G. Capogna

Minimum local analgesic doses of ropivacaine, levobupivacaine, and bupivacaine for intrathecal labor analgesia.

Background:Doses for intrathecal opioid–local anesthetic mixtures have been arbitrarily chosen. The aim of this study was to compare the analgesic efficacies of intrathecal ropivacaine, levobupivacaine, and bupivacaine for labor analgesia and to determine the analgesic potency ratios for these three drugs. For this purpose, the authors used the up–down sequential allocation model, which estimates the minimum local analgesic dose for intrathecal local anesthetic. Methods:Ninety-seven nulliparous term parturients in spontaneous labor, requesting combined spinal–epidural analgesia, were randomly allocated to one of three groups to receive 0.25% spinal ropivacaine, levobupivacaine, or bupivacaine. The initial dose of the local anesthetic drug was chosen to be 2.5 mg, and the testing interval was set at 0.25 mg. The subsequent doses were determined by the response of the previous parturient. Efficacy was accepted if the visual analog pain score decreased to 10 mm or less on a 100-mm scale within 30 min. The minimum local analgesic dose was calculated using the method of Dixon and Massey. Results:The intrathecal minimum local analgesic dose was 3.64 mg (95% confidence interval, 3.33–3.96 mg) for ropivacaine, 2.94 (2.73–3.16) mg for levobupivacaine, and 2.37 (2.17–2.58) mg for bupivacaine. The relative analgesic potency ratios were 0.65 (0.56–0.76) for ropivacaine:bupivacaine, 0.80 (0.70–0.92) for ropivacaine:levobupivacaine, and 0.81 (0.69–0.94) for levobupivacaine:bupivacaine. There were significant trends (P ≤ 0.021) for greater motor block with bupivacaine and levobupivacaine. Conclusions:This study suggests a potency hierarchy of spinal bupivacaine > levobupivacaine > ropivacaine.

The Relative Potencies for Motor Block After Intrathecal Ropivacaine, Levobupivacaine, and Bupivacaine

BACKGROUND:In this study, we sought to determine the median effective dose (ED50) for motor block of intrathecal ropivacaine, levobupivacaine, and bupivacaine and to define their motor-blocking potency ratios. METHODS:We enrolled 104 parturients undergoing elective cesarean delivery with combined spinal-epidural anesthesia and randomized them to one of three groups to receive intrathecal 0.5% (wt/vol) ropivacaine, levobupivacaine, or bupivacaine. The initial dose was 4 mg, and the testing interval was set at 1 mg. Efficacy was determined by the occurrence of any motor block in either lower limb (modified Bromage and hip motor function scale) within 5 min after the spinal injection. RESULTS:As assessed using up-down analysis, intrathecal ED50 for motor block was 5.79 mg for ropivacaine (95% CI 4.62–6.96), 4.83 mg for levobupivacaine (95% CI 4.35–5.32) and 3.44 mg for bupivacaine (95% CI 2.55–4.34) (P < 0.0007). The relative motor blocking potency ratios were ropivacaine/bupivacaine 0.59 (95% CI, 0.42–0.82), ropivacaine/levobupivacaine 0.83 (95% CI 0.64–1.09), and levobupivacaine/bupivacaine 0.71 (95% CI 0.51–0.98). CONCLUSIONS:There is a clinical profile of potency for motor block for the pipecolylxylidines when administered spinally: low, intermediate, and high for ropivacaine, levobupivacaine, and bupivacaine, respectively.

