T. Sikkenga, Pharm.D.
Patients who are under treatment for opioid (or any type of) addiction can be tough to manage as inpatients. This is especially true when patients with a history of opioid addiction are in significant pain for reasons where opioids are likely the best treatment. It is certainly a discussion to be had with your patient. But what if they have been intubated and no one knows their wishes in regard to receiving opioids?
Here I present the case of a patient who is on methadone for heroin addiction. He has been going to the methadone clinic for the past eight years. He presents to our hospital where he is admitted, intubated emergently, and started on a fentanyl drip.
What would you do if this were your patient? If it was your friend, child, or family member you’ve watched struggle with their addiction? What if it were YOU?
I chose this case for several reasons. It presents a potential controversy, puts into question patient dignity and/or morality, and offers insight on the idea of weaning fentanyl with methadone. I am a relatively new pharmacist, both in my career and at the institution I now work, and just recently got my feet wet into the critical care world. As I saw the order to DC methadone and start a fentanyl drip, I instantly called the physician. I was certain this would be an easy cancel, but the physician was adamant despite expressing my genuine concern for giving this to a patient in treatment for opioid addiction. I was working alongside our ICU pharmacist that night and we both were in awe. Maybe if I had let him call the physician, he’d be more likely to take his recommendation over a new pharmacist? Should I have attempted to recommend ketamine instead? I felt like I let this patient down.
Presented to ER with weakness & SOB; found to have PNA (mycoplasma +)
Req high flow O2, WBC 11, lactic 3.8, afebrile, other labs WNL
Hx heroin addiction and polysubstance abuse including opioids, meth, and cocaine. Has been receiving treatment at the methadone clinic for eight years (current methadone dose of 165 mg daily).
Hospital Course (20-day hospital stay): PNA with hypoxic respiratory failure
Day 0: Went from ER to ICU and within minutes was urgently intubated
For PNA: Received vancomycin + cefepime x 10 days, and doxycycline x 7 for +mycoplasma
(see chart at bottom for infusions)
Imagine, spending YEARS struggling with an addiction, and YEARS being treated for it, only to have someone who doesn’t know you make the decision to start you on an opioid drip. It’s fine though, he is intubated, so it’s not like he will remember or ever know, right? This is what I knew wasn’t true but tried to convince myself of after verifying the fentanyl drip. The ICU pharmacist kindly said, “HE technically won’t, but his brain will!”
The 2018 Critical Care Guidelines recommend opioids, or analgosedation, as first line treatment before sedatives as an approach to reduce the duration of mechanical ventilation, ICU length of stay, and pain intensity. Fentanyl is great because it has a high potency and with no histamine release, minimizing its risk of hemodynamic instability. However, its short half-life could result in tolerance, dependence, and withdrawal syndrome potentially leading to psychomotor agitation. The issue is that there is very limited data on how to taper fentanyl infusions. Methadone has been presented as a potential option given its use in treatment of opioid withdrawal and does not induce withdrawal symptoms when given to a patient with opioid agonist in their system. Several studies have demonstrated the use of methadone to prevent and/or treat withdrawal related to opioid use in pediatric population; however, little has been conducted in the adult critical care population. In the Journal of Critical Care, Wanzuita and colleagues found replacement of fentanyl infusion by enteral methadone (10 mg every 6 hours) decreases the weaning time from mechanical ventilation. In Annals of Pharmacotherapy, Al-Qadheeb and colleagues performed a case-control study examining the impact of enteral methadone on the ability to wean off continuously infused opioids in critically ill, mechanically ventilated adults. It excluded patients with a history of opioid drug abuse, but its results are still note-worthy. In patients on fentanyl infusions for at least 72 hours (with median of 9 days to first methadone dose), the median time to fentanyl discontinuation was shorter in the methadone group (4.5 versus 7.0 days; p = 0.002). The study did not use a standard dose of methadone, but rather per the physician’s judgement, which was on average 25 mg – 30 mg divided every 8 hours in the first three days of initiation. The low doses, and slightly longer interval between doses could have accounted for a longer time to down titrating the fentanyl. In a podcast from Pharmacy Joe (who also referenced Wanzuita), he mentions using methadone 10 mg enterally (or 5 mg IV) every 6 hours. He further states that the fentanyl infusion can usually be rapidly tapered off after 1 or 2 doses of methadone have been given and favors the addition of as needed fentanyl boluses for the nurse to administer if the patient begins to experience withdrawal.
