Minimum Local Analgesic Concentration Research Articles

Effect of Epidural Bolus Levobupivacaine and Lignocaine in Late Second Stage of Parturition in Combined Spinal Epidural Labor Analgesia

Background: Use of minimum local analgesic concentration in the epidural component of combined spinal epidural (CSE) effectively maintains analgesia in the first stage of labor. However, local anesthetic concentration needs to increase to achieve effective analgesia in the second stage as there are more recruitment of A-δ fiber occurs. This study compared the effect of epidural bolus of Levobupivacaine and Lignocaine in the late second stage of parturition in combined spinal epidural labor analgesia.Methods: This multicenterd, open-label, randomized controlled trial was conducted under supervision of Department of Anesthesia, Analgesia, and Intensive Care Medicine of Bangabandhu Sheikh Mujib Medical University from July 2019 to June 2020 including 80 parturients of 18-35 years old, ASA status I and II, full-term, primiparous, who were randomized into two groups to receive either 10ml bolus of 0.0625% levobupivacaine with fentanyl 2μg/ml or 10ml bolus of 0.5% lignocaine with fentanyl 2μg/ml after CSE analgesia at first stage of labor. Level of analgesia, duration of second stage of labor, quality of pain relief, maternal satisfaction, mode of delivery and APGAR score of neonate were evaluated.Results: During delivery, levobupivacaine group had a lower intensity of pain compared to lignocaine group (VAS score 1.89±0.67 vs 2.64±0.92, p = 0.001). Duration of second stage of labor in levobupivacaine group was significantly shorter compared to lignocaine group (48.4±16 minutes vs 63.5±28.4, p-value 0.007). Besides, quality of pain relief and maternal satisfaction were better in levobupivacaine group compared to lignocaine group. Moreover, instrumental delivery rate was high in lignocaine group. Fetal outcome measured as APGAR score was similar in both groups.Conclusion: Epidural bolus of levobupivacaine-fentanyl produces more adequate analgesia than lignocaine-fentanyl in late second stage of labor and does not increase instrumental delivery rate with similar fetal outcome.

Investigation of the Minimum Local Analgesic Concentration of Epidural Sufentanil Combined With Ropivacaine for Labor Analgesia

Worldwide, there are only few studies focusing on labor analgesia on the MLAC (minimum local analgesic concentration) or EC50 (median effective concentration) of sufentanil and ropivacaine. Therefore, we determine the MLAC or EC50 of sufentanil and ropivacaine for epidural analgesia by using an up-down sequential allocation and survey its adverse effect in a prospective blinded randomized trial. Sixty nulliparous full-term parturients who required labor analgesia were recruited and randomly divided into the sufentanil and ropivacaine groups. The formulation was 25 μg sufentanil combined with 0.1% ropivacaine (added 0.9% normal saline to 75 ml). According to the response of a previous parturient, the dosage of sufentanil was increased or decreased by 5 μg in the sufetanil group; meanwhile, we also administrated an initial concentration of 0.1% ropivacaine combined with 22.5 μg sufentanil (added 0.9% normal saline to 75 ml) in the ropivacaine group. The concentration of ropivacaine was increased or decreased by 0.01% following the response of the previous parturient. The Brownlee up-down sequential allocation was used to estimate the MLAC of epidural ropivacaine and its 95% confidence intervals in labor analgesia. There were no significant changes for the two groups, including for age, height weight, active stage, second stage of labor, and gestational weeks (P = 0.769, 0.900, 0.603, 0.441, 0.577, and 0.695, respectively). The VAS scores of the parturient decreased to varying degrees (P < 0.0001) after labor analgesia compared with VAS before labor analgesia, and the most effective analgesia was reached in 60 min. The EC50 dose of epidural ropivacaine combined with 0.3 μg/mL sufentanil was 0.09687%, and the 95% CI was 0.08944%~0.1043%. Five parturients had PONV, and the incidence rate was 16.7%; one parturient had pruritus, so the incidence rate was 3.3%. The EC50 dose of epidural sulfetanil combined with 0.1% ropivacaine was 18.76 μg with a 95% confidence interval of 13.5-24.48 μg. There were no significant differences in the active stage, second stage of labor, and maternal and fetal hemodynamic data between the two groups. Notably, the Apgar scores for 1min and 5min were 10scoresfor almost allof thesepatients. There were no significant differences between the two groups for maternal and fetal side effects, which had very low incidence rates. The MLAC of epidural sufentanil or ropivacaine could provide satisfactory and safe analgesia for parturients while having a low incidence rate of side effects.

