Effect of intravenous cocaine on uterine blood flow in the gravid baboon

Cocaine abuse during pregnancy is associated with adverse perinatal outcome, believed to be a result of potent vasoconstrictive effects that cocaine has on the maternal cardiovascular system. The direct effect of cocaine on the pregnant, nonhuman primates' uterine vasculature in vivo has not been examined. We investigated the effects of intravenous cocaine on maternal arterial blood pressure, uterine blood flow, and uterine vascular resistance in four unanesthetized, chronically instrumented pregnant baboons. Baboons were instrumented during the latter half of pregnancy, placing an ultrasonic flow probe around one uterine artery and catheters in the maternal inferior vena cava and aorta. Bolus intravenous cocaine hydrochloride doses of 0.05 mg/kg, 0.1 mg/kg, and 0.3 mg/kg by maternal weight were infused 30 minutes apart at least 5 days after surgical instrumentation. The maternal blood pressure rose 7.3% and 12.0% after the 0.1 mg/kg and 0.3 mg/kg cocaine infusions, respectively, and the uterine blood flow fell in a dose-dependent fashion 13.1% and 22.7%. Plasma norepinephrine levels rose in response to the 0.3 mg/kg cocaine infusion. These studies show that low doses of cocaine significantly reduce uterine blood flow in the pregnant baboon in a dose-dependent manner by increasing uterine vascular resistance.     

Fetal catecholamine, cardiovascular, and neurobehavioral responses to cocaine.

OBJECTIVE: Although maternal cocaine administration results in fetal cardiovascular and behavioral alterations, these responses have been attributed to hypoxia resulting from reduced uteroplacental blood flow. We studied the fetal catecholamine, cardiovascular, and neurobehavioral responses to direct fetal cocaine administration. STUDY DESIGN: Cardiovascular, electrocortical, and electroocular responses and plasma catecholamines were monitored in chronically catheterized fetal sheep (n = 7), 127 +/- 2 days' gestation, during a control period and after intravenous fetal injections of cocaine 0.5 and 1.0 mg/kg. RESULTS: Intravenous cocaine caused prompt increases in fetal plasma norepinephrine (372 +/- 73 to 531 +/- 112 and 842 +/- 233 pg/ml), epinephrine (27 +/- 7 to 46 +/- 13 and 49 +/- 11 pg/ml), and systolic blood pressure (46 +/- 2 to 53 +/- 2 and 55 +/- 2 mm Hg). Low-voltage electrocortical activity decreased from 61.7% +/- 3.0% to 38.4% +/- 3.9% in the first hour after the cocaine 0.5 mg/kg dose but recovered to baseline values during the second hour. After the cocaine 1.0 mg/kg dose, low-voltage electrocortical activity decreased to 40.7% +/- 2.0% and did not recover thereafter. Fetal blood gas values did not change. CONCLUSION: Direct fetal cocaine administration increases fetal plasma catecholamine levels and fetal blood pressure and suppresses low-voltage electrocortical activity. Chronic cocaine exposure may hamper central nervous system maturation and alter postnatal development.     

Effect of alpha 1 receptor blockade upon maternal and fetal cardiovascular responses to cocaine

