Sequential Allocation Study Research Articles

Minimum effective fluid volume of colloid to prevent hypotension during caesarean section under spinal anesthesia using a prophylactic phenylephrine infusion: An up-down sequential allocation study

Study objectiveThe aim of this study was to de termine the minimum effective fluid volume (MEFV) of hydroxyethyl starch 130/0.4 (HES) infused in a preload fashion which would prevent hypotension in 50% of parturients undergoing caesarean section. A secondary objective was to measure the hemodynamic effect of fluid loading on the subjects. DesignThis is a prospective, double-blinded, dose-finding study using an up-down sequential allocation design. SettingIn the operating room. PatientsThirty healthy parturients undergoing caesarean section under spinal anesthesia using a prophylactic phenylephrine infusion were included in this study. InterventionThe initial HES volume infused in the first patient was 500 mL. A failure of treatment to HES preload was defined as a single episode of systolic hypotension below 20% of baseline value. The next patient in the sequence was given a volume of HES adjusted by either an increment or a decrement of 100 mL according to the previous subject response to fluid preload. MeasurementsStroke volume and cardiac output were measured with a bioreactance-based non-invasive cardiac output monitor (NICOM). Main resultsThe MEFV of HES was 733 mL (95% CI: 388-917 mL). Fluid loading before the administration of the spinal anesthesia resulted in an increase in stroke volume and cardiac output. The combined effect of spinal anesthesia and a phenylephrine infusion reduced the maternal heart rate and cardiac output, but not the stroke volume. ConclusionOur study is the first to investigate variable fluid loading volumes in this population. A HES preload of approximatively 700 mL prevented maternal hypotension in 50% of the parturients under the conditions of this study. We suggest that up-down sequential allocation design is a useful tool to compare different fluid loading regimens in this setting.

Determination of the median effective dose (ED50) of spinal plain ropivacaine for motor block in adults.

The median effective dose (ED50) for motor blockade of spinal plain bupivacaine in adults was previously reported; however, that of ropivacaine is unknown. This study aimed to determine the ED50 for motor blockade of spinal plain ropivacaine in adults, evaluating the effect of age on this parameter. 133 patients in need of combined spinal and epidural anesthesia were enrolled in this sequential allocation study. They were divided into 6 groups according to age: 20-30, 31-40, 41-50, 51-60, 61-70, and 71-80years. Using the up-and-down method of Dixon, the ropivacaine dose was varied according to the preceding patient's reaction. The modified Bromage and hip motor function score was used to evaluate the degree of motor block after administration of ropivacaine. ED50 values were estimated by the method of Dixon and Massey. Other indexes, including the onset of motor block, the analgesia level, and the duration of motor block were also assessed. the ED50 for motor block of intrathecal ropivacaine was 20.96mg (95 % CI: 19.83-22.16mg) in 20-30, 19.05mg (95 % CI: 18.43-19.70mg) in 31-40, 17.91mg (95 % CI: 17.10-18.76mg) in 41-50, 17.91mg (95 % CI: 16.49-19.44mg) in 51-60, 16.11mg (95 % CI: 14.50-17.90mg) in 61-70, and 15.75mg (95 % CI: 13.98-17.73mg) in 71-80year-old patients. Maximum cephalic analgesic effects were obtained at the L4-T6 and L4-T2 levels, at 5 and 10min, respectively, after intrathecal administration of ropivacaine in all groups. the ED50 for motor block in spinal plain ropivacaine decreases with advancing age, indicating that age has an influence on the potency of spinal ropivacaine.

