Opioid Analgesia Without Addiction

I don’t have pull with the addiction-related organizations out there.  I’m never been a joiner, and I tend to notice the problems caused by medical societies over the good things that they supposedly accomplish.    For example PROP, or ‘Physicians for Responsible Opioid Prescribing’, have a specific mission.  Once a group has a mission, any considerations about individual patients go out the window.  PROP has propagated the message that opioids are NEVER beneficial for patients with chronic pain.

Legislators with no knowledge of clinical medicine hear that message, and respond by passing draconian laws that interfere with any considerations of individual patients.  I would guess that the people of PROP pat themselves on the back for encouraging laws that remove physician autonomy.  I’m sure they figure that they are smarter than all the family practice docs out there.  But in reality, they are only destroying the control of doctors over patient care, and handing that care over to politicians.  Way to go, PROP.

In the same way, the societies that hold meetings about meetings, that elect Secretaries who become Vice Presidents who become Presidents, get to publish the articles that describe clinical protocols.  The doc who spends every day talking with patients has no access to these sources, and little ability to influence those protocols.  Sometimes the societies and organizations get things right… and sometimes they get things wrong.  The latter is the case with post-op pain control in patients on buprenorphine products.

I’ve written about this before, as regular readers know.  Over the past 8 years I’ve had dozens, if not hundreds, of patients on buprenorphine undergo surgery.  The surgeries include coronary bypass, thoracotomy, rotator cuff repair, C-section, nephrectomy, total knee or hip replacement… and a host of minor surgeries with scopes and lasers.  I’ve treated these patients in a number of ways, in part because hospitals that provide emergency care have different ways of dealing with post-op analgesia.  I rarely have control over what they do acutely– but I almost-always take over pain control when patients are discharged.

In the past few months there have been several ‘articles’ stating that the best way to handle surgery, in people on buprenorphine products, is to stop the buprenorphine before surgery, and treat pain using opioid agonists.  This opinion is not supported by any data.  It is someone’s opinion– usually someone who has a title, i.e. someone who spends at least some of his/her time in society meetings.  That time is removed from the amount of time that could be spent treating and speaking with patients.  Frankly, the ‘higher’ a doctor is in society circles, the less time they spend in patient care.  That comment will anger the docs who it applies to.  I can hear them now– saying I’m only full of ‘sour grapes’. But maybe those same docs should look in the mirror, and wonder how they ended up as ‘President’ of a society.

I’ve used the approach claimed as best practice in the society journals– i.e stopping buprenorphine before surgery– and the same thing always happens.  Tolerance to opioid agonists rises very rapidly in the post-op period.  Patients are discharged on huge doses of opioid agonists.  And at some point, agonists must be discontinued for 24 hours to allow for re-induction with buprenorphine agents.  I’ve had several recent patients go through this exact process– and my frustration motivates this post.  One guy shot himself in the femur, and the bullet also passed through his lower leg.  He needed fasciotomy to avoid losing the leg. His Suboxone was discontinued at admission, and ten days later he was discharged on 30 mg of oxycodone every 2-3 hours– i.e. over 200 mg per day.  The other person was in a serious car accident, and had multiple fractures—  femur, pelvis, ribs, wrist– as well as internal injuries.  After 3 weeks he was released on over 300 mg of oxycodone per day!

On the other hand, I’ve had many patients go through the surgeries listed earlier while maintained on buprenorphine, 4-8 mg per day.  In ALL cases, they had excellent analgesia with lower doses of oxycodone than in the people who stopped buprenorphine.  Most patients did well on 15 mg of oxycodone every 3-4 hours– a max of 120 mg of oxycodone per day.  In a few cases– i.e. in the most painful operations, in the most sensitive patients– I had to use 30 mg of oxycodone every 4 hours.

The most amazing thing about the combination of buprenorphine and opioid agonists is the absence of tolerance to agonists, when buprenorphine is present.  I’ve had patients with recurrent injuries that required repeated surgeries, including a woman who tore her rotator cuff and the surgical repair THREE times over three months.  She took the same amount of opioid agonist for three months, with no noticeable decrease in efficacy.  After the final operation, after three months on significant amounts of opioid agonist, she simply stopped the agonist and resumed her full dose (16 mg) of buprenorphine.  She had no withdrawal, and not other complications.  She simply stopped the agonist and resumed buprenorphine treatment.