Does intrathecal analgesia reduce the subsequent minimum local analgesic concentration of epidural bupivacaine?

Does intrathecal analgesia reduce the subsequent minimum local analgesic concentration of epidural bupivacaine?

Combined spinal epidural vs epidural labour analgesia: does initial intrathecal analgesia reduce the subsequent minimum local analgesic concentration of epidural bupivacaine?

Labour analgesia initiated using a combined spinal-epidural (CSE) technique may reduce subsequent epidural bupivacaine requirements compared with an epidural-only technique. We compared the minimum local analgesic concentrations (MLAC) of epidural bupivacaine following initial intrathecal or epidural injection. In a prospective, double-blind study, 115 women requesting epidural analgesia were randomly assigned to receive either an epidural with bupivacaine 20 mg and fentanyl 40 μg or a CSE with intrathecal bupivacaine 2.5 mg and fentanyl 5 μg. Analgesia was assessed using a visual analogue pain score. When further analgesia was requested, bupivacaine 20 ml was given, and the concentration was determined using the technique of up-down sequential allocation. The MLAC of bupivacaine in the epidural group was 0.032% wt/vol (95% CI 0.020-0.044) compared with 0.047% wt/vol (95% CI 0.042-0.052) in the CSE group. Bupivacaine requirements for the second injection were increased following intrathecal analgesia by a factor of 1.45 (p = 0.026) compared with epidural analgesia.

Minimum local analgesic concentration of ropivacaine for intra-operative caudal analgesia in pre-school and school age children - analysis using the Dixon method

Deng et al. recently quantified the minimal local anaesthetic concentration of ropivacaine for intra-operative caudal analgesia in pre-school and school age children [1]. Although in their methods, the authors stated that the concentration of ropivacaine received by a particular subject was determined according to Dixon’s up and down method, the ED50 presented in the results was calculated using probit and logit regression only. We respectfully suggest that for proper analysis of the data, the ED50 with 95% CI should have been estimated from the up-down sequences using the method of Dixon and Massey. The sequences should then have been subjected to probit regression analysis as a backup or sensitivity test. We calculated the ED50 by averaging the midpoint concentration of all independent pairs of patients involving a crossover according to Dixon and Massey’s method [2, 3] using all 25 patients depicted in both groups. The ED50 (95% CI) values for school age and pre-school children are 0.143% (0.139–0.147) and 0.098% (0.093–0.103), respectively, compared with the authors’ results of 0.143% (95% CI: 0.132–0.157%) and 0.107% (95% CI: 0.089–0.122%). This would not have altered the overall result of the study, but is a more accurate presentation of their results. No external funding and no competing interests declared. Previously posted at the Anaesthesia Correspondence website: http://www.anaesthesiacorrespondence.com.

Minimum local analgesic concentration of ropivacaine for intra‐operative caudal analgesia in pre‐school and school age children

We compared the minimum local analgesia concentration of ropivacaine for intra-operative caudal analgesia in pre-school and school age children. Fifty-one boys, undergoing hypospadius repair surgery, were stratified into pre-school or school age groups. After induction of anaesthesia, caudal block was performed with ropivacaine 1 ml.kg⁻¹ of the desired concentration. The first child in each group received ropivacaine 0.125%, and subsequent concentrations were determined by the analgesic response of the previous patient using Dixon's up-and-down method. Under general anaesthesia with 0.7 minimum alveolar concentration of sevoflurane, the minimum local analgesia concentration of ropivacaine for intra-operative caudal block was 34% greater in school age than in pre-school age boys (0.143% (95% CI 0.132-0.157%) vs 0.107% (95% CI 0.089-0.122%), respectively; p < 0.001). This study indicates that a higher concentration of ropivacaine is needed for school age than pre-school age children to provide intra-operative caudal analgesia when combined with general anaesthesia.

