Perioperative Management of a Patient Taking Suboxone® at the Time of Ambulatory Surgery

In 2016, more than 11 million people reported misuse of opioids in the previous year. In an effort to combat opioid use disorder (OUD), the use of agonist/antagonist is becoming increasingly common, with more than 2.2 million patients reporting use of a buprenorphine containing medication such as Suboxone®. Buprenorphine is a unique opioid which acts as a partial μ agonist and ĸ antagonist. These properties make it an effective tool in treating OUD and abuse. However, despite its advantages in treating OUD and abuse, buprenorphine can make it difficult to control acute perioperative pain. We present a case in which the Mayo Clinic Arizona protocol for patients undergoing minimally invasive ambulatory surgery while taking Suboxone® is successfully executed, resulting in adequate postoperative pain control and timely discharge from the postanesthesia recovery unit.


Introduction
Buprenorphine is an opioid that acts as a partial agonist at the μ-opioid receptor and weak agonist at the ĸ-opioid receptor. It binds the receptor with high affinity with only partial agonism of the receptor, which prevents other opioids with full agonist properties from activating it. Each type of opioid receptor has different effects, so selective opioid receptor agonists have the advantage of avoiding some of the untoward effects caused by full opioid agonists (Table 1). When combined with naloxone, which is a mu antagonist that has poor oral absorption and undergoes extensive first pass hepatic metabolism, buprenorphine is a useful tool in discouraging opioid abuse [1]. If Suboxone ® is melted and injected intravenously, the naloxone component will completely block the μ-opioid receptor for a time.
In 2016, the prevalence of prescription and heroin abuse was estimated at 17 million people worldwide, resulting in more than 33,000 deaths in the United States alone. is equates to, on average, 130 deaths every day in the United States [2]. In an effort to combat these addictions, the use of agonist/antagonist medications (e.g., buprenorphine/naloxone) is becoming increasingly common with more than 2.2 million patients reporting use of a buprenorphine containing medication such as Suboxone ® [3].
Buprenorphine is a useful tool in the fight against opioid addiction and abuse. However, due to its unique pharmacodynamics properties, it presents a unique challenge to anesthesiologists trying to treat acute pain in the perioperative setting [4,5]. Although there is no consensus regarding optimal perioperative management of patients taking these medications, most strategies include a multimodal pain control approach with recommendations ranging from continuing buprenorphine and supplementing with full opioid agonists as necessary, to discontinuing buprenorphine preoperatively in exchange for full opioid agonists [6,7]. Utilizing a multimodal approach to pain control allows for blockade of pain transmission at multiple sites along the nervous system as well as blockade of a variety of pain receptors with less dangerous side effects (Figure 1 and 2). Multiple case reports illustrate the unpredictability of pain control in these patients despite utilizing these strategies [8][9][10].
At the Mayo Clinic in Arizona, one of three strategies is typically employed ( Table 2). e first strategy is to continue the patient's normal buprenorphine dose and employ a multimodal approach for acute perioperative pain control.
is strategy is typically employed in elective, outpatient procedures. e second approach is to begin a slow wean of buprenorphine 1-2 weeks prior to the surgery with a goal to transition to a short acting, full opioid agonist (hydrocodone, oxycodone, etc.) 72 hours preoperatively. is strategy is recommended in the case of an elective procedure with planned postoperative admission. In the event that a patient presents for an urgent/emergent case while still taking buprenorphine, an immediate cessation of all forms of buprenorphine is recommended while starting a high dose, opioid based, patient controlled analgesia infusion which can be de-escalated as the buprenorphine wears off, which may take 72 hours or longer [11].
We present a case of an otherwise healthy patient presenting for a routine ambulatory surgery while taking an opioid agonist/antagonist preoperatively.

