Intranasal Naloxone Delivery – Clinical Implications

Intranasal Naloxone Delivery – Clinical Implications

Lecture outline The epidemic of opiate overdoses Nasal naloxone: What is it? Optimizing nasal naloxone – general concepts 2 cases – Ambulance, Lay person delivered Literature support for intranasal naloxone Lay person delivered naloxone – life saving,

empowering How to effectively delivery nasal naloxone

Heroin Overdose

Some numbers related to Heroin IDU’s Approximately 50% have experienced an

overdose Approximately 90% have witnessed an OD In only 50-60% of ODs is an ambulance is called

(Burris et al., 2000; Darke, Ross & Hall et al., 1996)

60 -75% of deaths occur in the home (Darke, et al. 1999)

Heroin Overdose

Some numbers related to Heroin IDU’s 70-80% have no intervention before death

(Darke et al., 1999)

60% of fatal ODs - someone else is present(Darke & Zador, 1996; Loxley & Davidson, 1998; McGregor et al., 1998)

70% death occurs >1 hour after injection(Darke et al., 1999)

Opiate Overdose

Nasal Opiate reversal agent Naloxone

Opiate Overdose


Opiate OverdoseWhy these numbers matter in relationship to

today’s discussion Most heroin overdoses are witnessed and

reversible but due to legal fears – little intervention is instituted

There is also an epidemic (especially in my country, but increasingly here as well) related to accidental prescription opiate overdoses

There is time to intervene if an easy, effective intervention is instituted in the public domain.

Opiate Overdose

Why these numbers matter in relationship to today’s discussion An antidote DOES exist that is safe, has no

addiction potential, and can be administered by lay persons

Antidote delivery saves lives, is more palatable to witnesses than calling for help, and empowers the users to help themselves (actually leading to LESS use of heroin)

What is the antidote?

Naloxone

Naloxone – mechanism of action Displaces heroin (any opiate) off the receptor

Naloxone has a strongeraffinity to the opioidreceptors than the heroin, soit knocks the heroin off thereceptors for a short timeand lets the person breatheagain.

Heroin

Naloxone

Opiatereceptor

My interest and involvement in intranasal naloxone

1980’s Trained at an inner city medically under-served hospital. Large heroin user population, frequent OD’s, difficult IV access, onset

of HIV epidemic with huge fear involved in the prehospital and ER community.

I began sublingual and intralingual injections – worked well but still a needle

1990’s Began experimenting with nasal drug delivery for patients Designed first clinical trial on IN naloxone, recruited Dr. Erik Barton to

conduct the trial (published in 2002). Began using IN naloxone in our prehospital system 1999

My interest and involvement in intranasal naloxone

2000’s Introduced the concept and data to Harm Reduction group

in New Mexico who adapted immediately. Presented the concept at the U.S National Harm Reduction

conference – a seed was planted for lay person use. Convinced many other Ambulance agencies in US to adopt

the strategy Advised Project Lazarus, NYC, Boston, Melbourne, etc

regarding the concept.

Why do I think nasal naloxone delivery is important to this audience?

Ease of delivery and empowerment of bystanders Anyone can be trained quickly to deliver nasal naloxone Injection phobia eliminated - witnesses will deliver a nasal drug

Speed of delivery OD witness delivered IN naloxone saves lives / brain

Gentler awakening OD patient awakens less acutely, less intense (but still not pleasant)

Safety No needle stick risk – No risk of HIV, Hepatitis transmission

Costs Costs less than EMS activation, IV starts, hospital visit, etc

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 = runs down to

pharynx and swallowed Atomizer = sticks to broad

mucosal surface and absorbs

Usability / acceptance Drops = Minutes to give,

cooperative patient, head position required

Atomizer = seconds to deliver, better accepted

Opiate Overdose Cases

Case: Heroin Overdose

The ambulance responds to an unconscious, barely breathing patient with obvious intravenous needle marks on both arms – the case is consistent with heroin overdose

An intramuscular dose of naloxone (Narcan) is administered and the patient is successfully resuscitated.

Unfortunately, the medic suffers a contaminated needle stick after providing the intramuscular injection.

