Zusatz von Fentanyl zur Bupivacain – Periduralanalgesie bei Sectio Caesarea

Epidural anaesthesia for elective caesarean section can have advantages over general anaesthesia. The anaesthesiologist can avoid endotracheal intubation as well as fetal depression following placental transfer of systemic anaesthetics. However, despite reaching an effective blockade preoperatively, intraoperative discomfort and pain may occur during epidural anaesthesia with local anaesthetics alone, necessitating supplemental systemic analgesics or even conversion to general anaesthesia [21]. Addition of epidural fentanyl has been shown to improve onset and quality of perioperative analgesia without evident side effects for mother or newborn [24]. Nevertheless, administration of epidural opioids before cord clamping is still hotly debated, some fearing maternal and or neonatal depression [6, 26]. The aim of the present study was to investigate the quality of analgesia, associated side effects and the resulting maternal and neonatal plasma opiate concentrations after a single preoperative addition of 0.1 mg fentanyl to epidural bupivacaine analgesia in comparison to epidural bupivacaine analgesia alone. Methods. Following governmental and ethics committee approval, 43 elective consenting patients for caesarean section were randomized to receive double-blind injections of either 8 ml 0.5% bupivacaine+0.1 mg fentanyl (B+F group, n=22) or 8 ml 0.5% bupivacaine +2 ml saline (Bup group, n=21) into an epidural catheter. In both groups additional injections of bupivacaine were given to achieve sensory blockade up to T4. Systolic blood pressure, heart and respiratory rates were measured regularly. Quality of intraoperative pain relief was assessed at delivery, uterine eventration, and during uterine and abdominal closure using a visual analogue scale (VAS). The duration of postoperative analgesia was compared between groups, as well as the incidence of nausea, itching or sedation. Similarly, Apgar scores and umbilical arterial and venous blood gas analyses were compared. Fentanyl concentrations were determined in maternal venous blood sampled before and 20 and 40 min after epidural injection and at birth, and in umbilical venous and arterial blood sampled after delivery. Radioimmunoassay analysis was performed from plasma specimens centrifuged and frozen at ?20° C [19]. The statistical level of significance was defined as P<0.05. Results. Groups were comparable regarding age, weight and time of gestation. Total bupivacaine doses and injection to delivery times were similar in both groups. Figure 1 shows that there were 40% more pain-free (VAS=0) patients in the B+F group during uterine eventration and wound closure (P<0.05). Mean postoperative duration of analgesia was significantly longer in the B+F group (382 vs 236 min). The rate of nausea and mild itching was significantly higher in the B+F group. Respiratory depression was never detected in patients or newborns. Small group differences in blood pressure or respiratory rate were inconstant and clinically irrelevant, as were differences in umbilical venous pCO₂. One hundred and twenty-five blood samples were analysed for fentanyl concentrations. The mean fentanyl concentration before epidural injection was not zero, but 0.25 ng/mg (range 0.02–0.32). Maternal concentrations at 20 and 40 min after injection were 0.55 ng/ml (0.12–1.14) and 0.52 ng/ml (0.26–1.04) (Fig. 3). At delivery, mean maternal fentanyl concentration was 0.58 ng/ml (0.14–1.18); mean umbilical arterial and venous concentrations were 0.51 ng/ml (0.04–1.8) and 0.41 ng/ml (0.18–1.2), respectively. Rare results of fentanyl concentrations >1.0 ng/ml correlated neither with sedation, maternal respiratory rate and side effects, nor with Apgar scores and umbilical blood gas values. No Apgar score at 5 min was below 9, and no umbilical pH was below 7.20. Conclusion. We conclude that preoperative epidural addition of 0.1 mg fentanyl to 0.5% bupivacaine significantly improves intraoperative pain relief during elective caesarean section and prolongs postoperative analgesia. This important advantage of fentanyl is associated with an increased incidence of nausea and mild itching. No clinically significant fentanyl-associated depression of vigilance could be detected in the mother or newborn. The resulting plasma fentanyl concentrations are within safe limits. When administered epidurally and preoperatively for caesarean section, maternal plasma levels of fentanyl do not decrease significantly until birth. In the radioimmunoassay an unknown substance cross-reacts like fentanyl.     