Minimum local analgesic concentration of local anaesthetics

The minimum local analgesic concentration (MLAC) model was first described in 1995. The idea was to develop a clinical model for local anaesthetic drugs, similar to that which was in routine use for inhalation anaesthetics, the minimum alveolar concentration (MAC). Before this much of the clinical research into local anaesthetic drugs involved comparisons of fixed doses or combinations with other adjuvants. Most of these studies used supramaximal doses with the resulting conclusions of similar efficacy being difficult to interpret correctly, more commonly the problem was that researchers were not yet really appreciating the issue. It was becoming clear that to be able to distinguish marginal differences in treatments, we would learn more from ‘ineffective’ outcomes rather than ubiquitous or universal analgesia. Epidural analgesia in labour presented a most pragmatic clinical area to develop this approach. Since it was first described, the MLAC model has been adapted to a variety of clinical scenarios and utilized extensively in regional anaesthesia research. In this article, we will explain the principles underlying the MLAC model, some of the areas of research in which the MLAC methodology has been used and the understanding that has emerged.

The Effect of Sex on the Minimum Local Analgesic Concentration of Ropivacaine for Caudal Anesthesia in Anorectal Surgery

Caudal anesthesia is routinely used in our hospital for most of ambulatory anorectal surgery; patients need to recover as quickly as possible. The dose of local anesthetic may be different for male and female patients. We designed this study to investigate the effect of sex on the minimum local anesthetic concentration (MLAC) of ropivacaine for caudal anesthesia. In this double-blind, prospective study, we enrolled 70 ASA physical status I patients (35 male and 35 female) who were scheduled for anorectal surgery under caudal anesthesia, and allocated them to 2 study groups according to their gender. Each participant received a single injection of 20 mL ropivacaine through a caudal catheter. Using Dixon's up-and-down sequential allocation, the first participant received 0.2% and subsequent concentrations were determined by the analgesic response of the previous patients to the initial skin incision and laxity of the anal sphincter. The concentration change was 0.025%. The up-and-down sequences were analyzed using the Dixon and Massey method to quantify the caudal analgesic block effective concentrations in 50% of patients. The MLAC of ropivacaine for caudal analgesia was 0.296% (95% confidence interval, 0.286%-0.307%) in male patients and 0.389% (95% confidence interval, 0.372%-0.407%) in female patients (P < 0.01). We conclude that the ropivacaine MLAC for caudal anesthesia in female patients is 31% larger than in male patients.

Relative potencies of bupivacaine, levobupivacaine, and ropivacaine for neonatal spinal anaesthesia

