WHERE DO WE GO FROM

HERE?

Image Credit: https://www.methadoneman.org

BUPRENORPHINE

UNIQUE

PHARMACOLOGY #1

Partial Agonist

Image Credit: Provincial Opioid Addiction Treatment Support Program, UBC CPD

Respiratory Depression

(Morphine, Heroin)

(Buprenorphine)

(Naloxone)

BUPRENORPHINE

UNIQUE

PHARMACOLOGY #2

High Affinity

Image Credit: Wheeler K MD, Dept of Anesthesiology, University of Ottawa

Heroin

STANDARD DOSING BUPRENORPINE/NALOXONE

TO AVOID:

Withdrawal First!

No opioids x 12-24h

PRECIPITATED

WITHDRAWAL RISK

MICRODOSING BUPRENORPHINE/NALOXONE

“Bernese Method” (2010): 0.2mg initial dose + concurrent heroin; 12mg by day 9

Case studies, n=4 : Safe & well-tolerated (Hammig 2016, Klaire 2019)

No rigorous studies

https://www.bern.com/

EQUIPOISE: STANDARD DOSING VS. MICRODOSING

Standard dosing

No opioid use x 12-24h

≥Moderate withdrawal (barrier)

Reach therapeutic dose in 24h

Microdosing

May concurrently use opioids

No withdrawal required

6-7 days to therapeutic dose (risk?)

VGH FEASIBILITY STUDY: STANDARD & MICRODOSING

SCREENING

Selected presenting complaints

or Clinician referral

CONSENT/ENROLL & COUNSEL

RAs; Pharmacists, ER/CPAS addictions physicians

Standard Dosing Package

3 days

n=10

Microdosing Package

6 days

n=10

Follow-up 7d (RA) & 30d (SW)

Feasibility Outcomes: Enrollment; Qualitative Interviews/Focus groups

RAAC Referral

SCREENING

PROCEDURE:

DATA-DRIVEN

(BCCDC OVERDOSE

COHORT)

Substance misuse/intoxication

Abdominal pain

Localized swelling/redness

Depression/suicidal/deliberate self-harm

Prescription/medication request

Bizarre behavior

Overdose ingestion

Lower extremity pain

Shortness of breath

Chest pain, non-cardiac features

Back pain

Substance withdrawal

Anxiety/situational crisis

Altered level of consciousness

Head injury

Lower extremity injury

Laceration/puncture

Upper extremity injury

Headache

Chest pain, cardiac features

RAPID OPIOID DEPENDENCY SCREEN (RODS)

TAKE-HOME PROTOCOLS FOR INDUCTION DOSING

STUDY PROGRESS

May 2019-present: Physician/nurse/pharmacist education

July-Aug 2019: Rollout Standard Dosing Average 2 patients enrolled/week

Sept 2019: Hiatus due to RA availability

Oct 2019: Rollout Microdosing Standard dosing phase complete

Healthcare provider focus groups

EARLY LESSONS

Opioid use disorder: a cross-cutting issue 25-58 years

Homeless to high income

Varied presenting complaints: e.g., head injury, assault, weakness, bug bites, bizarre behavior, cellulitis, overdose, withdrawal

Small window to engage

Complex clinical cases = the norm! Pregnant

Acute pain/trauma

EtOH withdrawal

PATIENT FEEDBACK: STANDARD DOSING PHASE

6 contacted in 30d follow-up

2/6: remained on buprenorphine/naloxone at 30 days “Makes me feel better emotionally, physically, socially”

“Suboxone was my fresh start” and “changed my life”

1/6: on and off buprenorphine/naloxone during 30 days

3/6: “I was not ready”

6/6: Continue offering from the ED, others may benefit

CHALLENGES

Delays & Leaving AMA

Care spaces lacking

High volume/long waits

Social instability

Lost/stolen packages

Difficult follow-ups

INTENSIVE OVERDOSE OUTREACH TEAM FOLLOW-UP

T-1: 1-year pre ED visit

MoH data linkage

Pharmanetdays on OAT

T=0: Index ED visit

Offer BTG

Intake survey

Within 1 week

OOT contact for linkage to care

1,2,6, 12 months

OOT contact & follow-up survey

T+1: 1 year post ED visit

MoH data linkage; Pharmanet

SPH PI: A. Kestler

VGH lead: J. Moe

NALOXONE DOSING IN ERA OF ULTRA-POTENT

OPIOIDS

In overdoses due to suspected fentanyl/ultra-potent opioid (UPO),

are higher naloxone doses required to reverse toxicity?

