Haemodynamic effects of repeated epidural test-doses of adrenaline in the chronic maternal-fetal sheep preparation.

A randomized crossover study was designed using the chronically instrumented pregnant sheep preparation to study the possible effects of epidural injection of adrenaline as a single compound on the circulation of mother and fetus. Three consecutive identical doses of adrenaline were administered epidurally with a 30 min interval between treatments. In a randomized crossover fashion two dosages (10 and 15 micrograms) were tested on different days. The day after the last epidural experiment the same doses of adrenaline were given intravenously (i.v.). Between the two i.v. doses a 30 min interval was allowed for values to return to baseline. Twenty-seven experiments were performed in eight ewes. Epidural administration of adrenaline did not affect maternal mean arterial pressure, maternal heart rate, uterine blood flow, fetal mean arterial pressure, fetal heat rate, or maternal and fetal blood gases and acid-base status. After i.v. administration of adrenaline the uterine blood flow decreased in a dose-dependent fashion, but the other haemodynamic variables were not affected. In conclusion, this study indicates that consecutive epidural injections of adrenaline have no significant effect on maternal and fetal haemodynamic responses, uterine blood flow, blood gases and acid-base status in the gravid ewe. However, an i.v. injection of 10 or 15 micrograms adrenaline decreases the uterine blood flow and could compromise the fetus.

The effects of adding isoproterenol to 0.125% bupivacaine on the quality and duration of epidural analgesia in laboring parturients.

UNLABELLED: This study was conducted to determine the effects of adding isoproterenol to epidural bupivacaine and sufentanil on the quality and duration of analgesia during labor. In a double blind, randomized study, 80 women were divided into two groups, receiving three doses of 0.125% bupivacaine with 7.5 microg of sufentanil and either 12.5 microg of epinephrine (EPI group) or 5 microg of isoproterenol (ISO group). Contraction pain was measured using a 100-mm visual analog scale (VAS) before epidural analgesia, at 5-min intervals for 15 min after each epidural injection, and hourly thereafter. Overall, no significant differences were observed in VAS scores between the groups. However, in the ISO group, VAS scores at 10 and 15 min after the first and second administration were significantly lower than those in the EPI group. Analgesia after each administration lasted significantly longer in patients who received epinephrine. Because of the limited duration of analgesia in the ISO group, more patients in this group received a fourth epidural administration of 0.125% bupivacaine with epinephrine 1:800,000. In conclusion, the addition of isoproterenol to bupivacaine and sufentanil induces a faster onset of analgesia and reduces the duration of analgesia compared with bupivacaine with sufentanil and epinephrine. Therefore, it is preferable to use isoproterenol only once, as a test dose, after the placement of the epidural catheter. IMPLICATIONS: We analyzed the quality and duration of analgesia in laboring women after they received bupivacaine and sufentanil combined with isoproterenol or epinephrine epidurally. We found that the addition of isoproterenol to bupivacaine and sufentanil induces a faster onset of analgesia and reduces the duration of analgesia.

Hemodynamic effects of intravenous isoproterenol versus saline in the parturient.

The use of epinephrine as a test dose for epidural analgesia in obstetrics remains controversial. Isoproterenol as a test dose may be efficacious in the parturient. However, the effects of isoproterenol on the uterine blood flow (UBF) and umbilical blood flow (UMB) in the parturient are unknown. In a randomized, double-blind study, the hemodynamic variables in 60 nonlaboring women at term were studied 5 min before and for 10 min after an intravenous injection of either 5 micrograms isoproterenol or 5 micrograms saline. The UBF was assessed in 35 women and the UMB in 25 women using a color Doppler technique. The results of 50 women were used for further analysis. Maternal heart rate (MHR) was measured continuously, and maternal mean arterial pressure was measured every minute. MHR did not change after saline but increased significantly after injection of isoproterenol. UBF also increased significantly after isoproterenol during the same time interval. UMB did not change. Other hemodynamic variables did not change. We conclude that isoproterenol, 5 micrograms, may be a suitable test dose for epidural analgesia in obstetrics.