Previous studies in pregnant ewes have demonstrated that intravenous (IV) cocaine produces increased maternal blood pressure and vasoconstriction of the uterine arteries, resulting in decreased uterine blood flow and decreased fetal oxygen levels. To determine whether these responses to cocaine were mediated by alpha 1-adrenergic receptor stimulation, cocaine was administered to four pregnant ewes before and after phenoxybenzamine hydrochloride, an alpha 1 receptor antagonist. Before phenoxybenzamine infusion, cocaine 2.0 mg/kg produced a 53% increase in maternal mean arterial pressure (MAP), a 50% reduction in total uterine blood flow, and a 191% increase in uterine vascular resistance. Cocaine also increased fetal MAP by 24%, increased the fetal heart rate (FHR) by 51%, and reduced fetal PO2 by 29%. Alpha 1 receptor blockade after phenoxybenzamine 5.0 mg/kg was confirmed by a lack of change in uterine blood flow to IV norepinephrine 30 micrograms before cocaine administration. After phenoxybenzamine, cocaine produced no increase in maternal or fetal MAP. However, total uterine blood flow decreased 44%, uterine vascular resistance increased 59%, FHR increased 36%, and fetal PO2 fell 18%. Because the fetal responses mimicked the maternal responses to cocaine both before and after phenoxybenzamine, phenoxybenzamine apparently crossed the placenta to block fetal alpha 1 receptors as well. Alpha 1-adrenergic receptor stimulation is the major mechanism for the maternal and fetal hypertensive responses to cocaine. Although cocaine produces uterine artery vasoconstriction primarily by alpha 1 adrenergic receptor stimulation, its vasoconstrictive effects may involve other vasoactive neurotransmitters, such as dopamine or serotonin.     

Effect of maternal cocaine administration on maternal and fetal glucose, lactate, and insulin in sheep

Although cocaine use during pregnancy is an important cause of perinatal morbidity and mortality, there are no reports of its effect on maternal and fetal carbohydrate metabolism. Six pregnant ewes and their fetuses were instrumented under halothane general anesthesia at 113-119 days' gestation. Between 124-135 days' gestation, the ewes received a single infusion of vehicle or cocaine (1.0 or 2.0 mg/kg) into the jugular vein. At least 24 hours was allowed between successive injections. Maternal and fetal blood samples were drawn at 30 and 20 minutes before and at 5, 15, 30, and 60 minutes after the injection. Both maternal and fetal glucose and lactate concentrations increased (P less than .05) after injection of cocaine at 2.0 mg/kg. There were no significant changes in maternal or fetal plasma insulin concentrations after vehicle or cocaine administration. Induction of hyperglycemia and lactacidemia could be mechanisms whereby cocaine exerts its adverse effects during pregnancy.     

Cocaine in pregnancy: the effect of maternal administration of cocaine on the maternal and fetal pituitary-adrenal axes.

The effects of cocaine on the maternal and fetal pituitary-adrenal axis in vivo during pregnancy have not been reported. Six pregnant ewes and their fetuses underwent instrumentation at 113 to 119 days' gestation. Ewes were assigned to receive an intravenous bolus injection of vehicle or cocaine (0.5, 1.0, or 2.0 mg.kg-1) at 124 to 136 days' gestation. Maternal arterial blood gases, fetal pH and fetal PCO2 were unchanged after injection of cocaine or vehicle. After administration of 2.0 mg.kg-1 cocaine, arterial fetal PO2 fell 3.2 +/- 1.72 mm Hg (p less than 0.05) at +5 minutes, returning to baseline by +15 minutes. Maternal and fetal adrenocorticotropin levels rose within 5 minutes after the highest cocaine dose (p less than 0.05). There was a significant (p less than 0.05) increase in maternal cortisol at all doses of cocaine and in fetal cortisol at +15 minutes after the 2.0 mg.kg-1.     

Ovine fetal cardiorespiratory response to nicardipine

Nicardipine, a calcium antagonist associated with decreased uterine blood flow in near-term pregnant rabbits and fetal asphyxia after maternal administration in the rhesus monkey and sheep, was infused directly to the fetus in six chronically prepared pregnant ewes at 128 days' gestation. Changes in fetal mean arterial and diastolic blood pressure levels at 2 and 30 minutes after bolus injection of 50 micrograms were minimal; by 60 minutes these values had returned to preinfusion levels. No significant changes were observed after infusion of 100 micrograms of nicardipine. Fetal heart rate, fetal arterial blood gas values, and maternal cardiovascular variables did not change at either dose. Fetal plasma concentrations of nicardipine were 78 +/- 28 ng/ml and 114 +/- 48 ng/ml at 30 minutes after infusion of 50 micrograms and 100 micrograms, respectively, well within the range previously reported to be associated with fetal asphyxia. These data suggest that the previously reported fetal acidosis from maternal infusion of nicardipine may be primarily due to a decrease in maternal uterine blood flow rather than a direct fetal effect of the drug.     

