Up-down Sequential Allocation Research Articles

Dose dependent reduction in median effective concentration (EC50) of ropivacaine with adjuvant dexmedetomidine in labor epidural analgesia: An up-down sequential allocation study

Study objectiveAdjuvant dexmedetomidine can be used to reduce the required concentration of ropivacaine for labor epidural analgesia. However, the potency of dexmedetomidine has not been fully studied. The purpose of this study was to determine the median effective concentration (EC50) of ropivacaine with adjuvant dexmedetomidine. DesignProspective, double-blind, up-down sequential allocation study. SettingAcademic medical center specializing in the care of women and children. PatientsOne hundred and fifty healthy, term parturients requesting labor epidural analgesia were randomly assigned to 1 of 5 different concentrations of dexmedetomidine: 0 μg/ml, 0.3 μg/ml, 0.4 μg/ml, 0.5 μg/ml, or 0.6 μg/ml. InterventionsThe study solution for the first patient in each group included the randomly assigned concentration of dexmedetomidine in 0.1% ropivacaine. Subsequent patients in each randomization group received the assigned concentration of dexmedetomidine in a new concentration of ropivacaine as determined by the up-down allocation methodology. Effective analgesia was defined as pain on the visual analogue scale of<3 at30 min after administration of local anesthetic. The up-down sequential allocation method and probit regression were used to calculate the EC50 of epidural ropivacaine. MeasurementsThe primary outcome was pain 30 min after administration of local anesthetic via epidural catheter. Exploratory outcomes included side effects, neonatal outcomes, and obstetric outcomes. Main resultsThe EC50 values for ropivacaine in dexmedetomidine 0.4 μg/ml, 0.5 μg/ml, and 0.6 μg/ml (0.044% [95% CI 0.036% to 0.045%], 0.035% [95% CI 0.031% to 0.041%], and 0.039% [95% CI 0.034% to 0.045%], respectively) were lower compared to ropivacaine in dexmedetomidine 0 μg/ml and 0.3 μg/ml (0.086% [95% CI 0.081% to 0.092%], and, 0.069% [95% CI 0.056% to 0.076%], respectively). Differences between EC50 values for ropivacaine in dexmedetomidine 0.4 μg/ml, 0.5 μg/ml, and 0.6 μg/ml were not statistically significant. Results of our exploratory analyses did not reveal differences in side effects, neonatal outcomes, or obstetric outcomes. ConclusionsIn this study, the lowest concentration of dexmedetomidine in ropivacaine with the greatest clinical effect was 0.4 μg/ml, which is important because there may be no additional analgesic benefit of dexmedetomidine greater than 0.4 μg/ml.

A prospective, up-down sequential allocation study investigating the effectiveness of vital capacity breaths using high-flow nasal oxygenation versus a tight-fitting face mask to pre-oxygenate term pregnant women

BackgroundThe role of high flow nasal oxygenation (HFNO) for pre-oxygenation before obstetric general anaesthesia remains unclear. This study aimed to determine the number of vital capacity breaths using HFNO required to pre-oxygenate 90% of parturients to an end-tidal oxygen concentration fraction (FETO2) of ≥0.90 (termed EN90). MethodsUsing up-down, sequential allocation trial design, volunteer term parturients undergoing caesarean delivery were investigated with HFNO with their mouth closed, followed by mouth open, and if FETO2 ≥0.90 was not achieved after a maximum of 20 vital capacity breaths, pre-oxygenation was attempted with a face mask. The primary outcome was the number of vital capacity breaths required using HFNO (mouth open and closed) to achieve EN90. Secondary outcomes included assessment of EN90 using mouth open versus mouth closed and face mask pre-oxygenation, maternal satisfaction and evaluation of fetal cardiotocography. ResultsTwenty women at term were recruited. Successful pre-oxygenation occurred in 4 (20%), 3 (15%) and 14 (70%) women with HFNO mouth closed, HFNO mouth open, and via face mask respectively. At up to 20 vital capacity breaths, face mask pre-oxygenation was more successful at achieving EN90 compared with both HFNO with a closed (P=0.006) or open (P=0.001) mouth. Closed mouth HFNO did not outperform open mouth pre-oxygenation. ConclusionFace mask pre-oxygenation is more effective at achieving EN90 compared with to HFNO within a clinically acceptable number of vital capacity breaths. Further studies are needed to determine the role of HFNO in optimising the time before desaturation and for apnoeic oxygenation in term parturients.

