1
296 297 Volume 166 1, Part 2 MAGNESIUM SULFATE IS A POOR INHIBITOR OF OXYTOCIN-INDUCED UTERINE CONTRACfILITY IN PREGNANT SHEEP. Margaret L. Watt-Morse, Steve N. Caritis, Jye Ping Chiao" University of Pittsburgh, Magee-Womens Hospital, Pittsburgh, PA We have previously demonstrated that magnesium is a poor inhibitor of oxytocin-induced contractility in sheep. Steady state concentrations were maintained for only 2-3h in that study, but clinical studies suggest that magnesium sulfate requires more time to inhibit uterine contractility. In the present study, we evaluated inhibition of oxytocin-induced uterine contractility by magnesium sulfate after 24h of infusion. We inserted catheters in the femoral artery and vein and amniotic cavity of 6 pregnant sheep between 110 and 117 days gestation (term = 147). Two to four days after surgery, animals received a loading dose of magnesium sulfate followed by maintenance infusion to achieve magnesium concentrations of 6.1-7.8 mEq/L. Animals received 500 mU boluses of oxytocin prior to and after 4 and 24h of infusion. Uterine activity was quantified by integrating the area under the time uterine pressure curve. Mean inhibition of uterine contractility was 18% after 4h and 24h of magnesium infusion. Previous work from our laboratory shows that uterine contractility induced by the same oxytocin dose are inhibited 48-64% when ritodrine concentrations are 1-11 ng/m!. When compared with ritodrine, magnesium sulfate is a poor inhibitor of oxytocin- induced myometrial contractility in pregnant sheep. OlJfCOME OF MULTIPLE GESfATION COMPUCATED BY PRETERM B ,LCrock..x,MDalunus X , FPien:JC,B Sibai. Univ ... ilyofTennessee, MernJirls· Cum:ntly lhereisliuIeinfonnalionastothelalencyperiodandperinalaloutrornes after pPROM in multiple gestations. SpecificaJ)y, the relarive risks of mori>idity and mortality betw .... thepresenling andnon-presenling infants havemt been addressed. The JlIlIlXlS" of lhis clinical investigation is to report !he nannl history and clinical oUlCome in 101 jl'egnm:ies having !his complication. Method: The studyJX¥llalion included all such pregnancies managed at !his insIitution over a 10 yeat period. Outcome variables SIlldied included: IaterK:y from membrane ruplUre to delivery, maternal infeclious morbidity including placental histology, and neonatal morbidity wilh special enqilasis on difIererx:es between !he presenling (A) and non-presenting (B) ferus. Resu\ts: Themeangestation atPPROM was 3O.0±4.4 weeks (mnge 18-36). Therewere2tripletgestations.Eightweredeliveredonadmissionbecau<eofadvanced gestation. The median iaJmcy of the 93 remaining jI'Ognancies was only 1.08 days, with 91% delivering within 7 days. The latency to delivery, slratified by gestational age at rupIllre, is summarized in !he Figure (analysis by life-table meIOOdoJogy). Pathologic clmio-amnionilis was identified in 29% of placentas ('12[75). and 29.7% developed clinical chorioanmionilis. Outcomes of the 204 infants are summarized in !he Table. Three infants > 600 grams were slillbom. ConcIINom: The multiple gestation complicated by ppROM is associated with a brief latency regardless of gestational age. PairedanalysisreveaJsnodifIerenceininfantsurvival,butasignificant increase in respiratory morbidity in !he non-presenling infant A 1! <30WU Birth weight (gr.) 1468 1463 %5 miu Apgar <7 17.4 28.7' % HMOs 7.9 22.8' % Resp. insufficiency 21.4 18.5 % Intubation > 24 hrs 16.0 24.8" % 02 Rx > 24 hrs 23.4 29.6' % Sepsis 18.0 13.0 o 1 2 3 4 S 6 7 % Survival# 90.8 90.0 Latency (Days) 1/ birthweigltt >600 gr. 