Search

Background: Lipophilic opioids and local anesthetics are often given intrathecally in combination for labor analgesia. However, the nature of the pharmacologic interaction between these drugs has not been clearly elucidated in humans., Methods: Three hundred nulliparous women randomly received 1 of 30 different combinations of fentanyl and bupivacaine intrathecally using a combined spinal-epidural technique for analgesia in the first stage of labor. Visual analogue scale pain scores were recorded for 30 min. Response was defined by percentage decrease in pain score from baseline at 15 and 30 min. Dose-response curves for individual drugs were fitted to a hyperbolic dose-response model using nonlinear regression. The nature of the drug interaction was determined using dose equivalence methodology to compare observed effects of drug combinations with effects predicted by additivity., Results: The derived dose-response models for individual drugs (doses in micrograms) at 15 min were: Effect = 100 × dose / (13.82 + dose) for fentanyl, and Effect = 100 × dose / (1,590 + dose) for bupivacaine. Combinations of fentanyl and bupivacaine produced greater effects than those predicted by additivity at 15 min (P < 0.001) and 30 min (P = 0.015) (mean differences, 9.1 [95% CI, 4.1-14.1] and 6.4 [95% CI, 1.2-11.5] units of the normalized response, respectively), indicating a synergistic interaction., Conclusions: The pharmacologic interaction between intrathecal fentanyl and bupivacaine is synergistic. Characterization and quantification of this interaction provide a theoretical basis and support for the clinical practice of combining intrathecal opioids and local anesthetics.

The study objective was to show that fentanyl given five minutes prior to induction improved insertion conditions for the Classic Laryngeal Mask Airway. Previous work had shown fentanyl at 90 seconds to be unpredictable. A probit analysis design was used in which success/failure rates of different doses of fentanyl were measured and dose-response curves drawn from which the ED50 and ED95 with 95% confidence intervals were determined. Adult Chinese patients with American Society of Anesthesiologists physical status classification I or II and requiring anaesthesia for minor surgery with a laryngeal mask were recruited. They were randomly assigned to one of six dosage groups: 0.25, 0.5, 1.0, 1.5, 2.0 and 3.0 microg x kg1. Fentanyl was given prior to propofol 25 mg x kg(-1), and insertion was assessed 90 seconds later using six categories of patient response. Ninety-six patients, aged 18 to 63 years, were studied. The six dosage groups were similar As the fentanyl dose increased, fewer patients responded to insertion (P < 0.01). Dose-responses could be predicted for all categories, except resistance to insertion and laryngospasm. Probit analysis predicted an ED50 of 0.5 microg x kg(-1) and ED, of 7.5 microg x kg(-1) for ideal insertion conditions (i.e., no swallowing, gagging, body movement or laryngospasm). Commonly used fentanyl doses of 1 to 2 microg x kg(-1) only prevented patients responding to insertion in 70 to 80% of cases. When using propofol 2.5 mg x kg(-1), administering fentanyl five minutes before laryngeal mask insertion does not provide ideal insertion conditions in 95% of cases unless excessively large doses are used. An ideal dose of fentanyl that produces optimum insertion conditions could not be determined.

Probit analysis was used to predict an optimal dose of fentanyl, co-administered with propofol 2.5 mg.kg(-1), when inserting the laryngeal mask airway. In all, 21 male and 54 female healthy Chinese patients, aged 18-63 years, requiring anaesthesia for minor surgery were recruited. They were assigned to one of five groups: placebo, 0.5, 1.0, 1.5 and 2.0 microg.kg(-1). Insertion was performed 90 s after administration and insertion conditions assessed using a six-category score. Dose-response curves could only be drawn for swallowing and movement categories, and only the ED(50) could be predicted with certainty. To provide optimal conditions in over 95% of patients, fentanyl doses well above the clinical range were required. A standard fentanyl dose of 1 mug.kg(-1), co-administered with propofol 2.5 mg.kg(-1), provided optimal conditions in 65% of cases. Ninety seconds may have been insufficient time for fentanyl to reach its peak effect.

Objective: It has recently been suggested that systemic pethidine is ineffective in relieving labour pain. This study aims to evaluate the analgesic efficacy of pethidine in labour., Design: This is a double blinded randomised placebo-controlled study., Setting: Labour suite, Prince of Wales Hospital, Hong Kong. Population Fifty normal Chinese pregnant women in early labour., Methods: We planned to randomise 112 women in early labour to receive either intramuscular pethidine 100 mg or normal saline when they requested analgesia. An interim analysis was performed at sample size 50., Main Outcome Measures: The primary outcome assessed was the visual analogue scale (VAS) pain score after 30 minutes., Results: The study was terminated after recruitment of the first 50 women when planned interim analysis showed a significantly greater reduction of VAS pain score in the pethidine group (P= 0.009). The median difference in VAS pain score between the two groups at 30 minutes was -17 [95% CI -30 to -4]. Mean time to first subsequent request for analgesia was greater in the pethidine group (232 minutes, 95% CI 135 to 329 minutes) compared with the control group (75 minutes, 95% CI 54 to 95 minutes). Eight women (32%) in the pethidine group needed no further analgesia vs one woman (4%) in the control group (P= 0.011). Women in the pethidine group gave greater scores for sedation and satisfaction. Neonatal outcome was similar., Conclusions: Systemic pethidine was more effective at relieving labour pain than placebo. Its analgesic effect, however, was modest.

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.

