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; A. Avidan; Y. Golob; E. Y. Anteby; Y. Ezra; D. Hochner-Celnikier; D. D. Mankuta; S. Yagel; L. Kleinberg; S. Haroutinian; B. Bar-Oz; H. Kaniel; N. Novick; S. H. Halpern

doi:10.1093/bja/aen402

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, A. Avidan, Y. Golob, E. Y. Anteby, Y. Ezra, D. Hochner-Celnikier, D. D. Mankuta, S. Yagel, L. Kleinberg, S. Haroutinian, B. Bar-Oz, H. KanielN. Novick, S. H. Halpern

^*Corresponding author for this work

School of Pharmacy

Research output: Contribution to journal › Article › peer-review

16 Scopus citations

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.

Original language	American English
Pages (from-to)	369-378
Number of pages	10
Journal	British Journal of Anaesthesia
Volume	102
Issue number	3
DOIs	https://doi.org/10.1093/bja/aen402
State	Published - Mar 2009

Bibliographical note

Funding Information:
Y.G. was supported by research grants from the International Anesthesia Research Society—Clinical Scholar Research Award (2003) and from the Women’s Health Fund of the Hadassah Medical Organization (2003).

Keywords

Anaesthetic techniques, epidural
Anaesthetics local, ropivacaine
Complications, pre-eclampsia
Pregnancy

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10.1093/bja/aen402

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Ginosar, Y., Nadjari, M., Hoffman, A., Firman, N., Davidson, E. M., Weiniger, C. F., Rosen, L., Weissman, C., Elchalal, U., Avidan, A., Golob, Y., Anteby, E. Y., Ezra, Y., Hochner-Celnikier, D., Mankuta, D. D., Yagel, S., Kleinberg, L., Haroutinian, S., Bar-Oz, B., ... Halpern, S. H. (2009). Antepartum continuous epidural ropivacaine therapy reduces uterine artery vascular resistance in pre-eclampsia: A randomized, dose-ranging, placebo-controlled study. British Journal of Anaesthesia, 102(3), 369-378. https://doi.org/10.1093/bja/aen402

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

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.",

keywords = "Anaesthetic techniques, epidural, Anaesthetics local, ropivacaine, Complications, pre-eclampsia, Pregnancy",

author = "Y. Ginosar and M. Nadjari and A. Hoffman and N. Firman and Davidson, {E. M.} and Weiniger, {C. F.} and L. Rosen and C. Weissman and U. Elchalal and A. Avidan and Y. Golob and Anteby, {E. Y.} and Y. Ezra and D. Hochner-Celnikier and Mankuta, {D. D.} and S. Yagel and L. Kleinberg and S. Haroutinian and B. Bar-Oz and H. Kaniel and N. Novick and Halpern, {S. H.}",

note = "Funding Information: Y.G. was supported by research grants from the International Anesthesia Research Society—Clinical Scholar Research Award (2003) and from the Women{\textquoteright}s Health Fund of the Hadassah Medical Organization (2003).",

year = "2009",

month = mar,

doi = "10.1093/bja/aen402",

language = "American English",

volume = "102",

pages = "369--378",

journal = "British Journal of Anaesthesia",

issn = "0007-0912",

publisher = "Elsevier Ltd.",

number = "3",

}

Ginosar, Y, Nadjari, M, Hoffman, A, Firman, N, Davidson, EM, Weiniger, CF, Rosen, L, Weissman, C, Elchalal, U, Avidan, A, Golob, Y, Anteby, EY, Ezra, Y, Hochner-Celnikier, D, Mankuta, DD, Yagel, S, Kleinberg, L, Haroutinian, S, Bar-Oz, B, Kaniel, H, Novick, N & Halpern, SH 2009, 'Antepartum continuous epidural ropivacaine therapy reduces uterine artery vascular resistance in pre-eclampsia: A randomized, dose-ranging, placebo-controlled study', British Journal of Anaesthesia, vol. 102, no. 3, pp. 369-378. https://doi.org/10.1093/bja/aen402

TY - JOUR

T1 - Antepartum continuous epidural ropivacaine therapy reduces uterine artery vascular resistance in pre-eclampsia

T2 - A randomized, dose-ranging, placebo-controlled study

AU - Ginosar, Y.

AU - Nadjari, M.

AU - Hoffman, A.

AU - Firman, N.

AU - Davidson, E. M.

AU - Weiniger, C. F.

AU - Rosen, L.

AU - Weissman, C.

AU - Elchalal, U.

AU - Avidan, A.

AU - Golob, Y.

AU - Anteby, E. Y.

AU - Ezra, Y.

AU - Hochner-Celnikier, D.

AU - Mankuta, D. D.

AU - Yagel, S.

AU - Kleinberg, L.

AU - Haroutinian, S.

AU - Bar-Oz, B.

AU - Kaniel, H.

AU - Novick, N.

AU - Halpern, S. H.

N1 - Funding Information: Y.G. was supported by research grants from the International Anesthesia Research Society—Clinical Scholar Research Award (2003) and from the Women’s Health Fund of the Hadassah Medical Organization (2003).

PY - 2009/3

Y1 - 2009/3

N2 - 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.

AB - 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.

KW - Anaesthetic techniques, epidural

KW - Anaesthetics local, ropivacaine

KW - Complications, pre-eclampsia

KW - Pregnancy

UR - http://www.scopus.com/inward/record.url?scp=60249094013&partnerID=8YFLogxK

U2 - 10.1093/bja/aen402

DO - 10.1093/bja/aen402

M3 - Article

C2 - 19176534

AN - SCOPUS:60249094013

SN - 0007-0912

VL - 102

SP - 369

EP - 378

JO - British Journal of Anaesthesia

JF - British Journal of Anaesthesia

IS - 3

ER -

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

Abstract

Bibliographical note

Keywords

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