Effect of Epidural Fentanyl on Neonatal Respiration

Background: The addition of opioids to epidural infusions for laboring mothers may reintroduce the problem of neonatal depression seen with systemic opioids. The authors studied neonatal respiration and neurobehavior in newborns of mothers randomized to receive epidural analgesia with or without fentanyl.

Methods: One hundred thirty-eight women in labor received loading doses of plain bupivacaine. When pain-free, they received an infusion of either 0.125% bupivacaine alone or 0.0625% bupivacaine with 2.5 [micro sign]g/ml fentanyl. After delivery, transcutaneous oxygen tension and carbon dioxide tension were recorded in the newborns every 10 s until 90 min after delivery using a transcutaneous oxygen-carbon dioxide monitor. Umbilical venous and arterial acid-base status, Apgar scores, and Neurologic and Adaptive Capacity Scores 2 h and 24 h after delivery were measured. The umbilical venous plasma fentanyl concentration was correlated with indices of neonatal respiration and welfare in the fentanyl group.

Results: One hundred fourteen newborns delivered vaginally were studied. In the fentanyl group, the mean (range) maternal dose of fentanyl was 184 [micro sign]g (range, 53-400), and the umbilical venous fentanyl concentration was 0.077 ng/ml (range, <0.021 to 0.244). There were no significant differences between the groups for any indices of neonatal respiration or neonatal welfare, and the plasma fentanyl concentration did not correlate with any of these indices.     

Regional analgesia in early active labour: combined spinal epidural vs. epidural

We randomly allocated 93 women in early active labour and requesting epidural analgesia to receive either epidural ( n  = 48) or combined spinal–epidural analgesia ( n  = 45). For epidural analgesia 15 ml of bupivacaine 0.1% with 75 μg of fentanyl were injected into the epidural space. For combined spinal–epidural analgesia 1 ml of bupivacaine 0.25% with 25 μg of fentanyl were injected into the subarachnoid space. For both groups subsequent top-ups of 10 ml of bupivacaine 0.1% with fentanyl 20 μg were given using a lightweight patient-controlled epidural analgesia (PCEA) pump with a lockout time of 30 min. We assessed analgesia and the degree of motor blockade and found no significant differences in pain or maternal satisfaction scores between the two groups. The time to first top-up was significantly longer in the epidural group than in the CSE group (p = 0.01). The combined spinal–epidural group had significantly greater motor blockade at 30 min than the epidural group (p = 0.01), but there was no difference after this. The PCEA machine failed completely twice and temporarily many times. We conclude that the combined spinal–epidural technique confers no advantages in early active labour. Also, a lightweight PCEA pump needs to be more reliable before we can recommend its use.     

Effects of Adrenaline on maternal and fetal fentanyl absorption in epidural analgesia: A randomized trial

Background

The combination of low‐dose local anesthesia and lipophilic opioids such as fentanyl is established as a standard solution for labor epidural analgesia. Fentanyl increases efficacy, but may have negative effects on the neonate in terms of reduced neonatal neurologic and adaptive capacity scores and breast feeding. We hypothesized that addition of adrenaline 2 μg/mL to a solution of bupivacaine 1 mg/mL and fentanyl 2 μg/mL would reduce the systemic uptake of fentanyl, resulting in reduced serum fentanyl in the fetus at birth.

Methods

Forty‐one nulliparous women requesting epidural analgesia were randomized to epidural analgesia with or without adrenaline. Blood samples were drawn from the mother with regular intervals, and at delivery. An umbilical vein blood sample (used as a proxy for fetal exposure) was drawn after clamping.

Results

There were no significant differences between the groups in fentanyl concentrations in the umbilical vein and maternal serum at birth. There was a significantly lower mean area under the maternal serum‐concentration curve for the first 2 hours of treatment in the adrenaline group (mean difference 0.161 nmol h/L [0.034; 0.289], P = .015), implying slower systemic uptake in the adrenaline group initially. There were no significant differences in treatment duration, motor block, Apgar scores, umbilical pH and base excess, or mode of delivery.

