- Email: [email protected]
65 A Comparison of the Effect of Phenytoin a MGSO4 on Fetal Heart Rate Tracings Using Computer Analysis
SPO Abstracts
Volume 166 Number I, Part 2
65 ACOMP ARISON OF THE EFFECT OF PHENYTOIN & MGS04 ON FET AL HEART RATE TRACINGS USING COMPUTER ANAL YSIS, EGuzman, MConleyx, RStevmt x, KKapp!l. J Ivan x, P Kharabe x, Dept. ObslGyn, Newark Beth Israel Medical Center, Newark, New Jersey, One 01 the proposed advanhges in using phenytoin over MGS04 lor the prevention 01 eclampsia is i1$ lack of eUect on the Ie hi heart rde tracing, However, this has not been subshntiated in the literature, Because of the documented inter- and intra-observer variation in visual interpretation 01 fetal heart rate tracings (FHRT), we used computer anal9sis (SYSTEM 8000) to compare the effec1$ 01 these two medications on the FHRT's 01 30 preeclamptic women, Treatment groups were non-randomized and equal in number, FHRT's of 1hour duration obhined before and after treatment were analyzed in regard to the following parameters: heart rate accelerations ofl0 and 15 bu1$ per minute (BPM), episodes of high and 10'11 variation, and long and short term variability, No other medications were given during the study period, Using biophysical profile testing along with FHRT, all fetuses were considered well during the control period, Statistical analysis of FHRT parameters before and after treatment were analyzed with paired T-Test and statistical significance was reached at p<,05, There was no difference in gestational age, birth'lleight, APGAR scores, and computer scoring of FHRT's between the control periods of both treatment groups, Phenytoin had no effect on any of the computer measured FHRT parameters. On the other hand, MGS04 significantly decreased the frequency of accelerations ofl0 and 15 BPM, as well as short and long term variability, Though not significant, MGS04 doubled the amount 01 time the fetus spent in periods 0110'11 variation, Therefore, the use of phenytoin for eclampsia prophylaxis seems preferable to MGS04 in cases where febl well-being is in question or FHRT interpretation is difficult, as in prematurity.
67 EFFECT
66
68
AN EASILY ADMINISTERED PHENYTOIN REGIMEN FOR THE MANAGEMENT OF PREECLAMPSIA.
Michael lucas, Ralph DePaLma, Mark. Peters, Kenneth
Leveno, David Persons,x F. Gary Cunningham.
Dept. Ob/Gyn, Univ.
of Texas Southwestern Meel. Center I Dallas, Tx.
Current phenytoin regimens for seizure prophylaxis during labor typically involve relatively c~l ieated dosing schemes with varying rates of infusion or RlJltipLe intravenous dosages. Moreover, dosage adj us tments are reconmended based upon body weight. We sought to develop a single regimen that could be used regardless of body weight and that minimized side effects by prolonging the initial infusion. 1 gram of phenytoin was infused over ~ hour and pl asma Leve l s measured in 28 term pregnanci es cClfll>l icated by preeclan..,sia. In 14 of these pregnancies, phenytoin, 500 mg, was adninistered orally 10 hours post infusion. The results are surrnarized below: PLasma Phenytoin /Lg/ml Mean (SO)
IV Regimen (N=14) IV & PO Regimen
(N=14)
1 18(5) 22(6)
Elapsed Time (hours) Post Initiation of Phenytoin Infusion 2 8 16 24 32 11(4) 8(3) 15(5) 6(2) 5(2) 17(6)
13(5)
12(4)
12(4)
11(4)
Side effects were minor and included transient burning at the IV site, mi ld euphoria, dizziness and nystagrTlJs. A mi ld and as"""tomatic decrease in BP was observed in most women. Conment: Assuning that the therapeutic plasma levels for phenytoin in nonpregnant women (10~20 Ilg/ml) appLy during pregnancy, our regimen of a 1 gram phenytoin infusion followed 10 hours later by 500 mg
orally resulted in therapeutic levels for up to 32 hours in all but one woman. This patient weighed 265 lbs. suggesting that only very large women (in excess of 250 lbs.) require dosage adjustment. Moreover, a constant infusion spanning one hour avoids the c~lexities of adjusting infusion rates or giving ITlJltiple intravenous dosages.