Comparing the relative potency of new local anaesthetics such as levobupivacaine and ropivacaine with bupivacaine by the minimum local analgesic concentration model has not been described for neonatal spinal anaesthesia. This information is important to compare agents and to determine the most effective spinal dose. We performed a two-stage study to determine the ED50, the ED95, and the relative analgesic potency of isobaric spinal bupivacaine, levobupivacaine, and ropivacaine in infants. In phase 1, 81 infants were randomized in a Dixon-Massey study to describe the minimum local analgesic dose. In phase 2, a further 70 patients were randomly allocated to receive spinal anaesthesia with doses in the upper dose-response range to define the ED95. The ED50 doses for bupivacaine, levobupivacaine, and ropivacaine were estimated by isotonic regression to be 0.30 mg kg(-1) [95% confidence interval (CI) 0.25-0.43], 0.55 mg kg(-1) (0.50-0.64), and 0.50 mg kg(-1) (0.43-0.64), respectively. The ED(95), respectively, of bupivacaine, levobupivacaine, and ropivacaine were 0.96 mg kg(-1) (95% CI 0.83-0.98), 1.18 mg kg(-1) (1.05-1.22), and 0.99 mg kg(-1) (0.73-1.50). The relative potency ratios at the ED(50) were bupivacaine:levobupivacaine 0.55 (95% CI 0.39-0.88), bupivacaine:ropivacaine 0.61 (0.41-1.00), and levobupivacaine:ropivacaine 1.09 (0.84-1.45). Appropriate doses for infant spinal anaesthesia are 1 mg kg(-1) of isobaric 0.5% bupivacaine and ropivacaine and 1.2 mg kg(-1) of isobaric 0.5% levobupivacaine.

Minimum local analgesic concentrations of ropivacaine and levobupivacaine with sufentanil for epidural analgesia in labour

Background Sufentanil is often added to ropivacaine and levobupivacaine to provide epidural analgesia in labour. The aim of this study was to compare the analgesic potencies of epidural ropivacaine and levobupivacaine in combination with sufentanil 0.5 μg/mL, using the minimum local analgesic concentration (MLAC) model with up-down sequential allocation. Methods In this prospective study parturients with cervical dilation ⩾ 3 cm who requested epidural analgesia between 0800 and 1500 were enrolled. They were randomly allocated to receive 20 mL of either ropivacaine (group R) or levobupivacaine (group L) both with sufentanil 0.5 μg/mL. Thirty minutes after initial injection a continuous infusion was started and maintained until delivery. The numbers of additional doses of 0.2% ropivacaine and 0.25% levobupivacaine needed to maintain the visual analogue pain score <10/100 mm were recorded. The median effective concentrations were estimated from up-down sequential allocations and overall dose requirements of ropivacaine and levobupivacaine were compared. Results 53 women were recruited to the study. The MLAC of ropivacaine was 0.023% w/vol (95% CI, 0.005-0.041) compared with levobupivacaine which was 0.020% w/vol (95% CI, 0.008-0.032). The hourly dose of ropivacaine was 13.3 (SD 5.8) mg/h which was similar to levobupivacaine 14.4 (SD 9.7) mg/h. The total doses used for labour analgesia were 56.1 (SD 32.3) mg of ropivacaine (n = 26) and 58.6 (SD 27.5) mg of levobupivacaine (n = 26). Conclusion When sufentanil 0.5 μg/mL was added to either ropivacaine or levobupivacaine for labour analgesia, no significant difference in analgesic potency was observed.

Relative Analgesic Potencies of Levobupivacaine and Ropivacaine for Caudal Anesthesia in Children

Comparing relative potency of new local anesthetics, such as levobupivacaine and ropivacaine, by the minimum local analgesic concentration model has not been described for caudal anesthesia. Therefore, we performed a prospective, randomized, double-blind study to determine the minimum local analgesic concentrations of a caudal single shot of ropivacaine and levobupivacaine in children and to describe the upper dose-response curve. We performed a two-stage prospective, randomized, double-blind study comparing the dose-response curves of caudal ropivacaine and levobupivacaine in children. In phase 1, 80 boys were randomized to receive either ropivacaine or levobupivacaine. In the second phase a further 32 patients were randomly allocated to receive caudal anesthesia with doses designed to delineate the upper dose-response range (the 50% effective dose [ED(50)]-ED(95) range). There were no significant differences in ED(50) values for caudal ropivacaine and levobupivacaine. The ED(50) for levobupivacaine estimated from the Dixon Massey method was 0.069% (95% CI 0.056%-0.082%) and for ropivacaine was 0.075% (95% CI 0.058%-0.092%). Estimated by isotonic regression the ED(50) and ED(95) respectively of levobupivacaine were 0.068 (0.04-0.09) and 0.20% (95% CI 0.16%-0.24%). For ropivacaine ED 50 and ED95 were 0.066 (0.033-0.098) and 0.225% (95% CI 0.21%-0.24%). In children receiving one minimum alveolar anesthetic concentration of sevoflurane, there were no significant differences in the ED(50) for caudal levobupivacaine and ropivacaine. The potency ratio at ED(50) was 0.92 and 0.89 at ED(95), indicating that caudal levobupivacaine and ropivacaine have a similar potency.