Conclusions

The addition of adrenaline to an epidural solution containing fentanyl lowered maternal systemic serum fentanyl concentration during the first 2 hours, but did not lower serum fentanyl concentration in the umbilical vein and mother at delivery.     

The effect of epidural opioids on maternal oxygenation during labour and delivery

The effects of epidural fentanyl on the incidence of maternal hypoxaemia during labour and on neonatal welfare were examined. Women were randomly allocated to receive one of two epidural infusions, bupivacaine 0.125% alone or bupivacaine 0.0625% with 2.5 μg.ml⁻¹ fentanyl, and maternal arterial oxygen saturation was monitored continuously until delivery. The median incidence of desaturation (Spo₂ < 95%) during the active phase of the second stage of labour was significantly greater in the fentanyl group than in controls (2.9 versus 0.6 min.h⁻¹, p = 0.02). Similarly, the incidence ofdesaturation to Spo₂ < 90% was greater in the fentanyl group than in controls (p = 0.02). There was no correlation between maternal oxygenation or plasma fentanyl concentration and neonatal welfare as measured by umbilical arterial and venous blood gas and acid base status. Apgar score and Neurologic and Adaptive Capacity Score.     

Neonatal effects of adding epidural fentanyl to 0.5% bupivacaine for caesarean section

Epidural injection of opioids has been introduced to improve analgesia during labour and caesarean section. This study was designed to quantify placental transfer of fentanyl and to evaluate neonatal effects of adding fentanyl to 0.5% bupivacaine for epidural anaesthesia in women undergoing elective caesarean section at term. The parturients were randomly allocated to one of four groups of 20, who received either saline (control) or 50, 75 or 100 microg of fentanyl added to 20 ml of 0.5% bupivacaine. Apgar scores, time to sustained respiration and umbilical acid-base values did not differ among the groups. The median (interquartile range) umbilical artery to maternal vein fentanyl concentration ratio was 0.34 (0.26-0.48) when the fentanyl groups were taken together. Neurologic and adaptive capacity scores were evaluated at 2 and 24 h. Neonates whose mothers received fentanyl had lower scores with regard to supporting reaction at 2 h and active tone at 24 h, when compared to controls (P<0.05), but there were no differences among the groups with regard to the other test criteria in the neurobehavioural test. In conclusion, epidural injection of fentanyl 50-100 microg did not produce depression of the term neonate.     

A single dose of fentanyl and midazolam prior to Cesarean section have no adverse neontal effects

PURPOSE: Analgesia and sedation, routinely used as adjunct medications for regional anesthesia, are rarely used in the pregnant patient because of concerns about adverse neonatal effects. In an effort to obtain more information about maternal analgesia and sedation we studied neonatal and maternal effects of iv fentanyl and midazolam prior to spinal anesthesia for elective Cesarean section. METHODS: In this double-blinded, randomized, placebo-controlled trial, 60 healthy women received either a combination of 1 microg x kg(-1) fentanyl and 0.02 mg x kg(-1) midazolam intravenously or an equal volume of iv saline at the time of their skin preparation for a bupivacaine spinal anesthetic. Sample size was based on a non-parametric power analysis (power > 0.80 and alpha = 0.05) for clinically important differences in Apgar scores. Fetal outcome measures included Apgar scores, continuous pulse oximetry for three hours, and neurobehavioural scores. Maternal outcomes included catecholamine levels, and recall of anesthesia and delivery. RESULTS: There were no between-group differences of neonatal outcome variables (Apgar score, neurobehavioural scores, continuous oxygen saturation). Mothers in both groups showed no difference in their ability to recall the birth of their babies. CONCLUSIONS: Maternal analgesia and sedation with fentanyl (1 microg x kg(-1)) and midazolam (0.02 mg x kg(-1)) immediately prior to spinal anesthesia is not associated with adverse neonatal effects.     

