Inadequate postoperative pain management can lead to physical and psychological distress
in patients as well as impact surgical wound healing and increase the risk of developing
postoperative delirium and cardiopulmonary and thromboembolic events. Severe
postoperative pain may also result in the development of chronic post-surgical pain
(CPSP), which in turn can lead to prolonged use of opioids and increased health-care
costs. A descriptive survey study in 60 postpartum women who received cesarean section
suggested that the presence of postoperative pain significantly reduced the willingness
of breastfeeding and infant care. Furthermore, the incidence of CPSP after cesarean
delivery has been reported to vary from 1% to 18% up to 1 year after operation. More
specifically, an US nationwide survey reported that 79% of mothers who received cesarean
section reported experiencing pain at the incision site in the first two months and 18%
had persistent pain at least 6 months after operation. Placement of an epidural catheter
can be used for epidural anesthesia during cesarean section and continuous epidural
infusions of opioids or combined with local anesthetic after cesarean section can result
in high-quality analgesia effect for postpartum and postsurgical pain. Intrathecal
injection of morphine (ITM) is considered as the standard pain management strategies for
post-cesarean pain in Taiwan. However, correct placement of epidural catheter for
effective postoperative pain management is more technical demanding, and accidental dural
puncture is associated with increased risk of postdural puncture headache. ITM is
associated with severe mu-receptor agonist adverse reactions, such as pruritus,
nausea/vomiting, urinary retention, constipation, mental status change, and respiratory
depression. Therefore, the development of a safe, conveniently operated, and long-lasting
non-mu agonism analgesic strategy, which serves as background pain control modality up to
several days after cesarean section should provide clinically beneficial advantages in
the management of acute postoperative pain and prevention of development of CPSP in
postpartum women.
Sebacoyl dinalbuphine ester Naldebain® (SDE) is prodrug of nalbuphine, which was approved
by the Taiwan FDA in 2017. SDE is rapidly hydrolyzed by tissue of plasma esterase to
release nalbuphine. The bioavailability of nalbuphine following intramuscular injection
SDE was 85.4% with a mean absorption time up to 145 h, and it took approximately 6 days
for the complete release of SDE into the blood circulation. Therefore, a single
parenteral injection of SDE could provide long lasting analgesic effect in several phase
II trials. However, SDE has not been tested in the pain control after cesarean section.
Therefore, this PI-initiated prospective, randomized, open-label, non-inferiority trial
aims to investigate the clinical efficacy of SDE in management of acute postoperative
pain in term parturient who receive elective cesarean section to provide analgesic effect
that is not inferior to the standard ITM. A single intramuscular injection of SDE may
also prevent the development of CPSP after cesarean delivery, as SDE can provide
prolonged analgesic effect for up to 7 days.