OF LOW DOSE ASPIRIN THERAPY ON POLYUNSATURATED FATTY ACIDS IN PREGNANCY. M.C. McCoy,' H,H.Kay, YWang,' A.P.Killam, Dept. Ob/Gyn, Duke Univ" Durham, NC Preeclampsia is reported to be due to an imbalance between thromboxane and prostacyclin. Many investigators have found low dose aspirin (ASA) therapy effective in reducing the incidence and/or severity of preeclampsia because it inhibits cyclooxygenase and decreases thromboxane production, We recently reported that plasma levels of polyunsaturated fatty acids in the n-3 and n-6 classes, which are precursors for prostanoids such as thromboxane and prostacyclin, are decreased in preeclamptic patients. The purpose of this study was to determine if low dose ASA therapy affects the plasma levels of these fatty acid precursors, specifically whether these levels would increase with inhibition of cyclooxygenase, We assayed linoleic, linolenic, arachidonic, eicosapentaenoic and docosahexaenoic acids using HPLC as previously reported (AJOG 164:812,1991), Eleven pregnant patients at risk for preeclampsia or growth retardation were placed on ASA therapy (81 mg/d) at varying gestational ages. Blood was drawn before starting, after 3-4 days and after 3-4 weeks of ASA therapy. Results were analyzed using the two-tailed paired t-test and sign rank test. We found no significant change in the levels of fatty acids either at 3-4 days or 3-4 weeks compared to baseline. Conclusion: low dose ASA does not appear to change the levels of fatty acid precursors of the prostanoids.
CIRCULATING ENDOTHElIN-l IS NOT INCREASED IN PREECLAMPSIA. D. Shah, M. Frazer,' K. Badr.' Dept. of OB/GYN, The University of Texas Health Science Center, San Antonio, TX and Dept. of Internal Medicine, Vanderbilt University School of Medicine, Nashville, TN, Endothelin·1 is a novel, potent vasoconstrictor peptide released by vascular endothelial cells. Preeclampsia is a unique hypertensive disorder of pregnancy. Endothelial cell injury has been implicated in the pathophysiology of this disorder. Endothelial cell injury has been shown in vitro to cause release of
endothelin 1. Therefore, we conducted a prospective study of patients with hypertensive disorders of pregnancy and a control population to examine if circulating levels of endothelin 1 are elevated in these disorders. We studied 21 patients with the following diagnoses: severe preeclampsia (n=9); chronic hypertension (n = 6), of whom two had severe preeclampsia; and control patients (n = 6). The mean maternal age and gestational ages were similar in these three groups. More importantly, severe preeclampsia patients were selected by very strict criteria and most had evidence of thrombocytopenia. Blood samples were collected in cold EDTA tubes containing aprotinin, Endothelin was extracted immediately after collection of blood and measured by a standard radioimmunoassay. There was no difference between the endothelin 1 levels (mean ± SEM) in the patients with severe preeclampsia (2.1 ± 0.6), chronic hypertensives without superimposed preeclampsia (1.9±0.8 ). and the control population (1.7 ± 0.6) Our results are consistent with the current concept that endothelin 1 does not function as a circulating hormone. However, because of its prolonged duration of action and function as a locally acting hormone, demonstration of elevated circulating levels of ET·l is not necessary to support its participation in the vasospasm of preeclampsia.
299
Volume 166 Number I, Part 2
65 ACOMP ARISON OF THE EFFECT OF PHENYTOIN & MGS04 ON FET AL HEART RATE TRACINGS USING COMPUTER ANAL YSIS, EGuzman, MConleyx, RStevmt x, KKapp!l. J Ivan x, P Kharabe x, Dept. ObslGyn, Newark Beth Israel Medical Center, Newark, New Jersey, One 01 the proposed advanhges in using phenytoin over MGS04 lor the prevention 01 eclampsia is i1$ lack of eUect on the Ie hi heart rde tracing, However, this has not been subshntiated in the literature, Because of the documented inter- and intra-observer variation in visual interpretation 01 fetal heart rate tracings (FHRT), we used computer anal9sis (SYSTEM 8000) to compare the effec1$ 01 these two medications on the FHRT's 01 30 preeclamptic women, Treatment groups were non-randomized and equal in number, FHRT's of 1hour duration obhined before and after treatment were analyzed in regard to the following parameters: heart rate accelerations ofl0 and 15 bu1$ per minute (BPM), episodes of high and 10'11 variation, and long and short term variability, No other medications were given during the study period, Using biophysical profile testing along with FHRT, all fetuses were considered well during the control period, Statistical analysis of FHRT parameters before and after treatment were analyzed with paired T-Test and statistical significance was reached at p<,05, There was no difference in gestational age, birth'lleight, APGAR scores, and computer scoring of FHRT's between the control periods of both treatment groups, Phenytoin had no effect on any of the computer measured FHRT parameters. On the other hand, MGS04 significantly decreased the frequency of accelerations ofl0 and 15 BPM, as well as short and long term variability, Though not significant, MGS04 doubled the amount 01 time the fetus spent in periods 0110'11 variation, Therefore, the use of phenytoin for eclampsia prophylaxis seems preferable to MGS04 in cases where febl well-being is in question or FHRT interpretation is difficult, as in prematurity.
67 EFFECT
66
68
AN EASILY ADMINISTERED PHENYTOIN REGIMEN FOR THE MANAGEMENT OF PREECLAMPSIA.
Michael lucas, Ralph DePaLma, Mark. Peters, Kenneth
Leveno, David Persons,x F. Gary Cunningham.
Dept. Ob/Gyn, Univ.
of Texas Southwestern Meel. Center I Dallas, Tx.
