Post-op Pain on Suboxone

I often receive emails from patients on buprenorphine (or Suboxone) who are preparing for surgery or other painful medical procedures. Ideally in such cases, the surgeon would have a discussion with the person prescribing buprenorphine, in order to coordinate the plan for treating postoperative pain. In practice such discussions don’t seem to take place, leaving patients to scramble for effective pain control after surgery– when it is too late to take the steps necessary for a smooth perioperative course.
I am familiar with an NIH article that describes pain control in people who take buprenorphine. I’ve also prepared a handbook that describes the issues that must be considered in such patients; the handbook can be found easily-enough by searching for the User’s Guide to Suboxone.
Even with those descriptions ‘out there,’ I’ll get requests for a short, ‘just-the-facts’ note that patients can give to their surgeons. I realize that unfortunately, the average surgeon will not sit down for an in-depth discussion of post-op pain control, so I have prepared a few paragraphs that lay out the issues. People on buprenorphine who are having surgery are welcome to copy the paragraphs below and give them to their surgeons, in order to facilitate discussion.
Surgery in Patients on Buprenorphine
Buprenorphine is a partial opioid agonist that is used for several indications. In low doses—less than 1 mg—buprenorphine is used to treat pain (e.g. Butrans transdermal buprenorphine). In higher doses i.e. 4 – 24 mg per day, buprenorphine is used as a long-term treatment for opioid dependence and less often for pain management. At those doses, Buprenorphine has a unique ‘ceiling effect’ that reduces cravings and prevents dose escalation. Patients taking higher dose of buprenorphine, trade name Suboxone or Subutex, become tolerant to the effects of opioids, and require special consideration during surgical procedures or when treated for painful medical conditions.
There are two hurdles to providing effective analgesia for patients taking buprenorphine: 1. the high opioid tolerance of these individuals, and 2. The opioid-blocking actions of buprenorphine. The first can be overcome by using a sufficient dose of opioid agonist, on the order of 60 mg per day of oxycodone equivalents or more. The second can be handled by either stopping the buprenorphine a couple weeks before agonists are required—something that most patients on the medication find very difficult to do—or by reducing the dose of buprenorphine to 4-8 mg per day, starting the day before surgery and continuing post-operatively. Given the long half-life of buprenorphine, it is difficult to know exactly how much remains in the body after ‘holding’ the medication. That fact, along with the difficulty patients have in stopping the medication, leads some physicians to use the latter approach- i.e. to continue 4 mg of buprenorphine per day throughout the postoperative period. People taking 4-8 mg of daily buprenorphine report that opioid agonists relieve pain if taken in sufficient dosage, but the subjective experience is different, in that there is no feeling of euphoria.
Quick Notes:
Patients taking maintenance doses of buprenorphine do NOT receive surgical analgesia from the medication, as they are completely tolerant to the mu-opioid effects of buprenorphine after the first week or so on the medication.
Discontinuation of high dose buprenorphine or Suboxone treatment results in significant opioid withdrawal symptoms within 24-48 hours.
Normal amounts of opioid pain medication are NOT sufficient for treating pain in people on buprenorphine maintenance.
Opioid agonists will NOT cause withdrawal in people on buprenorphine. Initiating buprenorphine WILL cause withdrawal in someone who is tolerant to opioid agonists, unless the person is in physical withdrawal before initiating buprenorphine.
Non-narcotic pain relievers CAN and should be used for pain whenever possible in people on buprenorphine to reduce need for opioids.