Impact of the addition of sufentanil 5 μg or clonidine 75 μg on the minimum local analgesic concentration of ropivacaine for epidural analgesia in labour: a randomized comparison

Background Addition of lipophilic opioids or α 2-agonists to local anaesthetic solutions reduces local anaesthetic requirements and side effects. While the efficacy and side effects of these adjuvants are dose-related, information about their relative analgesic potencies is lacking, making it difficult to draw meaningful clinical conclusions. The aim of the present study was to assess the relative sparing of ropivacaine by clinically relevant doses of sufentanil and clonidine using the minimum local analgesic concentration (MLAC) model. Methods In this prospective, double-blind study, the sparing effect of sufentanil 5 μg and clonidine 75 μg on the MLAC of ropivacaine administered for labour epidural analgesia was compared in 78 women at <5 cm cervical dilatation. Women were randomly allocated to one of three groups: plain ropivacaine, ropivacaine with sufentanil 5 μg and ropivacaine with clonidine 75 μg. Results The MLAC of plain ropivacaine was 0.099% wt/vol (95%CI: 0.090 to 0.109) and was reduced to 0.036% wt/vol (95% CI: 0.024 to 0.049) when combined with sufentanil 5 μg and to 0.036% wt/vol (95% CI: 0.027 to 0.046) with clonidine 75 μg ( P < 0.001). The wt/wt local anesthetic sparing potency ratio of sufentanil to clonidine was 15.1 (95% CI: 10.3 to 23.4). Conclusions Sufentanil 5 μg and clonidine 75 μg produce similar reductions in the MLAC of ropivacaine. This finding will make feasible the assessment of the side effects of these adjuvants administered at equipotent doses in further studies.

Determination of the Full Dose–Response Relation of Intrathecal Bupivacaine, Levobupivacaine, and Ropivacaine, Combined with Sufentanil, for Labor Analgesia

Ropivacaine and levobupivacaine are local anesthetics that produce less motor block and greater sensory-motor separation when compared with equal milligram doses of bupivacaine. Although minimum local analgesic concentration studies suggested that they are less potent than bupivacaine, full dose-response studies have not been performed. The current trial describes the dose-response relation of levobupivacaine, ropivacaine, and bupivacaine, combined with sufentanil, when used for intrathecal labor analgesia. Four hundred fifty term parturients in active labor were included in this double-blind, randomized trial. Combined spinal-epidural anesthesia was performed, and ropivacaine, levobupivacaine, or bupivacaine was intrathecally administered in a dose of 1.0, 1.5, 2.0, 2.5, 3.0, or 3.5 mg, always combined with 1.5 microg sufentanil. Patients were considered responders to spinal analgesia if the visual analog scale score for pain was less than 25 mm within 15 min and the visual analog scale score remained less than 25 mm for 45 min. Patient demographics, obstetric data, maternal side effects, and fetal and neonatal well-being were noted. Group-specific dose-response curves were constructed using a probit regression model. The ED95 of bupivacaine was 3.3 mg (95% confidence interval, 2.9-4.1). The ED95s of ropivacaine and levobupivacaine were 4.8 mg (95% confidence interval, 4.0-6.7) and 5.0 mg (95% confidence interval, 4.1-7.0), respectively. Racemic bupivacaine was significantly more potent than ropivacaine (P=0.0027) and levobupivacaine (P=0.0006). Ropivacaine and levobupivacaine were of similar potency (P=0.91). This full dose-response study suggests that ropivacaine and levobupivacaine are of similar potency, whereas bupivacaine is more potent than both other drugs.