Effect of continuous infusion of fenoterol on maternal pelvic and fetal umbilical blood flow in pregnant sheep

The results from studies on the reactions of the uterine vascular bed upon intravenous administrations of beta-adrenergic drugs to the ewe are not all identical. This can be partly explained by different reactions of the pelvic vasculature on beta-adrenergic receptor stimulation. In order to assess whether any differences in flow reactions existed between the vascular beds of two maternal pelvic vessels upon beta-adrenergic receptor stimulation, we studied the effect of continuous maternal intravenous infusion with fenoterol on the blood flow in the maternal internal iliac and the median uterine artery in seven chronically instrumented pregnant sheep between 104 and 142 days gestation. Furthermore, the effects on umbilical venous blood flow, fetal heart rate, blood pressure and acid-base balance were analyzed. Maternal and fetal blood flows were measured with electromagnetic flow transducers. Fenoterol was administered to the ewe via a continuous intravenous infusion in two sequential periods of 30 minutes duration in a dose of 2 respectively 4 micrograms per minute. The blood flow in the internal iliac artery showed an increase of 10.5% (p less than 0.05) at the end of the infusion period and was still but not significantly elevated during the postinfusion period. No significant changes in median uterine artery blood flow were found during the fenoterol infusion, although an incremental trend was present. Fenoterol infusion to the mother had no effect on umbilical venous blood flow. Fetal pH and PO2 did not change, while fetal PCO2 was reduced (p less than 0.005) at the end of the infusion and recovery period, probably as a result of the concomitant maternal hyperventilation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Lack of effect of maternal cocaine administration on myometrial electromyogram and maternal plasma oxytocin concentrations in pregnant sheep at 124-146 days' gestational age.

Although cocaine abuse during human pregnancy is associated with an increased incidence of preterm labor, there are few reports on the effects of cocaine on myometrial activity during pregnancy in experimental animals. Cocaine (0.5, 1, or 2 mg/kg) or vehicle was randomly administered intravenously to 15 pregnant ewes between 124-146 days' gestation (term is 147 days). Neither cocaine nor vehicle administration altered total myometrial electromyographic activity from pre-dose levels 1 or 6 hours after administration. Maternal arterial plasma oxytocin did not change during the study. Using a positive control, we confirmed observations of other investigators that administration of 2 mg/kg cocaine significantly increases maternal arterial blood pressure. The results indicate that cocaine does not stimulate myometrial contractility significantly in late pregnancy in sheep.     

Does indomethacin alter the hemodynamic response to magnesium sulfate infusion and hemorrhage in gravid ewes?

The purpose of this study was to determine whether indomethacin alters the maternal and fetal hemodynamic response to magnesium sulfate (MgSO4) infusion and hemorrhage in gravid ewes. We studied seven chronically instrumented animals between 0.8 and 0.9 of timed gestation. The experimental sequence included: 1) at time 0, indomethacin, 2 mg/kg, or vehicle only intravenously (IV) over 5 minutes; 2) at 60 minutes, MgSO4 4 g IV over 5 minutes; 3) at 65 minutes, MgSO4 infusion at 4 g/hour; 4) at 150 minutes, maternal hemorrhage, 20 mL/kg, over 60 minutes; and 5) at 215 minutes, reinfusion of maternal blood over 60 minutes. Each animal was studied with and without indomethacin. Indomethacin, but not vehicle only, transiently increased maternal and fetal mean arterial pressure (MAP), decreased maternal and fetal heart rate, and decreased maternal cardiac output. Magnesium sulfate significantly decreased uterine vascular resistance and increased uterine blood flow both with and without indomethacin. Hemorrhage significantly decreased maternal MAP, heart rate, cardiac output, and uterine blood flow in both groups. The magnitude of each change was similar between the groups. For example, at the end of hemorrhage, maternal MAP was 36 +/- 7% below baseline (P = .0001) with indomethacin and 41 +/- 2% below baseline (P = .0001) in the vehicle-only group (P = not significant between groups). Hemorrhage significantly decreased fetal heart rate, pH, and PO2, and increased fetal MAP and PCO2 in both groups. We conclude that indomethacin did not alter the maternal or fetal hemodynamic response to MgSO4 infusion and hemorrhage in gravid ewes.     