Pencil-point needle bevel direction influences ED50 of isobaric ropivacaine with fentanyl in spinal anesthesia for cesarean delivery: a prospective, double-blind sequential allocation study

BackgroundThere is little evidence on the influence of bevel direction of a pencil-point needle on the median effective dose (ED50) of isobaric ropivacaine and fentanyl in spinal anesthesia for cesarean delivery. MethodsIn this prospective, double-blind, sequential allocation study, 82 parturients scheduled for elective cesarean delivery under combined spinal-epidural anesthesia were included. We sought to determine the median effective dose of intrathecal 0.75% isobaric ropivacaine plus fentanyl 15μg with two different bevel directions of a 26-gauge Whitacre needle using up-down sequential allocation. Parturients were randomly allocated to either Group Ce (needle aperture oriented in a cephalad direction) or Group Ca (aperture directed caudally). The initial dose was 0.75% ropivacaine 11.25mg plus fentanyl 15μg in both groups. Each dose was classified as effective if, after 15min and during the next 60min, there was inability to appreciate pin-prick as sharp at T4, a visual analogue pain score <2 and no requirement for an epidural rescue bolus. ResultsEighty patients were included in the analysis. The ED50 in group Ca was significantly higher (13.09mg, 95% CI 12.19–14.00) than in group Ce (10.10mg, 95% CI 9.54–10.65, P <0.001). ConclusionThe orientation of the distal aperture of a 26-gauge Whitacre needle during induction of spinal anesthesia for cesarean delivery influences the ED50 of 0.75% ropivacaine.

The median effective seated time for hypotension induced by spinal anesthesia at Cesarean delivery with two doses of hyperbaric bupivacaine: a randomized up-down sequential allocation study.

Extending the time a parturient is left sitting after induction of spinal anesthesia (i.e., the seated time) has had varying success in decreasing hypotension at Cesarean delivery. This may be due to the current lack of information concerning the dose-response relationship of seated time and rates of hypotension. Term parturients scheduled for Cesarean delivery were randomized to receive 11.25 or 15.0mg of 0.75% intrathecal hyperbaric bupivacaine, and they remained seated after injection for a length of time determined by an up-down sequential method. They were then placed in a wedged position and their blood pressure was measured every minute. Pre-delivery hypotension was considered present if there was a >20% from baseline drop in systolic blood pressure. The seated time at which 50% of parturients avoided pre-delivery hypotension (median effective seated time) was determined with isotonic regression. Fifty patients were studied. For the 11.25-mg and 15.0-mg groups, the median effective seated time (95% confidence interval [CI]) was 130 sec (95% CI 117 to 150) and 385 sec (95% CI 381 to 396), respectively. There exists a seated time after intrathecal injection of hyperbaric bupivacaine where 50% of parturients do not experience hypotension. This seated time increases with an increased dose of bupivacaine. Further work is required to determine the full relationship between seated time and hypotension for other doses of anesthetic and to investigate the clinical utility of this technique for prevention of hypotension. This trial was registered at www.clinicaltrials.gov (NCT01561274).

Minimum effective volume of normal saline for epidural volume extension.

Background:Rescue strategies like changes in tilt of table are used to raise the level of an inadequate sensory block following intrathecal injection. Epidural volume extension (EVE) refers to an injection of normal saline through epidural catheter following an intrathecal block. It results in a rapid increase in the sensory level of subarachnoid block. Thus, it has been postulated that EVE may be used as a rescue strategy for an inadequate post-spinal sensory block. However, the minimum effective volume (MEV) of normal saline for EVE induced increase in level of spinal block has not been researched till date. We proposed to determine the MEV of normal saline required for EVE induced increase in post-spinal block sensory level.Materials and Methods:This prospective sequential allocation study was conducted in consenting adult males after institutional ethical committee approval scheduled for lower limb surgery under combined spinal epidural (CSE) anesthesia, who had an inadequate level of sensory block. Herein, an inadequate level was defined as lower than T10 at 10 min after the intrathecal injection, with no ascent for two consecutive readings taken 2 min apart. The EVE was performed with normal saline injected through epidural catheter, and was considered successful if the level of sensory block increased by two or more dermatomal segments within 5 min of the injection. The volume of normal saline for EVE was decided by using the up-and-down method, with the first patient receiving 10 mL and a dosing interval of 1 mL in subsequent patients. The analysis was done using the formula of Dixon and Massey, which enabled calculation of the MEV with 95% CI. Quantitative parametric data is represented as mean ± SD and nonparametric data as median (range).Results and Conclusion:The MEV of normal saline to raise the level of sensory block by two or more dermatomal segments within 5 min of EVE is 7.4 mL (95% CI: 5.5-9.9 mL).

