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Describing the relationship between magnitude of response, probability of response, dose and time is difficult using traditional two-dimensional dose-response curves. We devised a novel way of presentation in four dimensions. Data from a previous study of epidural bupivacaine and ropivacaine given for labour analgesia were re-analysed. For a range of response magnitudes (5-95% reduction in pain score), estimates of doses associated with probabilities of response 0.05-0.95 were calculated using probit analysis. Three dimensional surface plots were constructed with axes x = magnitude of response, y = probability of response and z = log(dose) at intervals for 30 min. Arithmetic interpolation was used to assemble an animation depicting temporal changes in relationship between variables (fourth dimension). Response-probability-dose curves in three and four dimensions were constructed and presented for both drugs. We believe that this model is more aligned with the logic of clinical dose selection compared with traditional two-dimensional curves., (© 2013 The Association of Anaesthetists of Great Britain and Ireland.)

Background: The potencies of bupivacaine and ropivacaine have been compared using up-and-down methodology, but their complete dose-response curves have not been compared. The authors performed a random allocation-graded dose-response study of epidural bupivacaine and ropivacaine given epidurally for labor analgesia., Methods: Three hundred laboring nulliparous patients were randomly given epidural bupivacaine (5, 10, 15, 20, 30, or 40 mg) or ropivacaine (7, 15, 20, 30, 45, or 60 mg) in 20 ml of saline. Visual Analog Scale pain scores were recorded for 30 min. Response was defined by the percentage decrease in pain score from baseline at 30 min, and dose-response data were analyzed by using nonlinear regression., Results: Sigmoidal Emax model dose-response curves were fitted to the datasets for bupivacaine (R = 0.53) and ropivacaine (R = 0.59). The curves had similar steepness (Hill coefficient 2.02 [95% CI, 1.55-2.50] vs. 2.25 [1.70-2.79], P = 0.55). The ED50 (dose of the drug that reduces pain score to 50% of baseline at 30 min, also known as D50) of ropivacaine was greater than that of bupivacaine (15.3 [95% CI 13.7-17.1] mg vs. 11.3 [10.0-12.7] mg, P = 0.0003), but ED90 (D90) was similar (40.6 [32.4-51.1] mg vs. 33.4 [26.2-42.7] mg, P = 0.29). The potency ratio at ED50 for ropivacaine:bupivacaine was 0.75 (95% CI, 0.65-0.88)., Conclusions: Ropivacaine is less potent than bupivacaine, but otherwise they have similar dose-response characteristics. The difference in potency is not statistically significant at ED90 doses.

Background: Few studies have systematically investigated the effect of diluent volume on the efficacy of epidural local anaesthetics for labour analgesia and no data are available for ropivacaine. Our aim was to compare epidural ropivacaine given in three different volumes for labour analgesia., Methods: In a double-blinded study, we randomly assigned 60 labouring parturients with cervical dilatation <5 cm to receive epidural ropivacaine 30 mg diluted to 5 mL (group 5, n=20), 10 mL (group 10, n=20) or 20 mL (group 20, n=20) for analgesia. We measured visual analogue scale pain scores at the peak of contraction for 30 min plus onset and duration of analgesia., Results: Pain scores at 30 min were similar among group 5 (median 22 [interquartile range 0-44] mm), group 10 (9 [0-21] mm) and group 20 (37 [0-51] mm), P=0.35. The number of patients who achieved a decrease in pain score to < or =30% of baseline was similar among group 5 (12/20 (60%)), group 10 (17/20 (85%)) and group 20 (11/19 (58%)), P=0.13. Onset and duration of analgesia, the incidence of motor block and patient satisfaction were similar among groups., Conclusions: Under the conditions of this study, within the range of 5-20 mL, the volume and concentration were not significant factors influencing the efficacy of a single 30-mg bolus of epidural ropivacaine given for labour analgesia. This suggests that the most important factor influencing analgesic efficacy was drug mass.