Prostaglandin-induced ventricular fibrillation during cesarean section.

A case report is presented of ventricular fibrillation after intramyometrial injection of 1 mg dinoprostone (PGE(2)) during cesarean section performed under general anesthesia. Anesthesiologists should be aware of the potential cardiovascular side-effects of prostaglandins used by the obstetrician.

Spinal somatosensory evoked potentials after epidural isoproterenol in awake sheep.

PURPOSE: The use of 10-15 micrograms epinephrine as an epidural test-dose is controversial. Isoproterenol would be a better alternative. However, before 5 micrograms isoproterenol can be incorporated in an epidural test-dose, neurotoxicological studies have to be performed. The present study was designed to assess spinal somatosensory evoked potentials (spinal SSEP) before and after epidural isoproteronol. METHODS: Spinal SSEPs were recorded before, 30 min after, and 72 hr after 50 micrograms isoproterenol were given epidurally (L3-4) to six chronically instrumented awake sheep. The spinal SSEPs after epidural (L3-4) administration of 15 ml lidocaine 2% were used to evaluate the model. The SSEPs were generated by transcutaneous stimulation of the sciatic nerve in the thigh. Spinal SSEPs were recorded directly from the spinal cord at vertebra T12 using a monopolar epidural electrode referenced to a subcutaneous needle electrode in the adjacent paraspinal area. RESULTS: Thirty minutes and 72 hr after epidural injection of 50 micrograms isoproterenol the latency and the amplitude of the SSEP waves were similar to baseline values. After lidocaine, no SSEPs could be generated in three sheep while in three sheep the latency of wave 2 (W2) was prolonged and the amplitude diminished. CONCLUSION: Administration of epidural isoproterenol did not affect spinal SSEPs in this study indicating an absence of neurotoxic side effects.

Maternal expectations and experiences of labour pain and analgesia: a multicentre study of nulliparous women.

Six hospitals with large maternity units in five different European countries were involved in this multicentre study. At least 100 primiparae for each country were examined. All mothers received two standardized interviews, one during the last month of pregnancy, and one 24 h after delivery. Maternal expectations and experiences of pain, pain relief, and satisfaction with analgesia and childbirth were assessed by a 100 mm visual analogue scale (VAS). Almost all mothers were seen regularly by an obstetrician or a midwife during pregnancy, had prepared childbirth classes and received antenatal information on labor analgesia techniques. Differences between the five groups were noted in the level of education and socio-economic status. Maternal expectations of labor pain and the answers to the pre-delivery interview varied significantly between the centers, as did maternal knowledge, expectation and ultimate choice of analgesic technique. Generally speaking the level of maternal satisfaction with analgesia and childbirth experience was high; however, epidural analgesia was more effective than other methods of pain relief (P<0.0001). The most satisfied mothers were those who expected more pain, were satisfied with the analgesia received and had good pain relief after analgesia (P<0.001).

Hemodynamic effects of intravenous isoproterenol versus epinephrine in the chronic maternal-fetal sheep preparation.

Isoproterenol 5 micrograms may be an effective marker of accidental intravascular injection in women in labor; however, before isoproterenol can be incorporated in routinely used epidural test doses, the safety and usefulness should be determined in an animal model. This study was designed to examine the hemodynamic effects of isoproterenol in comparison with epinephrine in the pregnant ewe. Five doses of isoproterenol were tested and compared with two doses of epinephrine in a randomized cross-over fashion. After administration of isoproterenol there was a small decrease of uterine blood flow (UBF) and maternal mean artery pressure (MMAP), which both almost immediately returned to baseline. When epinephrine was used a more pronounced and more prolonged decrease of UBF occurred. Increasing doses of isoproterenol resulted in dose-dependent increases in maternal heart rate (MHR), while with epinephrine this was not the case. A significant increase in the cardiac output was seen after isoproterenol. Neither isoproterenol nor epinephrine affected fetal heart rate (FHR), fetal mean arterial pressure (FMAP), amniotic fluid pressure (Amn-pr), blood gases, or acid base status in the mother and the fetus. Provided that neurotoxic effects are absent, isoproterenol might be a better alternative than epinephrine as a test dose for possible intravenous placement of an epidural catheter in pregnant women.