Minimum effective volume of 0.5% ropivacaine for ultrasound-guided costoclavicular brachial plexus block: A dose finding study.

Costoclavicular brachial plexus block (CC-BPB) is a relatively new regional anaesthetic technique and there are no data on the minimum effective volume 90 (MEV90) of 0.5% ropivacaine required for an ultrasound-guided CC-BPB. To determine the MEV90 of 0.5% ropivacaine required to produce surgical anaesthesia with an ultrasound-guided CC-BPB. Prospective up-down sequential allocation study design. University teaching hospital in Hong Kong from March 2016 to December 2017. Forty-eight, ASA physical status I to III patients, aged 70 years or less and scheduled for elective forearm or hand surgery under an ultrasound-guided CC-BPB, were recruited. Ultrasound-guided CC-BPB was performed with the assigned volume of 0.5% ropivacaine. The Dixon 'up-and-down' sequential allocation method using the biased coin design was used to determine the MEV90 of 0.5% ropivacaine. The assigned volume of ropivacaine was based on the outcome of the previous patient. After a block failure the next patient received a volume increase of 2 ml. If the block was a success, the next patient was allocated, with a probability of b = 0.11, to receive 2 ml less, or, with a probability of 1 - b = 0.89, the same volume. A successful block was defined as a minimum score of 14 of 16 points, using a composite sensory and motor block score at 45 min after the injection. The study was stopped when 45 successful blocks were achieved. MEV90 with 95% confidence interval was calculated using the centred isotonic regression for point and interval dose response studies. The MEV90 of 0.5% ropivacaine for ultrasound-guided CC-BPB was 20.9 (95% confidence interval, 20.7 to 21.8) ml. The mean ± SD time to readiness for surgery was 31.4 ± 12.60 min. The MEV90 of 0.5% ropivacaine required to produce surgical anaesthesia with an ultrasound-guided CC-BPB is 20.9 ml. The trial was registered with the Chinese Clinical Trials Registry (www.chictr.org.cn, ChiCTR-IOR-15007515, principal investigator: Manoj Kumar Karmakar, date of registration: 4 December 2015). ChiCTR-IOR-15007515, Chinese Clinical Trials Registry (www.chictr.org.cn).

Comparison of the ED50 of intrathecal hyperbaric ropivacaine co-administered with or without intrathecal dexmedetomidine for cesarean section: A prospective, double-blinded, randomized dose-response trial using up-down sequential allocation method

Study objectiveStudies have showed that intrathecal dexmedetomidine as supplements to local anesthetics can improve the quality of the spinal anesthesia and reduce the local anesthetic requirement of spinal anesthesia for cesarean section. However, the magnitude of this effect has not been fully quantified. Therefore, we conducted the present study to investigate the ED50 of intrathecal hyperbaric ropivacaine with or without dexmedetomidine for cesarean section in healthy parturients. ED50 values obtained were compared to estimate the effect of intrathecal dexmedetomidine versus placebo on ropivacaine requirement. DesignSingle-blinded, prospective, randomized study. SettingDepartment of Anesthesia, Women's Hospital, Zhejiang University School of Medicine. PatientsSixty healthy parturients under elective cesarean section with combined spinal-epidural anesthesia were randomized into Group C (intrathecal ropivacaine alone) and Group D (intrathecal ropivacaine + 5 μg dexmedetomidine). InterventionsThe dose of intrathecal ropivacaine for the first parturient in both groups was 11 mg. An increment or decrement of 0.5 mg intrathecal ropivacaine was made for the subsequent parturient based on the effective or ineffective response of the previous parturient. Effective dose was defined as a bilateral T6 or above sensory block level was achieved within 15 min after induce of spinal anesthesia and no additional epidural anesthetics was required during surgery. The Dixon and Massay sequential method and Probit regression were applied to calculate the ED50 of intrathecal ropivacaine in both groups. MeasurementsCharacteristics of spinal anesthesia and side effects were recorded. Main resultsThe ED50 of hyperbaric ropivacaine calculated by Dixon and Massay formula was 11.4 mg (95% CI, 11.1–11.7 mg) in Group C, and 9.4 mg (95% CI, 9.0–9.7 mg) in Group D (P < 0.05). While using the Probit regression, the ED50 of intrathecal hyperbaric ropivacaine was 11.1 mg (95% CI, 10.7–11.6 mg) in Group C, and 9.1 mg (95% CI, 8.6–9.5 mg) in Group D. Shivering was less observed in Group D than in Group C (P < 0.05). There was no significant difference in the onset time of sensory block or motor block, the incidence of hypotension, bradycardia, nausea and vomiting, sedation and pruritus between the two groups. ConclusionUnder the conditions of the present study, intrathecal dexmedetomidine (5 μg) reduced the ED50 of intrathecal hyperbaric ropivacaine by approximately 18% for cesarean section in healthy parturients under combined spinal-epidural anesthesia.

