5.9 min
– ALS 11.6 min
– 5.7 min difference
Tiered-Response EMS
• ALS request by BLS on
scene (28% of the
time):
– ALS time 16.1 min
– 10.2 min difference
NOMAD:
Not One More
Anonymous Death
(overdose
prevention project)
http://
nomadoverdoseproject.
googlepages.com
How about some
fentanyl for your
pain?
How about some
fentanyl for your
pain?
IV Fentanyl
Versus
IV Morphine
IV fentanyl
vs IV morphine
• 54 adult patients with
acute pain
• Randomized to which
medication
IV fentanyl
vs IV morphine
– equivalent doses
– re-dosed every 5
min, up to 30 min
IV fentanyl
vs IV morphine
• Outcomes:
– initial and final visual
analog scale score
(0-100 scale)
– change in score
IV fentanyl
vs IV morphine
• Outcomes:
NO difference
IV Morphine
vs
IN Fentanyl
IV morphine vs IN
fentanyl
• 258 adult patients with
severe pain
IV morphine vs IN
fentanyl
• Outcomes: initial, final,
and change in verbal
rating score (0-10
scale)
IV morphine vs IN
fentanyl
• NO difference
IV morphine vs IN
fentanyl
• IN fentanyl (15%
serious adverse
events)
IV morphine vs IN
fentanyl
– 3.8% poor tolerance
– <1% atomizer
malfunction
IV morphine vs IN
fentanyl
• IV morphine
– 7% unable to
establish IV
– 3% difficult IV
Fentanyl in Children
Fentanyl in Children
• Borland M, Jacobs I,
and Geelhoed G.
Intranasal fentanyl
reduces acute pain...
Fentanyl in Children
...in children in the
emergency
department: A safety
and efficacy study.
Emergency Medicine
2002;14:275-280.
Fentanyl in Children
• 45 children aged 3-12
needing immediate
analgesia per triage
nurse
Fentanyl in Children
• IN fentanyl
administered followed
by q5 min pain scores
by patient, caregiver,
and staff
Fentanyl in Children
• Rescue medication
available at 20 minutes
Fentanyl in Children
• Safe and effective
– 35.5 % single dose
– 31.1% two doses
– 17.7% three doses
– 15.5% four doses
Fentanyl in Children
• Safe and effective
– one needed rescue
IV morphine at 20
minutes
Benzodiazepine
Medications
Benzodiazepine
• diazepam (Valium®)
• lorazepam (Ativan®)
• midazolam (Versed®)
• alprazolam (Xanax®)
Benzodiazepine
Ever use Ketamine?
Dosing - Midazolam
• Use the 5mg/1mL
concentration
• Adults: 5mg (2.5mg or
0.5mL per nare)
• Pediatrics: 0.2mg/kg
Dosing - Midazolam
• Seizure complaints are
common
• 71% - via EMS
Dosing - Midazolam
• Increase in dosage for
IN medication to stop a
seizure?
Optimal
dosing/concentrations
still unidentified
Dosing - Midazolam
• IV access is not easy
in seizing patients
Pharmacokinetics
Wermeling et al.
Pharmacokinetics and
pharmacodynamics of
a new intranasal
midazolam
formulation...
Pharmacokinetics
...in healthy volunteers.
Anesth Analg
2006;103:344-349.
Pharmacokinetics
• IN peaks faster and
higher than IM
Pharmacokinetics
• Lindhardt, et al.
Electroencephalographic
effects and serum
concentrations after
intranasal...
Pharmacokinetics
...and intravenous
administration of
diazepam to healthy
volunteers. Br. J Clin
Pharmacol 2001;52:521527
Pharmacokinetics
• In healthy volunteers 4mg IN diazepam
produced similar...
Pharmacokinetics
...electroencephalography (EEG)
findings to 5mg IV
diazepam
IV Diazepam
Versus
IN Midazolam
IV Diazepam Versus
IN Midazolam
• Arrival to seizure
cessation was 8.0 min
with diazepam IV
IV Diazepam Versus
IN Midazolam
• Arrival to seizure
cessation was 6.1
minutes with
midazolam IN
Prehospital
Intranasal Midazolam
Prehospital Intranasal
Midazolam
• Rectal diazepam 
intranasal midazolam
Prehospital Intranasal
Midazolam
• 124 patients witnessed
seizure
– 67 (54%) given no
medication
Prehospital Intranasal
Midazolam
– 18 (15%) given rectal
diazepam
– 39 (32%) given
intranasal midazolam
Outcomes
• Median seizure time
– per rectum (PR)
diazepam 30 min
– IN midazolam 11 min
Outcomes
• Patients with rectal
diazepam were more
likely to:
Outcomes
– more likely to be
intubated in the
emergency
department (ED)
Outcomes
– need additional
seizure (Sz)
medication in ED
Outcomes
– get admitted to the
intensive care unit
(ICU)
How about IN
midazolam at home?
Conclusions
THANK YOU
EMS
81010
Intranasal Medications:
Prehospital Setting
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EMS
81010
Release Date:
04/01/2010
The accreditation for this
program can be found by
signing in to
www.ttuhsc.edu/health.edu
EMS
81010
This continuing education activity is approved by the
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Medical Services for 1.5 Advanced CEH. You have
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