Maternal and preterm fetal sheep responses to dexmedetomidine

Abstract

Background The α2 adrenergic receptor agonist dexmedetomidine has some unique pharmacologic properties that could benefit pregnant patients (and their fetuses) when they require sedation, analgesia, and/or anesthesia during pregnancy. The purpose of the present study was to delineate maternal and fetal responses to an intravenous infusion of dexmedetomidine. Methods This study was conducted on surgically-recovered preterm sheep instrumented for physiologic recording and blood sampling. Maternal and fetal cardiovascular and blood gas parameters and fetal cerebral oxygenation levels were recorded before, during, and after 3 h of dexmedetomidine infusion to the ewe at a rate of 1 μg/kg/h. Results Drug infusion produced overt sedation but no apparent respiratory depression as evidenced by stable maternal arterial blood gases; fetal blood gases were also stable. The one blood parameter to change was serum glucose, By the end of the 3 h infusion, glucose increased from 49 ± 10 to 104 ± 33 mg/dL in the ewe and from 22 ± 3 to 48 ± 16 mg/dL in the fetus; it declined post-drug exposure but remained elevated compared to the starting levels (maternal, 63 ± 12 mg/dL, P = 0.0497; and fetal, 24 ± 4 mg/dL, P = 0.012). With respect to cardiovascular status, dexmedetomidine produced a fall in maternal blood pressure and heart rate with fluctuations in uterine blood flow but had no discernable effect on fetal heart rate or mean arterial pressure. Likewise, maternal drug infusion had no effect on fetal cerebral oxygenation, as measured by in utero near-infrared spectroscopy. Conclusions Using a clinically-relevant dosing regimen, intravenous infusion of dexmedetomidine produced significant maternal sedation without altering fetal physiologic status. Results from this initial acute assessment support the conduct of further studies to determine if dexmedetomidine has clinical utility for sedation and pain control during pregnancy.

Comparative Evaluation of Remifentanil and Dexmedetomidine in General Anesthesia for Cesarean Delivery

“…Dexmedetomidine has a high placental retention [ 21 ]. It has shown no significant effect on fetal HR, MAP, blood gas, or cerebral oxygenation in an animal study with pregnant sheep subjected to preterm surgical deliveries [ 22 ]. El-Tahan et al [ 18 ] found that Apgar scores, Neurologic and Adaptive Capacity Scores, and acid-base status were similar between the control and the neonates born to mothers receiving preoperative dexmedetomidine 0.2–0.6 μg/kg/h over 20 min.…”

Maternal and fetal arterial blood gas data during general anaesthesia for caesarean delivery of preterm twin lambs

“…Pregnant sheep and their fetuses are commonly utilized as animal models for investigations into human pregnancy and the causes and consequences of preterm birth. [1][2][3][4] As elegantly argued in Russell and Burch's landmark work, The principles of humane experimental technique, the continual refinement of practice in animal-based research is key to minimizing the impact of research on animal welfare and to ensuring the integrity of scientific data. 5 General anaesthesia causes major physiological alterations to the respiratory, cardiovascular, neurological, immune and endocrine systems and specific considerations exist for anaesthesia of pregnant patients.…”

Effects of maternal ritodrine hydrochloride administration on the heart rate of preterm fetal sheep with intraamniotic inflammation

“…On the day of surgery, general anesthesia was induced from 07:00 by intramuscular administration of 0.2 mg/kg xylazine (Bayer Yakuhin Ltd., Osaka City, Japan). Subsequently, 3 mg/kg/min dexmedetomidine hydrochloride (Maruishi Pharmaceutical Co., Ltd., Osaka City, Japan) [ 36 ] was administered via a peripheral intravenous line on the front right leg of the sheep obtained after xylazine administration. Acetaminophen (Terumo Co., Ltd., Tokyo, Japan) (1,000 mg/body/30 min) and antibiotics (1 g flomoxef sodium/body; biological half-life: 49.2 min; Shionogi Co., Ltd., Tokyo, Japan) were intravenously administered before surgery to control surgical pain and surgical site infection, respectively.…”