Programmed Intermittent Epidural Bolus Versus Continuous Epidural Infusion for Labor Analgesia: The Effects on Maternal Motor Function and Labor Outcome. A Randomized Double-blind Study in Nulliparous Women

BACKGROUND:Programmed intermittent epidural anesthetic bolus (PIEB) technique may result in reduced total local anesthetic consumption, fewer manual boluses, and greater patient satisfaction compared with continuous epidural infusion (CEI). In this randomized, double-blind study, we compared the incidence of motor block and labor outcome in women who received PIEB or CEI for maintenance of labor analgesia. The primary outcome variable was maternal motor function and the secondary outcome was mode of delivery. METHODS:Nulliparous, term women with spontaneous labor and cervical dilation <4 cm were eligible to participate in the study. Epidural analgesia was initiated and maintained with a solution of levobupivacaine 0.0625% with sufentanil 0.5 &mgr;g/mL. After an initial epidural loading dose of 20 mL, patients were randomly assigned to receive PIEB (10 mL every hour beginning 60 minutes after the initial dose) or CEI (10 mL/h, beginning immediately after the initial dose) for the maintenance of analgesia. Patient-controlled epidural analgesia (PCEA) using a second infusion pump with levobupivacaine 0.125% was used to treat breakthrough pain. The degree of motor block was assessed in both lower extremities using the modified Bromage score at regular intervals throughout labor; the end point was any motor block in either limb. We also evaluated PCEA bolus doses and total analgesic solution consumption. RESULTS:We studied 145 subjects (PIEB = 75; CEI = 70). Motor block was reported in 37% in the CEI group and in 2.7% in the PIEB group (P < 0.001; odds ratio = 21.2; 95% CI: 4.9–129.3); it occurred earlier (P = 0.008) (hazard ratio = 7.8; 95% CI: 1.9–30.8; P = 0.003) and was more frequent at full cervical dilation in the CEI group (P < 0.001). The incidence of instrumental delivery was 20% for the CEI group and 7% for the PIEB group (P = 0.03). Total levobupivacaine consumption, number of patients requiring additional PCEA boluses, and mean number of PCEA boluses per patient were lower in the PIEB group (P < 0.001). No differences in pain scores and duration of labor analgesia were observed. CONCLUSIONS:Maintenance of epidural analgesia with PIEB compared with CEI resulted in a lower incidence of maternal motor block and instrumental vaginal delivery.

Which induction drug for cesarean section? a comparison of thiopental sodium, propofol, and midazolam

STUDY OBJECTIVE To determine maternal and neonatal effects of three different induction drugs (thiopental sodium, propofol, and midazolam) for cesarean section. DESIGN Randomized, double-blind study. SETTING Inpatient obstetric department at a general hospital. PATIENTS 90 healthy patients undergoing elective cesarean section with general anesthesia. INTERVENTIONS 3 groups of 30 patients each receiving thiopental 5 mg/kg, propofol 2.4 mg/kg, or midazolam 0.3 mg/kg for induction of anesthesia. MEASUREMENTS AND MAIN RESULTS Time to induce anesthesia, hemodynamic changes, depth of anesthesia, recovery after anesthesia, placental transfer, and neonatal outcome (Apgar and neurobehavioral examinations) were studied. In the thiopental and midazolam groups, systolic blood pressure and heart rate rose following endotracheal intubation and skin incision (p < 0.001 and p < 0.0025, respectively), while in the propofol group, there was significant hypotension after induction (p < 0.005). Electroencephalographic patterns showed a light depth of anesthesia with propofol and midazolam between anesthesia induction and delivery, confirmed by the presence of clinical signs of light anesthesia in 50% of propofol patients and 43% of midazolam patients. Time to induce anesthesia was longer with midazolam (p < 0.0001). Neonates in the midazolam and propofol groups had lower Apgar and neurobehavioral scores than those in the thiopental group. Umbilical artery to umbilical vein ratios were above 1 in the propofol and midazolam groups. CONCLUSION Thiopental still remains the first-choice induction drug for cesarean section. The slow induction time with midazolam may put the mother at risk for pulmonary inhalation. A plane of anesthesia that may risk awareness and potential neonatal depression is the main drawback of the two newer induction drugs.

Minimum analgesic doses of fentanyl and sufentanil for epidural analgesia in the first stage of labor.