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.

Minimal Local Analgesic Dose of Intrathecal Bupivacaine and Ropivacaine in Patients Undergoing Cesarean Section: A Comparative Study

Introduction: Spinal anesthesia is a reasonable option for cesarean section. Bupivacaine and ropivacaine have been used as intrathecal drugs alone or in combination with various opiods. Ropivacaine is considered a valid and safe alternative to bupivacaine for intrathecal anesthesia. This study aims to determine the median effective dose (ED50) of intrathecal bupivacaine and ropivacaine for cesarean section and defines this as the minimum local anesthetic dose (MLAD). Methods: Forty pregnant women undergoing elective cesarean section were allocated and randomized into two groups. The initial dose was 13mg for both ropivacaine and bupivacaine groups and was increased or decreased of 0.3mg, using the up-down sequential allocation technique. Efficacy was accepted if adequate sensory dermatomal anesthesia to pinprick to T6 was attained within 20 minutes after intrathecal injection and required no supplemental epidural injection for procedure until at least 50 minutes after the intrathecal injection of test drugs. The MLAD for both bupivacaine and ropivacaine was calculated with 95% confidence interval using the formula of Dixon and Massey. Comparison of different variables between the groups was done using t-test with significant p value at &lt; 0.05. Results: The two groups were comparable in terms of demographic profile and clinical characteristics. The MLAD of ropivacaine and bupivacaine were 11.63 mg (95% CI, 11.5-12.92) and 10.459 mg (95% CI, 10.12-10.87) respectively. The potency ratio between spinal ropivacaine and bupivacaine was 0.89. Conclusion: Ropivacaine provided clinically surgical anaesthesia of shorter duration without compromising neonatal outcome and can be used as a safe alternative to bupivacaine.

Median Effective Dose of Intranasal Dexmedetomidine for Transthoracic Echocardiography in Children with Kawasaki Disease Who Have a History of Repeated Sedation

BackgroundThe aim of this study was to investigate the median effective dose (ED50) of intranasal dexmedetomidine for echocardiography in children with Kawasaki disease who had a history of repeated sedation.Material/MethodsThere were 73 pediatric Kawasaki disease patients aged 1 to 36 months enrolled in this study who had American Society of Anesthesiologists (ASA) I–II, were scheduled to undergo echocardiography under sedation. They were assigned to 2 groups (group A: age 1–18 months, and group B: age 19–36 months). Intranasal dexmedetomidine was administered before echocardiography. The dose of intranasal dexmedetomidine was determined with the up-down sequential allocation, and the initial dose was 2 μg/kg with an increment/decrement of 0.2 μg/kg. The ED50 of intranasal dexmedetomidine for sedation was determined with the up-and-down method of Dixon and Massey and probit regression. The time to effective sedation, time to regaining consciousness, vital signs, oxygen saturation, echocardiographic examination time, clinical side-effects, and characteristics of regaining consciousness were recorded and compared.ResultsThe ED50 of intranasal dexmedetomidine for sedation was 2.184 μg/kg (95% CI, 1.587–2.785) in group A and 2.313 μg/kg (95% CI, 1.799–3.426) in group B. There were no significant differences in the time to sedation and time to regaining consciousness between groups. Additionally, change in hemodynamic and hypoxemia were not noted in both groups.ConclusionsThe ED50 of intranasal dexmedetomidine was determined in children with Kawasaki disease who had a history of repeated sedation to be appropriate for repeated-routine sedation of echocardiographic examination in pediatric patients. The ED50 of intranasal dexmedetomidine for echocardiography in this circumstance is similar to that in children receiving initial sedation.