The patient admits to being infected with both HIV and hepatitis C. He remains alert for 2 hours with no further therapy in the ED and is discharged.

Case: Heroin Overdose

The medic now needs treatment - HIV prophylaxis The next few months will be difficult for him:

Side effects that accompany HIV medications Personal life is in turmoil due to issues of safe sex with

his spouse Mental anguish of waiting to see if he develops HIV or

hepatitis C.

He wonders why his system is not using the LMA-MAD nasal to deliver naloxone on all these patients.

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 emergency room 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:

IN naloxone is at least 80-90% effective at reversing opiate overdose

When compared directly it is equivalent in time of onset and 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 is safe, has

saved many lives and reduces medical resource consumption

Nasal Naloxone - Literature supportKey Articles – Australia EMS

Kerr, Addiction 2009 (LMA-

MAD): IN naloxone is as effective and as fast as IM naloxone at waking patients up with opiate overdose – but there is NO risk of contaminated needle stick and anyone can deliver the nasal drug with minimal training.

Nasal Naloxone - Literature supportKey Articles – Layperson

administered treatment

Doe-Simpkins, Am J Public Health 2009 (LMA-MAD): IN naloxone is safe and effective when delivered by laypersons who are present when a patient overdoses.

Lay person administered naloxone programs

The data are compelling

Opiate Overdose


Opiate Overdose epidemic, naloxone programs in USA


Naloxone programs USA

MMWR article 2012 (data as of 2010) 53,000 individual trained to use naloxone 10,000 rescues reported Most programs are combined with needle

exchange As of 2010 87% distributed injectable

naloxone, 8.5% nasal, rest either

Opiate Overdose


Naloxone programs - police


Naloxone programs - AustraliaExpanding Naloxone Availability in the ACT

“As a community we should be promoting interventions that can save lives, regardless of people’s backgrounds. Naloxone can reverse the potentially fatal effects of an overdose, but it needs to be given within minutes of an overdose occurring, which is why it makes sense to give it to people who may witness an overdose.”

said Carrie Fowlie, Executive Officer of the peak body the Alcohol Tobaccoand Other Drug Association ACT (ATODA).

Naloxone programs - AustraliaANEX Australia – Position statement

“Regulatory barriers in Australia need to be removed in order to allow non-medical personnel, including families of opiate users, access to Naloxone so that they may have access to this effective intervention to better respond to an overdose immediately.”

“steps should immediately taken to have Naloxone rescheduled to make it available across the counter in pharmacies. Legal protection should be provided to non-medical personnel whoadminister it.”

Opiate Overdose


Naloxone options

Options Advantages

“Disadvantages”

Single dose‐pre loaded‐syringe

Pre measured‐No add’lequipment

Cost (~$15 USD /dose)Fragile apparatusSingle dose

Intranasalatomizer

No needlesPremeasured

Cost (~15 USD /dose)Slightly less efficacySingle dose

Multi dose‐multi use‐10cc vial

Cost (~$0.27 /dose)Multiple doses

Need add’l needlesContamination issuesNeed to measure a dose in stressful setting – error potential

Sarz Maxwell

Nasal Naloxone – How to do it

Nasal Opiate

Naloxone training for lay public Components of Training

1. What is an overdose?

2. What causes an overdose?

3. Prevention messages

4. Recognition

5. Response

6. Aftercare

7. Follow‐up and refills

Opiate Overdose - Recognition


Opiate Overdose - Response


Stimulation - Sternal Rub


Call for help


Airway / Rescue Breathing


Nasal Opiate reversal agent - naloxone

Opiate Overdose - ResponseNasal Opiate reversal agent - naloxone


Airway / Rescue Breathing - continue

Opiate Overdose - AftercareRecovery position

IN naloxone for opiate overdose – my insightsWhy not? Is there a downside? Elimination of needle eliminates needle stick risk to provider They awaken more gently than with injected 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 and not even call

ambulance in many settings Empowers the users leading to LESS overdosesEvery ambulance system, police agency and many clinics and families

with high risk patients should be utilizing this approach.

Adelaide Advertiser Dec 2010

Questions?

Educational Web site: www.intranasal.net

http://www.intranasal.net/

Documents

Intranasal Naloxone Delivery – Clinical Implications