Intrathecal Hydromorphone vs Intrathecal Morphine to Treat Post Cesarean Pain in Patients With Opioid Use Disorder Taking Buprenorphine

Background:

Opioid use disorder (OUD) and neonatal abstinence syndrome (NAS) has increased significantly in pregnancy during the last decade. Lui et al found the rate of OUD in patients undergoing cesarean delivery increased 4 fold from 2007 to 2014. Untreated addiction can lead to increased risk of preterm birth, low birth weight and fetal death. Women with OUD were at higher risk for inpatient mortality and readmission following delivery, particularly those who had a cesarean delivery. Pregnancy outcomes are improved if women with OUD are treated with opioid agonist therapy during pregnancy. The American College of Obstetricians and Gynecologists recommends universal screening for substance use during pregnancy, and initiation of medication assisted treatment (MAT) with opioid agonist therapy. The most commonly used MATs are methadone and buprenorphine. Methadone, a full opioid agonist, is only dispensed via federally regulated opioid treatment programs and requires patients to present daily for their methadone treatment. Buprenorphine, a partial opioid agonist, can be prescribed by a physician and patients are able to treat themselves at home. Because buprenorphine is more easily dispensed, more patients are treated with buprenorphine for OUD.

Continuation of MAT is recommended during the peripartum period to help prevent relapse post-partum. Managing pain for parturients on MAT for OUD can be challenging, particularly for patients taking buprenorphine because of its ability to compete with other opioids at the mu receptor. Women delivering via cesarean who are taking buprenorphine for MAT generally have higher postop opioid use compared to women without OUD. This was particularly true for the immediate 24 hour postop period. A recent collaboration publication between the Society for Obstetric Anesthesiology and Perinatology and Society for Maternal Fetal Medicine highlights the lack of quality research on peripartum pain management in the OUD population.

Various strategies to improve postop pain management in this patient population have been used. Use of continuous epidural infusions postop does improve pain control but has the disadvantage of resulting in weakness that can limit mobility. Others have used low dose ketamine for management of post-cesarean pain. Use of intrathecal (IT) clonidine showed some benefit, however they have higher risk for intra- and postoperative hypotension. Continuous epidural or IV infusions tend to limit patients' functionality postop due to need to be physically connected to a device to receive these treatments.

Buprenorphine is a partial agonist at the mu opioid receptor and therefore has low activity. However, it has very high binding affinity for the mu opioid receptor making it very competitive with other opioid agonists. Hydromorphone also has high binding affinity for the mu opioid receptor, allowing it to more effectively compete for binding in the presence of buprenorphine. Morphine has lower binding affinity at the mu opioid receptor making it less able to compete with buprenorphine.