Pharmacokinetics and clinical effect during continuous epidural infusion with ropivacaine 2.5 mg/ml or bupivacaine 2.5 mg/ml for labour pain relief

Background: Ropivacaine has shown less systemic toxicity than bupivacaine, and comparatively low muscle-blocking properties could constitute another advantage when used epidurally for obstetric pain relief. We aimed primarily to compare maternal and foetal drug disposition following continuous epidural infusion of ropivacaine or bupivacaine.
Methods: Twenty-four full-term, nulliparous women were randomized to continuous epidural infusion (10 ml/h) of ropivacaine 2.5 mg/ml or bupivacaine 2.5 mg/ml for labour pain relief in a double-blind, parallel-group design. Maternal blood samples were collected up to 24 h after the end of infusion as well as taken from the umbilical cord at the time of delivery. Sensory and motor block as well as analgesia were assessed. All the women were monitored by cardiotocography and neonatal assessment was performed.
Results: The sensory block was adequate for both drugs. Higher plasma levels (total and free) were seen with ropivacaine, although the infusion with bupivacaine continued on average for about 2 hours longer. However, the ratios between maternal and umbilical blood concentrations were similar for both drugs. Normal neonatal Apgar and neonatal adaptive capacity scores (NACS) were found in both groups.
Conclusion: A continuous epidural infusion of 25 mg/h ropivacaine or bupivacaine both produced good labour pain relief. Higher total and free plasma concentrations were seen for ropivacaine. The ratios between maternal and umbilical plasma levels were similar for both drugs.     

Wiederholter Zusatz von Fentanyl zur peripartalen Bupivacain-Periduralanalgesie Klinische Wirkung und Fentanyl-Plasmaspiegel

A combination of epidural opioids with local anaesthetics has been used to improve pain relief during labor and to reduce side effects, such as muscle weakness, usually seen when local anaesthetics are used alone. The addition of epidural fentanyl (F) produces highly effective analgesia, the only side effect being mild itching. Initial trials investigated the improvement in analgesia after a single administration of F during first- but not during second-stage labor. Even though pain perception during second-stage labor under epidural analgesia with local anaesthetics can be severe, the addition of opioids was avoided for fear of neonatal or maternal depression. A recent report found maternal and umbilical plasma concentrations following injection of 100?μg F to be safe and the investigators speculated that repeated addition of epidural/F to injections of local anaesthetic may prove beneficial for the parturient without exposing the mother or fetus to risk. We therefore studied maternal analgesia, maternal and umbilical plasma levels and associated side effects following repeated addition of 100?μg F to bupivacaine epidural analgesia during labor. Methods. Following institutional and governmental approval 53 parturients were randomly assigned to receive either 8?ml bupivacaine 0.25%+0.1?mg fentanyl (B+F group; n=28) or 8?ml bupivacaine 0.25%+2?ml saline (BUP group; n=25) in an epidural catheter at L2/3. The same dose was reinjected upon the patients' request regardless of the degree of cervical dilatation. Blood pressure, heart rate, respiratory rate and the incidence of side effects were recorded before and following each epidural injection. Pain relief was determined at each injection and following cord clamping using the visual analogue pain scale (VAS; 0–100?mm). Maternal venous blood samples were collected to measure plasma F concentrations before and 20 and 40?min after each injection and at birth when umbilical venous and arterial blood was obtained. After centrifugation the samples were maintained at ?20°?C and then analyzed by radioimmunoassay. At delivery, Apgar scores and umbilical venous and arterial blood gas values were determined. Results. Both groups were comparable for age, weight, height, gestational age and parity. A total of 48 epidural injections were evaluated in the B+F group, 43 in the BUP group. No statistically significant group difference was found between the frequency of injections per delivery (B+F: 2.2; BUP: 1.8); regarding the time between the initial and the first top-up dose (B+F: 144?min; BUP: 140?min) or regarding the interval between the last injection and birth (B+F: 94 min; BUP; 90 min). However, the quality of pain relief during labor and particularly at birth was significantly improved by F (mean VAS in B+F group: 6?mm; mean VAS in BUP group: 42?mm). Mild itching was observed in 43% of patients receiving F, moderate shivering in 13% versus 40% in patients not receiving F. At control mean maternal F plasma levels were not zero but 0.25?ng/ml. After the initial injection and following the first and second top-up dose mean maximum maternal F plasma concentrations were 0.54?ng/ml (±0.32; ±SD), 0.88?ng/ml (±0.62) and 1.06?ng/ml (±0.4) (range 0.18–2.76?ng/ml), respectively. The increase in maternal F concentrations with increasing injection frequency was statistically significant (P<0.02). Mean umbilical venous and arterial F concentrations at birth were 0.72?ng/ml (±1.16) and 0.62?ng/ml (±0.52). No significant group differences were found regarding Apgar scores or umbilical blood gas analyses. In one newborn, radioimmunoassay resulted in unexplainably high umbilical F concentrations without any clinical signs of sedation, depressed vigilance and without any sequellae. Discussion. Repeated addition of 100?μg F to epidural anaesthesia with bupivacaine significantly improves analgesia and provides pain relief not only during the first but also through the very painful second stage of labor. In this study, F did not affect the onset or the duration of analgesia, probably due to the fact that bupivacaine was used at a fixed and (compared to other studies) relatively high concentration. We did not observe clinically relevant side effects in the mother or the newborn. Although epidural injections of 100?μg F were repeatedly administered, the mild dose-dependent increases of maternal and of umbilical plasma F concentrations had no effect and caused no clinical signs of depression. The specificity of radioimmunoassay for fentanyl in parturients is questioned.     