Hydrocodone (Vicodin) Addiction and Buprenorphine

I recently accepted a young man as a patient who was addicted to hydrocodone (the opioid in Vicodin), prompting a discussion about treatment options for someone who hasn’t been using very long, and who hasn’t pushed his tolerance all that high. Perhaps it will be informative to share my thought process when recommending or planning treatment in such cases. In part one I’ll provide some background, and in a couple days I’ll follow up with a few more thoughts on the topic.
Most people who have struggled with opioids learn to pay attention to their tolerance level—i.e. the amount of opioid that must be taken each day to avoid withdrawal or to cause euphoria (the latter about 30% more than the former). For someone addicted to opioids, the goal is to have a tolerance of ‘zero’—meaning that there is no withdrawal, even if the person takes nothing. That zero tolerance level serves as a goal, making having a high tolerance a bad thing, and pushing tolerance lower a good thing.
Tolerance is sometimes used as part of the equation when determining the severity of one’s addiction. But looking at tolerance alone can be misleading. Tolerance is a consequence of heavy use of opioids, and also a cause of heavy use of opioids. Tolerance usually goes up over time, so having a high tolerance probably correlates with length of addiction in some—- but not all— cases. Tolerance is also strongly related to drug availability. A person with a severe addiction, who only has access to codeine, will likely have a lower tolerance than a person with a more mild addiction, who has free access to fentanyl, oxycodone, and heroin.
I think it is more appropriate to measure the ‘severity of addiction’ by the degree of mental obsession that the patient has for opioids. Tolerance is one piece of information in determining that obsession, but tolerance alone can be misleading.
To get a sense of the obsession for opioids, I look at many factors. Has the person committed crimes to obtain the substance? Violent crimes? What has the person given up for his addiction? Has he been through treatment? How many times? How long did he stay clean after treatment? Have his parents or spouse thrown him out of the house, and if so, does he still use? Did he choose opioids over his career? Over his kids?
Answers to these questions provide a broad understanding about the addicted person’s relationship with the substance—an understanding that is necessary when considering the likely success or failure of one treatment or another. It is also important to consider the person’s place in the addictive cycle—i.e. early, likely in denial, cocky, with limited insight– or late, after many losses, more desperate—and perhaps more accepting of treatment.
I am a fan of buprenorphine as a long-term treatment for opioid dependence, as readers of this column know. I consider opioid dependence to be a chronic, potentially-fatal illness that deserves chronic, life-sustaining treatment— and buprenorphine, in my experience, is a very effective treatment in motivated patients. But tolerance becomes a factor, when considering buprenorphine for THIS patient.
Buprenorphine has a ‘cap’ or ‘ceiling effect’ that allows the medication to trick the brain out of craving opioids. In short, as the blood or brain concentration of buprenorphine drops between doses, the opioid effect remains constant, as long as the concentration is above the ceiling level. In order to achieve the anti-craving effects of buprenorphine, the dose must be high enough to create ‘ceiling level’ effects. If buprenorphine is prescribed in lower amounts—say microgram doses— the effect is identical to the effects of an agonist, since the dose/response curve is linear at lower levels.
Buprenorphine is a very potent opioid, and the effects of the medication are quite strong at the ceiling level. Comparisons to other opioids will vary in different individuals, but in general, a person on an appropriate dosage of buprenorphine develops a tolerance equivalent to that of a person taking 40 mg of methadone per day, or approximately 60-100 mg of oxycodone per day.
A person taking even a dozen Vicodin per day has a much lower tolerance to opioids. Such a person who starts buprenorphine treatment will obtain a very significant opioid effect from the drug— unless the dose of buprenorphine is raised very slowly over a number of days. And in that case, the person’s tolerance level would be pushed much higher.
So if our current patient starts buprenorphine, he will have a much higher opioid tolerance if/when the buprenorphine is eventually discontinued. I receive emails now and then from patients who are angry at their doctor for starting buprenorphine, feeling trapped by the considerable threat of withdrawal from stopping the drug. But at the same time, taking hydrocodone and acetaminophen in high amounts creates the risk of liver damage from the acetaminophen, as well as the considerable risks from opioid dependence.
And so the dilemma. Should buprenorphine be considered in such a case?

Uncoupling of analgesia, tolerance, and euphoria from mu-agonists using buprenorphine

I presented this topic at the Atlanta meeting of ASAM a couple weeks ago. There are too many slides, but the historical stuff was just too fascinating to leave out. I wanted to demonstrate, by lining it up on the side, how time has compressed the most critical discoveries to a very short period of time. In other words, it wasn’t until thousands of years of opium use that the general concept of endorphines and opioid receptors came along. We can only hope that similar understandings of the biological basis of tolerance and withdrawal will be comparatively soon.
My study shows something truly fascinating– that a partial agonist seems to anchor tolerance at a lower level, still allowing for potent analgesia, but preventing euphoria and dose escalation. I have used this combination in people with very major surgeries, that are known to be quite painful– i.e. knee and hip replacements, dental surgeries, gallbladder surgery, and median sternotomy.

The REAL Future of Partial Agonist Treatment— Pharma are you Listening?

