Strayerisms: Opiate Use Disorder Part 2

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EW King, DO -

I enjoy and appreciate dr strayer- always
I have been doing addiction medicine for about 4 years- part time

regarding dosing of BU for withdraw, I believe he said 4-8 mg q 30 min to 60 min; that is very aggressive, espcially for an ED practitioner who might not be able to re evaluate closely due to other obligations. Misinterpreting precipitated wd from wd is an issue. I have only done home induction since beginning my practice. I have a long detailed discussion with the patient. I typically start at 2-4 mg when they are in moderate withdraw, more usually 2 mg. then repeat dose q2-3 hours, with some leeway explained. you can always take more, but once too much is taken too early - game over.
i have caused a precipitated withdraw once- not a good feeling. We need to remember that a majority of patients have taken BU off the street on occassion for suppression of wd symptoms; many are very familiar with the drug's use- and many have precipitated wd themselves.

Reuben Strayer (@emupdates) -

thanks for your comments EW.

the optimal dosing for buprenorphine initiation remains very much unanswered. the classic dosing, low and slow, has been used for years, primarily by psychiatrists, and certainly has the most evidence behind it. However anecdote and evidence is mounting to start with higher doses. buprenorphine-precipitated withdrawal is a very slippery, difficult to predict adverse effect, and there is a growing opinion that the best treatment for BPW is....higher doses of bup. Some experts feel that BPW is most likely to occur in a "sour spot" in between very small doses (microdosing is a very slick way to avoid BPW in the right context) and very large doses, because with big doses (≥16 mg) you provide enough agonism, despite using a partial agonist, that opioid withdrawal syndrome is overcome.

we still have a lot to learn about buprenorphine.

EW King, DO -

thanks for responding
i agree, underdosing should be avoided
the drug can be magical for the lives of patients with sud
there is a lot of nuance in dosing and management

Paul J. V., D.O. -

Dr. Strayer, I totally agree that buprenorphine is drug of choice for opiate withdrawal in the ED. I have used buprenorphine about 40 times. I'm also the physician for opioid health home and have 8 patients I care for with suboxone. Tonight in ED I had a 29 y/o female (60kg) prescribed 20mg buprenorphine per day (over 3 divided doses) that had relapsed with heroin last 2 months. She came in about 24 hrs after last heroin dose in mild withdrawal. She was signed out to me for night shift with COWS of 10. After 2 hrs her COWS pretty suddenly came up to 26 and we started buprenorphine 8mg s/l. This was repeated every 20 min for total 24 mg in an hour. Unfortunately it seemed to precipitate worse withdrawal and she was combative, screaming, and uncontrollable. We tried sedation with propofol 170mg, midazolam 5mg, lorazepam, 4mg, and pheonbarb 260mg. All of these just seemed to make her worse and certainly not better. Ended up giving rocuronium and intubating. I've never seen this type of precipitated withdrawal before. i can't really find any literature on how to treat precipitated withdrawal but in our case giving more bupe didn't work, nor did benzodiazepines or barbiturates. i'm also not sure why the buprenorphine would precipitate worsening withdrawal when her COWS was 26 when we gave first dose. I'd love your opinion of this case

Reuben Strayer (@emupdates) -

Hi Paul. This is the third case like this I've heard of. It is so hard to know why, or how to treat it, or how to prevent it. This may be some variant of buprenorphine-precipitated withdrawal that arises from specific patient factors that we simply haven't identified yet. I haven't seen anything like this myself but I wonder, if the problem is opioid withdrawal syndrome, if it would respond to a high dose of a high affinity full agonist (fentanyl, or, even better, the ultra-high affinity sufentanil). You have to wonder, though, that when her "COWS jumped to 26" if there wasn't something happening other than OWS.

If you learn anything more about this case, please share. What you're describing seems to be rare but definitely not unheard of. Glad you were able to ultimately effectively manage the patient with RSI.