Epidural versus combined spinal epidural block for cesarean section

In a controlled study a single segment combined spinal epidural (CSE) block was compared with epidural block for cesarean section. Thirty healthy parturients were randomly divided into two groups. In both groups a T4 block was aimed at. Bupivacaine was used to provide analgesia in both groups. All patients receiving CSE block had good to excellent analgesia, while 11 patients (74%) receiving epidural block had similar pain relief. This was reflected in the requirement for additional analgesics, sedatives or N2O anesthesia. The muscular relaxation was also better following CSE block. The total dose of bupivacaine for a T4 block was three times larger in patients receiving only epidural block. The maternal and fetal blood bupivacaine levels were correspondingly about three times higher in the epidural group. Additionally, the incidence of maternal hypotension was higher in patients receiving epidural block. Apgar scores, blood gases and neurobehavioural evaluation did not show any differences between the two groups of neonates. No postspinal headache was noted. CSE block appears to combine the reliability of spinal block and the flexibility of epidural block while minimizing their drawbacks.     

Plasma concentrations of epidural bupivacaine in mother and newborn: 0.125% versus 0.375%

Central venous plasma concentrations of bupivacaine were determined in two groups of 15 parturients each who were given epidural analgesia for labor and vaginal delivery. One group received 10 ml of 0.125% bupivacaine plus epinephrine 1:800,000, the other group received 7 ml of 0.375% bupivacaine plus epinephrine 1:800,000. Plasma concentrations of bupivacaine in the umbilical venous (UV) and the umbilical arterial (UA) blood of their babies were also determined. The mean UA, UV, and maternal central venous (MV) plasma concentrations of bupivacaine differed significantly between the two groups: in patients given 0.375% bupivacaine UA values were 63% higher (P less than 0.01), UV values were 57% higher (P less than 0.01), and the MV values were 34% higher (P less than 0.05) than in patients given 0.125% bupivacaine. The measured plasma concentrations speak in favor of the less concentrated solution of bupivacaine in epidural analgesia for obstetrics. Seven milliliters of bupivacaine 0.375% is suitable for epidural analgesia in obstetrics but a low concentration-low dose technique, using 10 ml of bupivacaine 0.125% plus epinephrine 1:800,000 is safer. It provides good analgesia with minimal or no motor block and is associated with low maternal and neonatal plasma concentrations of bupivacaine, well below toxic levels and, to our knowledge, lower than in any other study.     