We compared epidural (n = 17) and intravenous (n = 20) patient-controlled analgesia (PCA) using pethidine (bolus 10 mg, lockout interval 10 min, 4-h maximum dose 3 mg.kg(-1)) after total gastrectomy. We found that mean (SD) pethidine consumption in the first 24 h was 33% less in the epidural group [255 (85) mg] than in the intravenous group [379 (129) mg, p = 0.002], although most of this difference occurred in the first 8 h. Plasma concentrations of pethidine were lower at 8 h (p < 0.01) in the epidural group, but were similar at 24 h. Pain scores, side-effects, patient satisfaction and patient outcome were similar between groups. Epidural and intravenous pethidine PCA provided similar efficacy after major abdominal surgery, although the epidural route can reduce the amount of pethidine used initially.

Opioids are routinely omitted at the induction of general anesthesia for cesarean delivery because of concerns about neonatal respiratory depression. The subsequent unmodified maternal stress response to tracheal intubation reduces placental perfusion. The short-acting opioid alfentanil may afford advantages at the induction, without subsequent neonatal depression. In this double-blinded study of elective cesarean deliveries, 40 patients were allocated randomly to receive either alfentanil 10 microg/kg (n = 18) or placebo (n = 22), 1 min before the induction of anesthesia with thiopental 4 mg/kg and succinylcholine 1.5 mg/kg. Anesthesia was maintained with 50% nitrous oxide, 0.5% isoflurane in oxygen, and atracurium. Neonates were assessed by using Apgar scores, Neurologic and Adaptive Capacity Scores, and umbilical cord blood gas and catecholamine analysis. After intubation, mothers receiving alfentanil had a smaller increase in mean arterial blood pressure, (11 +/- 15 vs 31 +/- 13 mm Hg, P < 0.001) and lower plasma norepinephrine concentrations, (336 +/- 152 vs 486 +/- 241 pg/mL, P < 0.05). Neonates in the alfentanil group had greater umbilical arterial oxygen tensions (27.8 +/- 7.0 vs 22.6 +/- 7.4 mm Hg), slightly reduced Apgar scores (both P < 0.05), but similar Neurologic and Adaptive Capacity Scores. One neonate in the alfentanil group required naloxone. The maternal stress response was attenuated in the alfentanil group but at the cost of early neonatal depression. However, all neonates should be monitored for possible immediate, but transient, respiratory depression.

Purpose: Meperidine has local anesthetic properties and, therefore, when given epidurally it has the potential to cause hemodynamic changes. Our objective was to study the hemodynamic effects of an analgesic dose of epidural meperidine (50 mg) in 34 ASA 1-2 term parturients scheduled for elective Cesarean section under epidural anesthesia., Methods: A lumbar epidural catheter was inserted and patients lay in the supine left wedge position. Intravenous fluid preload was withheld, and hemodynamic measurements comprising of mean arterial pressure, cardiac output and heart rate were made using automatic oscillotonometry (Dinamap 1486SX) and transthoracic electrical bioimpedance (Bomed NCCOM3). Following baseline measurements, the hemodynamic effects of sequential epidural injection of first, 10 ml saline, and 20 min thereafter, 50 mg meperidine diluted to 10 ml with saline, were recorded. Sensory blockade was assessed following each injection using loss of temperature discrimination to ice. Paired Student t tests were used to compare changes in hemodynamic variables., Results: Epidural meperidine produced a small increase from the saline values in the mean (SD) cardiac output of 5.81 +/-1.44 to 6.04+/-1.54 L x min(-1) (P<0.05), and mean arterial pressure of 77.1+/-8.8 to 79.3+/-9.9 mm Hg (P<0.05). Sensory changes, the upper level of which ranged from L1 to T1, were detected in 94% of patients given epidural meperidine. Epidural saline injection had no such hemodynamic effects, but produced a detectable sensory level in two patients., Conclusion: Epidural meperidine, 50 mg, caused minimal hemodynamic changes in term parturients.

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.

In a randomised, double-blind study, we compared a combination of morphine and alfentanil with morphine alone for patient-controlled analgesia (PCA) after Caesarean section under spinal anaesthesia. After surgery, patients were randomly allocated to receive PCA with a bolus dose of either morphine 0.75 mg plus alfentanil 0.125 mg (Group MA, n = 40) or morphine 1.5 mg alone (Group M, n = 37) with a lockout interval of 8 min and no hourly dose limit. Clinical assessments were made in the first 24 h, after which patients completed a written questionnaire. There were no differences between groups in PCA usage or visual analogue scale pain scores measured at 2, 4, 6 and 24 h. There was a low incidence of side-effects in both groups. In the questionnaire, patients in Group MA scored higher compared with Group M when asked to grade speed of onset and effectiveness of analgesia after a PCA bolus; there were no differences in grading for duration of analgesia or overall patient satisfaction. Addition of alfentanil to morphine may have advantages for PCA.

Pethidine is an effective epidural opioid for the treatment of acute pain. Its use has been well described in Australian and New Zealand practice, particularly in the field of obstetric anaesthesia. Reported methods of delivery have included bolus injection, continuous infusion and patient-controlled epidural analgesia. Areas of application have included treatment of postoperative pain, labour pain and intraoperative pain. Because of its intermediate lipid solubility, pethidine may have advantages over many other epidural opioids. However, potential for accumulation of norpethidine limits its use to relatively short durations of treatment.

Pethidine is the only member of the opioid family that has clinically important local anaesthetic activity in the dose range normally used for analgesia. Pethidine is unique as the only opioid in current use that is effective as the sole agent for spinal anaesthesia. In lower doses, intrathecal pethidine is also an effective analgesic for treating pain in labour. This paper reviews the pharmacology of intrathecal pethidine and clinical experience reported to date. Articles reviewed include those identified by a Medline search using keywords "intrathecal" or "spinal anaesthesia/ anesthesia" and "pethidine" or "meperidine". Reference lists from identified papers were scrutinized to identify further relevant articles.

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.