Paul J. V., D.O. -

Reuben, thanks so much for your reassuring response. I'm happy to report she was able to be extubated the following day. After conferring with her addiction specialist she was restarted on her previous dose of buprenorphine and discharged within 48hrs of arrival. Her urine tox screen was positive for methamphetamines and I'm not sure if that contributed to her presentation. We did give her fentanyl after intubation. If this occurs again I will plan on giving fentanyl earlier in course when other attempts at sedation fail. I hope I don't see it again. I hope she can continue in recovery.

Reuben Strayer (@emupdates) -

Thanks for the update. Situation does sound very methamphetamine-like but who knows. Glad things settled down.

Reuben Strayer (@emupdates) -

From Dr. Graham Snyder
A very dark and insidious thought came to me shortly after hearing Dr. Strayer's fantastic segment on Buprenorphine. Coincidentally, we had a lecture on buprenorphine right after I heard the podcast. For all the right reasons, the lecturer was gently chiding the audience of physicians for not more aggressively prescribing Bup. The justification is clear: addiction is one of the deadliest diseases we see, buprenorphine should help for multiple different physiologically plausible reasons. He had magnificent anecdotes of patients hurtling towards death who were saved and became functional and healthy once again once they were put on Bup.

The thought which is almost so dark to speak aloud, was "I have heard this before." I was told as fact that oxycontin would be the salvation of patients who were suffering. It would not be addictive because of the very physiologically plausible reason of the very slow release over 12 hours. They had magnificent anecdotes of patients saved from suffering by being prescribed Oxy. That any doctor who didn't prescribe it was a dinosaur and the choice was given: You are a dinosaur who is cruel and you withhold this medicine or you care about patients and you prescribe it-as most of us did, for sprained ankles for the next two decades.

Bayer used the same rationale, phrasing, even anecdotes showing how "Heroin - the less addictive alternative to morphine" should be prescribed to all the young men coming home from World War I with morphine addiction. They sold us and we dutifully prescribed it because to no do it would have been cruel and showing myself to be a behind the times doctor and heartless to boot.

I think Bup will work. I'm DESPERATE for it to work. I have gone through unspeakable heartbreak from the losses of loved ones with dependence and addiction. We should all get on board if this really is what we are being pitched. Of course, the drug companies now are much more sophisticated and I should be able to trust them now right??? but… I want evidence. Finding an opiate dependent person who wants help is so Easy there are hundreds of thousands of people ready to be studied. Give Me evidence. Real evidence, not anecdotes, not subgroup analysis drug company drivel. Give me Patient Oriented Outcomes that lives are being saved and I will jump in with both feet. Yes of course, patients who overdose and are reliable enough to regularly come to a clinic and receive buprenorphine and counseling are less likely to die than their less reliable cohort who refuses to but that is not evidence. If it is not intention to treat, it is simply finding the subgroup of people who have the means and will get better regardless and tells us nothing about what would happen if they got usual care.-Graham

Reuben Strayer (@emupdates) -

Thanks for your thoughtful comment Graham. Your skepticism is wise.

But bup is quite a different drug than oxy, because of its partial agonism and high affinity. It is far less abuse prone, because it is far less euphoric and because it blocks the actions of full agonists. It is FAR less toxic because of its ceiling effect. Not only do people essentially never die from bup overdoses, people on high doses of bup function normally or near normally; in stark contrast to oxy (or methadone).

Bup is a very effective treatment for OUD. It may also be a safer/more effective/better treatment than full agonists chronic pain, chronic pain very much overlapping with OUD and often caused by chronic opioid use, but bup for chronic pain is controversial and poorly understood and I didn't say much if anything about bup for chronic pain on the segment. On the other hand, suggesting that a drug is a safe and effective treatment for OUD is very different than suggesting that a drug is a safe and effective treatment for **acute pain,** which was the lie we were told about oxy. This is because OUD destroys your life, and the life of the people who love you, acute pain does not, so the harm:benefit equation is very shifted in a therapy of OUD vs. a therapy for acute pain. Also, OUD is, compared to acute pain, relatively uncommon, because acute pain is ubiquitous. I did mention bup for acute pain on the segment, and advised against it (though there is probably a role for it).