Effect of sufentanil on minimum local analgesic concentrations of epidural bupivacaine, ropivacaine and levobupivacaine in nullipara in early labour

The aim was to assess the effect of epidural sufentanil on relative analgesic potencies of epidural bupivacaine, ropivacaine and levobupivacaine by determining the minimum local analgesic concentrations during labour. In a randomised, double-blind study, 171 parturients were allocated to one of six groups receiving a 10-mL bolus of bupivacaine, ropivacaine or levobupivacaine alone or with sufentanil 0.75 microg/mL. The concentration of local anaesthetic was determined by the response of the previous parturient using up-down sequential allocation starting at a concentration of 0.13% wt/vol with a testing interval of 0.01%. Effective analgesia was defined as a visual analogue pain score < or = 15/100 mm within 30 min and lasting for 30 min. Median effective concentrations were estimated and two-sided P < 0.05 was significant. Local anaesthetic concentration, use of sufentanil and local anaesthetic drug were independent significant predictors of effective and ineffective analgesia. Bupivacaine was significantly more potent than levobupivacaine and ropivacaine. The relative potency ratios without sufentanil of 0.77:0.83:1.00 were reduced to 0.36:0.38:1.00 by the addition of sufentanil. The major factor influencing local anaesthetic requirements was the addition of sufentanil, which reduced overall requirements by a factor of 4.2 (95% CI 3.6-4.8); this effect was proportionately more enhanced for bupivacaine. Local anaesthetic requirements for bupivacaine, levobupivacaine and ropivacaine follow an analgesic potency hierarchy. Any potency differences are small when compared to the effect of sufentanil, which resulted in a four-fold reduction in local anaesthetic requirements. Sufentanil may also enhance the potency differences between bupivacaine and the two S-enantiomer agents.

Up-down studies: responding to dosing!

Since the publication of the first use of up-down sequential allocation in regional anaesthesia and the description of the minimum local analgesic concentration (MLAC) model in 1995, [1] Columb M.O. Lyons G. Determination of the minimum local analgesic concentrations of epidural bupivacaine and lidocaine in labor. Anesth Analg. 1995; 81: 833-837 PubMed Google Scholar the model has been extensively replicated and adapted to a variety of clinical and pharmacologic research issues. Now that a decade has passed, it seems appropriate for us to consider the contribution that these studies have made to our understanding of the pharmacodynamics of regional anaesthesia. In doing this, the authors debate the issues with MC briefly describing the methodology and then advancing the ‘pro’ position and RD the ‘con’. What follows are our attempts to keep the reader as fully appraised and hopefully interested as possible.

Gerard W. Ostheimer “What’s New in Obstetric Anesthesia” Lecture

Gerard W. Ostheimer “What’s New in Obstetric Anesthesia” Lecture

Demographic differences between consenters and non-consenters in an obstetric anesthesiology clinical study

Willingness to participate in obstetric anesthesiology clinical studies may be influenced by age, parity or ethnicity. This study was designed to determine whether there were demographic differences between consenters and non-consenters in a minimum local analgesic concentration clinical study. Four hundred and fifty-two women were approached for the study and the age, ethnicity and parity of patients who consented or declined to participate were collected. Ethnicity was categorized as Asian or Pacific Islander, black, Hispanic, white, or other. Parametric data were analyzed using t-tests and non-parametric data using χ 2 tests. There were no significant differences in the consent rate based on age or parity. Black Americans were more likely to consent than Asian Americans ( P < 0.001) and as likely to consent as white Americans. There were no statistically significant differences in the consent rate between Caucasian and Asian Americans. More studies are needed to determine the socioeconomic and demographic factors that affect consent rates of labor patients.