Failure of exogenous prostacyclin to change placental and fetal blood flow in preeclampsia

Seven patients with acute preeclampsia and six with superimposed preeclampsia were infused intravenously with incremental doses of prostacyclin (up to 8 ng/min/kg during 80 minutes). Prostacyclin infusion was accompanied by significant decreases in maternal blood pressure and consistent rises in maternal plasma or urinary 6-keto-prostaglandin F1 alpha, but it caused no changes in maternal or fetal pulse rate or uterine contractility. Moreover, prostacyclin did not change the placental and umbilical blood flow, which were measured before and at the end of infusion. All women experienced facial flushing and two complained of headache during infusion. There was no difference in prostacyclin effects between women with acute or superimposed preeclampsia. These results may be taken as evidence that intravenous prostacyclin is not a specific therapy to increase placental or umbilical blood flow in preeclampsia.     

Pregnancy increases cardiovascular toxicity to cocaine

The effects of intravenous cocaine on heart rate and blood pressure were studied in pregnant and oophorectomized nonpregnant ewes. In response to intravenous cocaine doses of 1.0 and 2.0 mg/kg, both pregnant and nonpregnant ewes demonstrated dose-dependent increases in systolic, diastolic, mean arterial, and pulse pressures with return to baseline by 30 to 60 minutes after cocaine administration. However, at both doses (1.0 and 2.0 mg/kg) pregnant ewes demonstrated greater increases in mean arterial pressure (+29.6%, +48.7%) than nonpregnant ewes (+15.6%, +27.7%) during the first 5 minutes after cocaine administration. Thereafter the responses were similar. Thus pregnancy increases the cardiovascular toxicity to cocaine.     

The effect of nicotine on fetal breathing movements in conscious pregnant ewes.

Nicotine (0.14--0.25 mg/kg), injected intravenously or intraarterially into conscious pregnant ewes, caused a decrease in fetal PaO2 within 5 minutes, persisting for up to 30 minutes. There was a significant fall in the incidence of fetal breathing movements. These changes did not occur if the ewe was treated with an alpha-blocking agent (phentolamine) or if the nicotine was infused for 30 minutes at 0.27 to 0.85 mg/minute. Nicotine crossed the placenta; fetal concentrations equaled those in the ewe 5 minutes after the injection and remained at or above maternal levels for 1 hour. Nicotine given directly to the fetus (0.005--0.03 mg/kg estimated fetal weight) stimulated fetal breathing movements in a dose-related manner. We suggest that the maternal injection of nicotine results in a fall of uterine blood flow by a sympathomimetic action, leading to transient fetal hypoxemia and a reduction of fetal breathing movements and that a similar phenomenon may occur when a pregnant woman smokes cigarettes.     

Nitroglycerin application during cesarean delivery: plasma levels, fetal/maternal ratio of nitroglycerin, and effects in newborns

OBJECTIVE: We sought to investigate maternal and fetal nitroglycerin metabolization and to assess the clinical condition of neonates after intravenous nitroglycerin application during cesarean delivery. STUDY DESIGN: At the time of the uterine puncture incision, either 0. 25 mg or 0.5 mg nitroglycerin or a physiologic sodium chloride solution was administered as an intravenous bolus. Plasma concentrations of nitroglycerin and its metabolites were measured in maternal venous blood and in umbilical blood samples taken immediately after cord clamping. Arterial blood pressure, pulse rates, and Apgar scores were recorded for the neonates 1, 5, and 10 minutes after birth. RESULTS: Sixty-two patients were included in the pharmacokinetic study. Median maternal plasma levels 1 and 5 minutes after injection of 0.5 mg nitroglycerin were 80 and 3.2 ng/mL, respectively; median maternal plasma levels 1 and 5 minutes after injection of 0.25 mg nitroglycerin were 38 and 1.2 ng/mL, respectively. In the umbilical vein 1 minute after application of 0. 5 mg or 0.25 mg nitroglycerin, the plasma levels were 0.41 and 0.09 ng/mL, respectively, and in the umbilical artery they were 0.03 and 0.008 ng/mL, respectively. Circulatory parameters and Apgar scores in the neonates did not differ significantly from those found in the placebo group. CONCLUSION: The level of nitroglycerin in umbilical plasma was two to three orders of magnitude lower than that found in maternal plasma and clearly in a subtherapeutic range. There was no indication that prenatal application of nitroglycerin to facilitate obstetric management is hazardous for neonates.     