Unlabelled: Studies have shown better obstetric outcome when ropivacaine 0.25% was used for labor epidural analgesia compared with bupivacaine 0.25%, but it is controversial whether there is any difference at smaller concentrations. In a prospective, double-blind trial, we randomized 350 ASA physical status I and II parturients with term cephalic singleton pregnancies to receive epidural labor analgesia using ropivacaine or bupivacaine. Analgesia was initiated with a 0.25% solution and maintained with a continuous infusion of a 0.1% solution with fentanyl 0.0002%. Supplementary boluses of 0.25% solution were given when requested. Labor was managed according to institutional standard labor ward protocols. Among patients who delivered vaginally, the duration of the first stage of labor was shorter in the ropivacaine group (median, 520 min; interquartile range, 377-745 min) compared with the bupivacaine group (645 min; interquartile range, 460-820 min; P = 0.009), but there was no difference in any other obstetric or neonatal outcomes. The mode of delivery was similar between groups, with operative (instrumental vaginal and cesarean) delivery rates of 61.8% (95% confidence interval, 54.4%-68.8%) in the ropivacaine group and 58.4% (95% confidence interval, 50.9%-65.5%) in the bupivacaine group (P = 0.72)., Implications: In a randomized-controlled study, we found no major outcome advantage of continuous epidural infusion of ropivacaine 0.1% with fentanyl 0.0002% over bupivacaine 0.1% with fentanyl 0.0002% for labor analgesia. Although ropivacaine was associated with a shorter first stage of labor, the relative difference is probably of limited clinical importance, and there was no difference in the mode of delivery.

Objective: To examine the status of obstetric epidural analgesia services in Hong Kong public hospitals in 2001, and to compare findings with those from a similar survey conducted in 1995., Design: Postal questionnaire survey., Setting: Hospital Authority hospitals in Hong Kong offering an obstetric and delivery service., Participants: Chiefs of Service of departments of anaesthesia and coordinators of obstetric anaesthesia and analgesia service., Main Outcome Measures: The availability of an obstetric epidural analgesia service, specialist staff allocation to the service, existence of clinical protocols, rate of epidural analgesia, techniques of epidural administration, obstetric outcome or mode of delivery, and the incidence of adverse events associated with the use of epidural analgesia., Results: Between 1 January and 31 December 2001, all eight Hospital Authority hospitals with an obstetric service provided epidural analgesia for labour pain relief, but only six (75%) offered a 24-hour service. A dedicated anaesthetist provided obstetric anaesthesia and analgesia during office hours in all units, but after hours in only three. This level of service provision compared favourably with that available in 1995, when only 82% of public maternity units provided epidural analgesia and only 36% offered a 24-hour service. The median epidural analgesia rate was 15% (range, 8%-20%) compared with 10% in 1995. The incidence of adverse events and complications was very low. Formal written protocols for the conduct of epidural analgesia for labour were used in six units. All units used mixtures of local anaesthetic combined with opioid, administered as intermittent boluses, continuous epidural infusion, or patient-controlled epidural analgesia., Conclusions: Although there has been progress and improvement in the provision of obstetric epidural analgesia services in our public hospitals, the rate is still relatively low and the provision of services after hours is limited. Further progress will likely be hindered by current or future cutbacks in public hospital budgets.

Background and Objectives: Epidural infusion of 0.2% ropivacaine is recommended by the manufacturer for labor analgesia, but lower concentrations may be effective. The objective of this study was to compare 0.1% ropivacaine with 0.2% ropivacaine and to examine the effect of addition of fentanyl., Methods: In a randomized double-blind study, 58 nulliparous laboring parturients had epidural analgesia established with 0.2% ropivacaine and were then randomized to receive one of the following epidural infusions at 10 mL/h: 0.2% ropivacaine (group R2, n = 19), 0.1% ropivacaine (group R1, n = 19), or 0.1% ropivacaine with 2 microg/mL fentanyl (group RF, n = 20). Supplementary analgesia was provided on request with 5-mL boluses of 0.2% ropivacaine., Results: All solutions provided effective analgesia during early labor, with all groups requiring similar numbers of supplementary top-ups. Visual analog pain scores in groups R2 and RF were equivalent and lower than in group R1 (P =.006). Hypotension was more frequent in group RF compared with groups R2 and R1 (P =.014). Patient and midwife satisfaction and obstetric and neonatal outcomes were similar among groups. Maternal venous plasma concentrations of ropivacaine were greater in group R2 compared with groups R1 and RF (P =.008), but umbilical venous concentrations were similar., Conclusions: We conclude that epidural infusion of 0.1% ropivacaine alone at 10 mL/h provided adequate analgesia in the first stage of labor, and that the addition of 2 microg/mL fentanyl to that concentration improved analgesia to a quality similar to 0.2% ropivacaine alone.