'P<O.05 •• p= 0.08 298 299 SPO Abstracts 359 SAFETY AND EFFICACY OF THE OXYTOCIN ANTAGONIST ATOSIBAN IN THREATENED PRETERM LABOR: INITIAL U.S. TRIAL. TM Goodwin RH Paul (Univ. of So. California, Women's Hospital, Los Angeles, CA), H Silver (UC Davis), M Parsons, R Chez, W Spellacy (Univ. of So. Florida), R Hayashi (Univ. of Michigan), L Norlh,' R Merriman X ( R W J Pharmaceulical Research Inslitute). Alosiban (deTVT/DETO-OXY) is a potenl anlagonist of oxytocin which lacks significant cardiovascular. pUlmonary. and central nervous syslem aClivities. A double blind, placebo conlrolled trial was conducled to tesl the hypolhesis Ihat intravenous Atosiban (300 I1g/min) is more effeclive than bedrest in reducing Ihe frequency of preterm, contractions. 120 women between 20 and 36 weeks gestation with >4 uterine contractions/hour were randomized to receive placebo (N=60) or Atosiban (N=60) for 2 hours. Eighl subjecls (4 Atosiban and 4 placebo) were excluded after randomizalion. The IWO groups did nol differ in demographic characterislics or cervical findings. Baseline conlraclion frequency, as determined by external tocqdynamometry was similar in Alosiban and controls (l5.1±.4.8 vs. 16.8±.6. 7, mean±.SD). The overall mean decrease in contraction frequency was 8.2±.5.8 for Alosiban compared 10 4.6±.5.8 for controls (p=O.OOI) In palienls receiving Atosiban, 27/56 (48%) had ,,;4 conlractions/hour during Ihe second hour of infusion compared to 11156 (20%) of conlrols (p=O.003). Five Atosiban patienls had cervical change compared 10 8 controls (NS). Mild gaslroinlestinal symptoms were noted in 2 Atosiban patients and in one controL Atosiban is more effective than bedrest in reducing preterm uterine activity. No significant adverse effects were observed with a two hour infusion. We are currently studying the safety and efficacy of Atosiban in patients with preterm lahor evidenced by cervical change. AMNIOTIC flUID lAMELlAR BOOY COUll!: A RAPID rD RELIABlE ,fETAl. lU116 MAll.UTY TEST. C. Dalence, L. Bowie, J. Dohnal, E. Farre 11, x M. Vye,x Evanston Hospita 1 and Northwestern Un ivers ity Medical School, Evanston, IL The lamellar body count (LBC), a rapid and quantitative test for fetal lung maturity (FLM), has previously been shown to correlate with other tests for FLM. Lamellar bodies are structures secreted by fetal Type II pneumocytes and consist almost entirely of surfactant phospholipids. In this study, we compared the ability of the LBC vs a lung phospholipid profile to predict the respiratory outcome of 118 well documented cases. Fetal lung phospholipid profiles were performed by thin-layer chromatography. Maturity was indicated by a ratio of phospholip- ids (lecithin+PG+PE+PI)/sphingomyelin .3:1. LBC was determined for all a..,iotic fluid specimens using the platelet channel of a conventional Coulter counter. Calibrated spheres and conmer- cial controls were used to verify the accuracy of the particle counts. Data and predictive values (PV) are sunmarized below: Clinica 1 Lung Profile LBC LBC OutCllll! <3:1 :.3:1 s30K >3OK siOK >1OK RDS 10 1 14 0 10 4 loRDS 9 92 44 60 9 95 Sens/Spec 0.91/0.91 1.00/0.58 0.72/0.91 -+¥y/-py 0.53/0.99 0.24/1.00 0.53/0.96 Using a value greater than 3D,OOO/uL to predict FLM, the LBC showed no false negative results while the phospholipid profile had one false negat ive. Therefore, the LBC demonstrated 100% sensitivity in the critical function of predicting the absence of RDS. Furthermore, we found the number of false positives indicated by the LBC could be minimized by using a second cutoff of 10,OOO/uL to indicate a high-risk for RDS. LBC values between 10,OOO/uL and 30,OOO/uL appear to be of intermediate risk for developing RDS (4 of 39 cases). Conclusion: The LBC appears equiva lent to tradit iona 1 phospho 1 ipid determinat ion in predict- ing fetal lung maturity. However, the LBC offers considerable advantage over tradit iona 1 phospholipid determinat ion based upon its simple technique and rapid availability.