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 <10 mm 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.

Effect of sex and pregnancy on the potency of intrathecal bupivacaine: determination of ED50 for motor block with the up–down sequential allocation method

The up-down sequential allocation model has been adapted to estimate the relative potency ratios for analgesia and motor block of the most commonly used epidural and intrathecal local anaesthetics. The aim of this study was to establish the median effective doses (ED50) for motor block with intrathecal bupivacaine and to estimate the ED50 ratios of these in male, female and pregnant patients. In this prospective, double-blind, parallel group, up-down sequential allocation study, we enrolled 30 male patients, 30 female, non-pregnant patients and 30 pregnant patients undergoing elective surgery under combined spinal-epidural anesthesia. The first two groups consisted of male or female patients undergoing elective lower limb surgery and the third group consisted of pregnant women at term (>36 and <41 weeks) with singleton pregnancies undergoing elective caesarean delivery. Patients received intrathecal isobaric bupivacaine 0.5% as part of the spinal-epidural anaesthesia technique. The initial dose was 4 mg and the testing interval was 1 mg with subsequent doses being determined by the outcome in the previous patient in the same group. The end point for efficacy was the occurrence of motor block in the lower limbs within 5 min. There were significant (P < 0.0001) differences in ED50 estimates for motor block with intrathecal bupivacaine: 6.9 mg for men [95% confidence interval (CI), 5.2-8.6), 5.2 mg for women (95% CI, 4.5-5.8) and 3.4 mg for pregnant women (95% CI, 2.9-4.0). We have demonstrated a hierarchy of potencies for motor block with intrathecal bupivacaine for men, women and pregnant women suggesting possible relevant differences owing to the effects of both sex and pregnancy.

Ultrasound reduces the minimum effective local anaesthetic volume compared with peripheral nerve stimulation for interscalene block

BackgroundPrevious studies have demonstrated that lower local anaesthetic (LA) volumes can be used for ultrasound (US)-guided interscalene brachial plexus block (ISB). However, no study has examined whether US can reduce the volume required when compared with nerve stimulation (NS) for ISB. Our aim was to do this by comparing the minimum effective analgesic volumes (MEAVs). MethodsAfter ethics approval and informed consent, patients undergoing shoulder surgery were recruited to this randomized, double-blind, up–down sequential allocation study. The volume used for both US and NS was dependent upon the success or failure of the previous block. Success was defined as a verbal rating score of 0/10, 30 min after surgery. Ten needle passes were allowed before defaulting to the opposite group. Patients received general anaesthesia. Pain scores and analgesic consumption were assessed by a blinded observer. Statistical comparisons of continuous variables were performed using Student’s t-test and Mann–Whitney U-test as appropriate. Categorical variables were analysed using χ2 test. MEAV values were estimated using log-transformed up–down independent pairs analysis and probit regression. Significance was assumed at P<0.05 (two-sided). ResultsThe MEAV required to provide effective analgesia was significantly (P=0.034) reduced to 0.9 ml [95% confidence interval (CI) 0.3–2.8] in the US group from 5.4 ml (95% CI 3.4–8.6) in the NS group. Fewer needle passes were needed to identify the brachial plexus with US (1 vs 3; P<0.0001) and patients had less pain at 30 min after surgery (P=0.03). ConclusionsUS reduces the number of attempts, LA volume, and postoperative pain when compared with NS for ISB.

