The effects of S+-ketamine and racemic ketamine on uterine blood flow in chronically instrumented pregnant sheep.

UNLABELLED: Ketamine could be a useful maternal analgesic in obstetric surgery, as it might avoid the need for opioid administration and associated side effects in the newborn. Racemic ketamine passes the placental barrier and has oxytocin-like properties but does not seem to affect uterine blood flow (UBF). S(+)-ketamine was recently approved for clinical use, but its effects on UBF have not been evaluated. Therefore, we studied the effects of S(+)-ketamine on maternal and fetal hemodynamic variables. Equianalgesic doses of S(+)-ketamine (10 mg.kg(-1).h(-1)) or racemic ketamine (20 mg.kg(-1).h(-1)) were infused in 12 chronically instrumented pregnant sheep. Maternal and fetal vital signs, blood gases, and UBF were recorded over 120 min. Neither compound affected uterine perfusion or maternal and fetal hemodynamics. Whereas racemic ketamine increased maternal (+19%) and fetal (+11%) PCO(2) significantly, S(+)-ketamine was without effect. However, both compounds significantly decreased maternal (racemic, -0.05; S(+), -0.03) and fetal (racemic, -0.06; S(+), -0.02) pH. The effects of racemic ketamine and S(+)-ketamine on uterine perfusion are similar, and because of its limited effect on hemodynamics and respiration, S(+)-ketamine might therefore be of interest as an analgesic in the obstetric setting. IMPLICATIONS: The effects of S(+)-ketamine on uterine perfusion and maternal/fetal hemodynamics are similar to those of the racemic mixture in chronically instrumented pregnant sheep. A decreased effect of S(+)-ketamine, as compared with the racemic mixture, on maternal and fetal PCO(2) levels was noted.

Fetal plasma concentrations after intraamniotic sufentanil in chronically instrumented pregnant sheep.

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 microg 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 microg 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 microg 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 microg sufentanil intraamniotically did not affect maternal or fetal hemodynamics, uterine blood flow, or arterial blood gases. Fetal heart rate increased after administration of 50 microg 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.