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)     

Transfer of lidocaine across the sheep placenta to the fetus. Hemodynamic and acid-base responses of the fetal lamb.

Placental transfer of lidocaine administered to pregnant sheep and removal of the drug from the fetal circulation were determined. Responses of the hemodynamic and acid-base state in the mother and fetus were also studied. Lidocaine readily crossed the placenta and appeared in the fetal blood as early as one minute following injection. Disappearance of lidocaine in the asphyxiated fetus tended to be slower than in the normal one. Lidocaine produced a transient fall in the fetal heart rate which was accompanied by a decrease in blood pH and oxygenation. Lidocaine also reduced umbilical blood flow and, in some instances, uterine blood flow. Decrease in umbilical blood flow was more pronounced in the initially asphyxiated fetus.     

Effect of nicotine upon uterine blood flow in the pregnant rhesus monkey

Acute effects of nicotine upon the uterine blood flow, blood pressure, maternal and fetal acid-base state, and oxygenation were determined in eight pregnant rhesus monkeys near term. Nicotine was infused intravenously to the mother in a dose of 100 microgram/kg per body weight/minute over 20 minutes. The flow rate was measured with the use of the electromagnetic flowmeter. Significant decrease in the uterine arterial blood flow rate, as much as 38% of the control value, was observed during the first 15 minutes of the infusion while aortic pressure increased by 14%. Acidosis and hypoxia resulted in the fetus. Considered together with our previously reported data, the present investigation appears to indicate that the adverse effects of nicotine to the fetus are due to the combined effects of the reduced uterine blood flow and the transmitted nicotine to the fetus.     

Fetal heart rate and uterine activity following paracervical block

Bupivacaine without adrenaline was used for paracervical block (PCB) anesthesia in 60 low-risk parturients in whom there were no signs of fetal asphyxia. In order to evaluate its effects on fetus and uterine activity, 30 patients were given a "high dose" of 50 mg Bupivacaine, an amide-type local anesthetic agent, while 30 patients were given a "low dose" of 25 mg. Continuous fetal heart rate (FHR) monitoring in both study groups revealed nine patients with typically post PCB bradycardia and five patients with moderate PHR depression. All of them were born with excellent Apgar score. Although a decrease in fetal heart rate following PCB was noted in both groups more significant reduction was associated with the high dose block (P less than 0.05). In 11 cases, FHR depression was clearly associated with increased uterine activity, while in another three cases it was not (P less than 0.005). Oxytocin administration during the block did not affect fetal heart rate or uterine activity. The results indicate that FHR depression following PCB using Bupivacaine is dose dependent, transient and not dangerous to a normal fetus. No adverse maternal effects were noted. It is suggested that fetal heart rate depression following PCB using Bupivacaine is related to increased uterine activity.     

Maternal, fetal and neonatal effects of beta-adrenergic stimulation in connection with cesarean section

To investigate the combined metabolic effects of beta-mimetic therapy and general anesthesia on maternal and fetal/neonatal metabolism, 14 patients were treated with isotonic saline, 11 with intravenous fenoterol (3 microgram/min) and 9 with intravenous isoxsuprine (150 microgram/min) for 30 minutes prior to cesarean section. The maternal heart rate and blood pressure as well as the maternal and fetal acid-base balance were followed. The neonatal glucose level was monitored for 36 hours after delivery. The heart rate and the diastolic and systolic blood pressure values increased during the operation in each group, without any marked differences between the groups. At delivery, the mean maternal BD (base-deficit) value was higher in the fenoterol patients than in the control patients, indicating a trend towards metabolic acidosis. The other values of acid-base balance in the maternal and umbilical arterial and venous blood did not reveal any differences between the groups. The neonatal glucose level at 2 hours after delivery was higher in the fenoterol group than in the control group. The other values recorded during 36 hours revealed no differences between the groups. Beta-mimetic treatment preceding general anesthesia in cesarean section does not have unfavorable effects on the mother, the fetus or the newborn. Such therapy thus does not seem contraindicated when uterine contractions should be rapidly suppressed in cases of fetal distress before operation.     

