This document discusses emerging trends in illicit opioid use, including highly potent fentanyl analogs like carfentanil and acetylfentanil. It notes a rise in overdoses involving these substances, which are often mixed with heroin or cocaine. Two case studies describe patients requiring high doses of naloxone or prolonged infusions to reverse overdoses from acetylfentanil consumed via electronic cigarette or fake pills containing fentanyl. The document provides guidance that standard naloxone doses remain effective for most opioid overdoses but higher doses may be needed for strong suspicions of poly-opioid use involving fentanyl mixes. It emphasizes supporting airway and respiration over waiting for

1. ACP – CE – 2016 08 UPDATE Smack is Whack
SMACK IS WHACK!
cc: e_monk - https://www.flickr.com/photos/10676369@N07

2. Objectives
• Discuss and differentiate Carfentanil,
Acetylfentanil, and Fentanyl Citrate
• Discuss current and emerging trends in illicit
IV Opioid use
• Discuss treatment strategies for management
of ultra-potent polyopioid overdoses

3. Resources

4. WWW.EROWID.ORG

7. Not this Fentanyl

8. Not this one either…

9. Fentanyl and Fentanyl Analogs
• Fentanyl patented in 1960, and began to be
used by the late 60’s as an alternative opioid
in hemodynamically unstable patients.
• Use widespread by 1990’s with introduction of
alternative delivery routes, such as
transdermal preperations (Duragesic)
• By 2012, Fentanyl is most widely used
synthetic opioid in the world.
– 1700 KG annually

10. History
• Over the years, “poly-opioid” overdoses have popped up.
• 1990’s – 2000’s Heroin / Fentanyl mixes sporadically in New
England area
• 2013 – Sharp rise in illicit fentanyl OD’s in Canada and the
US.
• 2015 EuroPol special report to the EU
• 2015 (March) DEA issues nationwide alert on illcit Fentanyl
mixes (OCT) CDC issues health advisory on same.
• 2016 (MAY) DEA report noting a 72% increase in Opioid
OD’s, many of these with Fentanyl compounds (“mixes).
• 2016 (August) received queries about new “Super Heroin”.

11. • Eight people were revived using naloxone, an opioid-reversing drug.
• Others were revived by manual resuscitation, with a bag that
simulates breathing. One of the victims had to be given naloxone
three times because the heroin and whatever it was laced with was
so strong, according to Merry.
• "It's way too early to tell what the heroin in these latest cases was
laced, with but I suspect it was fentanyl and maybe something else,"
said Lemley. "A majority of the overdoses cases are laced with
fentanyl, Xanax or something. It's very rare to find pure heroin these
days."

14. Important Note
• Similar to previous fentanyl overdose outbreaks, most of the more
than 700 fentanyl-related overdose deaths reported to DEA during
this timeframe were attributable to illicitly-manufactured
fentanyl—not diverted pharmaceutical fentanyl—and either mixed
with heroin or other diluents and sold as a highly potent form
(sometimes under the street name “China White”).
• The DEA report noted that the “true number is most likely higher
because “many coroners’ offices and state crime laboratories do
not test for fentanyl or its analogs unless given a specific reason to
do so.”
– National Heroin Threat Assessment Summary. DEA Intelligence Report. April
2015.http://www.dea.gov/divisions/hq/2015/hq052215_National_Heroin_Thr
eat_Assessment_Summary.pdf
• Another assessment shows that traditional testing with gas
chromatography/mass spectrometry will often not detect
AcytleFentanyl.

16. NOTE
• Over the same period, a spike in cocaine use
has been noted by the DEA and several
reports of Cocaine and Fentanyl mixes
common as well.
• In a 2013 CDC assessment in RI:
– 53% of illicit fentanyl had cocaine , while only
33% had other opioids (Heroin).
– Centers for Disease Control and Prevention. Notes from the field: Acetyl fentanyl
overdose fatalities - Rhode Island, March-May 2013. MMWR: Morbidity & Mortality
Weekly Report [serial online]. August 30, 2013; 62(34):703-
704. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6234a5.htm

18. A tale of two opioids

19. So what is the deal?
• Acetylefentanyl and Carfentinil appear to be the
two primary illicit (non-pharmacutical, not
diverted) opioids on the street. They are often
mixed with Heroin.
– There are other opioids on the horizon, like W-18 and
W-5
• These new poly-opioid mixes are often going
under the old name of “china white”
• The potency as well as the increased receptor
binding , have resulting in a spike in OD deaths.