Effects of ethanol on the circulation and acid-base balance of pregnant sheep

Nine infusions of 15 cc/kg/120 min of 9.5% ethanol were administered to 4 chronically catheterized ewes, at 109-135 days' gestation. Stabilization periods ranged from 6 to 28 days postoperatively. Maternal and fetal concentrations of ethanol were almost identical (r = 0.9925), with peak levels of 122 +/- 20 mg/100 ml (mean +/- 1 SE) and 121 +/- 19 mg/100 ml, respectively, at the end of infusion. Maternal pH decreased from 7.50 +/- 0.02 to 7.44 +/- 0.02 (P less than 0.005) at 120 minutes. Maternal glycemia increased from 76 +/- 14 mg/100 ml to 162 +/- 23 mg/100 ml (P less than 0.005) at 120 minutes. Maternal heart rate, blood pressure, PO2, O2 content, PCO2, and bicarbonate remained unchanged. Fetal PO2 increased during and following infusion from 18.9 +/- 0.9 mmHg to 22.0 +/- 1.0 mmHg (P less than 0.005) at 180 minutes. Fetal blood pressure increased from 51.3 +/- 3.1 mmHg to 53.7 +/- 3.3 mmHg (P less than 0.01) at 30 minutes. Fetal pH, PCO2, glucose, and lactate levels remained unchanged. The authors conclude that ethanol crosses the sheep placenta readily, causes maternal acidosis and hyperglycemia, and increases fetal PO2, blood pressure, and heart rate without any effects on fetal acid-base status.     

Single dose of labetalol in hypertensive pregnancy: effects on maternal hemodynamics and uterine and fetal flow velocity waveforms.

The short-term effect of 0.8 mg/kg of an intravenous bolus of labetalol on maternal and fetal hemodynamics was investigated in ten women with pregnancy-induced hypertension. The maximum effect occurred within 35 minutes after labetalol administration. At that point, the mean arterial pressure had decreased by 18% and there was a slight decrease in maternal heart rate. As to flow velocity waveforms, no significant change was found in mean systolic/diastolic (S/D) ratio of the uterine artery, umbilical artery or fetal middle cerebral artery. However, in two subjects with a marked reduction in blood pressure also the uterine artery S/D ratio decreased.     

Placental transfer of the thromboxane synthetase inhibitor ridogrel in the late-pregnant ewe.

OBJECTIVES: To assess the occurrence of placental transfer of the thromboxane synthetase inhibitor ridogrel in the pregnant ewe and to determine its effect on prostanoid levels in the ewe and fetal lamb, on uterine contractility and on maternal and fetal hemodynamics. STUDY DESIGN: Five chronically instrumented pregnant ewes at 122 days of gestation received intravenous infusions of 5 mg/kg/3 h ridogrel and solvent. Maternal and fetal arterial samples were obtained at predetermined intervals to determine concentrations of ridogrel and prostaglandin metabolites TXB2, 6-keto-PGF1alpha, PGF2alpha, and PGE2. Maternal and fetal responses of blood flow and pressures were determined. RESULTS: Fetal ridogrel levels were 25% of maternal concentrations. Ridogrel showed rapid and marked thromboxane synthetase inhibition and augmentation of levels of prostaglandin metabolites. There was no evidence of change in amniotic pressure, uterine blood flow, maternal and fetal blood pressure and heart rate. CONCLUSION: Ridogrel is a potent thromboxane synthetase inhibitor which passes the sheep placenta, does not influence maternal and fetal hemodynamics and uterine contractility, and shows similar antiplatelet activity in the ewe and the fetal lamb.     