Comparison of the potency of phenylephrine and norepinephrine bolus doses used to treat post-spinal hypotension during elective caesarean section

BackgroundPhenylephrine, although considered the vasopressor of choice, can cause reflex bradycardia and a fall in cardiac output. Norepinephrine, due to its direct positive chronotropic and reflex negative chronotropic actions, is expected to overcome this problem. However, limited information about its effective dose for management of post-spinal hypotension, and its potency compared to phenylephrine, is available. MethodsOne hundred consecutive patients who developed post-spinal hypotension were treated with a predetermined dose of either phenylephrine or norepinephrine. Correction of hypotension after one minute was considered ‘success’. The starting dose for the first patient and testing interval (the incremental or decremental dosing) were 100 μg and 10 μg in the phenylephrine group, and 6 μg and 0.5 μg in the norepinephrine group. Doses for subsequent patients were determined by the responses of previous patients according to the Narayana rule for up-down sequential allocation. ED95 and ED50 of phenylephrine and norepinephrine boluses and their potency ratio were calculated. ResultsUsing Probit analysis, ED95 and ED50 values were 43.1 µg (95% CI 39.5 to 65.0 µg) and 33.2 µg (95% CI 5.1 to 37.0 µg) for phenylephrine, and 3.7 µg (95% CI 3.5 to 4.7 µg) and 3.2 µg (95% CI 1.8 to 3.4 µg) for norepinephrine. The relative potency ratio of norepinephrine and phenylephrine was 11.3 (95% CI 8.1 to 16.9). ConclusionBased on the results of this study, norepinephrine is about 11 times more potent than phenylephrine. When used as bolus doses for treatment of hypotension, 100 μg phenylephrine should be approximately equivalent to 9 μg norepinephrine.

Effect of Baricity of Bupivacaine on Median Effective Doses for Motor Block.

BackgroundThe median effective dose (ED50) of a drug gives the amount or dose of drug needed to produce effective therapeutic response or desired effect in at least 50% of the population taking it. Our study focused on determining the ED50 required for effective motor block using hyperbaric and plain bupivacaine, and evaluated the influence of baricity on the ED50 required for motor block.Material/MethodsA total of 38 patients were randomly assigned into 2 groups according to the baricity of bupivacaine: group P received plain bupivacaine and group H received hyperbaric bupivacaine. The patients were administered 0.5% plain or hyperbaric bupivacaine intrathecally. The dosage of anesthetics in each patient was calculated according to the standard up-down sequential allocation method of Dixon. The first patient in each group received a dose of 7.5 mg bupivacaine, and a dose of 1.0 mg was used as the testing interval. The dose was increased or decreased by 1.0 mg for each patient according to the estimated score of motor block.ResultsThe ED50 required for effective motor block in spinal anesthesia was 7.20 and 10.05 mg in groups H and P, respectively. Their relative motor blocking potency ratio was found to be 0.72.ConclusionsThe ED50 for motor block was significantly decreased using hyperbaric bupivacaine intrathecally compared with plain bupivacaine, and the baricity of bupivacaine obviously affected the ED50 for the motor block.

Determination of the median effective dose (ED50 ) of spinal chloroprocaine in labour analgesia.

The primary goal of this study was to determine the median effective dose (ED50 ) of spinal chloroprocaine for labour analgesia. Thirty-eight parturients requesting neuraxial analgesia were enrolled. Doses of 1% chloroprocaine were determined by the technique of up-down sequential allocation, with an initial dose of 20 mg and steps of 2 mg. The chloroprocaine spinal dose was given as the spinal component of a combined spinal-epidural, which was then supplemented with an epidural dose of 7.5 μg sufentanil in 7 ml saline. Effective analgesia was defined as a score ≤ 10 mm within 15 min on a 100-mm visual analogue pain scale. Using the isotonic regression estimator method, the ED50 of chloroprocaine for the spinal component of a combined spinal-epidural for labour was calculated to be median (95%CI) 12.0 (9.3-17.0) mg.