Case Presentation
A 37-year-old female (ASA II, 161 cm, 62 kg) with a 10-year history of chronic pelvic and abdominal pain on daily Suboxone ® 2.9 mg (buprenorphine 2.9 mg/naloxone 0.71 mg) PO, prescribed to help treat her chronic pain, presents for a  laparoscopic inguinal hernia repair under general anesthesia. Her medical history is significant for depression for which she takes Prozac. Her chronic abdominal pain began shortly after undergoing a total abdominal hysterectomy approximately 10 years previously. Since the time of the hysterectomy, she had undergone three open left inguinal hernia repairs. Additionally, she had undergone a right inguinal hernia repair, a salpingo-oophorectomy, a laparoscopic cholecystectomy, 6 laparoscopic surgeries for lysis of adhesions, and 2 cesarean sections. She was seen by multiple pain specialists who performed procedures including trigger point injections, nerve blocks, and radio frequency ablations-all of which offered some degree of transient pain relief. Pharmacologic therapies trialed to help manage her pain included ibuprofen, acetaminophen, duloxetine, gabapentin, muscle relaxants, oxycodone, and Suboxone ® (buprenorphine/naloxone). While taking the Suboxone ® , her pain varied from 4/10 to 6/10 on a numerical rating score. She has a remote, 2.5 pack-year smoking history. e patient's only allergy was to morphine which caused itching and fatigue. Preoperative physical exam was unremarkable aside from diffuse tenderness to palpation of her abdomen with her worst pain in the left lower quadrant. She rated her pain as 4/10 preoperatively.
Preoperatively, she received acetaminophen 1 gram PO, celecoxib 200 mg PO, gabapentin 300 mg PO, and dexamethasone 4 mg IV. She was given fentanyl 100 mcg IV and midazolam 2 mg IV in addition to lidocaine 100 mg IV, propofol 200 mg IV, and rocuronium 50 mg IV for induction. Her airway was secured with an endotracheal tube after an uneventful induction. Sevoflurane and dexmedetomidine infusion at a rate of 0.4-0.5 mcg/kg/hr were utilized for maintenance of general anesthesia. Intraoperative analgesics included ketamine 40 mg IV, fentanyl 200 mcg IV, and hydromorphone 0.6 mg IV during the 2-hour case. e surgeon infiltrated the surgical site with local anesthetic (0.25% bupivacaine mixed with liposomal bupivacaine) at the conclusion of the procedure. Her intraoperative course was unremarkable, and at the conclusion of the surgery she was extubated and taken to the postanesthesia care unit (PACU) with stable vital signs. e patient arrived in the PACU at approximately 9: 25 am and spent 3.5 hours there. During this time, she received fentanyl 100 mcg IV given in four 25 mcg boluses 15 minutes apart, Toradol 30 mg IV, and Tylenol 1 gram PO. All of these analgesics were given during the third hour of her PACU stay. She reported a pain score of 5/10 at the time of discharge which she was comfortable with.

Discussion
Evaluating whether a patient is a reasonable candidate to continue their agonist/antagonist medication perioperatively should be based on both patient specific and surgical factors. Continuing perioperative buprenorphine is a strategy that should be considered for surgeries that are not associated with significant postoperative pain. While it is reasonable to expect adequate analgesia with a multimodal approach, patients should be counseled beforehand not to anticipate a pain-free perioperative experience. Many patients taking agonist/antagonist opioids can benefit from continuing these medications perioperatively but, in particular, those being treated for OUD are at a high risk for relapse if buprenorphine is discontinued [12,13].
Developing a strategy for perioperative pain control requires a pre-emptive, multimodal approach. Peripheral nerve blocks or neuraxial anesthetic techniques should be utilized whenever possible. Where these techniques are not  Case Reports in Anesthesiology possible, surgeons should infiltrate the incision with long acting local anesthetic. Higher than normal amounts of opioids will be required due to the antagonistic properties of these oral medications, and anesthesiologists should dose opioids appropriately in these patients. While pure opioid agonists are less effective in the setting of concurrent oral agonist/antagonist medications usage, they can still provide analgesia and should be used.

Conclusion
In our experience, it is reasonable and safe for select patients taking combined agonist/antagonist opioids to undergo ambulatory surgery without bridging to short acting pure opioid agonists. Evaluation to determine whether a patient is a candidate for this strategy should include multiple factors. ese factors include type of surgery, dose of buprenorphine, reason for agonist/antagonist therapy (OUD treatment vs. chronic pain treatment), and access to postoperative care from pain specialists. Perhaps the most important of these factors is the original reason for treatment: chronic pain vs OUD. Strong consideration should be given to continuing perioperative buprenorphine in patients taking the medication for treatment of OUD due to the high rate of relapse that occurs when changing to a full opioid agonist in this population. Anesthesiologists, surgeons, and addiction medicine specialists should work closely to develop a multimodal approach specific to the patient in order to control acute postsurgical pain and decrease the likelihood of OUD relapse.

Conflicts of Interest
e authors declare that they have no conflicts of interest.