Dose Requirement of Intrathecal Bupivacaine for Cesarean Delivery Is Similar in Obese and Normal Weight Women

The effect of BMI on the spread of intrathecal bupivacaine is controversial. This study assessed the ED95 of intrathecal bupivacaine for elective cesarean delivery in obese and normal weight women. We studied normal weight (BMI < 25 kg x m(-2)) and obese (BMI > 30 kg x m(-2)) women with singleton term pregnancies undergoing elective cesarean delivery. The study was conducted as a single blinded, up-down sequential allocation study (modified by the Narayana rule). All patients received a combined spinal-epidural anesthesia with a variable intrathecal dose of hyperbaric 0.75% bupivacaine, plus fentanyl 10 microg and morphine 100 microg. The first patient received 9 mg of bupivacaine. Supplemental anesthesia was provided through the epidural catheter if required. The primary outcome was successful analgesia, defined as a sensory block to at least T6, and no request for supplemental anesthesia. The ED95 for the satisfactory outcome was determined by a logistic model with non-log-transformed doses. Twenty-four normal weight and sixteen obese patients were enrolled. The estimated ED95 for all forty patients was 12.92 mg (95% CI: 11.49 to 34.77). The estimated ED95 for the normal weight and the obese subgroups were similar at 12.78 mg (95% CI: 10.75 to + infinity) and 11.86 mg (95%CI: 11.31 to 15.61), respectively. If single shot spinal anesthesia is used for cesarean delivery, obese and normal weight patients should receive similar doses of hyperbaric bupivacaine. Although in our study the effective dose 95% could not be precisely determined, it is possible to state that it is at least 11.49 mg.

Estimation of the minimum motor blocking potency ratio for intrathecal bupivacaine and lidocaine

Background The up-down sequential allocation model has been adapted to investigate a variety of clinical and pharmacological issues in neuraxial anaesthesia including the estimation of relative potency ratios for analgesia and motor block of the most commonly used epidural and intrathecal local anaesthetics. The aim of this study was to establish the median effective doses (ED50) for motor block with intrathecal lidocaine and bupivacaine and to define the relative motor blocking potency ratio. Methods In this prospective, randomised, double blind, parallel group, up-down sequential allocation study, we enrolled 71 parturients undergoing elective caesarean section under combined spinal-epidural anaesthesia. The women received either intrathecal lidocaine 2% w/v or bupivacaine 0.5% w/v. The initial dose was 4 mg for bupivacaine and 12 mg for lidocaine. Subsequent doses were determined by the outcome in the previous parturient, according to the up-down sequential allocation technique. The end point was the occurrence of any motor block in either lower limb within 5 min. Results The intrathecal ED50 for motor block was 13.7 mg for lidocaine (95% CI, 13.1 to 14.4) and 3.4 mg for bupivacaine (95% CI, 2.6 to 4.1) ( P < 0.0001) and the relative motor blocking potency ratio was 4.1 (95% CI 3.3 to 5.2). Conclusions Intrathecal bupivacaine was 4.1 times more potent than lidocaine for motor block.

Hyaluronidase reduces local anaesthetic volumes for sub-Tenon’s anaesthesia

Volumes of local anaesthetics for sub-Tenon's anaesthesia vary. Lower volumes produce less akinesia, whereas higher volumes increase chemosis and intra-ocular pressures. Hyaluronidase is often added to local anaesthetics to improve akinesia without increasing the volume of the injection, but this is controversial. This randomized, sequential allocation study examines the addition of hyaluronidase on the minimum local anaesthetic volume (MLAV) required for a sub-Tenon's block. Sixty-two patients having sub-Tenon's blocks for cataract surgery were randomized into two groups. The control group (n=31) received 2% w/v lidocaine and the study group (n=31) received 2% w/v lidocaine with hyaluronidase 15 IU ml(-1). Using parallel up-down sequential allocation from a 4 ml starting volume, the volumes in both groups were changed using a testing interval of 1 ml according to the quality of globe akinesia. The median effective local anaesthetic volume (MLAV) was calculated for both groups using probit regression. The groups were similar for age, sex, and ocular axial length. The MLAV in the hyaluronidase group was 2.6 ml [95% confidence interval (CI), 2.1-3.l] and 6.4 ml (95% CI, 5.1-8.1) in the control group (P<0.002). Hyaluronidase permits a significant 2.4-fold (95% CI, 1.8-3.4) reduction in MLAV for sub-Tenon's anaesthesia.