In this study, we sought to determine the minimum analgesic doses and relative potencies of fentanyl and sufentanil when they are used as the sole epidural analgesic during the first stage of labor. Nulliparous parturients (n = 66) in spontaneous labor at term gestation and requesting epidural analgesia were enrolled into this prospective, double-blinded, randomized, sequential-allocation study. Each woman received fentanyl or sufentanil diluted with 0.9% wt/vol saline to a volume of 10 mL. The initial dose was arbitrarily chosen to be 125 &mgr;g for fentanyl and 25 &mgr;g for sufentanil, with subsequent doses being determined by the response of the previous patient (testing interval, 5 &mgr;g for fentanyl and 1 &mgr;g for sufentanil). Efficacy was accepted if the visual analog score decreased to ≤10 mm on a 100-mm scale within 30 min. The minimum analgesic dose or median effective dose was 21.1 &mgr;g (95% confidence interval [CI], 20.2–21.9 &mgr;g) for sufentanil and 124.2 &mgr;g (95% CI, 118.1–130.6 &mgr;g) for fentanyl (P < 0.0001). The sufentanil/fentanyl potency ratio was 5.9 (95% CI, 5.6–6.3). In conclusion, we have established the equivalent doses and relative potencies of fentanyl and sufentanil for epidural analgesia in the first stage of labor.

Minimum Analgesic Dose of Epidural Sufentanil for First-stage Labor Analgesia: A Comparison between Spontaneous and Prostaglandin-induced Labors in Nulliparous Women

Background The aim of this prospective, double-blind, sequential allocation study was to compare the effects of spontaneous and prostaglandin-induced labor on the minimum analgesic dose of epidural sufentanil in the first stage of labor. Methods Seventy healthy, nulliparous women, at more than 37 weeks’ gestation with cervical dilatation from 2 to 4 cm, requesting epidural pain relief in labor were enrolled. The subjects were assigned to two different groups according to whether labor was spontaneous or induced with dinoprostone 0.5 mg. Parturients received 10 ml of the study solution through a lumbar epidural catheter. The initial dose was sufentanil 25 &mgr;g, and subsequent doses were determined by the response of the previous patient in the same group using up–down sequential allocation. The analgesic effectiveness was assessed using 100-mm visual analog pain scores. The up–down sequences were analyzed using the method of independent paired reversals and probit regression. Results The minimum analgesic dose of sufentanil in spontaneous labor was 22.2 &mgr;g (95% CI: 19.6, 22.8) and 27.3 &mgr;g (95% CI: 23.8, 30.9) in induced labor. The minimum analgesic dose of sufentanil in induced labor was significantly greater (P = 0.0014) than that in spontaneous labor (95% CI difference: 2.9, 9.3) by a factor of 1.3 (95% CI: 1.1, 1.5). Conclusion Prostaglandin induction of labor produces a significantly greater analgesic requirement than does spontaneous labor.