Labor pain relief using bupivacaine and sufentanil: patient controlled epidural analgesia versus intermittent injections.

OBJECTIVES: To determine whether the use of patient-controlled epidural analgesia (PCEA) versus intermittent injections (CIT) resulted in local anesthetic dose reduction. STUDY DESIGN: PCEA and CIT using a mixture of 0.125% bupivacaine with sufentanil 1 or 0.75 microgram/ml were compared in 60 and 195 parturients, respectively. Assessments included pain scores, local anesthetic consumption, degree of motor blockade, type of delivery and neonatal outcome. Statistical analysis was done using Student's t test and Chi-squares. RESULTS: PCEA and CIT provided effective analgesia during labor and delivery. A higher dose of opioid significantly reduced the use of local anesthetic solution in PCEA-patients. There was no difference in motor blockade, type of delivery and neonatal outcome. CONCLUSION: Patient-controlled epidural analgesia is an effective, safe and acceptable alternative to conventional intermittent epidural injections for pain relief during labor and delivery.

Hydroxyethyl starch versus lactated Ringer's solution in the chronic maternal-fetal sheep preparation: a pharmacodynamic and pharmacokinetic study.

Administration of fluids intravenously prior to spinal and epidural analgesia in obstetrics is required to prevent maternal hypotension and fetal hypoxia. A colloid solution, such as hydroxyethyl starch (HES), might be preferable considering the capacity to stay intravascularly for a longer period. In this study the placental transfer of HES and the hemodynamic effects after infusion were investigated using a chronic maternal-fetal sheep preparation. Either 500 mL HES 10% or 750 mL lactated Ringer's solution (RL) was infused intravenously into the ewe over 30 min. Fetal and maternal blood were assayed for HES, blood gases, and acid-base status before and at regular intervals after infusion. Maternal and fetal cardiovascular variables were recorded continuously for 90 min. After HES infusion, maternal HES levels peaked at 30 min ranging from 6.9 mg/mL to 12.1 mg/mL and declined at 24 h to levels between 0.3 mg/mL and 2.8 mg/mL. Mean fetal HES concentrations remained below 0.3 mg/mL. Infusion of HES decreased hemoglobin (Hb) and plasma viscosity (PV) in the mother. Infusion of RL decreased Hb, but did not change PV. Infusion of HES significantly increased uterine blood flow (UBF), cardiac output (CO), total oxygen-delivery capacity, and uterine artery oxygen delivery. In contrast, infusion of RL did not significantly change these variables. Infusion of HES increases UBF, CO, and uterine and total oxygen-carrying capacity in the pregnant ewe. No significant transplacental transfer of HES was shown.

Intubating conditions and neuromuscular effects of mivacurium during propofol-alfentanil anaesthesia.

In three groups of 20 patients, anaesthetized with propofol and alfentanil, tracheal intubation conditions and the onset of neuromuscular blockade after administration of three different doses of mivacurium chloride (0.11, 0.15, and 0.19 mg/kg = 1.5 x ED95, 2 x ED95, and 2.5 x ED95) were assessed. Intubation conditions were found to be clinically acceptable (good or excellent) in 83% of patients. Eighty-two per cent of patients were successfully intubated on the first attempt after 60-90 s. No difference in intubation scores or number of intubation attempts among the three dosage groups were found. We conclude that mivacurium chloride allows smooth intubation in most patients within 60-90 s, even with the lowest dose (0.11 mg/kg), after a propofol-alfentanil induction of anaesthesia. However, because there were a few patients in whom intubating conditions were inadequate at 60-90 s, we are reluctant to advocate the preference of mivacurium chloride over suxamethonium for rapid sequence induction in emergency situations.

The effects of intravenous and epidural sufentanil in the chronic maternal-fetal sheep preparation.