Effects of uterine contraction and a beta-stimulant on placental and fetal brain blood flow in correlation with fetal heart rate changes

The effects of uterine contraction on placental and fetal brain blood flow in correlation with fetal heart rate change and also beta-stimulant on placental and fetal brain blood flow during late deceleration were studied in late pregnant rabbits. We determined the fetal heart rate (FHR) and placental and fetal brain blood flow by a thermocouple method under urethane anesthesia. Fetuses exposed to a more than 30% decrease in placental blood flow by uterine contraction developed more than 20% bradycardia and also a significant decrease in fetal brain blood flow. There are a significant relationship between the decrease in FHR and fetal brain blood flow. beta-stimulant administered to the mother suffering from already severely hypoxic fetal bradycardia increased FHR in accordance with the increase in the placental blood flow and moreover there was recovery from decreased fetal brain blood flow.     

Maternal and fetal hemodynamic effects of diazoxide.

Effects of diazoxide on systemic and uterine hemodynamics as well as on fetal circulation and blood respiratory gases were investigated in chronically instrumented pregnant sheep. Diazoxide was administered intravenously either to the ewe or directly to the fetus in doses calculated on the basis of body weight. Transfer of drug across placenta was also investigated. Results showed that: a) when injected into the mother, there was consistent hypotensive effect with increased cardiac output and decreased systemic vascular resistance; uterine blood flow might not change or might decrease slightly with moderate hypotension; when maternal systemic arterial pressure fell to critical closing pressure level, uterine flow decreased significantly; but despite these maternal changes, the fetal circulatory functions were not significantly altered; b) when injected into the fetus in doses up to 15 mg/kg, diazoxide failed to alter fetal circulation appreciably; c) diazoxide crossed the placenta when injected intoeither mother or fetus according to a definite gradient; fetal levels were always lower than maternal levels because of rapid loss of the drug by the fetus; d) moderate maternal and fetal hyperglycemia occurred after drug administration.     

Fetal breathing and adaptation to maternal hemorrhage in the sheep.

The effect of maternal hemorrhage in chronic preparations was studied on fetal lambs in the last month of gestation. Fourteen to 20 per cent of maternal blood was estimated to have been removed within 30 minutes, which resulted in a drop of 30 per cent of mean maternal arterial pressure. A fetal bradycardia started 28 +/- 13 minutes after the beginning of maternal hemorrhage. It lasted 30 +/- 15 minutes and was concomitant with a rise in fetal arterial pressure. It was followed by a long-lasting fetal tachycardia of 130 +/- 38 minutes and was corrected only by reinfusion of blood to the mother. The fetal blood gases demonstrated a mild asphyxia with a persistent metabolic acidemia until reinfusion of blood to the mother. Maternal and fetal plasma cortisol levels rose significantly at the end of the hemorrhage. Tracheal fluid flow did not change. Fetal breathing recorded 20 hours before and 24 hours after the experiment did not show consistent changes, but during fetal bradycardia there was no fetal breathing. Recent clinical investigations in this field have been made in the human fetus to estimate standards of fetal well being. These peculiar animal experiments do not show any significant improvement by recording fetal breathing over the recording of prelabor fetal heart rate.     

Maternal and fetal cardiovascular indices during fetal hypoxia due to cord compression in chronically cannulated sheep. I. Responses to timolol

Timolol, one of the newer beta-adrenergic antagonists, has less depressive effects on the heart than propranolol, so that it has the potential for use by pregnant women. In chronically cannulated ewes, timolol at 0.01 and 0.1 mg/kg of body weight induced maternal and fetal bradycardia; the higher dose also depressed uterine blood flow and fetal PaO2. When this higher dose preceded brief compression of the umbilical cord, uterine flow was further depressed and the usual posthypoxia rebound tachycardia did not develop. Both the blocking of fetal responses to hypoxia (precluding detection of fetal distress) and the reduction in uterine flow led us to conclude that timolol taken by a mother could pose particular hazards for her fetus in hypoxic conditions, such as during cord compression at parturition.     