Epidural fentanyl plus bupivacaine 0.125 per cent for labour: analgesic effects

Ninety-five healthy nulliparous women, ASA physical status I–II with an uncomplicated pregnancy and single fetus in vertex position were given lumbar epidural analgesia. Patients in Group A (n = 35) received bupivacaine 0.125 per cent with epinephrine 1800.000; Groups B (n = 30) and C (n = 30) received the same agents as Group A but with the addition to the initial dose of 50 or 100 µg of fentanyl respectively. All patients were evaluated for duration and quality of analgesia, duration of labour, method of delivery and total dose of bupivacaine used. The addition of either 50 or 100 µg of fentanyl resulted in longer duration of analgesia (93 ± 9 min and 106 ± 8 min respectively vs 55 ± 7) and reduced bupivacaine total doses (64 ± 0.03 and 55 ± 1.5 respectively vs 109.5 ± 1.3). Only the addition of 100 µg of fentanyl improved significantly the quality of analgesia (43.3 per cent of excellent scores vs 6.6 per cent in Group B and 5.7 per cent in Group A). Addition of fentanyl did not affect the duration of labour, the method of delivery and the neonatal neurobehaviour scores.RésuméQuatre-vingt-quinze femmes nullipares en bonne santé ASA classe I–II lors ďune grossesse non-compliquée ont reçu une analgésie épidurale lombaire. Les patientes du groupe A(n = 35) ont reçu de la bupivacaïne 0.125 pour cent avec épinéphrine 1:800,000: les patientes du groupe B (n = 30) et C (n = 30) ont reçu les mêmes médicaments que celles du groupe A mais avec ľaddition ďune dose initiale de 50 ou 100 µg de fentanyl respectivement. Les patientes furent évaluées pour la durée et la qualité de ľanalgésie, la durée du travail, la méthode ďaccouchement et la dose totale de bupivacaïne utilisée. Ľaddition de 50 et 100 µg de fentanyl a prolongé la durée de ľanalgésie (93 ± 9 minutes et 106 ± 8 minutes respectivement versus 55 ± 7) et a réduit les doses totales de bupivacaïne (64 ± 0.003 et 55 ± 1.5 respectivement versus 109.5 ± 1.3). Seule ľaddition de 100 µg de fentanyl a amélioré significativement la qualité de ľanalgésie (43.3 pour cent des scores excellents versus 6.6 pour cent dans le groupe B et 5.7 pour cent dans le groupe A). Ľaddition de fentanyl n’a pas affecté la durée du travail, et la méthode de ľaccouchement et le score néonatal.

Effect of μ-opioid receptor A118G polymorphism on the ED50 of epidural sufentanil for labor analgesia

BACKGROUND A common polymorphism of the μ-opioid receptor gene (OPRM1, p.118A/G), which has been shown to effect the response to neuraxial opioids, occurs in 30% of Caucasian women. This double-blind up-down sequential allocation study was designed to examine the effect of p.118A/G on the ED50 of epidural sufentanil for labor analgesia. METHODS Nulliparous women were recruited at 35 weeks of gestation (n=77) and genotyped for p.118A/G. Those subsequently requesting epidural labor analgesia were enrolled. Each woman received epidural sufentanil diluted with 0.9% saline to a volume of 5 mL. The initial sufentanil dose was 21 μg, with subsequent doses determined by the response of the previous patient (testing interval 1 μg). Efficacy was accepted if the visual analogue score decreased to <10mm on a 100-mm scale within 30 min of drug administration. RESULTS Twenty patients were excluded, leaving 57 women from whom data were analyzed: 33 in Group A (wild-type A118 homozygotes) and 24 in Group G (heterozygotes and homozygotes G118). The ED50 for epidural sufentanil was 25.2 μg in Group A (95% CI 23.2-26.4) and 20.2 μg in Group G (95% CI 14.2-23.6) (P=0.03). The potency ratio for epidural sufentanil in Group G compared to Group A was 1.25 (95% CI 1.00-1.64). CONCLUSION Women carrying the variant allele of p.118A/G of OPRM1 (G118) had a lower ED50 for epidural sufentanil given for early labor analgesia than women homozygous for the wild-type allele.

Propofol and thiopentone for caesarean section revisited: maternal effects and neonatal outcome

In 56 women undergoing elective caesarean section, general anaesthesia was induced with either propofol 1% or thiopentone 2.5% followed by 50% nitrous oxide in oxygen and isoflurane 0.75% until delivery. In the thiopentone group the arterial pressure rose following tracheal intubation and skin incision, while in the propofol group there was a significant tendency to hypotension immediately following induction of anaesthesia. There were differences in electroencephalogram (EEG) between the groups, while laryngoscopy, intubation and surgical stimulation had no effect on EEG pattern. Recovery after anaesthesia did not differ between groups. None of the patients had recall of the intraoperative period, but 53% of patients induced with propofol showed signs of light anaesthesia between induction and delivery. Neonates in the propofol group had lower Apgar scores 1 min after birth than those in the thiopentone group, but these differences were no longer significant at 5 min. No differences were noted in neurobehavioural status at 1, 4 and 24 h.

