REPEATED ADDITION OF FENTANYL TO EPIDURAL BUPIVACAINE ANALGESIA DURING LABOR - CLINICAL EFFICACY AND PLASMA-CONCENTRATIONS OF FENTANYL

A combination of epidural opioids with local anaesthetics has been use d to improve pain relief during labor and to reduce side effects, such as muscle weakness, usually seen when local anaesthetics are used alo ne. The addition of epidural fentanyl (F) produces highly effective an algesia, the only side effect being mild itching. Initial trials inves tigated the improvement in analgesia after a single administration of F during first- but not during second-stage labor. Even though pain pe rception during second-stage labor under epidural analgesia with local anaesthetics can be severe, the addition of opioids was avoided for f ear of neonatal or maternal depression. A recent report found maternal and umbilical plasma concentrations following injection of 100 mu g F to be safe and the investigators speculated that repeated addition of epidural/F to injections of local anaesthetic may prove beneficial fo r the parturient without exposing the mother or fetus to risk. We ther efore studied maternal analgesia maternal and umbilical plasma levels and associated side effects following repeated addition of 100 mu g F to bupivacaine epidural analgesia during labor. Methods. Following ins titutional and governmental approval 53 parturients were randomly assi gned to receive either 8 ml bupivacaine 0.25%+0.1 mg fentanyl (B+F gro up; n=28) or 8 ml bupivacaine 0.25%+2 ml saline (BUP group; n=25) in a n epidural catheter at L2/3. The same dose was reinjected upon the pat ients' request regardless of the degree of cervical dilatation. Blood pressure, heart rate, respiratory rate and the incidence of side effec ts were recorded before and following each epidural injection. Pain re lief was determined at each injection and following cord clamping usin g the visual analogue pain scale (VAS; 0-100 mm). Maternal venous bloo d 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 wer e maintained at -20 degrees C and then analyzed by radioimmunoassay. A t delivery, Apgar scores and umbilical venous and arterial blood gas v alues were determined. Results. Both groups were comparable for age, w eight, height, gestational age and parity. A total of 48 epidural inje ctions were evaluated in the B+F group, 43 in the BUP group. No statis tically significant, group difference was found between the frequency of injections per delivery (B+F: 2.2; BUP: 1.8); regarding the time be tween the initial and the first top-up dose (B+F: 144 min; BUP: 140 mi n) or regarding the interval between the last injection and birth (B+F : 94 min; BUP; 90 min). However, the quality of pain relief during lab or 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 o bserved in 43% of patients receiving F moderate shivering in 13% versu s 40% in patients not receiving F. At control mean maternal F plasma l evels were not zero but 0.25 ng/ml. After the initial injection and fo llowing the first and second top-up dose mean maximum maternal F plasm a 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 i ncrease in maternal F concentrations with increasing injection frequen cy was statistically significant (P<0.02). Mean umbilical venous and a rterial F concentrations at birth were 0.72 ng/ml (+/-1.16) and 0.62 n g/ml (+/-0.52). No significant group differences were found regarding Apgar scores or umbilical blood, gas analyses. In one newborn, radioim munoassay resulted in unexplainably high umbilical F concentrations wi thout any clinical signs of sedation, depressed vigilance and without any sequellae. Discussion. Repeated addition of 100 mu g F to epidural anaesthesia with bupivacaine significantly improves analgesia and pro vides 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 ons et or the duration of analgesia, probably due to the fact that bupivac aine was used at a fixed and (compared to other studies) relatively hi gh concentration. We did not observe clinically relevant side effects in the mother or the newborn. Although epidural injections of 100 mu g F were repeatedly administered, the mild dose-dependent increases of maternal and of umbilical plasma F concentrations had no effect and ca used no clinical signs of depression. The specificity of radioimmunoas say for fentanyl in parturients is questioned.