Background: Ropivacaine has been introduced for use in epidural analgesia in labor. However, there have been few formal dose-response studies of ropivacaine in this setting., Methods: The authors performed a prospective, randomized, double-blind study examining the effectiveness of five different doses of ropivacaine (10, 20, 30, 40, and 50 mg) administered epidurally in a volume of 10 ml to establish analgesia in 66 parturients who were in active labor with cervical dilatation less than 4 cm. A dose was considered effective when the visual analog scale pain score decreased by 50% or more from baseline., Results: A sigmoid dose-response curve and a probit log dose-response plot (linear regression coefficient, r = 0.84; coefficient of determination, r2 = 0.71) were obtained. The ED50 (median effective dose) obtained based on the maximum likelihood estimation was 18.4 mg (95% confidence interval, 13.4-25.4 mg). Time to onset of analgesia, duration of analgesia, time to two-segment regression of sensory block level, and incidence of motor block were not affected by the dosage of ropivacaine administered (P = 0.93, 0.12, 0.55, and 0.39, respectively). However, the upper level of sensory block was dose-related (P < 0.01)., Conclusion: In a traditional dose-response study, the ED50 of ropivacaine required to initiate epidural analgesia in early labor was found to be 18.4 mg (95% confidence interval, 13.4-25.4 mg).

We have compared intrathecal bupivacaine 1.25 mg and fentanyl 25 micrograms (group A) with bupivacaine 2.5 mg and fentanyl 25 micrograms (group B), for combined spinal-epidural analgesia in 49 labouring parturients in a prospective, randomized, double-blind study. Onset and quality of analgesia were similar in both groups, with median visual analogue scale pain scores of 0 achieved in 5-10 min. Median duration of analgesia was longer in group B (median 120 (range 90-120) min) compared with group A (75 (75-105) min) (P = 0.013). Median upper sensory level was higher in group B compared with group A at 15 min (T6-7 vs T11, P = 0.003) and at 30 min (T6 vs T11-12; P = 0.001). Motor block was greater in group B: seven patients had a modified Bromage score > or = 1 compared with none in group A at 15 min (P = 0.017). Group B also had a greater decrease in arterial pressure. Patient-midwife satisfaction scores and other side effects were similar. We conclude that intrathecal bupivacaine 1.25 mg with fentanyl 25 micrograms provided analgesia of similar onset and quality compared with bupivacaine 2.5 mg and fentanyl 25 micrograms. Although the duration of analgesia was shorter, the incidences of motor block and hypotension were less with the smaller dose.

We report the use of combined spinal-epidural analgesia during labour in three parturients with moderately severe mitral stenosis. In each case, rapid analgesia was achieved using intrathecal fentanyl 25 micrograms without major haemodynamic changes. Maintenance analgesia was then established gradually using a dilute epidural infusion of bupivacaine 0.1% and fentanyl 0.0002%, with the avoidance of large or rapid boluses of local anaesthetic. Supplementary analgesia in the latter stages of labour was provided using slow epidural boluses of fentanyl, with or without a low concentration of bupivacaine, which was sufficient to allow controlled instrumental deliveries. We conclude that combined spinal-epidural analgesia is a useful technique for providing analgesia and maintaining haemodynamic stability in parturients with mitral stenosis.

We have investigated the addition of adrenaline to pethidine for patient-controlled epidural analgesia after elective Caesarean section. In a randomised, double-blind study, patients received patient-controlled epidural analgesia for 24 h using pethidine 5 mg.ml-1 with adrenaline 5 micrograms.ml-1 (adrenaline group, n = 40) or pethidine 5 mg.ml-1 without adrenaline (plain group, n = 38). Visual analogue scale pain scores at rest and on coughing measured 2 h, 6 h and 24 h after surgery were similar between the two groups. There was a trend towards lower mean total consumption of pethidine in the adrenaline group (231.5 mg; SD 140.5 mg) compared with the plain group (289.5 mg; SD 139.5 mg; p = 0.071). Patients in the adrenaline group had higher visual analogue scale scores for nausea at 2 h and 24 h and higher scores for pruritus at 2 h compared with the plain group. Addition of adrenaline to pethidine for patient-controlled epidural analgesia does not appear to have significant clinical advantages.

We have investigated the addition of adrenaline to epidural pethidine for postoperative analgesia in 40 patients after Caesarean section. In a randomised, double-blind study, patients received pethidine 25 mg with adrenaline 50 micrograms (adrenaline group, n = 20) or pethidine 25 mg without adrenaline (plain group, n = 18) epidurally at the first request for postoperative analgesia. The median duration of analgesia was longer in the adrenaline group (196 min; IQR 123-286) compared with the plain group (96 min; IQR 43-113; p = 0.002) and plasma concentrations of pethidine in the first 30 min after injection were lower in the adrenaline group (p = 0.003). Visual analogue scale pain scores in the first 30 min after injection and onset of analgesia, defined by the time for pain scores to decrease by 50%, were similar between groups. Addition of adrenaline to epidural pethidine has advantages for analgesia after Caesarean section.