Alkalinization improves the quality of lidocaine-fentanyl epidural anaesthesia for caesarean section

This double-blind randomized study of 116 healthy women was undertaken to evaluate whether alkalinization potentiated the analgesic effects of epidural fentanyl-lidocaine for elective Caesarean section. After a test-dose of 3 ml, lidocaine 2% with adrenaline 1:200,000, all patients received 100 μg, fentanyl in 5 ml saline and they were then divided into two groups, to receive incremental doses of 5 ml lidocaine 2% with adrenaline 1:200,000 with or without 0.1 mEq · ml−1 sodium bicarbonate, to obtain anaesthesia to T4. The addition of bicarbonate to lidocaine resulted in a mean (SD)pH increase from 6.58 (0.01) to 7.14 (0.02) and in a mean PCO2 increase from 3.8 (0.8) to 345.1 (5.9) mmHg. Onset of sensory analgesia to the S1 segment as well as the interval between the block and the delivery of the baby were shorter in the bicarbonate group (respectively 15.4 (6.9) vs 18.9 (4.8) min and 28.9 (9.5) versus 33.9 (11.8) min; P < 0.01 and 0.05). No differences were noted in the onset to T4 or in the degree of motor block. The percentage of patients experiencing pain during surgery and requiring intravenous analgesics was higher in the group which did not receive bicarbonate (3% vs 16%; P < 0.05). There were no differences in intraoperative maternal side-effects, neonatal outcome or in maternal venous and umbilical venous and arterial lidocaine concentrations between the groups. The concentrations of fentanyl in maternal plasma, umbilical artery, and the umbilical artery to maternal vein ratio were greater in the alkalinized group (P < 0.001). In conclusion, alkalinization improves the quality and reliability of epidural anaesthesia provided with fentanyl and lidocaine for Caesarean section in healthy mothers.RésuméCette étude randomisée à double inconnue est réalisée chez 116 patientes en bonne santé pour évaluer si l’alcalinisation potentialise les effets analgésiques de l’association fentanyllidocaïne en épidurale pour la césarienne programmée. Après une dose-test de lidocaïne 2% adrénalinée à 1:200,000 3 ml, toutes les patientes reçoivent fentanyl 100 μg dans du soluté physioloque et sont divisées en deux groupe. Elles reçoivent des doses progressives de lidocaine 2% adrénalinée à 1:200,000 5 ml avec ou sans bicarbonate de sodium 0,1 mEq · ml−1 jusquà ce que le niveau T4 soil atteint. L’addition de bicarbonate à la lidocaïne augmente en moyenne (±SD) le pH de 6,58 (0,01) à 7,14 (0,02) et la PCO2 en moyenne de 3,8 (0,8) à 345,1 (5,9) mmHg. Le debut de l’anesthésie sensorielle mesurée au niveau S1 et l’intervalle entre l’initiation du bloc et la naissance sont plus courts pour le groupe bicarbonate (respectivement 15,4 (6,9) min vs 18,9 (4,8) min et 28,9 (9,5) vs 33,9 (II,8) min; P < 0,01 et 0,05). On ne note pas de difference quant au début de l’analgésie à T4 ou au degré du bloc moteur. Le pourcentage de patientes qui ressentent de la douleur pendant la chirurgie et qui reçoivent un analgésique iv est plus élevé dans le groupe qui ne reçoit pas de bicarbonate (3% vs 16%; P < 0,05). On ne trouve pas de différence entre groupes pour l’incidence des effets secondaires, le pronostic néo-natal ou les concentrations plasmatiques ombilicales artérielles et veineuses. La concentration plasmatique de fentanyl dans l’artèreombilicale est plus élevée dans le groupe bicarbonate ainsi que le rapport veineux ombilical-artère matemelle (P < 0,001). En conclusion, l’alcalinisation améliore la qualité et la fiabilité de l’anesthésie épidurale produite par le fentanyl et la lidocaïne pour la césarienne de patientes en bonne santé.