⫸STICKY⫷ Non-opiate receptor mediated respiratory failure from fentanyl

[JTemperance]

I'm not sure how effective this would be / how risky it could be.

My main worry is that wcs seems to cause total unresponsiveness, so somebody experiencing it wouldn't be able to treat themselves.

Second, I would be very conservative about reccomending treatments that will increase the severity of respiratory/cardiac depression. Slamming clonidine seems like it could seriously drop cardiorespiratory drive.

Honestly best advice i currently have (which is likely not super feasible) is don't use alone, and have a positive pressure bag mask so that the observer can force respiration. These can be bought online.

Yes, I should say that I was just thinking out loud and that I would not advise anyone to do something like that, nor would I do so myself, at least not until there was much better information on the issue.

I admit it's frightening, though, so I do feel an urge to come up with some kind of strategy to mitigate the risk. Your advice re: positive pressure bag mask is well-taken, and since I'm lucky enough to have someone I can shoot with, it could be useful for me personally.

One other question I had was: how common do non-reversible (w/ Narcan) fentanyl "overdoses" appear to be? Is it something EMTs are encountering a lot out in the field?

 

[Skorpio]

One other question I had was: how common do non-reversible (w/ Narcan) fentanyl "overdoses" appear to be? Is it something EMTs are encountering a lot out in the field?

I think this question is very important.

 

[G_Chem]

“Prior to the new synthetic opioid era, community programs reported nearly 100% naloxone post administration survival rates with current approved doses of naloxone.”

“The existence of naloxone resistance in animal models and dose response for reversal of fentanyl toxicity observed in animals and humans further supports the need for higher doses of naloxone not currently available.”

“Faul, et al. looked at emergency medical providers from 2012 to 2015 using the National Emergency Service Information System and found that the percentage of patients receiving multiple sequential naloxone treatments increased from 14.5% in 2012 to 18.2% in 2015.” (A time period where fentanyl use increased dramatically.)

“The abrupt increase in synthetic opioid deaths was further substantiated by an analysis that separated synthetic opioids, such as fentanyl, into a unique category during the years of 2013–2016. Overall, the analysis revealed an 87.7% increase in deaths associated with synthetic opioids. In contrast, death rates due to natural and semisynthetic opioids remained relatively stable.”

“Klebacher, et al. examined the incidence of intranasal naloxone redosing in New Jersey Emergency Medical system from 2014 to 2016. This study found that the incidence of requiring a second dose of naloxone in response to an opioid overdose was 9%, with a 2% rate requiring a third dose.”

“Sommerville, et al. reported characteristics of fentanyl overdose in Massachusetts from 2014 to 2016. This study reported 83% of patients required greater than 2 naloxone doses (usually nasal 2 mg/2 ml) in suspected fentanyl cases before a response was observed. However, for those fatal deaths, 36% had evidence of an overdose within seconds to minutes after drug use. Ninety percent were pulseless upon EMS arrival.”

Higher doses of naloxone are needed in the synthetic opioid era - Substance Abuse Treatment, Prevention, and Policy

There has been a dramatic increase of deaths due to illicit fentanyl. We examined the pharmacology of fentanyl and reviewed data on the number of repeat doses of naloxone used to treat fentanyl overdoses. Multiple sequential doses of naloxone have been required in a certain percentage of opioid...

substanceabusepolicy.biomedcentral.com

While it doesn’t necessarily give the info you seek, does give a pretty good precedence of fentanyl overdoses needing much more than is typically dosed in narcan. That’s why they hand em out like tic tacs.

-GC

 

[G_Chem]

“Among patients with presumed exposure to fentanyl/ultra-potent opioids, 56.9% (617/1,085) responded to an initial naloxone dose ≤0.4 mg compared with 80.2% (170/212) of heroin users, and 30.4% (7/23) responded to an initial naloxone dose >0.4 mg compared with 59.1% (1,434/2,428) of heroin users. Among patients who responded, median cumulative naloxone doses were higher for presumed fentanyl/ultra-potent opioids than heroin overdoses in North America.”

“Numerous reports describe fentanyl overdoses initially unresponsive to IN naloxone and only transiently reversed with IV naloxone (if at all), requiring additional IV doses or continuous infusions to prevent recurrence of toxicity and respiratory depression.”

“Remarkably, serum fentanyl levels in several patients hospitalized for such an overdose were up to three times greater than the highest therapeutic concentration for analgesia, and were almost four times greater than the maximum therapeutic level among those patients who died. In those fatal cases, postmortem testing detected no norfentanyl, the primary metabolite of fentanyl, presumably because the patients died before metabolism could occur, thus it is unlikely that any dose of naloxone could have reversed the effects of such an immense overdose.”

That last line sums up my findings, most fentanyl deaths occur so quickly there was no time to administer narcan. Making the data on naloxone resistant fatalities hard to find.

-GC

 

[S.J.B.]

One other question I had was: how common do non-reversible (w/ Narcan) fentanyl "overdoses" appear to be? Is it something EMTs are encountering a lot out in the field?

It's worth noting that at supervised injection sites in Vancouver, they've avoided any fatal overdoses using naloxone for reversal and not having immediate access to invasive procedures like intubation, despite the fact that Vancouver is one of the world epicentres for fentanyl poisoning deaths. I'm not saying that the syndrome described in the paper in the OP isn't contributing to deaths, but it's contribution is certainly speculative at this point, and I would imagine that polydrug-induced respiratory depression is the predominant cause of most fentanyl-related poisoning deaths. Certainly something worth investigating further.

 

[JTemperance]

It's worth noting that at supervised injection sites in Vancouver, they've avoided any fatal overdoses using naloxone for reversal and not having immediate access to invasive procedures like intubation, despite the fact that Vancouver is one of the world epicentres for fentanyl poisoning deaths. I'm not saying that the syndrome described in the paper in the OP isn't contributing to deaths, but it's contribution is certainly speculative at this point, and I would imagine that polydrug-induced respiratory depression is the predominant cause of most fentanyl-related poisoning deaths. Certainly something worth investigating further.

That's exactly the kind of thing I was hoping to find out – how common are fentanyl ODs that can't be reversed by a sufficiently strong & timely dose of naloxone? It would be useful to know whether the Vancouver sites have other respiratory aids on hand or if they can speed up transit to a hospital for intubation etc. But on that's as suggestive as the other data, in the opposite way.

Unfortunately, other factors shorten the window of survival for a "traditional" mu-opioid OD with fentanyl as compared with heroin. So it seems quite possible to die before Narcan can be administered without being caused by Wooden Chest Syndrome, maybe even before any of the drug metabolizes into norfentanyl. (BTW, do we know how long that takes on average?)