This study examines the placental transfer and hemodynamic and acid-base changes after intravenous (i.v.) and epidural administration of sufentanil in the chronically instrumented maternal-fetal sheep preparation. A dose of 50 micrograms sufentanil was injected either i.v. or epidurally into seven ewes. Neither i.v. nor epidural injection of sufentanil affected maternal mean arterial pressure (MMAP), uterine blood flow (UBF), maternal heart rate (MHR), fetal mean arterial pressure (FMAP), fetal heart rate (FHR), or blood gases and acid-base status in mother and fetus, After i.v. administration, a peak sufentanil level of 1.28 ng/mL +/- 0.285 (SD) was detected in maternal plasma. A peak plasma level of 0.037 ng/mL +/- 0.041 (SD) was attained in the fetus. A constant maternal-fetal concentration ratio of 5.5 from 15-60 min after the i.v. injection was found. After epidural injection a mean peak plasma level of 0.059 ng/mL +/- 0.042 (SD) was reached in the mother 25 min after injection. Sufentanil levels were undetectable in fetal plasma after epidural injection into the mother. Because placental transfer of sufentanil is small, the maternal and fetal cardiovascular and acid-base effects are minimal in the pregnant ewe.

Neuroepithelial bodies in relatively mature lungs: an investigation in prenatal and newborn lambs.

Lungs of fetal and neonatal lambs were found to contain small, inconspicuous and widely dispersed neuroepithelial bodies (NEB). Under the light microscope, NEB could only be identified with certainty by their positive immune reaction to antibodies against serotonin. At the ultrastructural level, a large number of dense-cored vesicles was found in the corpuscular cells of the NEB. However, the number of intracorpuscular nerve endings was small. We conclude from these findings that, in the lamb, NEB act primarily as local regulators of lung function and that their reflex-mediated actions may be of secondary importance. This may be related to the fact that lungs of lambs at birth are relatively mature compared to those of various other species. Increased maturation of lungs and a concomitant decreased risk of insufficient oxygenation might be associated with the presence of an oxygen-sensitive chemoreceptor with primarily local actions for prevention of hypoxia.

Comparison of the addition of three different doses of sufentanil to 0.125% bupivacaine given epidurally during labour.

In a double-blind, randomised, prospective study 150 women in labour received intermittent epidural injections of 10 ml 0.125% bupivacaine with adrenaline (1:800,000) with 5, 7.5 or 10 micrograms of sufentanil added. The onset, duration, and quality of analgesia were compared. Motor block, type of delivery and neonatal Apgar scores were noted. The onset, duration, and quality of analgesia were generally similar in the three groups, except following the second injection when the quality of analgesia was significantly superior in the sufentanil 7.5 and 10 micrograms groups. Motor blockade and type of delivery did not differ between the groups and there were no differences in neonatal Apgar scores. No patient required more than three injections. We conclude that 7.5 micrograms sufentanil is the optimal dose to add to intermittent epidural injections of 10 ml 0.125% bupivacaine with adrenaline (1:800,000) for pain relief in labour.

Carbon dioxide pneumoamnios causes acidosis in fetal lamb.

Recently developed techniques of video-endoscopic surgery may offer new hope for the future of fetal surgery. To allow this approach, the amniotic cavity has to be temporarily enlarged, either by carbon dioxide (CO2) insufflation or by amnioinfusion. In 6 anesthetized ewes, CO2 insufflation of the amniotic cavity produced severe fetal hypercapnia (from 57.6 +/- 1.6 to 87.0 +/- 7.0 torr) and acidosis (from 7.22 +/- 0.03 to 7.11 +/- 0.08) despite normal maternal CO2 pressure and pH. CO2 pneumoamnios does not therefore appear to be an ideal working medium. Fetal endoscopic surgery through amnioinfusion of physiologic fluid may be a safer alternative.

Hydralazine does not restore uterine blood flow during cocaine-induced hypertension in the pregnant ewe.