297 Outcome of Multiple Gestation Complicated by Preterm Prom (pPROM)

Embed Size (px)

Citation preview

296

297

Volume 166 ~umber 1, Part 2

MAGNESIUM SULFATE IS A POOR INHIBITOR OF OXYTOCIN-INDUCED UTERINE CONTRACfILITY IN PREGNANT SHEEP. Margaret L. Watt-Morse, Steve N. Caritis, Jye Ping Chiao" University of Pittsburgh, Magee-Womens Hospital, Pittsburgh, PA

We have previously demonstrated that magnesium is a poor inhibitor of oxytocin-induced contractility in sheep. Steady state concentrations were maintained for only 2-3h in that study, but clinical studies suggest that magnesium sulfate requires more time to inhibit uterine contractility. In the present study, we evaluated inhibition of oxytocin-induced uterine contractility by magnesium sulfate after 24h of infusion. We inserted catheters in the femoral artery and vein and amniotic cavity of 6 pregnant sheep between 110 and 117 days gestation (term = 147). Two to four days after surgery, animals received a loading dose of magnesium sulfate followed by maintenance infusion to achieve magnesium concentrations of 6.1-7.8 mEq/L. Animals received 500 mU boluses of oxytocin prior to and after 4 and 24h of infusion. Uterine activity was quantified by integrating the area under the time uterine pressure curve. Mean inhibition of uterine contractility was 18% after 4h and 24h of magnesium infusion. Previous work from our laboratory shows that uterine contractility induced by the same oxytocin dose are inhibited 48-64% when ritodrine concentrations are 1-11 ng/m!. When compared with ritodrine, magnesium sulfate is a poor inhibitor of oxytocin­induced myometrial contractility in pregnant sheep.

OlJfCOME OF MULTIPLE GESfATION COMPUCATED BY PRETERM

P~~OM). B ,LCrock..x,MDalunusX, FPien:JC,B Sibai. Univ ... ilyofTennessee,

MernJirls· Cum:ntly lhereisliuIeinfonnalionastothelalencyperiodandperinalaloutrornes after pPROM in multiple gestations. SpecificaJ)y, the relarive risks of mori>idity and mortality betw .... thepresenling andnon-presenling infants havemt been addressed. The JlIlIlXlS" of lhis clinical investigation is to report !he nannl history and clinical oUlCome in 101 jl'egnm:ies having !his complication. Method: The studyJX¥llalion included all such pregnancies managed at !his insIitution over a 10 yeat period. Outcome variables SIlldied included: IaterK:y from membrane ruplUre to delivery, maternal infeclious morbidity including placental histology, and neonatal morbidity wilh special enqilasis on difIererx:es between !he presenling (A) and non-presenting (B) ferus. Resu\ts: Themeangestation atPPROM was 3O.0±4.4 weeks (mnge 18-36). Therewere2tripletgestations.Eightweredeliveredonadmissionbecau<eofadvanced gestation. The median iaJmcy of the 93 remaining jI'Ognancies was only 1.08 days, with 91% delivering within 7 days. The latency to delivery, slratified by gestational age at rupIllre, is summarized in !he Figure (analysis by life-table meIOOdoJogy). Pathologic clmio-amnionilis was identified in 29% of placentas ('12[75). and 29.7% developed clinical chorioanmionilis. Outcomes of the 204 infants are summarized in !he Table. Three infants > 600 grams were slillbom. ConcIINom: The multiple gestation complicated by ppROM is associated with a brief latency regardless of gestational age. PairedanalysisreveaJsnodifIerenceininfantsurvival,butasignificant increase in respiratory morbidity in !he non-presenling infant A 1!

<30WU ~30WkI

Birth weight (gr.) 1468 1463 %5 miu Apgar <7 17.4 28.7' % HMOs 7.9 22.8' % Resp. insufficiency 21.4 18.5 % Intubation > 24 hrs 16.0 24.8" % 02 Rx > 24 hrs 23.4 29.6' % Sepsis 18.0 13.0

o 1 2 3 4 S 6 7 % Survival# 90.8 90.0 Latency (Days) 1/ birthweigltt >600 gr. 'P<O.05 •• p= 0.08

298

299

SPO Abstracts 359

SAFETY AND EFFICACY OF THE OXYTOCIN ANTAGONIST ATOSIBAN IN THREATENED PRETERM LABOR: INITIAL U.S. TRIAL. TM Goodwin RH Paul (Univ. of So. California, Women's Hospital, Los Angeles, CA), H Silver (UC Davis), M Parsons, R Chez, W Spellacy (Univ. of So. Florida), R Hayashi (Univ. of Michigan), L Norlh,' R Merriman X ( R W J Pharmaceulical Research Inslitute).

