Subcutaneous Buprenorphine Is an Acceptable Preoperative Analgesic in Pregnant Ewes Undergoing Hysterotomy (Ovis aries)
Methodological status quo is often closely guarded in animal research because changes are seen as a threat to approaches that have proven successful. Current practices are often considered within the group as “best practice.” Perioperative analgesia is an important consideration in humane animal research to prevent central sensitization and can contribute to the benefits of multimodal anesthesia, but many research groups do not provide preoperative analgesia to pregnant ewes. We conducted this study to challenge the belief that preoperative buprenorphine negatively impacts the recovery of the ewe and therefore fetal health. Pregnant ewes at approximately 85 days of gestation were divided into 2 groups (each n = 6) that all had the same hysterotomy and fetal catheterization surgery performed. The first group received buprenorphine (0.3 mg, SC) preoperatively, and the second group received the buprenorphine postoperatively. Isoflurane use, time to each step of the recovery process, intraoperative maternal plasma cortisol, and fetal arterial blood values after 4 days of recovery were compared between groups. Equivalence of outcomes between groups was assessed while controlling for potential confounding variables (maternal body weight and length of isoflurane) using 2 one-sided tests with regression adjustment. Average isoflurane concentration after induction, maternal cortisol levels, fetal blood pH, and fetal blood pO2 were equivalent between the groups. The time from cessation of isoflurane to the time of spontaneous breath or extubation and the time from extubation to time of eating or standing were all shorter in the preoperative buprenorphine group. Fetal hematocrit was also lower in the preoperative buprenorphine group. Our study not only refutes that preoperative buprenorphine causes prolonged recovery of the pregnant ewe and detrimental health effects to the fetus but also describes the benefits of preoperative buprenorphine.
Potential Confounders (Median ± IQR) in Pregnant Ewes Treated Preoperatively with Vehicle (Saline) or Buprenorphine (Bup; 0.3 mg, SC). (A) Body weight at intake and (B) anesthesia duration (n = 6 per group).
Maternal Outcomes (median ± IQR) with or without Immediately Preoperative Buprenorphine and the Relationship between the Treatment Effect (with 90% CI) and the Zone of Statistical Equivalence (gray). Values for (A) time-averaged isoflurane after induction, (B) time from isoflurane off to weaned from ventilator, (C) time from isoflurane off to extubated, (D) time from extubated to eating, (E) time from extubated to standing, and (F) postoperative plasma cortisol levels in ewes treated preoperatively with vehicle (Saline) or buprenorphine (Bup; 0.3 mg subcutaneous). *Groups not equivalent by 2 one-sided tests with regression adjustment for confounders. Per group n = 6 except time to weaned from ventilator Bup where n = 5.
Fetal Outcomes (median ± IQR) with or without Immediately Preoperative Maternal Buprenorphine and the Relationship between the Treatment Effect (with 90% CI) and the Zone of Statistical Equivalence (gray). Four days after surgery, fetal values for (A) arterial blood pH, (B) partial pressure of oxygen (pO2), and (C) hematocrit in groups in which the ewes treated preoperatively with vehicle (Saline) or buprenorphine (Bup; 0.3 mg subcutaneous). *Groups not equivalent by 2 one-sided tests (TOST) with regression adjustment for confounders. Per group n = 6 (twins averaged within each ewe).
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