Effects of intrathecal and i.v. small-dose sufentanil on the median effective dose of intrathecal bupivacaine for Caesarean section

Spinal anaesthesia with bupivacaine combined with sufentanil has been widely used for Caesarean section. However, the main site of action (spinal vs central) of intrathecal (IT) sufentanil is controversial. The aim of this study was to examine the predominant mechanism of action of IT, small-dose sufentanil when added to bupivacaine for Caesarean section, by comparing the effects of IT and i.v. sufentanil 2.5 microg on the median effective dose (ED50) of bupivacaine. Ninety parturients undergoing elective Caesarean section with a combined spinal-epidural technique were enrolled into this prospective, double-blind, up-down sequential allocation study. According to the up-down sequential allocation, parturients received varying doses of bupivacaine alone (C group) or co-administered with i.v. sufentanil 2.5 microg group (IVS group; n = 30) or IT sufentanil 2.5 microg group (ITS group; n = 30). The possible maternal or neonatal adverse effects were also recorded. The ED(50) of bupivacaine was 6.3 mg (95% CI 6.2-6.5) in the C group, 5.2 mg (95% CI 5.1-5.4) in the IVS group, and 3.0 mg (95% CI 2.9-3.1) in the ITS group. The ED50 in the ITS group was significantly lower as compared with the other two groups (P < 0.0005). With the exception of pruritus that exclusively occurred in the ITS group (P = 0.011, compared with the other two groups), no significant differences among groups were observed regarding the frequencies of the maternal or neonatal adverse effects. Compared with an equal dose of sufentanil i.v., intrathecally administered sufentanil 2.5 microg has a significant local anaesthetic-sparing effect via a predominantly spinal mechanism for Caesarean section.

A BIS-guided study of sevoflurane requirements for adequate depth of anaesthesia in Caesarean section.

Caesarean section carries a high risk of awareness, especially in the period prior to neonatal delivery. We investigated the concentration of sevoflurane required to maintain bispectral index (BIS) < 60 until delivery occurred. We enrolled 23 parturients into an up-down sequential allocation study. The median effective end-tidal concentration (EC(50)) of sevoflurane was defined as that which maintained BIS < 60 between skin incision and delivery in 50% of patients. This was calculated using Dixon and Massey's method. Receiver operating characteristic curve analysis was used to establish BIS response probability thresholds. The EC(50) for sevoflurane was 1.22% (1.08-1.33, 95% CI). The probability of maintaining BIS < 60 was < 55% at a concentration of < 1.1%; this increased to 80% at concentrations of 1.2-1.3%. We conclude that sevoflurane concentrations of at least 1.2-1.3% should be administered in uncomplicated Caesarean section, so as to minimise the risk of awareness and recall.

Epidural test dose with levobupivacaine and ropivacaine: determination of ED50 motor block after spinal administration

When a test is required to detect a possible intrathecal catheter, many would seek to use the same local anaesthetic as that used for epidural analgesia. The rapid onset of inappropriate motor block after a local anaesthetic administered epidurally implies intrathecal spread. Because of claims of greater sensory-motor separation, or because of reduced potency compared with bupivacaine, the efficacy of the new local anaesthetics in intrathecal testing has been questioned. The aim of this study was to establish the feasibility of a test dose for an inadvertent intrathecal catheter using ropivacaine and levobupivacaine, and to establish the dose required. Sixty women undergoing elective Caesarean section with a combined spinal- epidural technique were enrolled into this prospective, double-blind sequential allocation study. The women were randomized to receive plain levobupivacaine 0.5% or ropivacaine 0.5% intrathecally. The dose was determined according to up-down sequential allocation. The end-point was any evidence of lower limb motor block within 5 min of injection. The ED(50) motor block at 5 min was 4.8 mg (95% CI, 4.49, 5.28) for levobupivacaine and 5.9 mg (95% CI, 4.82, 6.98) for ropivacaine (95% CI difference, 0.052, 1.98) (P=0.04). The estimated ED(95) motor block was 5.9 mg (95% CI 5.19, 6.71) for levobupivacaine and 8.3 mg (95% CI, 6.30, 10.44) for ropivacaine. The potency ratio between the two drugs was 0.83 (95% CI, 0.69, 0.99). Both local anaesthetics produce evidence of motor block within 5 min of intrathecal injection and could serve as tests of intrathecal administration. Derived ED(95) values suggest 10 mg doses should be effective, but this study did not measure predictive value. Ropivacaine is less potent for motor block than levobupivacaine by a factor of 0.83 (P<0.04).