Dorsal column function after epidural and spinal blockade: implications for the safety of walking following low-dose regional analgesia for labour

Walking after regional blockade for labour using low-dose combinations of bupivacaine and fentanyl is possible due to the maintenance of lower limb motor power. In order to investigate concerns that dorsal column function, important in maintaining balance, is impaired after such techniques, clinical assessment of lower limb proprioception and vibration sense was evaluated in parturients after either low-dose epidural ( n  = 30) or spinal blockade ( n  = 30) for labour analgesia and compared with spinal anaesthesia ( n  = 30) for elective Caesarean section using a larger total dose of local anaesthetic. Of the patients receiving low-dose regional labour analgesia 7% ( n  = 4) had abnormal dorsal column function compared with 97% ( n  = 29) receiving spinal anaesthesia for Caesarean section (p < 0.001). All patients in the Caesarean section group developed lower limb motor weakness, compared with only 10% ( n  = 6) in the low-dose groups (p < 0.001). There were no significant differences between the low-dose groups with respect to sensory block, motor block or dorsal column function. Overall, 90% of patients receiving low-dose bupivacaine/fentanyl regional labour analgesia had both normal lower limb motor power and dorsal column function. Assessment of these parameters is recommended before allowing patients to walk after low-dose regional techniques for labour.     

Neonatal effects of patient-controlled analgesia using fentanyl in labor

Patient-controlled analgesia (PCA) has been used at our institution for the past 5 years, as an alternative labor analgesic when epidural analgesia is contraindicated. This retrospective study evaluates the effects of maternal PCA fentanyl on infants of greater than 32 weeks gestational age. The neonatal charts (n=32) were reviewed for birth weight, gestational age, 1 min and 5 min Apgar scores, use of naloxone and umbilical venous gases. Infants requiring naloxone were defined as narcotized. Results from narcotized and non-narcotized neonates were compared with the Wilcoxon two-sample test. Fourteen infants had a 1 min Apgar score or= 7, except in the three infants who had received naloxone. Gestational age, birth weight, method of delivery, PCA duration, time from last dose to delivery, total fentanyl used and rate of fentanyl infusion were not predictive of low 1 min Apgar scores. Three infants with a 1 min Apgar of 4 required naloxone. The total fentanyl received by mothers of infants who required naloxone was significantly higher than the group of mothers whose infants did not require naloxone (770 +/- 233 microg vs 298 +/- 287 microg, P = 0.027) Use of PCA fentanyl in this high-risk obstetric population was associated with a 44% incidence of moderately depressed neonates with an Apgar score 相似文献   

Epidural ropivacaine hydrochloride during labour: protein binding, placental transfer and neonatal outcome

This study was undertaken: (i) to quantify the effects of labour and epidural analgesia on plasma alpha1-acid glycoprotein concentration, (ii) to examine the effects of changes in plasma alpha1-acid glycoprotein concentration on plasma protein binding and placental transfer of ropivacaine, and (iii) to examine the association between umbilical venous ropivacaine concentration and neurobehavioural function in the neonate. Multiparous patients undergoing induction of labour received a continuous epidural infusion of 0.1% ropivacaine following an epidural bolus. A significant association was demonstrated between maternal plasma alpha1-acid glycoprotein concentration and 1/free fraction of ropivacaine 60 min after starting ropivacaine administration (r(2) = 0.77) but not at delivery. No significant correlation was demonstrable between maternal unbound ropivacaine concentration and either neonatal (cord) ropivacaine concentration or UV/MV (a measure of placental transfer). Thirty minutes after delivery, 9/10 neonates had neurological and adaptive capacity scores < 35, whereas only three infants had scores < 35 at 2 h. All scores exceeded 35 16 h after delivery. No association between mean (SD) umbilical venous ropivacaine concentration [0.09 (0.08) mg x l(-1)] and neurological and adaptive capacity scores was demonstrated.     

Clinical effects and pharmacokinetics of ropivacaine and bupivacaine for epidural analgesia during labor