lastly, there is abundant evidence that bup improves patient-oriented outcomes in OUD. papers below. there are many more.

thanks again for your thoughts. happy to further discuss.

reuben

https://www.dropbox.com/s/xb7ykrpsuxuftyb/Morgan%202019%20OD%20Following%20Naltrexone%20v%20Buprenorphine%20Claims%20Review%20-%20Drug%20Alcohol%20Dep.pdf?dl=0

https://www.dropbox.com/s/nvvb7ntbolnjto7/Mattick%202014%20Bup%20v%20Maintenance%20%26%20Placebo%20for%20OUD%20-%20Cochrane.pdf?dl=0

https://www.dropbox.com/s/tcou65dyfzbhlb3/Thomas%202014%20Bup%20for%20OUD%20Evidence%20Assessment%20-%20Psych%20Services.pdf?dl=0

https://www.dropbox.com/s/ynnc9179wf1u96k/Weiss%202017%20Rx%20Opioid%20Treatment%20Study%20What%20We%20Have%20Learned%20-%20Drug%20Alcohol%20Dep.pdf?dl=0

https://www.dropbox.com/s/wpq48lm4zedylx2/Larochelle%202018%20MAT%20after%20OD%2C%20Bup%20%26%20MD%20Reduce%20Mortality%20%28not%20naltrexone%29%20-%20AnnIM.pdf?dl=0

https://www.dropbox.com/s/tas3s7ofy4q75m6/Sordo%202017%20Mortality%20Risk%20During%20and%20After%20MAT%20-%20BMJ.pdf?dl=0

https://www.dropbox.com/s/9yma9ll4vrmx74u/Pierce%202016%20Psychological%20Support%20Doesn%27t%20Work%20for%20OUD%20-%20Addiction.pdf?dl=

glenn b. -

Can you recommend an online course to satisfy the x waiver requirement?

Reuben Strayer (@emupdates) -

The PCSS course is free. It's a bit of a slog but most say it's no big deal.

https://learning.pcssnow.org/p/onlinematwaiver

Ravi S. -

Dr. Strayer,
Would be able to provide any good references on the treatment of Buprenorphine induced withdrawal? I read Dr. Paul J.V.'s note- very anxiety inducing case.
Thanks,
Ravi Singh

Reuben Strayer (@emupdates) -

Hi Ravi

Paul JV's case is distinctly uncommon and it's not even clear that what was going on there was BPW (buprenorphine-precipitated withdrawal). That said, BPW is probably the most important adverse effect an emergency clinician dosing bup in the ED is likely to encounter. Best approach is of course to prevent it by making sure the patient is in adequate spontaneous withdrawal.

There is almost no published literature on the management of BPW. Here is some:

https://www.dropbox.com/sh/3sie21g3l8ijmmc/AACWDjIrONJzb3xSyVtX_lsaa?dl=0

The classic teaching is to manage BPW with non-agonists (clonidine, neuroleptics, benzos, ketamine, etc) but there is an emerging consensus around using *higher doses of buprenorphine* to treat BPW and anecdotally, this seems to work most of the time and it makes sense pharmacologically that it would. But very little data.

reub

Ravi S. -

Thank you Dr. Strayer

Donald W. C., M.D. -

Dr Strayer , I enjoyed your opinion piece and agree with much of it. However I so vehemently disagreed with your contention that " abstinence doesn't work" that I felt compelled to record a response that I sent to EMRAP in hopes that they might provide a different experts opinion to balance yours. They have chosen not to use it. If your interested It can be found here:
https://www.dropbox.com/s/70sfqlxhg92hajg/strayer%20response%20copy.mp3?dl=0

Reuben Strayer (@emupdates) -

Donald, thank you for your lucid and thoughtful comments.