Current phenytoin regimens for seizure prophylaxis during labor typically involve relatively c~l ieated dosing schemes with varying rates of infusion or RlJltipLe intravenous dosages. Moreover, dosage adj us tments are reconmended based upon body weight. We sought to develop a single regimen that could be used regardless of body weight and that minimized side effects by prolonging the initial infusion. 1 gram of phenytoin was infused over ~ hour and pl asma Leve l s measured in 28 term pregnanci es cClfll>l icated by preeclan..,sia. In 14 of these pregnancies, phenytoin, 500 mg, was adninistered orally 10 hours post infusion. The results are surrnarized below: PLasma Phenytoin /Lg/ml Mean (SO)
IV Regimen (N=14) IV & PO Regimen
(N=14)
1 18(5) 22(6)
Elapsed Time (hours) Post Initiation of Phenytoin Infusion 2 8 16 24 32 11(4) 8(3) 15(5) 6(2) 5(2) 17(6)
13(5)
12(4)
12(4)
11(4)
Side effects were minor and included transient burning at the IV site, mi ld euphoria, dizziness and nystagrTlJs. A mi ld and as"""tomatic decrease in BP was observed in most women. Conment: Assuning that the therapeutic plasma levels for phenytoin in nonpregnant women (10~20 Ilg/ml) appLy during pregnancy, our regimen of a 1 gram phenytoin infusion followed 10 hours later by 500 mg
orally resulted in therapeutic levels for up to 32 hours in all but one woman. This patient weighed 265 lbs. suggesting that only very large women (in excess of 250 lbs.) require dosage adjustment. Moreover, a constant infusion spanning one hour avoids the c~lexities of adjusting infusion rates or giving ITlJltiple intravenous dosages.
OF LOW DOSE ASPIRIN THERAPY ON POLYUNSATURATED FATTY ACIDS IN PREGNANCY. M.C. McCoy,' H,H.Kay, YWang,' A.P.Killam, Dept. Ob/Gyn, Duke Univ" Durham, NC Preeclampsia is reported to be due to an imbalance between thromboxane and prostacyclin. Many investigators have found low dose aspirin (ASA) therapy effective in reducing the incidence and/or severity of preeclampsia because it inhibits cyclooxygenase and decreases thromboxane production, We recently reported that plasma levels of polyunsaturated fatty acids in the n-3 and n-6 classes, which are precursors for prostanoids such as thromboxane and prostacyclin, are decreased in preeclamptic patients. The purpose of this study was to determine if low dose ASA therapy affects the plasma levels of these fatty acid precursors, specifically whether these levels would increase with inhibition of cyclooxygenase, We assayed linoleic, linolenic, arachidonic, eicosapentaenoic and docosahexaenoic acids using HPLC as previously reported (AJOG 164:812,1991), Eleven pregnant patients at risk for preeclampsia or growth retardation were placed on ASA therapy (81 mg/d) at varying gestational ages. Blood was drawn before starting, after 3-4 days and after 3-4 weeks of ASA therapy. Results were analyzed using the two-tailed paired t-test and sign rank test. We found no significant change in the levels of fatty acids either at 3-4 days or 3-4 weeks compared to baseline. Conclusion: low dose ASA does not appear to change the levels of fatty acid precursors of the prostanoids.
CIRCULATING ENDOTHElIN-l IS NOT INCREASED IN PREECLAMPSIA. D. Shah, M. Frazer,' K. Badr.' Dept. of OB/GYN, The University of Texas Health Science Center, San Antonio, TX and Dept. of Internal Medicine, Vanderbilt University School of Medicine, Nashville, TN, Endothelin·1 is a novel, potent vasoconstrictor peptide released by vascular endothelial cells. Preeclampsia is a unique hypertensive disorder of pregnancy. Endothelial cell injury has been implicated in the pathophysiology of this disorder. Endothelial cell injury has been shown in vitro to cause release of
endothelin 1. Therefore, we conducted a prospective study of patients with hypertensive disorders of pregnancy and a control population to examine if circulating levels of endothelin 1 are elevated in these disorders. We studied 21 patients with the following diagnoses: severe preeclampsia (n=9); chronic hypertension (n = 6), of whom two had severe preeclampsia; and control patients (n = 6). The mean maternal age and gestational ages were similar in these three groups. More importantly, severe preeclampsia patients were selected by very strict criteria and most had evidence of thrombocytopenia. Blood samples were collected in cold EDTA tubes containing aprotinin, Endothelin was extracted immediately after collection of blood and measured by a standard radioimmunoassay. There was no difference between the endothelin 1 levels (mean ± SEM) in the patients with severe preeclampsia (2.1 ± 0.6), chronic hypertensives without superimposed preeclampsia (1.9±0.8 ). and the control population (1.7 ± 0.6) Our results are consistent with the current concept that endothelin 1 does not function as a circulating hormone. However, because of its prolonged duration of action and function as a locally acting hormone, demonstration of elevated circulating levels of ET·l is not necessary to support its participation in the vasospasm of preeclampsia.
299