Antepartum continuous epidural ropivacaine therapy reduces uterine artery vascular resistance in pre-eclampsia: a randomized, dose-ranging, placebo-controlled study

Br J Anaesth. 2009 Mar;102(3):369-78. doi: 10.1093/bja/aen402. Epub 2009 Jan 27.

Abstract

Background: No therapy is currently available to improve the reduced uteroplacental blood flow (UPBF) that characterizes pre-eclampsia. We hypothesized that sympathectomy induced by epidural local anaesthesia reduces uterine vascular resistance (which is inversely correlated with UPBF) in pre-eclampsia.

Methods: Ten pregnant women between 24 and 32 weeks of gestation with pre-eclampsia and uterine artery flow abnormalities were randomized to antepartum continuous epidural therapy (ACET) or control. ACET was initiated by a 5 day dose-ranging trial (ACET-1) of 0.04, 0.06, 0.08, and 0.1% ropivacaine and saline placebo, each at 10 ml h(-1) for 24 h. Doses were randomized and double-blind. Doppler ultrasound indices of vascular resistance were assessed at baseline and after each 24 h dosing period in both uterine arteries. Subsequently, these ACET patients were administered 0.1% ropivacaine until delivery (ACET-2), with one additional randomized double-blind placebo day.

Results: Five patients were randomized to ACET. In each patient, one uterine artery exhibited a dose-dependent reduction in vascular resistance (P=0.035), a response that returned to baseline following placebo (P<0.001). The contralateral uterine artery exhibited either increased vascular resistance or no change. In all cases, the uterine artery that responded to ACET had higher baseline resistance than its pair (P=0.043). Baseline right-left difference in resistance between paired uterine arteries was greatly diminished following ACET. Although ACET patients had a mean (sd) duration to delivery of 19 (9) days compared with control 2 (1) days (P=0.008), this should be interpreted with caution because of demographic differences between groups.

Conclusions: ACET reduces uterine artery resistance in pre-eclampsia <32 weeks. Uteroplacental re-distribution is a novel observation and warrants further investigation.

Trial registration: ClinicalTrials.gov NCT00197340.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Amides / administration & dosage
  • Amides / pharmacology*
  • Anesthesia, Epidural / methods
  • Anesthetics, Local / administration & dosage
  • Anesthetics, Local / pharmacology*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Fetal Development / drug effects
  • Humans
  • Pre-Eclampsia / diagnostic imaging
  • Pre-Eclampsia / physiopathology*
  • Pre-Eclampsia / therapy
  • Pregnancy
  • Prenatal Care / methods
  • Prospective Studies
  • Ropivacaine
  • Sympathectomy, Chemical / methods
  • Ultrasonography, Doppler / methods
  • Ultrasonography, Prenatal / methods
  • Uterus / blood supply*
  • Uterus / diagnostic imaging
  • Vascular Resistance / drug effects*
  • Young Adult

Substances

  • Amides
  • Anesthetics, Local
  • Ropivacaine

Associated data

  • ClinicalTrials.gov/NCT00197340