Alosiban (deTVT/DETO-OXY) is a potenl anlagonist of oxytocin which lacks significant cardiovascular. pUlmonary. and central nervous syslem aClivities. A double blind, placebo conlrolled trial was conducled to tesl the hypolhesis Ihat intravenous Atosiban (300

I1g/min) is more effeclive than bedrest in reducing Ihe frequency of preterm, contractions. 120 women between 20 and 36 weeks gestation with >4 uterine contractions/hour were randomized to receive placebo (N=60) or Atosiban (N=60) for 2 hours. Eighl subjecls (4 Atosiban and 4 placebo) were excluded after randomizalion. The IWO groups did nol differ in demographic characterislics or cervical findings. Baseline conlraclion frequency, as determined by external tocqdynamometry was similar in Alosiban and controls (l5.1±.4.8 vs. 16.8±.6. 7, mean±.SD). The overall mean decrease in contraction frequency was 8.2±.5.8 for Alosiban compared 10 4.6±.5.8 for controls (p=O.OOI) In palienls receiving Atosiban, 27/56 (48%) had ,,;4 conlractions/hour during Ihe second hour of infusion compared to 11156 (20%) of conlrols (p=O.003). Five Atosiban patienls had cervical change compared 10 8 controls (NS). Mild gaslroinlestinal symptoms were noted in 2 Atosiban patients and in one controL Atosiban is more effective than bedrest in reducing preterm uterine activity. No significant adverse effects were observed with a two hour infusion. We are currently studying the safety and efficacy of Atosiban in patients with preterm lahor evidenced by cervical change.

AMNIOTIC flUID lAMELlAR BOOY COUll!: A RAPID rD RELIABlE ,fETAl. lU116 MAll.UTY TEST. C. Dalence, L. Bowie, J. Dohnal, E. Farre 11, x M. Vye,x Evanston Hospita 1 and Northwestern Un ivers ity Medical School, Evanston, IL

The lamellar body count (LBC), a rapid and quantitative test for fetal lung maturity (FLM), has previously been shown to correlate with other tests for FLM. Lamellar bodies are structures secreted by fetal Type II pneumocytes and consist almost entirely of surfactant phospholipids. In this study, we compared the ability of the LBC vs a lung phospholipid profile to predict the respiratory outcome of 118 well documented cases. Fetal lung phospholipid profiles were performed by thin-layer chromatography. Maturity was indicated by a ratio of phospholip­ids (lecithin+PG+PE+PI)/sphingomyelin .3:1. LBC was determined for all a..,iotic fluid specimens using the platelet channel of a conventional Coulter counter. Calibrated spheres and conmer­cial controls were used to verify the accuracy of the particle counts. Data and predictive values (PV) are sunmarized below: Clinica 1 Lung Profile LBC LBC OutCllll! <3:1 :.3:1 s30K >3OK siOK >1OK

RDS 10 1 14 0 10 4 loRDS 9 92 44 60 9 95

Sens/Spec 0.91/0.91 1.00/0.58 0.72/0.91 -+¥y/-py 0.53/0.99 0.24/1.00 0.53/0.96 Using a value greater than 3D,OOO/uL to predict FLM, the LBC showed no false negative results while the phospholipid profile had one false negat ive. Therefore, the LBC demonstrated 100% sensitivity in the critical function of predicting the absence of RDS. Furthermore, we found the number of false positives indicated by the LBC could be minimized by using a second cutoff of 10,OOO/uL to indicate a high-risk for RDS. LBC values between 10,OOO/uL and 30,OOO/uL appear to be of intermediate risk for developing RDS (4 of 39 cases). Conclusion: The LBC appears equiva lent to tradit iona 1 phospho 1 ipid determinat ion in predict­ing fetal lung maturity. However, the LBC offers considerable advantage over tradit iona 1 phospholipid determinat ion based upon its simple technique and rapid availability.