We have evaluated the use of a disposable device, the Patient Controlled Epidural Infusor, for patient-controlled epidural analgesia (PCEA) using pethidine, for pain relief in the first 24 hours after elective Caesarean section. Patients using the Patient Controlled Epidural Infusor (n = 20) were compared with a control group (n = 20) who received PCEA using a standard electronic device. Efficacy, as assessed by visual analogue scores, was comparable to that achieved in the control group. Patient and nursing satisfaction was high and similar to that in the control group. There was a low incidence of side-effects with both devices. Patients using the disposable device used less pethidine than patients using the electronic device (median (interquartile range) 181 (100-275) mg versus 238 (213-375) mg; p = 0.035). Use of this disposable device is an acceptable alternative to more expensive and bulkier electronic devices for PCEA after Caesarean section.

We investigated the effect of diluent volume on analgesia and systemic absorption from epidural meperidine after cesarean section in a randomized, double-blind study. At the first request for postoperative analgesia, 36 parturients were given epidural meperidine 25 mg diluted with saline to either 2 mL (12.5 mg/mL), 5 mL (5 mg/mL), or 10 mL (2.5 mg/mL). Visual analog pain scores measured in the first 30 min were greater in the 2-mL group compared with both the 5-mL group (P = 0.028) and the 10-mL group (P = 0.031). Onset of analgesia (time for visual analog pain scores to decrease by 50%) was also slower in the 2-mL group (17.5 min) compared with the 5-mL group (9 min; P = 0.015) and the 10-mL group (12 min; P = 0.003); there were no differences between the 5-mL group and the 10-mL group. Duration of analgesia and plasma concentrations of meperidine were similar among groups. No adverse side effects were recorded. Previous work has suggested that injection of epidural opioids in large volumes increases the potential risk of respiratory depression from cephalad spread of the drug. Therefore, we conclude that analgesia is optimum when epidural meperidine is administered diluted to 5 mL.

We compared patient-controlled epidural analgesia (PCEA) with patient-controlled intravenous analgesia (PCIA) using pethidine or fentanyl in a randomized, double-blind crossover study of 80 patients after caesarean section. Patients received pethidine by PCEA or PCIA, or fentanyl by PCEA or PCIA, with a crossover of the route of administration at 12h. For pethidine, pain scores were lower with PCEA vs PCIA from 4 to 16h (P < 0.05). Pethidine consumption was lower with PCEA vs PCIA from 12 to 24h (P = 0.0005). Patients preferred PCEA to PCIA (P = 0.015). For fentanyl, pain scores were lower with PCEA vs PCIA at 12h (P = 0.045). Fentanyl consumption was lower with PCEA vs PCIA from 0 to 12h (P = 0.0007). Patients had similar preference for PCEA and PCIA. Pain scores and side-effects were similar between drugs. Plasma pethidine was similar between groups. Plasma fentanyl was higher with PCIA vs PCEA at 12h (P = 0.002). PCEA has advantages over PCIA and pethidine may be the preferred drug.

Background: Epidural meperidine is effective for postoperative analgesia, but the optimum dose has not been evaluated., Methods: Five doses of epidural meperidine (12.5, 25, 50, 75, and 100 mg) given at the first request for analgesia after cesarean section were compared. Visual analog pain scores, duration of analgesia as defined by time to first patient-controlled epidural analgesia demand, plasma concentrations of meperidine, side effects, and subsequent 24-h consumption of meperidine were evaluated., Results: All doses were effective, but patients took longer to become pain-free after 12.5 mg (median 30 min) compared with 25 mg (median 12 min, P = 0.038), and duration of analgesia was shorter after 12.5 mg (median 83 min) compared with 25 mg (median 165 min, P = 0.0005). Increasing dose to more than 25 mg did not improve onset or duration of analgesia. Plasma concentrations of meperidine were less than minimum effective analgesia concentration for all doses except 100 mg. There was more frequent nausea (P = 0.004) and dizziness (P = 0.0002) after 100 mg compared with smaller doses., Conclusions: Epidural meperidine provides effective postoperative analgesia, although of relatively short duration. A single dose of 25 mg is superior to 12.5 mg, but there is no benefit from increasing the dose to 50 mg or greater.

We evaluated a disposable device (Baxter PCA Infusor) for patient-controlled epidural analgesia (PCEA) using pethidine in twenty women after lower segment caesarean section. Efficacy, as measured by visual analogue pain scores, was comparable with historical controls from PCEA studies using electronic devices. Three patients reported inadequate analgesia, attributable in two cases to problems with epidural catheter. PCEA was stopped in one patient because of side-effects. Pethidine consumption ranged from 125 to 1500 mg (median 575 mg) in 48 hours. Plasma concentrations of pethidine varied widely. Disposable devices for PCEA after caesarean section provide an alternative to bolus administration or PCEA using more expensive and cumbersome electronic devices, although we suggest currently available apparatus requires modifications to improve clinical performance.