Fetal plasma concentrations after intraamniotic sufentanil in chronically instrumented pregnant sheep

Abstract

Background: Rapid progress is being made in fetal surgery. Because the fetus is capable of pain perception after the 26th week of gestation, adequate postoperative fetal pain management is essential. The preferred approach would provide fetal analgesia without affecting the mother. Intraamniotically administered sufentanil may be an interesting option if it achieves therapeutic plasma concentrations (PCs) in the fetus but not the mother. Methods: After approval of the study, 25 or 50 μg sufentanil was administered intraamniotically in 10 chronically instrumented pregnant ewes. Maternal and fetal vital signs, arterial blood gases, and uterine blood flow were recorded over 120 min. Sufentanil PCs were determined before and 1, 3, 5, 10, 15, 30, 45, 60, 90, and 120 min after injection. Statistical analysis was performed using one- or two-way analysis of variance followed by Dunnett or Tukey test, as appropriate (P < 0.05; data presented as median [95% confidence interval]). Results: After 25 μg sufentanil, fetal PC stabilized at 134 ± 89 pg/ml (after 10 min), and maternal PCs stabilized at 44 ± 11 pg/ml (after 15 min). After 50 μg sufentanil, fetal PCs stabilized at 134 ± 35 pg/ml (after 15 min), and maternal PCs reached 80 ± 25 pg/ml (at 30 min). Injection of 25 μg sufentanil intraamniotically did not affect maternal or fetal hemodynamics, uterine blood flow, or arterial blood gases. Fetal heart rate increased after administration of 50 μg sufentanil (maximum change at 10 min: + 16 ± 12%). Conclusion: The sheep fetus absorbs sufentanil after intraamniotic instillation. Significantly greater PCs were obtained in the fetal lamb as compared with the ewe. This suggests that investigation of intraamniotic opioids for fetal analgesia might be worthwhile.