I’ve come to realize that buprenorphine effectively ‘anchors’ tolerance when patients take opioid agonists, as long as the buprenorphine is continued.  Patients always say the same thing:  that the pain was reduced by the agonist, but that it didn’t ‘feel’ like the agonist they used to take.  In fact, patients who could never control pain pills found that they COULD control agonists if they stayed on buprenorphine.

A couple years ago I presented these findings at an annual meeting of ASAM.  The slides can be found here.  I believe that some day, combinations of buprenorphine and opioid agonists will be the standard approach to pain treatment.  The combination allows for opioid analgesia without tolerance, without euphoria, and with little or no risk of addiction.  If THAT doesn’t piqué your interest, you have no business reading about opioid dependence!

I picture combinations of buprenorphine and fentanyl… especially since both are now FDA-approved as transdermal patches.  Or perhaps a combination of fentanyl lozenges and sublingual buprenorphine.  The possibilities are endless.  Throughout history, the miracle of opioid analgesia has been cursed by the attachment to tolerance, dependence, and addiction.

Imagine if that curse was lifted from opioid analgesia.    Can you even dare to imagine that world?  I’m telling you… it is closer than you think—- and there for the taking.

Broken Bones on Suboxone; Need Pain Relief

Originally Posted 1/11/2014
I received the following email from a Suboxone patient (from another practice) after he experienced a painful injury.  He shared what happened at the hospital when he was trying to get relief from pain, while taking Suboxone (the active component is buprenorphine).
Hey there.  Just to let you know, i was on 24 mg of Suboxone when I jumped off a fence and crushed bones in both feet.  The injury was among the most painful things I have gone through in my life.  At the hospital they did not understand Suboxone even though I tried to explain to them how it worked.  They couldn’t get a painkiller to break through and I was nearly passing out from the pain.  They finally used Ketamine and it worked immediately.  However, they only used it 3 times and its effect don’t last more than about 20 minutes in my case.  Then they switched to IV Fentanyl….I’m not sure of the dose but I know it was high and after a few injections they hooked me up to a drip bag.  Just wanted to share this info in case anyone finds themselves in a situation like mine where I was ready to strangle a doctor because they tried all of the regular oxycodone, hydromorphone, morphine, etc. all the while I was almost (or maybe even) in a state of shock from the pain.
Hope this can help someone out in the future.
I wrote back the following message, with a few minor changes:
Thank you for sharing your story.  As you may know, I was an anesthesiologist for ten years before developing my own addiction to pain medications.  I have been in the position, many times, of treating pain in patients after surgeries or accidental injuries.  Pain relief is possible in every case, if a competent doctor takes the time and effort to control the pain.  There are arguments within the field of medicine over the use of narcotics for chronic pain, but those arguments do not extend to acute pain.  There are no reasons a person should be allowed to suffer from pain in a US hospital—beyond incompetence or failure of the system.
Buprenorphine complicates pain treatment in two ways; by blocking mu receptors and by contributing to a higher opioid tolerance. Opioid agonists (pain medications) compete with buprenorphine for binding at mu opioid receptors.  Larger doses of buprenorphine cause greater blockade of mu receptors, requiring larger amounts of agonist to treat pain.  When I read your description of the different things tried, my impression was that your pain control was delayed by your doctors trying too many things, instead of sticking with one thing until it worked.
Some opioids (notably morphine) trigger histamine release, which causes hives, lowers blood pressure, and limits the dose that can be given in a short amount of time.  Large doses of high-potency opioids like fentanyl or sufentanil cause muscles to tighten, and in rare cases cause rigidity of the chest that interferes with breathing.  But that side effect is rare, and not a major concern in modern acute care facilities.
For the most part, oxycodone (oral) or hydromorphone or fentanyl (IV) could be given in almost infinite amounts, and at some dose either medication will provide pain relief.  Doctors should remember their training from medical school, when they learned to focus on the patient rather than the numbers.  In your case, nasal oxygen and pulse oximetry should have been applied, and attention directed to your respiratory rate. Oxycodone (oral) or hydromorphone (IV) should have been titrated upward until your respiratory rate was 12-14 breaths per minute.  At that point you would have been relatively comfortable.
Anesthesiologists regularly use respiratory rate to determine whether additional narcotics are indicated in patients near the end of surgery.  The dose of hydromorphone (Dilaudid) necessary in your case may have been high, but respiratory rate decreases gradually as opioid effect increases and pain is relieved, allowing for safe use of virtually any amount of narcotic. The term for this type of care is ‘titrating to effect.’ With appropriate monitoring (present in every ER, OR, recovery room, or ICU), titrating in this way is very effective.  Some hospitals place limits on intravenous opioid doses on general med/surg units, but there are no such limits in units with 1:1 nursing, oxygen, and pulse-oximetry.
There were other ways to provide pain relief, depending on whether you were the hospital CEO, a major donor, or a guy labelled a ‘drug addict.’  They could have placed an epidural and run local anesthetic at a dose low-enough to allow you to walk with assistance while greatly reducing your pain.  Or they could have used a higher dose of anesthetic that provided complete pain relief.  Higher doses of anesthetic cause temporary muscle weakness that may have kept you from walking, but you probably weren’t walking anyway, given the injuries you described.
Readers are invited to use the ‘share’ button to create a print-friendly version, and to place a copy in your wallet—in case you ever find yourself in a buprenorphine knowledge-free zone!