Effects of local anesthetic agents on the uterine vasculatures and myometrium.

Intravascular procaine, lidocaine, mepivacaine, and bupivacaine decrease blood flow to the placental and nonplacental vascular beds of gravid ewes by stimulating vasoconstriction and myometrial contractility. These effects appear to be direct ones since they are not affected by alpha-adrenergic blockade. Dose-response curves determined in nonpregnant ewes indicate that significant decreases in blood flow may occur at arterial blood concentrations encountered clinically. It is proposed that reduced placental blood flow is the cause of fetal bradycardia following paracervical block anesthesia. The implications of these findings in obstetric anesthesia are discussed.     

Maternal psychological stress and fetal asphyxia: a study in the monkey.

Fifteen pregnant rhesus monkeys near term were anesthetized with pentobarbital. Catheters were placed into the right femoral arteries of the mother and fetus, the fetuses being retained in utero. After repair of all incisions, the mothers were placed on their sides and allowed to recover from anesthesia. As they awakened, their fetuses regularly developed blood chemical and, frequently, vital signs changes indicative of deepening asphyxia. In eight cases, anesthesia was reinstated with intravenous pentobarbital, 30 mg. per kilogram. This caused an immediate and significant improvement in oxygenation of the fetus in all instances. The remaining animals were transferred to restraining chairs where the blood chemical and cardiovascular statuses of the mothers and fetuses were followed over the next 3 to 72 hours. During this time, the mothers, fully awake, were subjected to both "contrived" and "incidental" episodes of psychological stress stimulation. In the majority of instances, these periods of stress to the mothers caused episodes of bradycardia and hypotension in their fetuses. These induced vital signs changes of the fetuses appeared regularly about 50 seconds after the beginning of the periods of stress stimulation of the mother. Similarly, the vital signs changes frequently began returning toward more normal values with 1 to 2 minutes after the alleviation of maternal stress. Blood samples drawn in single cases before, during, and after recovery from bradycardia identified an associated increase in asphyxia of the fetuses. These episodic aggravations of the already existent fetal asphyxia of the fetuses. These episodic aggravations of the already existent fetal asphyxia brought about by stress stimulation of the mother are interpreted as resulting from activation of the maternal sympathetic nervous system causing vasoconstriction throughout the abdominal viscera and an accompanying retardation in intervillous space perfusion.     

Effects of reduced uterine blood flow on accelerations and decelerations in heart rate of fetal sheep

Experiments were conducted in unanesthetized fetal sheep during the last third of gestation to examine the effects of prolonged reversible reductions in uterine blood flow on mean fetal heart rate, accelerations and decelerations in fetal heart rate, and fetal arterial pressure. With use of a Teflon vascular clamp placed around the maternal common internal iliac artery, uterine blood flow was reduced, leading to a reduction in fetal arterial oxygen saturation from 60% to 30% for 2 hours. This was associated with an initial transient fetal bradycardia and hypertension followed by tachycardia. Mean fetal heart rate remained significantly elevated for 2 hours following the release of the vascular clamp. There was no change in the number, amplitude, or duration of accelerations, but there was a significant increase in both the number and amplitude of decelerations during the period of reduced uterine blood flow.     