Intravenous clonidine hydrochloride toxicity in pregnant ewes

Administration of intravenous clonidine hydrochloride has been advocated to rapidly control blood pressure in severe preeclampsia. To examine clonidine's acute maternal and fetal effects were intravenously injected 300 micrograms clonidine in eight chronically prepared normotensive near term ewes. Unlike intravenous saline solution injection, clonidine produced significant toxicity--intraamniotic pressure increased 97 +/- 27% (p less than 0.05), uterine blood flow decreased 55 +/- 7% (p less than 0.001), maternal and fetal serum glucose increased 158 +/- 23% and 249 +/- 91%, respectively (p less than 0.001), and maternal and fetal Po2 decreased to 44 mm Hg +/- 4 mm Hg and 13 mm Hg +/- 1 mm Hg, respectively (p less than 0.05). Maternal and fetal blood pressure and serum cortisol were unaffected by clonidine, whereas heart rate decreased. No adverse maternal or fetal effects were noted with serum clonidine concentrations less than 1.0 ng/ml. Direct fetal infusion of clonidine did not lower fetal arterial Po2 levels, although heart rates decreased and serum glucose levels increased. The multiple effects of clonidine infusion are best explained by actions on alpha 2-adrenergic receptors. These results suggest that intravenous administration of clonidine may adversely affect the fetus by direct actions and by alterations in maternal physiology.     

Effects of diazoxide on maternal and fetal circulations in normotensive and hypertensive pregnant sheep

Diazoxide is a potent antihypertensive agent due to its peripheral vasodilator action. For this reason it is used in the management of hypertensive crises in pregnancy. To assess the effects of an intravenous bolus injection of diazoxide on maternal and fetal hemodynamics an experimental study was performed in 11 chronically instrumented pregnant sheep. In six ewes hypertension was induced by surgical removal of one kidney and reduction of arterial blood flow to the remaining kidney (one-kidney renovascular hypertension). The other five ewes remained normotensive. In a second operation, one week after the first one, the animals were equipped with electromagnetic flow transducers and catheters for monitoring of blood flow in a renal, a uterine, and an umbilical artery and for measurement of maternal and fetal arterial blood pressures, and blood sampling. Maternal heart rate was derived from the arterial pressure curve, fetal heart rate from a fetal ECG. Experiments were begun on the third day after the second operation. In each experiment a bolus of 300 mg of diazoxide was administered intravenously, with or without rapid simultaneous infusion of 500 ml of a plasma expander. A total of 17 experiments were performed in the one-kidney hypertensive ewes (Group H), nine with and eight without plasma expander. In the five normotensive animals (Group NH) 10 experiments were done, four with and six without plasma expansion. During the control periods maternal arterial pressure was approximately 30 mm Hg higher in Group H than in Group NH. In Group H also maternal heart rate, and renal and uterine vascular resistances were significantly elevated. All fetal variables were equal in both groups. Administration of diazoxide without simultaneous plasma expansion resulted in both groups in a significant fall in maternal arterial pressure, a rise in maternal heart rate, and a fall in uterine and renal blood flows with a rise in vascular resistance. Fetal arterial pressure and umbilical blood flow showed no significant changes, but fetal heart rate showed a transient fall together with a drop in fetal pO2 and pH, although acidosis did not occur. When diazoxide was combined with a plasma expander maternal blood pressure did not change significantly in Group NH, but fell in Group H. Maternal heart rate rose significantly in both groups. The decrease in uterine and renal blood flows which occurred when diazoxide was given without plasma expansion was not observed.(ABSTRACT TRUNCATED AT 400 WORDS)     