Your comparison of deaths related to OUD with tobacco and alcohol use disorder is very important: many more people die from chronic alcohol use and many more still die from chronic tobacco use, and I could not agree more that we have become tragically inured to the harms of alcohol and tobacco because their use and misuse is so normalized. But while the total number of people harmed by alcohol and tobacco dwarfs opioids, opioids are, in fact, more lethal, and the higher total numbers of alcohol/tobacco deaths are of course because the number of alcohol and tobacco users is vastly larger than the number of opioid users. I use dramatic language because the problem is dramatic: when we see a person with alcohol or tobacco use disorder in the ED, we absolutely should do whatever we can to move them to reduce their use and move them to recovery–but the chance that that patient will be dead in 30 days from causes directly related to their AUD or TUD is tiny, and the same cannot be said of opioids. The chance that a person with OUD seen in the ED will be dead in 30 days is higher than just about any other disease we see. 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6920606/

You disagree that emergency docs play a significant role in causing opioid addiction through their prescriptions, compared to the much larger number of prescribers in primary care and pain medicine. Again, I agree with you, we caused less OUD than our higher-prescribing colleagues, but:

1. So what? We are the keepers of our house, not theirs, and insofar as we have leaky faucets (i.e. injudicious opioid prescribing) in our house, is that not ours to fix? 
2. The patients we see in the ED are uniquely vulnerable to the harms of an opioid prescription because that patient is more likely to get their **first** opioid prescription from an emergency doc, and it's the **first** prescription that often sets the patient down the path to opioid misuse and addiction. 

You say "there is no evidence" that emergency docs' prescriptions lead to addiction. That is not true. 

https://pubmed.ncbi.nlm.nih.gov/28199807/
https://pubmed.ncbi.nlm.nih.gov/25534654/https://pubmed.ncbi.nlm.nih.gov/26875061/
https://pubmed.ncbi.nlm.nih.gov/30054152/
https://pubmed.ncbi.nlm.nih.gov/32609923/
https://pubmed.ncbi.nlm.nih.gov/31229392/
https://www.annemergmed.com/article/S0196-0644(16)30705-3/fulltext

It is no longer a controversial statement that in some percentage of patients (probably between 1 in 50 and 1 in 100 patients who receive an opioid prescription),  the event that precipitates long term opioid use/misuse is a prescription for pain. It is sobering to consider how many patients I may have set down that path when I was prescribing 30 percocets 5-10 times per shift, which is what I, and many of us who trained in the 90s and 00s, were trained to do.

Of course the majority of patients who receive a prescription for pain do not develop addiction, that's not what's important–what's important is the magnitude of potential benefit and harm when considering an opioid prescription to an opioid-naive patient. The benefit is the amelioration of suffering from acute pain when an opioid is prescribed in addition to non-opioid alternatives. In some patients with severe acute pain (renal colic, fracture), that benefit is non-trivial. But if we take the most generous interpretation of the literature and stipulate that 1 in 100 patients prescribed opioids for severe acute pain is set down the path of addiction and misuse, the harms to that one person are so immense (in many cases life destroyed if not ended, lives of those who love the patient often destroyed) that I don't think it's a stretch to suggest that when you consider not only the likelihood but also the magnitude of harms and benefits, it is plainly obvious that in the vast majority of patients in whom you are considering an opioid prescription, the balance tilts heavily to harm.

The likelihood of your patient developing misuse from your opioid prescription can be predicted based on several risk factors and is proportional to the number of pills prescribed. So when you say it's "laughable" that a 3-day prescription for opioids for ankle sprain could cause addiction, I will say, if you're going to prescribe opioids for an ankle sprain, please prescribe as few as possible, and a 3 day supply is much less likely to cause trouble than a 1-week supply. But I, like many of us, was trained to prescribe 1 week, and 20 years ago the notion that 1 week could cause addiction was not just laughable, it was considered cruel not to prescribe 1 week, in fact there was a stigmatizing name applied to docs who were reluctant to treat pain with large doses of opioids: opiophobia. We know now that this was industry marketing and it was astoundingly effective. And let me reinforce the larger point: how much suffering from pain will a 3-day supply of opioids for ankle sprain prevent, above round-the-clock high dose ibuprofen and acetaminophen? If you cause 1 person out of 100, to be set down the path to OUD from a 3-day prescription of opioids for an ankle sprain, which will be well treated with tylenol and motrin, is that acceptable? If you sprained your ankle, and there was a bottle of 100 pills, and all of them will cause you to have a little less pain for a couple of days, 1 of them will ruin your life, would you take a pill out of that bottle?