Staircase sign: a newly described uterine contraction pattern seen in rupture of unscarred gravid uterus

Although extremely rare, rupture of an unscarred gravid uterus poses significant morbidity and mortality to both fetus and mother. In the past, loss of uterine contraction was thought to be characteristic of uterine rupture, while recent evidence shows that uterine contraction pattern is not associated with uterine rupture. We report two cases of rupture in the unscarred term uterus. Both patients were multiparous and denied any past medical complications, previous cesarean delivery or myomectomy. Uterine rupture occurred in the latent phase of labor at 1 cm dilation (Case 1) and during an intravenous oxytocin infusion after three doses of intravaginal misoprostol (Case 2). Case 2 required cesarean hysterectomy and blood transfusion. Case 1 was monitored with an external tocodynamometer, while Case 2 was monitored with an internal pressure transducer. External monitoring demonstrated the classic sign of complete loss of uterine tone. In contrast, internal monitoring demonstrated an increase in uterine resting tone. Both techniques revealed a stepwise gradual decrease in contraction amplitude followed by sudden onset of profound and prolonged fetal bradycardia (staircase sign). In cases of uterine rupture, differing baseline characteristics between contraction patterns were dependent on uterine monitoring technique. In both techniques a stepwise gradual decrease in contraction amplitude was followed by prolonged fetal bradycardia.     

Effects of protein-calorie malnutrition on transplacental kinetics of aminoisobutyric acid in rats.

In order to find out if inefficient transport of amino acids contributes to a decrease in fetal weight during maternal malnutrition, we injected [14C]- and [3H]-labelled aminoisobutyric acid (AIB), respectively, in the mother and its fetuses and determined its transplacental kinetics on day 20 of gestation in rats fed a 21 per cent (control) or a low (5 per cent) protein diet. Rats fed a low protein diet consumed significantly less food than did the rats fed a control diet and thus suffered from protein-calorie malnutrition. A low protein diet led to a significant (P less than 0.05) decrease in maternal and fetal volume of distribution of AIB, a decrease in the clearance of AIB from the mother to the fetus and an increase in the time required for the fetal plasma AIB concentration following maternal injection to exceed the maternal plasma AIB concentration. The clearance of AIB from the fetus into the mother or to outside (e.g. amniotic fluid) was not altered by protein deficiency. It is concluded that a decrease in the efficiency of the placenta to deliver amino acids to the fetus may be a contributing factor in fetal growth retardation during maternal protein malnutrition.     

Effect of respiratory acidosis on the rabbit fetus in utero

This report deals with acid-base relationships between maternal and fetal bloods. The new aspect is the presentation of nonsteady state measurements made simultaneously in both mother and fetus during the production of respiratory acidosis in the mother.Pure respiratory acidosis was induced in 12 pregnant rabbits near term by allowing them to breathe selected concentrations of carbon dioxide. The pH, Pco₂, and standard HCO₃^? determinations were made on maternal arterial and fetal umbilical vein blood. In all instances, both the mother and the fetus showed a decrease in pH and an elevation of arterial Pco₂ without a change in standard HCO₃^? concentrations. Severe respiratory acidosis over a 90 minute period did not produce metabolic acidosis in the mother or the fetus. In the presence of pure respiratory acidosis in the pregnant rabbit, measurements of pH, Pco₂, and standard HCO₃^? in the mother's blood provide reasonably accurate information of their concentrations in fetal blood. However, it cannot be concluded that other types of acid-base changes in the mother will be reflected by similar changes in the fetus.     

Physiologic changes in pregnant women and their fetuses during jet air travel

The physiologic reactions of pregnant women and their fetuses were studied during routine commercial flights. Ten healthy pregnant women (32 to 38 weeks of gestation) each undertook two flights. Maternal respiratory and heart rates, transcutaneous PO2 and PCO2, blood pressure, uterine activity, and fetal beat-to-beat heart rate variability were continuously monitored. During these flights, maternal heart rate and blood pressure increased, and PO2 decreased significantly while PCO2 remained unchanged. Respiratory rate showed a short increase during takeoff and landing but remained unchanged during the rest of the flight. Mean fetal heart rate was within normal limits during the whole flight. No bradycardia, prolonged tachycardia, or significant loss of heart rate variability was observed. This study indicates no hazards of commercial flights to the mother and the fetus in uncomplicated pregnancies.     