OBJECTIVE: To compare the analgesic efficacy, pharmacokinetics and histamine release of ropivacaine and bupivacaine with fentanyl in continuous epidural perfusion during labor and childbirth. MATERIAL AND METHODS: Prospective study of 40 women at full-term pregnancy who requested epidural analgesia. The patients were randomly assigned to 2 groups of 20: group R received an initial bolus dose of 10 mL of 0.25% ropivacaine and group B received 0.25% bupivacaine, followed in both groups by epidural infusion of the assigned drugs at a concentration of 0.125% plus 0.30 mg of fentanyl at a rate of 5 mL/h through a patient-controlled analgesia device that allowed additional bolus doses. The studied variables were age, weight, height, sensory and motor block, mean blood pressure and maternal-fetal heart rates, number of bolus doses, total local anesthetic administered, duration and type of delivery, oxytocin increase, Apgar at 1 and 5 minutes, plasma levels of local anesthetic (30 minutes after the initial dose, at the end of dilation, in the umbilical vein, and 30 minutes after switching off the perfusion pump), time to clearance, elimination half-life, and a test of histamine release by radioimmunoassay. RESULTS: No significant differences were observed in the course of labor or in Apgar scores. The plasma concentrations of ropivacaine were higher than those of bupivacaine (p<0.03). Clearance of both drugs was similar. The elimination half-life of ropivacaine was significantly less than that of bupivacaine (5.2 +/- 0.7 h vs. 10.8 +/- 1.06 h). CONCLUSIONS: Analgesia was equally effective in both groups, without adverse maternal-fetal effects, with spontaneous micturition and absence of motor blockade in both groups. The plasma concentrations were higher with ropivacaine but were not toxic.     

A comparison of patient-controlled analgesia fentanyl and alfentanil for labour analgesia

PURPOSE: To determine the analgesic efficacy of equipotent doses of PCA (patient-controlled analgesia) fentanyl and PCA alfentanil for labour pain. METHODS: Twenty three, ASA I - II parturients between 32-42 wk gestational age in whom epidural analgesia was contraindicated were randomized to receive PCA fentanyl (Group F)or alfentanil (Group A). Plain numbered vials contained 21 ml fentanyl 50 microg x ml(-1) or alfentanil 500 microg x ml(-1). A one millilitre loading dose was administered. The PCA solution was prepared by diluting 10 ml study drug with 40 ml saline and the PCA pump was programmed to deliver a dose of 2 ml, delay of five minutes and a basal rate of 2 ml x hr(-1). Maternal measurements obtained were hourly drug dose, total dose, Visual Analog Pain Score (VAPS) q 30 min, sedation score q 1 hr and side effects. Neonates were assessed by 1,5, and 10-min Apgar scores, umbilical venous and arterial blood gases and neurobehavioural scores at four and 24 hr. RESULTS: Mean VAPS from 7 - 10 cm cervical dilatation were higher in Group A than in Group F (85.7+/-13.9 vs. 64.6+/-12.1; P<0.01) There were no inter-group differences in VAPS from 1-3 cm, or from 4-6 cm dilatation, in maternal sedation scores or side effects, or in neonatal outcomes. CONCLUSION: In the doses prescribed in this study, PCA fentanyl was found to provide more effective analgesia in late first stage labour than PCA alfentanil.     

腰麻-硬膜外联合麻醉对剖宫产母婴肾素-血管紧张素-醛固酮系统的影响

目的 研究腰麻－硬膜外联合麻醉（CSEA）对剖宫产母婴肾素－血管紧张素－醋固酮系统（RAAS）的影响。方法 将60例ASA Ⅰ级行择期剖宫产的健康产妇随机分为硬膜外麻醉组（EA组，n＝30）和CSEA组（n＝30)。分别于注射局麻药前(T0)、切皮后即刻（T1）、胎儿晚出后即刻（T2）、术毕即刻（T3）和术后24h（T4）取母体静脉血和胎儿娩出后胎儿脐动、静脉血测定血清素活性（PRA）、血管紧张素Ⅱ（AT-Ⅱ）和醛固酮（ALD）浓度；评定麻醉效果，记录痛觉阻滞平面达T7水平的时间，注射局麻药至胎儿娩出时间（I－DI）及新生儿娩出1min、5min的Apgar评分。结果 两组术中SP、DP、HR、SpO2的变化及新生儿娩出1min、5min的Apgar评分。结果 两组术中SP、DP、HR、SpO2的变化及新生儿娩出1min、5min的Apgar评分差异无显著性（P＞0.05）。同EA组相比，CSEA组麻醉起效时间明显缩短（P＜0.01）。两组母体于T1、T2、T4的PRA、AT－Ⅱ、ALD值均比T0、T3值明显降低（P＜0.01），胎儿脐动、静脉血中三者值差异不明显，但明显低于母体T0、T3值（P＜0.01）。结论 CSEA用于剖宫产手术时，只要运用得当，不会对母婴AAS产生不良影响。     