Maternal estradiol response to alterations in uteroplacental blood flow

Low levels of maternal estrogens are commonly regarded as indicators of fetal stress. We continuously monitored distal aortic blood flow by flowmeter, fetal heart rate, and amniotic fluid pressure in seven pregnant baboons near term. Four of the animals received a constant intravenous infusion of [7-3H]dehydroepiandrosterone and [4-14C]estradiol for 270 minutes. A 50% reduction in mean distal aortic blood flow was imposed after 60 minutes by means of partial occlusion of the aorta with a snare device and released at 180 minutes. Blood was collected at 10-minute intervals from 30 to 60 minutes, 120 to 180 minutes, and 240 to 270 minutes. Concentrations of dehydroepiandrosterone, dehydroepiandrosterone sulfate, estradiol, and cortisol in maternal plasma were determined by radioimmunoassay. Metabolic clearance rates of dehydroepiandrosterone and estradiol were calculated from plasma concentrations of [3H]dehydroepiandrosterone and [14C]estradiol. There was no significant change in maternal levels of dehydroepiandrosterone, dehydroepiandrosterone sulfate, or cortisol with alterations in distal aortic blood flow. Three animals exhibited no fetal heart rate evidence of fetal stress; estradiol levels declined during occlusion and returned toward control after release of the snare. Four animals exhibited repetitive late decelerations under conditions of reduced flow; estradiol was unchanged or rose slightly during occlusion but increased three- to 10-fold after release whereas the metabolic clearance rate of both dehydroepiandrosterone and estradiol remained stable. We conclude that placental hypoperfusion without fetal stress results in decreased conversion of aromatizable substrate and elevated maternal estradiol levels during acute hypoxemic fetal stress probably represent increased production of fetal androgen.     

Maternal and fetal effects of low-dosage bupivacaine paracervical block

Vasoconstriction of the uterine arteries, hypertonus of the uterus, and the direct toxic effects of a local anesthetic on the fetus or a combination of the above have been presented as etiological factors of fetal bradycardia following paracervical block. The reduce fetal side-effects a superficial and lowdosage technique of PCB have been advocated. We have studied the effects of 25 mg of bupivacaine PCB using the above technique on fetal heart rate pattern (FHR), fetal acid-base balance, uterine activity, placental blood flow and maternal and fetal plasma levels of bupivacaine in 38 patients. The analgesic effect of a single 25 mg of bupivacaine PCB was good in 76%, moderate in 12% and poor in 12% of the cases. No changes in maternal heart rate or in blood pressure were noted. Fetal bradycardia defined as a decrease of mean fetal heart rate of at least 20 bpm or an absolute rate less than 100 bpm and a duration greater than two minutes occurred in 12% of the cases. The mean amplitude of the baseline fetal heart rate variability decreased significantly after PCB and a silent pattern (an amplitude less than 5 bpm) was observed in 20% of the cases. The most frequent (27%) pathological finding in our study was the disappearance of FHR accelerations after PCB. Similarly early and late decelerations of FHR occurred more often after PCB than during the control period before the block. The fetal pH from scalp blood samples did not, on average, decrease after PCB, but did so in cases with fetal bradycardia. Intervillous blood flow as measured by the 133Xe washout method did not change when measured before and after PCB. In addition in three cases with fetal bradycardia the changes in the intervillous blood flow were minimal. No significant changes in the mean uterine tone, amplitude and frequency of contractions were observed after PCB. However, an obvious uterine hypertonus was observed after PCB was observed in three cases of fetal bradycardia but not in two other cases of bradycardia or in the 8 cases of silent FHR pattern. Mean maternal bupivacaine concentration 20 minutes after PCB was 0.14 +/- 0.06 microgram/ml and 0.07 +/- 0.04 microgram/ml at birth. Simultaneous fetal and umbilical venous and arterial concentrations were correspondingly 0.04 +/- 0.02 microgram/ml, 0.03 +/- 0.01 microgram/ml and 0.03 +/- 0.01 microgram/ml, and they were significantly lower than respective maternal concentrations.(ABSTRACT TRUNCATED AT 400 WORDS)