Effect of serotonin on uteroplacentofetal circulatory system in pregnant rabbit

The effects of serotonin (5-hydroxytryptamine) on the uteroplacentofetal circulatory system were studied in pregnant rabbits. Serotonin infusion (50 micrograms/kg) induced transient, but significant fetal bradycardia (deceleration), without any significant changes in maternal blood pressure, heart rates, pO2, pCO2 and uterine activities. Pretreatment with methysergide, a serotonin antagonist, with a dose of 2.5 mg/kg blocked the inhibitory effect of serotonin on fetal heart rate. However, methysergide itself produced the uterine contraction associated with mild fetal bradycardia. Direct injection of serotonin (1,000 micrograms/kg) into fetuses did not produce any changes in fetal heart rates. These data indicated that serotonin would influence the uteroplacental vasculature, which in turn induced fetal bradycardia.     

The effects of isoproterenol on fetal oxygenation.

Infusion of isoproterenol (1 microgram/kg/min, i.v.) into the anesthetized pregnant rhesus monkey near term consistently reduced fetal oxygenation, despite diminishing myometrial activity. The decline in pO2 of fetal arterial blood (mean = 4.3 +/- 2.3 mmHg S.D.) was accompanied by an increase in pCO2 tension (mean = 4.6 +/- 2.7 mmHg) and a decline in pH (mean = 0.04 +/- 0.02 S.D.). There was an increase in heart rate and a widening of pulse pressure in the mother and also in the adequately oxygenated fetus providing evidence that the agent crosses the placenta. The poorly oxygenated fetuses developed bradycardia and hypotension. Administration of isoproterenol directly to the fetus elicited similar changes in the composition of blood, and in blood pressure and heart rate, to those observed after administration of the agent to the mother.     

Lidocaine toxicity after maternal pudendal anesthesia in a term infant with fetal distress

There have been many reports of lidocaine toxicity especially after maternal paracervical block anesthesia. We recently treated a term infant with evidence of fetal distress who presented with symptoms of lidocaine toxicity after maternal pudendal anesthesia. The infant developed apnea and bradycardia soon after birth which responded to mechanical ventilation and epinephrine. A prolonged Q-T interval was noted on day 1 which normalized by day 3. Cord blood was assayed and revealed an elevated lidocaine level. Lidocaine toxicity has been associated with fetal distress secondary to fetal ion trapping in the presence of acidosis. Although good response to supportive therapy occurred in our patient, other methods of therapy such as exchange transfusion and treatment of seizures may be required in some cases. Awareness of this now uncommon syndrome will lead to prompt diagnosis, appropriate work-up, and management.     

Spontaneous labor and elective induction--a prospective randomized study. I. Effects on mother and fetus.

In a prospective randomized study spontaneous and oxytocin induced labor "for convenience" have been compared with respect to uterine activity, duration of labor, the condition of the fetus and the newborn infant. The study consists of 84 normal patients, of whom 43 were induced at full term by amniotomy and oxytocin infusion using the Cardiff Infusion System Mark II; 41 patients served as controls. No difference in maternal age, number of previous pregnancies and pelvic score one week before the day of delivery were found between the groups. The following parameters were calculated: duration of labor, uterine activity, amount of bleeding in the third stage of labor, number of early and late decelerations as well as number of episodes of bradycardia in the CTG-recordings, birth weight, Apgar score one and five minutes post-delivery and blood gases in mother and child 60 seconds after delivery. No significant differences between the two groups were found. It is concluded that there are no increased risks to mother or fetus compared to normal labor provided that there is cephalic presentation and normal pregnancy, careful selection with respect to the length of pregnancy and the condition of the cervix and that the Cardiff infusion system is used with intrauterine pressure recording and continuous fetal heart monitoring.