Purpose <p>The objective of this study was to investigate the <i>ex vivo</i> effects of various intravenous anesthetic drugs on the contractility of gravid human myometrium. We hypothesized that these drugs would cause a concentration-dependent decrease in spontaneous uterine contractility and oxytocin coadministration would modify their contractile response.</p> Methods <p>We conducted an <i>ex vivo</i> laboratory study with individual myometrial strips obtained from patients undergoing elective Cesarean delivery. We subjected the myometrial strips to concentration–response testing in organ bath chambers with intravenous agents—propofol, etomidate, and ketamine, with or without oxytocin—in a pattern of 0.5 log molar increase from 10<sup>−7</sup> M to 10<sup>−4</sup> M. The control group received oxytocin alone without any study drug. We recorded contractility parameters, and the primary outcome was the motility index (amplitude × frequency).</p> Results <p>The motility index with each study drug decreased with increasing concentrations. The overall motility index (estimated mean difference [95% confidence interval]) with etomidate (<b>−</b>6% [−77 to −13]; <i>n</i><b> =</b> 29; <i>P</i><b> =</b> 0.007) and ketamine (<b>−</b>66% [−82 to −35]; <i>n</i><b> =</b> 29; <i>P</i><b> &lt;</b> 0.001) was significantly lower than that of the oxytocin control group, while the difference between propofol and oxytocin was not statistically significant (<b>−</b>38% [−70 to 29]; <i>n</i><b> =</b> 25; <i>P</i><b> =</b> 0.47). The addition of oxytocin reversed contractility decreases induced by all anesthetic drugs, with no significant differences observed between the study drug + oxytocin and oxytocin control groups. Nevertheless, when compared with a study drug alone, the addition of oxytocin significantly increased the strength of contraction (area under the curve) of etomidate (207% [30 to 624]; <i>n</i><b> =</b> 27; <i>P</i><b> =</b> 0.002) and ketamine (234% [95 to 471]; <i>n</i><b> =</b> 27; <i>P</i><b> &lt;</b> 0.001) but not of propofol.</p> Conclusions <p>All the studied intravenous anesthetic drugs produced a concentration-dependent decrease in uterine contractility; nevertheless, the addition of oxytocin reversed this effect and increased contractility. Coadministration with oxytocin of etomidate and ketamine, but not propofol, resulted in a significant increase in myometrial contractility.</p>

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Spontaneous and oxytocin-induced contractility of gravid human myometrium with exposure to intravenous anesthetic agents: an ex vivo laboratory study

  • Natalia C. Portela,
  • Thomas Drew,
  • Jose C. A. Carvalho,
  • Tess E. Engel,
  • Mrinalini Balki

摘要

Purpose

The objective of this study was to investigate the ex vivo effects of various intravenous anesthetic drugs on the contractility of gravid human myometrium. We hypothesized that these drugs would cause a concentration-dependent decrease in spontaneous uterine contractility and oxytocin coadministration would modify their contractile response.

Methods

We conducted an ex vivo laboratory study with individual myometrial strips obtained from patients undergoing elective Cesarean delivery. We subjected the myometrial strips to concentration–response testing in organ bath chambers with intravenous agents—propofol, etomidate, and ketamine, with or without oxytocin—in a pattern of 0.5 log molar increase from 10−7 M to 10−4 M. The control group received oxytocin alone without any study drug. We recorded contractility parameters, and the primary outcome was the motility index (amplitude × frequency).

Results

The motility index with each study drug decreased with increasing concentrations. The overall motility index (estimated mean difference [95% confidence interval]) with etomidate (6% [−77 to −13]; n = 29; P = 0.007) and ketamine (66% [−82 to −35]; n = 29; P < 0.001) was significantly lower than that of the oxytocin control group, while the difference between propofol and oxytocin was not statistically significant (38% [−70 to 29]; n = 25; P = 0.47). The addition of oxytocin reversed contractility decreases induced by all anesthetic drugs, with no significant differences observed between the study drug + oxytocin and oxytocin control groups. Nevertheless, when compared with a study drug alone, the addition of oxytocin significantly increased the strength of contraction (area under the curve) of etomidate (207% [30 to 624]; n = 27; P = 0.002) and ketamine (234% [95 to 471]; n = 27; P < 0.001) but not of propofol.

Conclusions

All the studied intravenous anesthetic drugs produced a concentration-dependent decrease in uterine contractility; nevertheless, the addition of oxytocin reversed this effect and increased contractility. Coadministration with oxytocin of etomidate and ketamine, but not propofol, resulted in a significant increase in myometrial contractility.