Your comments about the role of abstinence in recovery from opioid addiction are important and even inspiring–I salute you, Donald, and anyone who can achieve successful recovery with abstinence. I also do not doubt that many people with OUD can achieve successful abstinence-based recovery, in time, if adequately supported, when their lives have been stabilized. That does not apply to people in the throes of uncontrolled addiction who are using street-purchased injectable opioids and present to the emergency department after naloxone rescue or after being assaulted while trying to score heroin or after being arrested for theft or after they contract an STI for selling sex, all in the name of not getting dopesick. We know beyond a shadow of a doubt that these folks are much less likely to succeed with abstinence, and not succeeding too often is relapse/overdose/death. 

https://pubmed.ncbi.nlm.nih.gov/23786852/
https://pubmed.ncbi.nlm.nih.gov/29913516/
https://pubmed.ncbi.nlm.nih.gov/15204673/
https://pubmed.ncbi.nlm.nih.gov/26452239/
https://pubmed.ncbi.nlm.nih.gov/28446428/
https://pubmed.ncbi.nlm.nih.gov/23488511/
https://pubmed.ncbi.nlm.nih.gov/12606177/

This is no longer controversial, Donald, even though the people who need the most convincing are the patients themselves, who want to be "clean." Entrenched opioid addiction is not a failure of willpower, it is a disease of deranged brain chemistry, and it is abundantly clear and there is no longer any doubt that folks who are highly destabilized by opioid addiction must have their addiction stabilized, firstly by medicalizing (instead of criminalizing) access to the drugs they need to prevent withdrawal–which for many is literally unbearable–and then by replacing extraordinarily dangerous street opioids with safe, prescribed opioids. Both of these objectives are of course accomplished by buprenorphine treatment.   

I hope it does not sound presumptuous to assert that the worse a person with OUD is doing in life, the more likely that person is to fail abstinence, and by failing abstinence we mean relapse/return to use, and in 2021, relapse is extraordinarily dangerous.  So it is not surprising that a high-functioning person with OUD, who has a high-paying job, and is well-supported and well regarded and generally doing well, that person is much more likely to succeed in abstinence. That person is also much less likely to present to the ED for the second time today after naloxone rescue from overdose.

I do not accept your comparison of a street opioid dealer to a buprenorphine prescriber. Every minute an opioid-addicted person is therapeutic on bup is a minute they are safe from withdrawal, cravings, and overdose. People who have been stabilized on buprenorphine return to their homes, families, and jobs–they return to health. That is what recovery is. If that person wishes, at some later time, when they have returned to health, to attempt abstinence, I support that, and I have guided some patients in my addiction clinic to that, but that is a path to be undertaken cautiously, as the studies above make quite clear, and is certainly not a path to be entertained in the emergency department. The emergency clinician who encounters a patient with OUD in the emergency department should be entirely focused on getting buprenorphine into that patient as quickly and as reliably as possible, because OUD is so lethal, and every minute an OUD patient has bup in their system, they are safe. Safety first, stabilization second, and then, maybe, later, abstinence, if that's what the patient wants.

Ultimately we disagree on the meaning of recovery, but I think there is room for both views, as long as we agree that abstinence-based recovery is a possibility only after stabilization, and stabilization of OUD out of the emergency department is buprenorphine. 

Thank you, Donald, for your thoughtful reply that obviously comes not only from a wealth of relevant experience on both sides of the prescription pad but also from a clear interest in doing right for people with addiction. 

reuben

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