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

EMS Objectives 1. Recognize the anatomy of the intranasal route and its implications for the prehospital setting.

EMS Objectives 2. Identify pharmacology of common intranasal medications used in the prehospital setting.

EMS 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):

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 Jan; 26(1):39-43

End Points Clinical rating scale (CRS)Clinical rating scale (CRS) –nausea –vomiting – see hand out...

End Points Physicians’ ratings were blinded to patient groupPhysicians’ ratings were blinded to patient group

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

End Points Vital signs measured at 0, 10 and 30 minVital signs measured at 0, 10 and 30 min Pupil measurements taken at times 0, 10, 30 min via cameraPupil 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 Non-user User BeforeLater

Naloxone in the Emergency Department Kelly et al. Intranasal naloxone for life threatening opioid overdose. Emergency Medicine Journal 2002; 19(4):375Kelly et al. Intranasal naloxone for life threatening opioid overdose. Emergency Medicine Journal 2002; 19(4):375

Naloxone in the Emergency Department Dose of mg INDose of mg IN End point was time to spontaneous respirationEnd point was time to spontaneous respiration

Naloxone in the Emergency Department Key limitations: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):

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)

nomadoverdoseproject. googlepages.com

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 NO differenceOutcomes: 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

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:

Fentanyl in Children 45 children aged 3-12 needing immediate analgesia per triage nurse45 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 staffIN fentanyl administered followed by q5 min pain scores by patient, caregiver, and staff

Fentanyl in Children Rescue medication available at 20 minutesRescue medication available at 20 minutes

Fentanyl in Children Safe and effectiveSafe and effective –35.5 % single dose –31.1% two doses –17.7% three doses –15.5% four doses

Fentanyl in Children Safe and effectiveSafe and effective –one needed rescue IV morphine at 20 minutes

Benzodiazepine Medications

Benzodiazepine diazepam (Valium®)diazepam (Valium®) lorazepam (Ativan®)lorazepam (Ativan®) midazolam (Versed®)midazolam (Versed®) alprazolam (Xanax®)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 EMS71% - 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:

Pharmacokinetics IN peaks faster and higher than IM

Pharmacokinetics Lindhardt, et al. Electro- encephalographic effects and serum concentrations after intranasal...

Pharmacokinetics...and intravenous administration of diazepam to healthy volunteers. Br. J Clin Pharmacol 2001;52:

Pharmacokinetics In healthy volunteers - 4mg IN diazepam produced similar...In healthy volunteers - 4mg IN diazepam produced similar...

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

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

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

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