Buprenorphine-based Complex Pain Management for Sickle Cell Disease Patients Undergoing Hematopoietic Stem Cell Transplant: Pilot Prospective Clinical Trial for Inpatient Analgesic Therapy
Mayuko Sakae, Christine Jun, Stefanie Mooney, Stephanie WongAbstract
Background
Bone marrow transplant (BMT) offers potential cure for a spectrum of otherwise incurable diseases. The BMT process can lead to multi-systemic complications presenting with pain, especially severe in patients with complex pain history due to congenital diseases, cancer, non-malignant hematologic disorders and bone marrow failure disorders. Sickle cell disease (SCD) is an inherited hematologic disease with life-long pain starting in early childhood. Because of the frequent and long-term pain experience resulting in hyperalgesia and chronic opioid use prior to BMT, SCD patients undergoing BMT often experience excruciating pain uncontrolled by rapid escalation of opioid use leading to extremely high-dose. Growing body of literature have shown superior effects of buprenorphine, opioid agonist-antagonist, over full-agonist opioids for chronic SCD pain in the outpatient setting. This pilot prospective clinical trial for buprenorphine-based inpatient pain management was conducted for SCD patients’ acute, severe pain to assess for the inpatient use efficacy of buprenorphine in the setting of BMT, a significant pain escalation factor. This trial was initiated after observing serial cases of SCD patients' BMT-related severe pain, refractory to exceedingly high, supratherapeutic doses of traditional full-agonist opioids.
Methods
Buprenorphine was started as scheduled and as-needed analgesics intravenously, supplemented by full-agonist opioids for SCD patients enrolled in clinical trials with BMT upon Supportive Medicine consultation for uncontrolled pain. Patients' 24-hour opioid requirement by morphine equivalent daily doses (MEDD) were assessed at 3 time points: 1) immediately prior to pain-level escalation; 2) consultation day for uncontrolled pain; 3) discharge day. MEDDs were retrospectively compared to those of SCD patients treated only with full-agonist opioids during their BMT admission.
Results
The cases treated only by full-agonist opioids had remarkable MEDD escalation by 1330 - 16300% by the day of discharge compared to the time point immediately prior to escalation of BMT pain. Buprenorphine-supported cases had significantly smaller MEDD increase by 220 - 317% by the time of discharge. (Table1) The need for the adjunct pain medications was remarkably higher for the cases treated by full-agonist opioids compared to the cases treated primarily by Buprenorphine with some supplemental full-agonist opioids. The full-agonist opioid treatment cases required additional neuroleptic agents and anesthetic infusion indicated for opioid-resistant pain, namely ketamine infusion. The cases treated primarily by buprenorphine neither required any anesthetics nor neuroleptic agents. (Table 2)
Conclusions
Our pilot prospective clinical trial case series revealed the benefits of starting buprenorphine prior to full-agonist opioid dose escalation during BMT admission for SCD patients. Our data suggests markedly more potent pain control and limiting opioid tolerance development by adding Buprenorphine prior to BMT-related pain becomes uncontrollable by high-dose opioids with multiple dose titrations and supplemental analgesics’ need. Further studies will help establish clearer indication and timing to start buprenorphine for SCD patients undergoing BMT, the potentially curative treatment. Buprenorphine may also provide the same advantages for treating pain in patients with other similarly complex diseases with relentless pain, challenged by severe opioid-resistant pain during BMT due to the pre-existing hyperalgesia and high opioid-tolerance. We plan to develop a clinical trial of buprenorphine-based complex pain management for SCD patients to compare to other hematologic-oncologic disorders’ cohort undergoing BMT.