Taking Buprenorphine, Having Surgery

Originally Posted 8/12/2013
I will get to ‘Part II’, but today I talked with a patient about something that happens too often, that deserves to be pointed out.  The person was in the ER with an injury that resulted in tib/fib francture.  The ER doc provided no analgesia, in the ER or at discharge, telling the patient “you would get sick if I gave you pain medicine because you are on Suboxone.”
I have a few paragraphs typed up that I send to dentists, surgeons, and other physicians when a patient on buprenorphine has a painful procedure.  I am pasting it below so that it can be copied, printed, and given to physicians to encourage them to do a bit of continuing medical education on the topic.  Those of you who are already enlightened, please leave comments if you see something that you would change.   I have literature to back up this type of approach;  send me an email if you’d like the reference.
Painful Procedures and Buprenorphine Patients
Buprenorphine is a partial opioid agonist that is used for several indications.  In low doses—less than 1 mg/day—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 higher 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 or impossible to do—or by reducing the dose of buprenorphine to 4-8 mg per day, starting the day before surgery and continuing through the post-op period.  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 (including myself) 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 say that opioid agonists relieve pain if taken in sufficient dosage, but the subjective experience is different, in that there is less ‘euphoria.’
Important points:
Patients on daily maintenance doses of buprenorphine do NOT receive surgical analgesia from buprenorphine alone, as they are tolerant to the mu-opioid effects of buprenorphine.
The naloxone in Suboxone does not reach the bloodstream in significant amounts, and has no relevance to the issue of post-operative pain and Suboxone/buprenorphine.
Discontinuation of high dose buprenorphine/Suboxone results in opioid withdrawal symptoms within 24-48 hours, similar to the discontinuation of methadone 40 mg/day.
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 taking buprenorphine.  Initiating buprenorphine WILL precipitate withdrawal in someone tolerant to opioid agonists, unless the person is in opioid 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. Note that Ultram has opioid and non-opioid effects; the opioid effects are blocked by buprenorphine.
I have had success in people taking 4 mg of buprenorphine/day, using oxycodone, 15-30 mg every 4 hours.  Some patients can control their own intake of oxycodone while on buprenorphine, but some patients CAN’T.  Overdose IS possible, if patients take excessive amounts of the opioid agonist. Consider providing multiple prescriptions with ‘fill after’ dates, each for a very short period of time (e.g. 2 days each) to that patients do not have access to large amounts of opioids at one time.
For longer post-operative periods I have used combinations of long and short-duration agonists, e.g. Oxycontin 20 mg BID plus oxycodone, 15 mg q4 hours PRN.
The risk of death is significant for opioid addicts not on buprenorphine.  Buprenorphine/Suboxone has opioid-blocking effects that reduce risk of overdose and death.  Asking a person to stop or ‘hold’ their Suboxone is introducing significant risk of injury.  Opioid addicts are NOT generally able to stop Suboxone without replacing it with illicit opioids.
J Junig MD PhD