EMS 81010 Intranasal Medications: Prehospital Setting Todd Davis, MD, EMT-B Emergency Medicine University of Cincinnati Cincinnati, OH

EMS

81010

Intranasal Medications: Prehospital Setting

Todd Davis, MD, EMT-BEmergency Medicine

University of Cincinnati Cincinnati, OH

EMS

81010

Objectives1. Recognize the anatomy of

the intranasal route and its implications for the prehospital setting.

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Objectives2. Identify pharmacology of

common intranasal medications used in the prehospital setting.

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Objectives3. 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):490-496


• .08 milligrams (mg)


• 2 mg


• 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 Clinical rating scale ((CRSCRS))

– nauseanausea

– vomitingvomiting

– see hand out...see hand out...

End Points

• Physicians’ ratings Physicians’ ratings were blinded to patient were blinded to patient groupgroup

End Points

• CRS measured at 0, 1, CRS measured at 0, 1, 5, 10, 15, and 30 5, 10, 15, and 30 minutes (min)minutes (min)

End Points

• Vital signs measured Vital signs measured at 0, 10 and 30 minat 0, 10 and 30 min

• Pupil measurements Pupil measurements taken at times 0, 10, 30 taken at times 0, 10, 30 min via cameramin via camera

Rating Scale Graph

• CRS revealed signs of withdrawal by 1 minute

• No significant difference in vital signs

Pupil Size

Naloxone

Naloxone

Non-user

User

Before Later

Naloxone in the Emergency Department• Kelly et al. Intranasal Kelly et al. Intranasal

naloxone for life naloxone for life threatening opioid threatening opioid overdose. overdose. Emergency Emergency Medicine JournalMedicine Journal 2002; 2002; 19(4):37519(4):375

Naloxone in the Emergency Department• Dose of 0.8-2.0mg INDose of 0.8-2.0mg IN

• End point was time to End point was time to spontaneous spontaneous respirationrespiration

Naloxone in the Emergency Department• Key limitations:Key limitations:

– unblinded study unblinded study without control groupwithout control group

– unblinded reviewersunblinded reviewers

2005Society 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

INVersus

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


–24% advanced life support (ALS) dispatched based on additional information

Tiered-Response EMS


–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 minALS time 16.1 min

– 10.2 min difference 10.2 min difference

NOMAD:Not One More

Anonymous Death (overdose

prevention project)

http://http://nomadoverdoseproject.nomadoverdoseproject.

googlepages.comgooglepages.com

How about some How about some fentanyl for your fentanyl for your

pain?pain?

How about some How about some fentanyl for your fentanyl for your

pain?pain?

IV FentanylIV FentanylVersusVersus

IV MorphineIV Morphine

IV fentanylIV fentanylvs IV morphinevs IV morphine

• 54 adult patients with acute pain

• Randomized to which medication


–equivalent doses

–re-dosed every 5 min, up to 30 min


• Outcomes:

– initial and final visual analog scale score (0-100 scale)

–change in score


• Outcomes: NONO difference difference

IV MorphineIV Morphinevsvs

IN FentanylIN Fentanyl

IV morphine vs IN IV morphine vs IN fentanylfentanyl

• 258 adult patients with severe pain


• Outcomes: initial, final, and change in verbal rating score (0-10 scale)


• NO difference


• IN fentanyl (15% serious adverse events)


– 3.8% poor tolerance3.8% poor tolerance

– <1% atomizer <1% atomizer malfunctionmalfunction


• IV morphine

–7% unable to establish IV

–3% difficult IV

Fentanyl in ChildrenFentanyl in Children


• Borland M, Jacobs I, and Geelhoed G. Intranasal fentanyl reduces acute pain...


...in children in the emergency department: A safety and efficacy study. Emergency Medicine 2002;14:275-280.