20. Acetylfentanyl

21. Carfentanil

22. Lets add some facts to the hype…
• Potency?
• Affinity?
• Street level doses
• Outliers?

23. The Outliers

24. Case #1
• 36 year old male developed the habit of using a electronic cigarette
filled with acetylfentanyl to aid relaxation. He purchased his
acetylfentanyl online.
• He had been using the ecigarette with increasing frequency while
on medical leave, and his wife reported finding him weakly
responsive on more than one occasion.
• At approximately 3 am, the family activated 911 for altered mental
status. His presentation included respiratory depression, pinpoint
pupils, hypoxemia, and a GCS of 6.
• He responded to serial doses of intravenous naloxone with
improvement in his mental status and respiratory condition.
• Due to the need for repeated dosing, he was placed on a naloxone
infusion and recovered uneventfully in intensive care.
• J Emerg Med. 2016 Mar;50(3):4336. doi:
10.1016/j.jemermed.2015.10.014. Epub 2015 Nov 14.

25. Case #2
• March 2016 : At one California facility 18 patients presented to ER
opioid OD in a single 8 day period
– 5 required CPR, with one on bypass. 3 others required intubation, and
2 others required BVM use. All but one required Narcan IV. 4 required
prolonged naloxone infusions.
• All had consumed what they thought was hydrocodone/APAP tabs
(Vicoden) purchased “on the street”.
– Testing revealed all tabs were actually “fake” and contained Fentanyl
instead.
– Each pill tested contained between 600 mcg – 6.9 mg acytlefentanyl.
• Sutter, M. E., Gerona, R., Davis, M., Roche, B., Colby, D., Chenoweth, J., . . . Albertson, T.
(2016, June 20). Fatal Fentanyl: One Pill Can Kill. Acad Emerg Med Academic Emergency
Medicine. doi:10.1111/acem.13034

26. So what does this mean to me????

27. Do you need more Narcan?
• Short Answer: Yes and No.
• Long Answer:
– Acytlefentanyl is more potent than morphine, but has a similar
affinity (strength of bond) as morphine. At normal recreational
doses traditional doses of Naloxone should be effective.
– Carfentanil is both more potent, and has approximately 31x the
affinity for mu receptors than morphine. But…
• 0.1 mg of Naloxone for a Morphine OD would be about 3.1 mg of
naloxone in a pure Carfentinal OD
• 0.4 mg of naloxone needed in a pure Carfentanil OD would be about
12.4 mg
– In any case, patients who do not respond to 10 mg of naloxone
IV in the first 60 min will not respond until other causes have
been addressed.

28. But what if????
• Remember:
– No one ever died of a naloxone deficit
– Patient die from Airway Failure
– Patients die from Respiratory Failure
– Patients die from complications of Aspiration
– and rarely hemodynamic collapse (–treat with
vasopressors)

29. So what is the guidance…..
• Well, the following guidance is from the
medical Directors.
• NOTE: Drug information changes all the time,
so as we know better, we will change, we will
update, and we will do better.

30. Dosing
• The standard naloxone dose remains unchanged
– Naloxone:
• IV/IO/SL: 0.1-2 mg slowly.
• Repeat as needed every 1-2 minutes to a maximum of 10 mg. IM/IN: 2 mg (1
mg in each nare if given IN.)
• Repeat as needed to a maximum of 10 mg.
• If IV access is unavailable. Use nasal atomizer
• The medical directors would like to emphasize that higher doses of
naloxone (those exceeding 2-4 mg) should be reserved only for
patients with a strong suspicion of illicit poly-opioid (i.e. IV/IN use of
Heroin / Fentanyl mixes).
• These higher doses should not be considered for more routine opioid
overdoses or for altered mental status patients where illicit poly-
opioid use is not a strong concern.
• In any case, providers should only the minimum amount to restore
respiratory effort.

31. Remember
• A failure to respond to Naloxone doesn’t mean you need
more naloxone, it could mean there are other factors to
consider….
– Hypoxia
– Anoxic Injury
– Non-opioid drug use
– Stroke, CVA, Hypoglycemia, AEIOU-TIPS….
• As a general rule, patients who do not respond to 10 mg of
naloxone IV in the first 60 min will not respond until other
causes have been addressed.

32. Airway first!
• Finally, the medical directors would like to remind
everyone that these patients die of airway and
respiratory failure, not from a naloxone deficit.
• Therefore the goal of patient care remains
the support of airway and respiratory functions.
Narcan is just one option to accomplish that.
• Intubation or Bag Valve Mask support may also
be appropriate based on clinical judgement.

33. Remember…
• In addition, the comments in the protocols
about bypassing Narcan and moving directly
to intubation remain valid.
• “If patient has obviously aspirated, consider
bypassing Narcan administration and intubate
as required”
– Protocol R-2 Opiate Overdose Dated May 1, 2016

34. No patient should suffer a delay in care
“waiting for Narcan to work”

35. Drug Lab Standby’s