I just wrote a note to a friend who works in the molecular sciences– she has been studying opioid receptors since the early 1980’s, when things were just getting started on a molecular level. I’m keeping her name to myself, but I’ll share a few thoughts about what is needed to advance the treatement of opioid dependence– and make a few million dollars along the way (are you listening, RB?)
Hi ——,
(private chit chat that would bore everyone)
Anyway, today I realized what is needed in order to take partial agonist treatment of opioid dependence to the next level.
The problem with buprenorphine is that the ‘ceiling effect’ occurs at a relatively high tolerance level, approximately equal to 40 mg of methadone. That causes at least two problems. First, going off Suboxone is a lot of work, as the person still has a great deal of withdrawal to go through. That may be a good thing early in the process, as it may help keep people on Suboxone, but after a year or so, when people want to try going off the medication, it is a major barrier that opens the floodgates to those old memories of using, etched in the emotions associated with withdrawal.
The second problem with the high ceiling/tolerance level is that surgery is a hassle. People needing surgery need HIGH amounts of oxycodone to get any analgesia—I usually give 15-30 mg every 4 hours. Pharmacists shudder to release those doses, and some surgeons and anesthesiologists balk.
The horizontal part of the dose/response curve is the essential part of buprenorphine; that is what tricks the brain into ‘thinking’ that nothing is wearing off, and in that way eliminating cravings. But that flat dose/response relationship could occur at lower tolerance levels and still work the same way.
Since I’m wishing for the moon, a series of molecules with progressively lower ceiling levels would be ideal, with the last molecule in the series being Naltrexone. Although actually, naltrexone doesn’t work—it has NO mu agonism, so there is no tricking of the brain, and no reduction of cravings. We would want something close to naltrexone, but with a tiny bit of opioid activity that does not vary with dose.
A shorter half-life would also be helpful. Preparing for surgery requires weeks to get the buprenorphine out of the system. Of course a shorter half-life means it is easier to get around buprenorphine by people who want to play with agonists, so again, these new molecules would be intended as ‘step down’ meds from early-stage buprenorphine treatment.
Do we know enough about molecular actions at the mu receptor to design molecules with these properties? Or are we still at the point of making somewhat random changes and assaying the result? Do you know of any labs doing this type of work?
I figured you’re the person to ask!
Thanks ——–
Jeff

Buprenorphine for low-dose opioid use

A reader wrote with a question that I don’t think I’ve addressed on the blog.

Do you have a threshold for how much narcotic a patient must be using before you will put them on buprenorphine? I am concerned about narcotic addicts that are using 6-10 Vicodin (hydrocodone) a day for example. Many have very mild withdrawal symptoms, but are never-the-less unable to stop on their own.
This is an insightful question that provokes enough discussion to fill at least one blog post. I don’t have a simple answer, other than to go on a case-by-case basis and try to determine who, if anyone, might be able to walk away from opioids completely (i.e. a person who I would be less likely to put on buprenorphine, as doing so would drive tolerance higher) vs. those who will need maintenance treatment eventually, even if their doses are not yet very high.

Patients have a right to know if they are having their tolerance increased in my opinion, given the misery involved in bringing tolerance down. It is also important to tell people with lower tolerances that they are going to get a buzz from buprenorphine for a few days because of the potency of buprenorphine. This opiate stimulation is likely to occur even with a very small piece of a Suboxone tablet; a quarter tab or 2 mg of buprenorphine has almost the same potency as 16 mg because of the ‘ceiling effect.’ The potent opioid effect may make the doctor liable for a car accident, or could even lead to overdose if the patient combines buprenorphine with other respiratory depressants.

In general, the ‘break even’ point on the tolerance scale is 80-100 mg of hydrocodone or about 60 mg of oxycodone per day. In other words, if the person is taking 8-10 of the larger-strength Vicodin per day, I would consider Suboxone to be of about equal potency.

In considering whether a person’s use and tolerance are high enough to call for buprenorphine, some people focus too much on the initial potency relationships, and forget that opioid dependence is almost always a long-term condition. I’m not sure by your last sentence whether you realize or not that the presence or absence of bad withdrawal is a red herring for acheiving sobriety from opioids. Many addicts mistakenly think that withdrawal is the primary force that keeps them actively addicted. In late addiction they find that desperation helps them get through withdrawal over and over, but they continue to relapse– as soon as they feel well!

From a scientific perspective, I have not seen evidence of a correlation between the severity of addiction and the addict’s tolerance level (if anyone has seen such a study, please forward me the reference). At the same time, I don’t think I would feel comfortable starting buprenorphine in a person taking a couple Tylenol 3’s per day. Luckily (?), this type of situation has been rare in my experience. I should do chart reviews and publish the exact numbers, but out of the 500 or so people presenting with opioid dependence over the past 5 years, I would guess that the average tolerance level is approx. 120-150 mg of daily methadone (range of 30-400 mg per day), or approx. 160 mg of oxycodone per day (range of 40-700 mg of oxycodone per day). Yes, I had two people—interestingly, both women– come in at those upper daily doses of methadone and oxycodone. The methadone patient had been labeled a ‘fast metabolizer’ of methadone as reason for the ridiculously high dosage. The reason seemed good enough, until I found, when converting her to other agonists for pain, that her tolerance was ultra-high to ALL opioid agonists—telling me that she was not metabolizing the methadone fast enough to prevent her body’s response to the high dosage, and calling the entire ‘fast metabolizer’ issue into question. The woman taking the large amount of oxycodone had inherited a tidy sum of money; hundreds of thousands of dollars, all gone after one year of using.

Ouch.