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

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

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.

Levobupivacaine for Epidural Analgesia in Labor: The Sparing Effect of Epidural Fentanyl

Evidence suggests that levobupivacaine has similar pharmacodynamic properties to racemic bupivacaine. We sought to investigate whether this similarity extends to opioid sparing when levobupivacaine is used for epidural analgesia in laboring women by quantifying the effect of fentanyl on the minimum local analgesic concentration (MLAC) of levobupivacaine. One-hundred-six women requesting epidural analgesia for labor pain were recruited in this randomized, double-blinded, up-down sequential allocation study. Each received 20 mL of one of three test solutions: levobupivacaine control, levobupivacaine and fentanyl 2 μg/mL, or levobupivacaine and fentanyl 3 μg/mL. The initial levobupivacaine concentration was 0.07% wt/vol in each group, with subsequent concentrations of levobupivacaine being determined by the response of the previous patient (testing interval 0.01% wt/vol). Efficacy was accepted if the visual analog score decreased to 10 mm or less on a 100-mm scale within 30 min. The MLAC of levobupivacaine in the control group was 0.091% wt/vol (95% CI, 0.052–0.130). Fentanyl at concentrations of 2 μg/mL and 3 μg/mL significantly reduced the MLAC of levobupivacaine to 0.047% wt/vol (95% CI, 0.023–0.072) and 0.050% wt/vol (95% CI, 0.035–0.065), respectively (P < 0.001). A dose-dependent effect was not demonstrated. We conclude that fentanyl significantly reduces levobupivacaine requirements for epidural analgesia in labor. Implications Determination of minimum local analgesic concentrations by the technique of sequential allocation allows the interaction between epidural opioids and local anesthetics to be quantified. This study demonstrates that the addition of fentanyl significantly reduces levobupivacaine requirements for epidural analgesia.

Potency, Impotency, and Importance!

Potency, Impotency, and Importance!

Epidural pain relief in labour: potencies of levobupivacaine and racemic bupivacaine

We have compared the minimum local analgesic concentrations (MLAC) of levobupivacaine relative to racemic bupivacaine in a prospective, randomized, double-blind, sequential allocation study. Women in labour were given a 20-ml bolus of epidural levobupivacaine or bupivacaine diluted to a concentration determined by up-down sequential allocation. The initial concentration was 0.07% w/v for both drugs. Efficacy was defined using a visual analogue pain score (VAPS) at 10 mm or less within 30 min. The MLAC of levobupivacaine was 0.083% w/v (95% CI 0.065-0.101) and the MLAC of bupivacaine 0.081% w/v (95% CI 0.055-0.108). In molar terms, the MLAC of levobupivacaine was 2.87 mmol litre-1 (95% CI 2.25-3.49) and the MLAC of bupivacaine 2.49 mmol litre-1 (95% CI 1.69-3.32). With regard to the commercial preparations, the potency ratio levobupivacaine: bupivacaine was 0.98 (95% CI 0.67-1.41), and this is unlikely to be of clinical relevance. In molar terms, the ratio was 0.87 (95% CI 0.60-1.25). With regard to toxicity, the evidence should be evaluated in the light of a possible 13% potency difference in molar concentration in favour of racemic bupivacaine.