Maternal and preterm fetal sheep responses to dexmedetomidine

Abstract

Background: The α(2) 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 3h 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±33mg/dL in the ewe and from 22±3 to 48±16mg/dL in the fetus; it declined post-drug exposure but remained elevated compared to the starting levels (maternal, 63±12mg/dL, P=0.0497; and fetal, 24±4mg/dL, P=0.012). With respect to cardiovascular status, dexmedetomidine produced a decrease 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.

Fig. 1

Mean ± SD measurements of maternal (triangles, ▲) and fetal (squares, ■) arterial blood pH (panel A), oxygen saturation (SaO₂; panel B), carbon dioxide (PCO₂; panel C), standard base excess (SBE; panel D), and glucose (panel E). Arterial blood glucose levels in the ewe and fetus were the only parameters to change in response to agent administration; from 30 min onward, glucose values are significantly different (P <0.05) from their respective baseline (experimental time 0) levels as indicated by the line and asterisk.

Fig. 2

Mean ± SD measurements of maternal heart rate (panel A), mean arterial pressure (MAP; panel B), and uterine blood flow (UBF; panel C). Data are presented as 1 min averages with the SD (error bars) marked every 5 min for clarity. Maternal heart rate and MAP data points identified by the line and asterisk are significantly different from their respective baselines (P < 0.05).

Fig. 3

Mean ± SD measurements of fetal heart rate (panel A), and mean arterial pressure (MAP; panel B). Data are presented as 1 min averages with the SD (error bars) marked every 5 min for clarity. Fetal heart rate and MAP did not significantly change during the experiment.

Fig. 4

Median (black lines) and 1^st and 3^rd quartile deviations (gray lines) measurements of fetal cerebral oxygenated hemoglobin (oxyHb), deoxygenated hemoglobin (deoxyHb), and total hemoglobin (totalHb). All are expressed as percent of baseline with data presented at 1 min intervals. Results of the statistical analyses are detailed in Table 1