Abstract
Background: The management of pain in adults with sickle cell disease (SCD) is complex, with the intermingling of both acute vaso-occlusive events and chronic daily pain. Sixty percent of adults with SCD suffer with every day chronic pain. In patients with frequent acute visits we use aggressive disease modifying therapy to decrease the risk of VOC yet there remains a subset of patients who continue to have frequent acute visits for pain. In addition, there are patients maintained on high doses of oral opioids as outpatients who continue to have high levels of daily pain. There is little data that escalating doses of opioids is associated with benefit, yet significant data to support that higher doses are associated with harms. We consider these to be cases of opioid failure. Identifying therapies for these patients that improve quality of life is essential.
Buprenorphine is a partial mu opioid receptor agonist and kappa antagonist, and has a very high affinity for the mu receptors, with an elimination half-life of 28-37 hours for the sublingual administration. The reduced risk of overdose, lower risk for misuse, diminished withdrawal symptoms, and blunting of opioid craving make it an appealing alternative to full opioid agonists in a subset of patients with SCD who continue to have significant pain or are unable to wean off of ineffective opioid therapy. The purpose of this report is to describe our experience converting patients with SCD and chronic pain from chronic opioid therapy to buprenorphine.
Methods: Routine clinical care in our clinic includes offering buprenorphine transition to patients on chronic opioid therapy with numerous acute care visits despite the use of disease modifying therapy; or patients on chronic opioid therapy reporting significant ongoing pain. Patients are typically weaned to lower opioid doses (goal 90 oral morphine equivalents) prior to the planned induction with buprenorphine. Once patients are at the goal dose, they are asked to hold opioids for 12-24 hours prior to presentation so that they are in at least mild opioid withdrawal prior to their first dose of buprenorphine to avoid precipitated withdrawal. The patient is assessed with the Clinical Opiate Withdrawal Scale (COWs) and if their score is 5 or higher they are administered their first dose of sublingual buprenorphine. If COWs scores are less than 5, buprenorphine is not initiated and the subject is asked to return the following day or earlier if withdrawal symptoms begin. Patients are reassessed with the COWs and dosed with buprenorphine hourly until withdrawal has ceased. The dose needed to minimize withdrawal is considered the working total daily dose. Patients are sent home and return the next day to start their once daily dose of buprenorphine. Urine toxicology testing is done the day of planned induction. Data on acute visits 6 months prior and 6 months post induction and on complications associated with induction were pulled from the electronic health record.
Results: 21 patients have been converted from full agonist opioids to buprenorphine from 3/2015-6/1/2018. The average age of the patients at the time of induction was 36.1 years (SD 9.1), 62% were female. Sixteen (76 %) of the patients had sickle cell anemia, the remainder had variant genotypes. The mean dose (in morphine equivalents) of full agonist opioid that patients were on prior to weaning of opioids was 196.8 mg (SD 222.7) and just prior to induction was 85 mg (SD 70 mg) with a range of 11.4 to 315 mg. Seventeen patients tolerated the induction without any complications, 2 patients had abdominal cramps but were successfully converted, 2 patients has adverse reactions (1 had numbness of tongue and 1 with worsening of asthma) and buprenorphine was stopped. Of the 19 patients successfully converted, two chose to stop buprenorphine and resume taking full opioid agonists. For the 13 patients with 6 months of follow-up post induction, the median number of acute care visits prior to induction was 12.5 and post was 4.0 (Figure).
Conclusions: Adults with sickle cell disease on chronic full agonist opioid therapy can be safely converted to buprenorphine. Acute care utilization has dropped significantly for patients post induction. Assessment of patient reported outcomes such as quality of life and pain interference are being collected. Buprenorphine appears to be a safe and effective medication in the management of pain in adults with SCD.
Lanzkron:PCORI: Research Funding; GBT: Research Funding; Prolong: Research Funding; Pfizer: Research Funding; selexys: Research Funding; NHLBI: Research Funding; HRSA: Research Funding; Ironwood: Research Funding.
