CATR: Can you tell us about your background?
Dr. Acampora: I used to work as a cardiac anesthesiologist. Later, my interest turned to addiction medicine, and I trained in psychiatry and addiction psychiatry. I currently work in a pain clinic where I helped develop a strategy for managing buprenorphine in the perioperative period.

CATR: Where does the challenge lie in the perioperative management of patients on buprenorphine maintenance?
Dr. Acampora: We had people on buprenorphine maintenance coming for surgery, and the approach had been to taper them off buprenorphine, because the anesthesiologists were concerned that the buprenorphine would block the action of other opioids and therefore interfere with the analgesic protocol. However, as the opioid crisis was rising and more attention was paid to helping people with addictions, we recognized the need to avoid a situation where a person is off the medication and vulnerable to relapse. So, the challenge is in simultaneously addressing pain and risk of relapse.

CATR: The addiction clinician would primarily be concerned about relapse; the anesthesiologist primarily about pain. And the patient would be worried about both.
Dr. Acampora: Exactly. The major idea behind our protocol is realizing that by giving buprenorphine at a lower dose, at a certain time, it does not block the action of additional opioids, and it can produce a synergistic analgesic effect.

CATR: Is this based on a theoretical model, or is there other evidence?
Dr. Acampora: We did a deep literature search and looked for research that addressed this. And buried in the background, there was evidence of the unique properties of buprenorphine. Before we delve into the evidence, it’s worth noting that when buprenorphine was originally designed, scientists were trying to address the historic problem with opioids: Though they were effective for pain, they also had addictive properties. They were trying to split those characteristics apart and get an effective analgesic that wasn’t addicting. In 1976, scientists designed this drug that potentially was going to be used over the counter. They found it was a very potent analgesic at low doses, but there was also a ceiling effect. And even back then, they also saw it as a potential treatment for opioid addiction (Jasinski D, Arch Gen Psychiatr 1978;35(4):501–516).

CATR: For a time, we kept hearing that buprenorphine isn’t good at treating pain. All the while, of course, there was the buprenorphine patch, which is FDA approved for pain. Where do these mixed feelings about buprenorphine as an analgesic come from?
Dr. Acampora: It turns out that the analgesic properties of opioids used to be tested in a laboratory by looking at receptor occupancy. Researchers would study how opioids competed against each other. The stunning thing is that buprenorphine at low doses up to 4 mg is more competitive than fentanyl. But the distortion is in the idea that if something still hurts, then give more. Of course, buprenorphine is a partial agonist, which means there’s a limit to this analgesic effect. In other words, as potent as it is, it has a limited perceived maximum effect.

CATR: Interesting. So, the next thing was for you to look for more data.
Dr. Acampora: Exactly. There was a very good preclinical study showing that low-dose buprenorphine reduced pain when used in combination with full opioid agonists, which is the opposite of what some people feared—that it would block these other opioids. We then looked for clinical evidence, and we found cases around the country and internationally where people were mixing buprenorphine with full agonist opioids. But the real breakthrough was a very elegant set of studies done in the early 2000s by a group led by Mark Greenwald. They did PET scans on people with heroin addiction, and they tagged ­carbon-11 onto carfentanil, which is a hyperpotent opioid. Then they used that carfentanil as the trace to see how many opioid receptors were available. After 4 sets of measurements using these PET data, they came up with a graph that illustrated that you could use a low dose of buprenorphine, up to 2 or 4 mg, that would only occupy 40% of the receptors and leave other receptors available for full opioid agonists (Greenwald M et al, Drug Alcohol Depend 2014;144:1–11).

CATR: PET imaging clearly showed the availability of opioid receptors when low buprenorphine doses were given.
Dr. Acampora: Yes. And that was the breakthrough that allowed us to come up with a scheme that in brief says, “If anyone’s on 8 mg or less of buprenorphine a day, just keep them on the buprenorphine.” The key is splitting the 8 mg daily dose into 4 mg twice a day. And you can keep giving people buprenorphine in the operating room and postoperatively even if you’re giving other opioids. The PET data also showed us that when people were given 16 mg of buprenorphine consistently, 40% of the opioid receptors were available 24 hours after the last dose (Greenwald M et al, Drug Alcohol Depend 2014;144:1–11). So, that countered the theory that you’re getting in the way of good analgesia if you don’t stop the buprenorphine days ahead of surgery.

CATR: Can you tell us more about how you approach buprenorphine dosing before surgery?
Dr. Acampora: Sure. Before we delve into dosing specifics, it’s important to keep in mind that communication is key. The buprenorphine prescriber needs to be involved in the discussion with the surgeon and the anesthesiologist so that there’s a team approach. The surgeon and the anesthesiologist will have more expertise in how much pain there will be, and the addiction provider is going to be the guardian of the patient’s recovery. And for some procedures where only mild perioperative pain is expected, you don’t need to lower the buprenorphine regardless of dose, and the pain can be managed with non-opioid medications.