A Randomized Sequential Allocation Study to Determine the Minimum Effective Analgesic Concentration of Levobupivacaine and Ropivacaine in Patients Receiving Epidural Analgesia for Labor

This study was designed to determine and compare the minimum local analgesic concentrations of levobupivacaine and ropivacaine when used in epidural obstetric analgesia. In a double-blind study, healthy women requiring epidural analgesia for labor pain were randomized to receive either ropivacaine or levobupivacaine. Drugs were administered as a 20-ml epidural bolus. The concentration of each started at 0.11% and increased or decreased at intervals of 0.01%, depending on the response of the previous patient, using the technique of up-down sequential allocation. Minimum local analgesic concentrations were calculated using the formula of Dixon and Massey. Efficacy was assessed using visual analog pain scores and motor and sensory block assessments, and safety was assessed by recording maternal and fetal/neonate vital signs and adverse events. Forty-seven patients received levobupivacaine, and 47 received ropivacaine. Minimum local analgesic concentrations for levobupivacaine (0.077%; 95% CI, 0.058-0.096%) were lower than those for ropivacaine (0.092%; 95% CI, 0.082-0.102%). The 0.015% difference was not statistically significant. There was no notable difference between treatment groups in the proportion of patients reporting drug-related adverse events. Levobupivacaine was 19% more potent than ropivacaine and provided similar safety results.

The Site of Action of Epidural Fentanyl Infusions in the Presence of Local Anesthetics: A Minimum Local Analgesic Concentration Infusion Study in Nulliparous Labor

We have previously demonstrated that continuous epidural infusions of fentanyl without local anesthetics elicit analgesia by a systemic mechanism. In this study, we examined the hypothesis that, in the presence of epidural bupivacaine, continuous infusions of epidural fentanyl elicit analgesia by a spinal mechanism. Forty-eight nulliparous women in active labor participated in this prospective, randomized, double-blinded study. Women received lumbar epidural analgesia with 20-30 mL bupivacaine 0.125% until pain free. Subjects were then randomized to either IV or epidural (EPI) fentanyl infusion groups. Each infusion delivered fentanyl 30 microg/h. All women received an epidural infusion of bupivacaine at a rate of 20 mL/h, the concentration of which was determined by the response of the previous woman in the same group to the analgesic regimen used. Unlike previous studies that assessed the minimum local analgesic concentration (MLAC) for bolus administration at the initiation of analgesia, this study assessed MLAC(infusion) for the maintenance of analgesia throughout the first stage of labor. MLAC(infusion) was determined using the up-down sequential analysis described by Dixon and Massey. The MLAC(infusion) of epidural bupivacaine was 0.063% (95% confidence interval, 0.058-0.068) and 0.019% (95% confidence interval, 0.000-0.038) in the IV and EPI groups respectively. A continuous infusion of fentanyl was more than three times as potent when administered by the epidural than by the IV route. This marked increase in potency for the epidural route is highly suggestive for a predominantly spinal mechanism of action for infused epidural fentanyl under the conditions of this study. This study determined the median effective concentration for epidural infusions of bupivacaine during labor analgesia. Coadministered epidural fentanyl infusions were more than three times more potent than IV fentanyl infusions, suggesting a predominantly spinal mechanism of opioid action under these study conditions.

Analgesia during labour: from taboo to evidence-based medicine

Peripartum care of parturients has contributed a great deal to the development of modern anaesthesia during the past 150 years. The introduction of general and regional anaesthesia provided new options of relieving pain during delivery and preventing suffering. However,provision of effective labor analgesia gave and still gives rise to controversy as to whether interfering with natural events such as delivery was justifiable on a religious,moral or ideological level. A new era of obstetric pain relief was initiated when a study design was devised to define the Minimum Local Analgesic Concentration (MLAC) needed for epidural analgesia. Using the MLAC model as a scientifically based pharmacodynamic measure of analgesia, empirically developed "recipes" can be compared and validated. The importance of this clinical model will be put into a pharmacological context including issues such as the up-down sequential allocation technique, dose-response curves and differential nerve blockade.