Cocaine abuse is widespread, and its use by the parturient has potential significant adverse effects in both the mother and the newborn. This study was undertaken in gravid ewes to determine the effects of treatment of cocaine-induced hypertension with hydralazine (Apresoline) on the maternal and fetal cardiovascular systems, catecholamine response, blood gas and acid-base status, and uterine blood flow (UBF). Twenty-one experiments were performed in 15 chronically instrumented ewes near term gestation. After a 30-min control period, cocaine was given intravenously to all ewes for 55 min to induce and maintain increased maternal mean arterial pressure (MMAP) and reduced UBF. The sheep were randomly assigned to receive either cocaine alone (n = 11, control group) or hydralazine (n = 10, treatment group), starting 15 min after the cocaine administration. Both drugs were discontinued 55 min after the start of the cocaine administration, followed by a 35-min recovery period. In the control group, cocaine administration resulted in a 31 +/- 13% (SD) increase in MMAP (P less than 0.05) and a 26 +/- 21% reduction in UBF (P less than 0.05). In the treatment group, the initial cocaine administration resulted in a similar increase in MMAP and decrease in UBF. Hydralazine therapy restored MMAP toward baseline after 20 min of administration, but UBF remained reduced (37 +/- 17%) throughout therapy (P less than 0.05) and recovery (18 +/- 13%) (P less than 0.05). The maternal heart rate increased maximally by 121 +/- 33% (P less than 0.05) after the administration of hydralazine, compared with a 14 +/- 21% increase (P less than 0.05) in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)

Maternal and neonatal effects of adding epidural sufentanil to 0.5% bupivacaine for cesarean delivery.

STUDY OBJECTIVE: To determine the maternal and fetal effects of the addition of epidural sufentanil to 0.5% bupivacaine for cesarean delivery. DESIGN: Randomized, double-blind, prospective study. SETTING: University Hospitals, Katholieke Universiteit Leuven, Leuven, Belgium. PATIENTS: Sixty women at term scheduled for elective cesarean section, all of whom had elected epidural anesthesia. INTERVENTIONS: The 60 women were divided into three groups of 20, with each group receiving a different 1 ml study solution: saline (control) or sufentanil 20 micrograms or sufentanil 30 micrograms added to 0.5% bupivacaine and epinephrine (1:200,000). MEASUREMENTS AND MAIN RESULTS: In the mother, the quality of anesthesia, the duration of postoperative analgesia, the volume of anesthetic, and the frequency of side effects were examined. The neonates were evaluated at 5 and 10 minutes after birth by Apgar scores and between 60 and 120 minutes after birth by both the screening test developed by Prechtl and the Neurological and Adaptive Capacity Scoring System. Immediately after delivery, maternal and umbilical vein blood were drawn and assayed for sufentanil levels. Adding sufentanil significantly improved the quality of anesthesia without depressing the neurobehavioral status of the baby. CONCLUSION: The epidural injection of sufentanil added to 0.5% bupivacaine with epinephrine improved the quality of anesthesia during elective cesarean section without jeopardizing the safety of the baby.

The effects of the addition of sufentanil to 0.125% bupivacaine on the quality of analgesia during labor and on the incidence of instrumental deliveries.

In a double-blinded, randomized, prospective multi-center study of 695 women, we investigated whether epidural injection of sufentanil added to 0.125% bupivacaine with epinephrine (1:800,000) reduces the total amount of local anesthetic required, resulting in less motor blockade and reduced incidence of instrumental deliveries, and improves the quality of analgesia provided by this low concentration of local anesthetic without jeopardizing the safety of the baby. In addition, other potential benefits of sufentanil (such as decrease in the incidence of shivering) and side effects were examined. It was found that adding incremental doses of 10 micrograms sufentanil up to a maximum of 30 micrograms reduced the incidence of instrumental deliveries from 36 to 24% (P less than 0.01) and significantly improved quality and duration of analgesia without depressing the neurobehavioral status of the baby. No other benefits from adding sufentanil were found. The only side effect that occurred more frequently after sufentanil was pruritus. We conclude that epidural injection of 10-30 micrograms sufentanil added to 0.125% bupivacaine with epinephrine (1:800,000) improved the quality of analgesia during labor and reduced the incidence of instrumental deliveries without jeopardizing the safety of the baby.