Antepartum continuous epidural ropivacaine therapy reduces uterine artery vascular resistance in pre-eclampsia: a randomized, dose-ranging, placebo-controlled study
Y Ginosar, M Nadjari, A Hoffman, N Firman, E M Davidson, C F Weiniger, L Rosen, C Weissman, U Elchalal, ACET study group, A Avidan, E M Davidson, N Firman, Y Ginosar, Y Golob, C F Weiniger, C Weissman, E Y Anteby, U Elchalal, Y Ezra, D D Mankuta, M Nadjari, S Yagel, A Hoffman, L Kleinberg, S Haroutinian, L Rosen, B Bar-Oz, H Kaniel, N Novick, S H Halpern, Y Ginosar, M Nadjari, A Hoffman, N Firman, E M Davidson, C F Weiniger, L Rosen, C Weissman, U Elchalal, ACET study group, A Avidan, E M Davidson, N Firman, Y Ginosar, Y Golob, C F Weiniger, C Weissman, E Y Anteby, U Elchalal, Y Ezra, D D Mankuta, M Nadjari, S Yagel, A Hoffman, L Kleinberg, S Haroutinian, L Rosen, B Bar-Oz, H Kaniel, N Novick, S H Halpern
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.
Source: PubMed