CATR: What about procedures where more than mild pain is expected?
Dr. Acampora: Based on what I mentioned about dosing, if patients are on 8 mg or less, then they can stay on the same dose. I usually instruct them to take their usual dose on the days leading to the procedure, and then take half that dose on the day of surgery. So, if they’re on 8 mg daily, then they would take 8 mg in the morning till the day before surgery, and they would take 4 mg on the morning of the surgery. The inpatient team then takes over and keeps them on 4 mg twice a day and adds other opioids on top of that as needed. The buprenorphine is transmucosal—either sublingual or buccal—and does not interfere with the need to be NPO before the procedure.

CATR: What about doses greater than 8 mg? Say a patient is scheduled for surgery on Wednesday; how do you approach the dose on prior days?
Dr. Acampora: For doses higher than 8 mg, and up to 16 mg, the patient can take the regular dose on Tuesday, but we recommend splitting the dose on that day. Then on Wednesday the patient takes 4 mg in the morning; thereafter, the inpatient team takes over prescribing and keeps the patient on 4 mg twice a day, with additional opioids as needed. For patients taking doses above 16 mg, they would go down to 8 mg twice a day on Tuesday, and then, similarly, on Wednesday they would take 4 mg in the morning, and then the inpatient team keeps them on 4 mg twice a day, with additional opioids as indicated.

CATR: What happens after that?
Dr. Acampora: We tell patients: “While you’re in a controlled environment, we will focus on the pain. And then as soon as it looks like you’re going home, we are going to put the emphasis back on relapse prevention.” Postoperatively, we gradually raise the buprenorphine dose back to where it was. For example, you have someone undergoing hip surgery on Wednesday. Then on Thursday and Friday the patient is getting both the buprenorphine and the regular opioid. But then you can start gradually lowering the dose of the full agonist as you go up on the buprenorphine. Sometimes, patients go to physical rehab instead of going home, and I’ve had cases where they are still getting both the buprenorphine and the opioid in rehab. But as each day goes by postop, they should be getting less and less of the full opioid agonist and head back toward their original dose of buprenorphine. Of course, you also want to arrange for them to see their buprenorphine prescriber soon after their discharge home.

CATR: What about people on the injectable or implant buprenorphine formulations? The implant is equivalent to 8 mg or less, so I suspect that shouldn’t be much of a problem. But what about the injectable, which can be the equivalent of 16–32 mg depending on the dose?
Dr. Acampora: Yes, the implant should be less of a problem, but both formulations are new, and we need to learn more about them. And, especially with the injectable formulation, it may be better to switch to transmucosal buprenorphine before scheduled procedures.

CATR: We also run into situations where a patient is on oral or extended release naltrexone. How would you approach naltrexone dosing before elective surgery?
Dr. Acampora: For oral naltrexone, the patient would take the full dose up to 2 days before, take half the dose the day before, and skip the dose on the day of the procedure. In the case of the injectable, we try to coordinate that the last dose is given 3–4 weeks before surgery. Then, after the procedure, naltrexone can be reintroduced carefully at low doses several days after the last dose of opioid analgesics—optimally with input from an addiction specialist.

CATR: And how would you approach methadone dosing perioperatively?
Dr. Acampora: With methadone, for doses above 60 mg, we instruct the patient to skip the dose on the day of the procedure, and we give 20 mg preoperatively, then 3 times per day after surgery. We always confirm the dose and coordinate this plan with the methadone clinic. Our institution has set the typical maximum daily dose at 60 mg, but we have given some people 80 mg a day because they were on a higher dose preoperatively. Just like with buprenorphine, the key for analgesia is splitting the methadone dose. And other opioids can be added by the treatment team.

CATR: We’ve spoken about elective surgery, but what happens if a patient is on one of these medications and needs emergency surgery?
Dr. Acampora: The operating room is a controlled environment. The anesthesiologist can overwhelm any opioid agonist or antagonist, and control breathing and vital signs. The urgent care team knows what to do.

CATR: Any additional advice for the busy clinician?
Dr. Acampora: I urge clinicians to be open minded and realize that we need to give the patient safety from relapse in addition to comfort and good analgesia. We can achieve this with the right communication between the different providers and by using a team approach that puts the patient at the center.

CATR: Thank you for your time, Dr. Acampora.

Editor’s note: For a much more in-depth review of the use of buprenorphine along with opioids, please keep a lookout for Dr. Acampora’s upcoming article in the Journal of Clinical Psychiatry.