Effect of adrenaline on plasma concentrations of fentanyl during epidural anaesthesia for caesarean section

The present study was designed to assess the effect of adrenaline on the plasma concentrations of fentanyl in mothers and umbilical vessels after epidural administration for caesarean section. Thirty patients undergoing elective caesarean section were allocated randomly into two groups. Group 1 (n = 16) received 100 microg fentanyl, 10 ml of 0.5% bupivacaine and 10 ml 2% lidocaine, while group II (n = 14) received 100 microg fentanyl, 10 ml of 0.5% bupivacaine with adrenaline 1:200 000, and 10 ml of 2% lidocaine with adrenaline 1:80 000. Blood samples were obtained from the maternal antecubital vein (MV) at various times up to 6 hours after epidural injection, and from umbilical vein (UV) and arteries (UA) at birth for determination of plasma fentanyl by radioimmunoassay. Fentanyl Cmax and Tmax in MV did not differ significantly between the two groups. In umbilical vessels, plasma fentanyl concentrations were comparable in the two groups: (0.12 +/- 0.08 ng ml(-1) and 0.13 +/- 0.08 ng ml(-1) in UV and 0.08 +/- 0.07 ng ml(-1) and 0.06 +/- 0.05 ng ml(1) in UA of groups I and II respectively). The maximum plasma concentration in UV was 0.24 ng ml(-1) in group I and 0.25 ng ml(-1) in group II. There was no significant correlation between umbilical vessel (vein or artery):MV ratio and dose to delivery interval and no difference between the two groups in Apgar score or umbilical cord pH.     

The addition of fentanyl to epidural bupivacaine in first stage labour

Epidural analgesia was studied in 100 healthy Chinese women with uncomplicated pregnancies in first stage labour. Patients were randomly allocated to receive 8 ml of one of the following five solutions: bupivacaine 0.125% with fentanyl 50 micrograms or fentanyl 100 micrograms, bupivacaine 0.25% plain, bupivacaine 0.25% with fentanyl 50 micrograms or fentanyl 100 micrograms. There was no difference in quality of analgesia among groups as measured by the reduction of visual analogue pain scores 20 minutes after the epidural dose. The duration of analgesia was similar among groups with the overall median duration being 105 minutes. There was no difference in method of delivery or neonatal Apgar scores. The least concentrated mixture providing good quality analgesia for the first stage of labour was the combination of bupivacaine 0.125% with fentanyl 50 micrograms.     

Fentanyl concentration in maternal and umbilical cord plasma following intranasal or subcutaneous administration in labour

BackgroundThe effect that the route of maternal fentanyl administration has on placental transfer of drug to the neonate is not well studied. Plasma concentration ratios are an indicator of fetal exposure, relative to the mother.MethodsA cohort study (n=30) was conducted to measure fentanyl concentrations in maternal plasma, and arterial and venous cord blood, among women administered either intranasal or subcutaneous fentanyl for labour pain relief. Maternal and cord blood samples were collected within 30 min of birth to determine the fentanyl plasma concentration and to assess relative neonatal exposure. Neonatal outcomes were assessed by Apgar scores, need for resuscitation and nursery admission.ResultsThirty paired samples were obtained from healthy parturients with uncomplicated term pregnancies. Highest observed umbilical venous and arterial concentrations were 0.71 ng/mL and 0.56 ng/mL, respectively, and fetal to maternal fentanyl plasma concentration ratios ranged between 0.23 and 0.73, indicating low fetal exposure. While the total intranasal fentanyl dose administered was significantly higher than the subcutaneous fentanyl dose, this did not result in a higher fetal to maternal ratio. All neonates in both groups had 5-min Apgar scores >7, two neonates required short-term stimulation and oxygen (unrelated to fentanyl) and no neonate was admitted to the nursery.ConclusionThis study is the first to examine fetal and maternal fentanyl concentrations after subcutaneous administration. This research supports the safe use of fentanyl for labour analgesia for women.