SYSTEMATIC REVIEWINCLUSION & SEARCH

P: >12 yo w opioid toxicity

Non-medical opioid use

I: Naloxone + dose

C: None necessary

O: Reversal or Adverse effect

D: Interventional

Observational

Case reports/series

Records identified from

literature searches

(n = 14,038)

Records screened by titles and

abstracts

(n = 8,929)

Records excluded

(n = 7,903)

Full-text articles

assessed for eligibility

(n = 1,026)

Studies excluded

(n = 865)

• Population ineligible (n =140)

• No naloxone dose reported (n=8)

• No outcomes of interest (n = 94)

• Study design ineligible (n =522)

• Not retrievable (n = 64)

• Language exclusion (n= 33)

Studies included

(n = 174)

Duplicates removed

(n = 5,109)

Grey Literature

(n = 14)

CUMULATIVE DOSE IN RESPONDERS: N. AMERICA

Studies 1974-2014 Studies 2015 or later

Drug Type Median (IQR) Median (IQR)

Fentanyl/

Ultra-Potent Opioids1.8 (1.0, 4.0) 3.4 (3.0, 4.1)

Heroin 0.8 (0.4, 0.8) 2 (1.4, 2.0)

CONCLUSIONS

In opioid toxicity due to fentanyl/UPOs vs. other opioids,

higher cumulative naloxone doseshave been used by providers in North America to achieve adequate reversal

CLINICAL & POLICY IMPLICATIONS

Titrate naloxone doses to clinical effect

Ensure adequate doses in Take-Home Naloxone kits

(3x 0.4mg in B.C.)

EMERGING PROVINCIAL

TRENDS

Food for thought

↑ DECLINED EHSTRANSPORTS

POST-OVERDOSE

Figure Credit: Slaunwhite A, BC Centre for Disease Control

Reasons for trends?

Patient outcomes?

Engagement opportunities?

↑ METHAMPHETAMINE USE

Figure Credit: Buxton J, BC Centre for Disease Control

Transitions vs concurrent use?

Methods/patterns of use?

Harm reduction implications?

CONCLUSION: KEY MESSAGES

ED based interventions for OUD workMultiple EDs around BC actively engaged

Coordination & scale-up needed in BC

New directionsMicro-dosing

Increased Outreach

Fentanyl/Ultra-potent opioids & Naloxone Dosing

Understanding OUD & stimulant use combo better

THANK YOU!

Buprenorphine/naloxone Standard Dosing vs. Microdosing Feasibility Study

Katherin Badke PharmD, Megan Pratt MSW, Barbara Harvey RN, Lara Gurney RN, Pouya Azar MD, Heather Flemming MD, Anne Sutherland MD, Gord Garner, Logan Carroll, Deb Bailey, Barbara Lee PhD, Andy Kestler MD, Keith Ahamad MD, Emma Garrod RN, Misty Bath RN, Corinne HohlMD MSc, Penny Brasher PhD, Jane Buxton MD, Amanda Slaunwhite PhD. Funding: VCHRI, UBC.

Naloxone Dosing in the Era of Fentanyl/UPO Overdoses

Jesse Godwin MD, Roy Purssell MD, Fiona O’Sullivan PhD, Jeffrey Hau MSc, Elizabeth Purssell MD MSc, Jason Curran MSc, Mary Doyle-Waters PhD, Penelope Brasher PhD, Jane Buxton MD, Corinne Hohl MD MSc. Funding: CIHR.

St. Paul’s BTG implementation team

Keith Ahamad MD, Tanya Campbell RN, Emma Garrod RN, Brad Ho PharmD, Arnold Leung, Aylar Macarai PharmD, & Cindy San Pharm D

BTG iOOT team

K. Ahamad MD, Misty Bath RN, Jane Buxton, Jim Christenson MD, E. Garrod RN, Eric Grafstein MD, Reka Gustafson MD, Isabelle Miles MD, Jess Moe MD, Seonaid Nolan MD, Roy Purssell MD, Frank Scheuermeyer MD, Christy Sutherland MD, Kelsey van Pelt MPH, & Evan Wood MD

Regional & provincial collaborators

K. Ahamad MD, Melissa Allan MD, Britt Bailey MD, Brendan Behan RN, Floyd Besserer MD, Brighid Cassidy MD, Miranda Compton MSW, E. GarrodRN, Leslie Lappalainan MD, Sophie Low-Beer MD, Ian Mitchell MD, Jess Moe MD, Devon Tucker MD, Jason Wale MD, & Josh Williams MD