In regard to our patient, even less is known about the ideal way to manage these medications. In a paper by Alford, et al, recommendations for providing acute pain management in methadone (or buprenorphine) patients for treated for addiction include continuing the maintenance drug and incorporating nonopioids and/or opioids with short half-lives. It also debunks the concern that the use of opioids for acute analgesia could lead to addiction relapse. However, both of these statements again did not fit our patient. We do not carry IV methadone, and the enteral route was unavailable, and because we couldn’t continue methadone with the fentanyl drip, and the drip was continued for two weeks, we cannot say for certain whether this played a cognitive role for addiction relapse based on the article’s references. He also does not perfectly fit into the studies referenced, and we used half of his normal home methadone dose of 80 mg once a day as we transitioned him from fentanyl versus the other dosing strategies mentioned. Unlike the rest of the study patients, this patient was previously on methadone treatment prior to starting fentanyl. It is interesting to see the result of our treatment plan and how we were able to get him off the ventilator. Given this patient’s critical course and reluctance to extubate for nearly two weeks, the conversion of ketamine to methadone while titrating off fentanyl seemed to be an effective method for success. He was extubated only a few hours after his third dose of methadone.
Hospital days and correlating infusions during mech. ventilation to extubation (Day 0 to Day 16)
Method of Transitioning (Fentanyl → Ketamine → Methadone)
Day 13: Decision to add ketamine (bolus x 1 then titratable drip) in hopes to get off fentanyl and then back on to methadone. Attempted to wean from vent but patient agitated and too sedated.
Day 14: First dose of methadone 80mg (half of his normal dose) given. Attempted to wean and patient follows commands without agitation.
Day 15: Patient opened eyes and followed commands.
Day 16: Propofol changed to dexmedetomidine in the morning and patient given his third methadone dose; Patient was soon able to be extubated but still required high flow oxygen.
Following discharge, I was interested to know if and/or how the fentanyl affected his addiction/recovery, if it set him back at all, and whether he followed up with the methadone clinic. I first followed-up with the clinic and they were able to tell me that the patient has been following up! After consideration, and for more completeness to this story, I decided to call the patient as well (now three weeks post discharge). I was relieved to know he was back at the clinic, which he mentioned following up with right away and is back on his dose of 165 mg daily. Despite having some lingering fatigue, he reported being back to work and is just trying to “get back into the swing of things”. He was very open with me about his addiction course which began when he was a teen suffering constant back pain and nerve pain due to issues with his spine. At some point he was started on morphine for the pain and over time developed tolerance. The doses continued to increase until it didn’t cover the pain anymore, and he instead turned to heroin. It is my hope that the fentanyl does not have any effect on him/his treatment moving forward; it certainly invites into question as to whether subconsciously the brain remembers the reintroduction of opioids or was potentially offset but the titration back to the methadone prior to being extubated.
- Devlin JW, Skrobik Y, Gélinas C, et. Al. Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption in Adult Patients in the ICU. Crit Care Med. 2018;46(9):e825.
- Wanzuita R, Poli-de-Figueiredo LF, Pfuetzenreiter F, Cavalcanti AB, Westphal GA. Replacement of fentanyl infusion by enteral methadone decreases the weaning time from mechanical ventilation: a randomized controlled trial. Crit Care. 2012;16(2):R49. Epub 2012 Dec 12.
- Al-Qadheeb NS, Roberts RJ, Griffin R, Garpestad E, Ruthazer R, Devlin JW. Impact of enteral methadone on the ability to wean off continuously infused opioids in critically ill, mechanically ventilated adults: a case-control study. Ann Pharmacother. 2012 Sep;46(9):1160-6. Epub 2012 Aug 7.
- Alford DP, Compton P, Samet JH Acute Pain Management for Patients Receiving Maintenance Methadone or Buprenorphine Therapy. Ann Intern Med. 2006 January 17; 144(2): 127–134.