• 45 children aged 3-12 45 children aged 3-12 needing immediate needing immediate analgesia per triage analgesia per triage nursenurse


• IN fentanyl IN fentanyl administered followed administered followed by q5 min pain scores by q5 min pain scores by patient, caregiver, by patient, caregiver, and staffand staff


• Rescue medication Rescue medication available at 20 minutesavailable at 20 minutes


• Safe and effectiveSafe and effective

– 35.5 % single dose35.5 % single dose

– 31.1% two doses31.1% two doses

– 17.7% three doses17.7% three doses

– 15.5% four doses15.5% four doses


• Safe and effectiveSafe and effective

– one needed rescue IV one needed rescue IV morphine at 20 morphine at 20 minutes minutes

Benzodiazepine Benzodiazepine MedicationsMedications

BenzodiazepineBenzodiazepine

• diazepam (Valiumdiazepam (Valium®®))

• lorazepam (Ativanlorazepam (Ativan®®))

• midazolam (Versedmidazolam (Versed®®))

• alprazolam (Xanaxalprazolam (Xanax®®))

BenzodiazepineBenzodiazepine

Ever use Ketamine? Ever use Ketamine?

Dosing - MidazolamDosing - Midazolam

• Use the 5mg/1mL concentration

• Adults: 5mg (2.5mg or 0.5mL per nare)

• Pediatrics: 0.2mg/kg


• Seizure complaints are common

• 71% - via EMS71% - via EMS


• Increase in dosage for IN medication to stop a seizure?

Optimal dosing/concentrations

still unidentified


• IV access is not easy in seizing patients

PharmacokineticsPharmacokineticsWermeling et al. Pharmacokinetics and pharmacodynamics of a new intranasal midazolam formulation...

PharmacokineticsPharmacokinetics...in healthy volunteers. Anesth Analg 2006;103:344-349.

PharmacokineticsPharmacokinetics• IN peaks faster and

higher than IM

PharmacokineticsPharmacokinetics• Lindhardt, et al.

Electro-encephalographic effects and serum concentrations after intranasal...

PharmacokineticsPharmacokinetics...and intravenous administration of diazepam to healthy volunteers. Br. J Clin Pharmacol 2001;52:521-527

PharmacokineticsPharmacokinetics• In healthy volunteers -In healthy volunteers -

4mg IN diazepam 4mg IN diazepam produced similar... produced similar...

PharmacokineticsPharmacokinetics

......electro-encephalography (EEG) (EEG) findings to 5mg IV findings to 5mg IV diazepamdiazepam

IV DiazepamIV DiazepamVersusVersus

IN MidazolamIN Midazolam

IV Diazepam Versus IV Diazepam Versus IN MidazolamIN Midazolam

• Arrival to seizure cessation was 8.0 min with diazepam IV

IV Diazepam Versus IV Diazepam Versus IN MidazolamIN Midazolam

• Arrival to seizure cessation was 6.1 minutes with midazolam IN

Prehospital Prehospital Intranasal MidazolamIntranasal Midazolam

Prehospital Intranasal Prehospital Intranasal MidazolamMidazolam

• Rectal diazepam intranasal midazolam


• 124 patients witnessed seizure

–67 (54%) given no medication


–18 (15%) given rectal diazepam

–39 (32%) given intranasal midazolam

OutcomesOutcomes

• Median seizure time

–per rectum (PR) diazepam 30 min

– IN midazolam 11 min

OutcomesOutcomes

• Patients with rectal diazepam were more likely to:

OutcomesOutcomes

–more likely to be intubated in the emergency department (ED)

OutcomesOutcomes

–need additional seizure (Sz) medication in ED

OutcomesOutcomes

–get admitted to the intensive care unit (ICU)

How about IN How about IN midazolam at home?midazolam at home?

ConclusionsConclusions

THANK YOU

Intranasal Medications: Prehospital Setting

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Release Date:

04/01/2010

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Documents

EMS 81010 Intranasal Medications: Prehospital Setting Todd Davis, MD, EMT-B Emergency Medicine University of Cincinnati Cincinnati, OH