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.

The ED90 of Prophylactic Oxytocin Infusion After Delivery of the Placenta During Cesarean Delivery in Laboring Compared with Nonlaboring Women: An Up-Down Sequential Allocation Dose-Response Study

(Anesth Analg. 2015;121:159–164) Postpartum hemorrhage is a leading cause of maternal mortality and is most frequently caused by uterine atony. Prophylactic administration of oxytocin during the third stage of labor has been shown to lower both uterine atony and the risk of postpartum hemorrhage. However, laboring patients who have already been administered oxytocin and subsequently undergo cesarean delivery due to labor dystocia will likely require a greater than normal amount of oxytocin to achieve adequate uterine tone because of desensitization. The purpose of this study was to determine the effective dose (ED90) of oxytocin infusion for these laboring patients compared with the effective dose for nonlaboring patients who undergo elective cesarean delivery.

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).

The median local analgesic dose of intrathecal bupivacaine with hydromorphone for labour: a double-blind randomized controlled trial

Neuraxial hydromorphone has been reported to provide rapid onset of labour analgesia, effective segmental pain relief, and a longer duration of action than commonly used lipophilic opioids. This study was conducted to test the hypothesis that intrathecal hydromorphone reduces the dose requirement for intrathecal bupivacaine to induce rapid analgesia for women in the first stage of labour. In this double-blind randomized controlled sequential allocation trial, 88 labouring parturients received combined spinal-epidural analgesia at 2-6 cm cervical dilation. Participants received intrathecal bupivacaine alone or bupivacaine plus hydromorphone 100 μg with the bupivacaine dose determined using up-down sequential allocation. An effective dose was defined as a visual analogue pain score of ≤10 mm (on a 100-mm pain scale) reported within 20 min of injection. The median effective doses were calculated using the formula of Dixon and Massey and verified using isotonic regression. A decrease was observed in the median local analgesic doses (effective dose [ED50]) estimated according to the formulas of Dixon and Massey, with a between-group difference of -0.45 mg. The precision of the estimate was wide-ranging (95% confidence interval -1.23 to 0.33), so no definitive conclusion can be drawn. Further research is needed to determine whether or not intrathecal hydromorphone 100 μg changes the dose of intrathecal bupivacaine required to induce labour analgesia within 20 min. The trial was conducted in 2007 prior to widespread acceptance of the standard for clinical trial registration.

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.

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.

Comparison of relative potency of intrathecal bupivacaine for motor block in pregnant versus non-pregnant women

Background Pregnancy is associated with facilitated spread of spinal and epidural anesthesia. There are limited data available for relative potency of motor block of neuraxial local anesthetics in non-pregnant versus pregnant women. The purpose of this study was to investigate the median effective dose (ED 50) of intrathecal isobaric bupivacaine for motor block in non-pregnant and pregnant women and to estimate the respective potency ratio. Methods American Society of Anesthesiologists physical status I and II pregnant ( n = 35) and non-pregnant ( n = 35) patients undergoing elective cesarean delivery or elective gynecological surgery under combined spinal–epidural anesthesia were enrolled. According to the up-down sequential allocation technique, the dose of intrathecal isobaric bupivacaine for each patient was determined by the response of the previous patient in both groups. The initial dose of bupivacaine was 4 mg and the testing interval was set at 0.5 mg. Efficacy was determined by the occurrence of motor block in either lower limb as assessed by the modified Bromage scale within 5 min of spinal injection. Results The ED 50 of intrathecal bupivacaine for motor block was 4.51 (95% confidence interval (CI) 4.27–4.76) mg for non-pregnant women and 3.96 (95% CI 3.83–4.08) mg for pregnant women. The relative potency ratio for motor block for pregnant versus non-pregnant women was 1.14 (95% CI 1.05–1.24), ( P = 0.0037). Conclusions Intrathecal bupivacaine was 1.14 times more potent for motor block in pregnant versus non-pregnant women. Our current data confirm the difference in local anesthetic requirement between non-pregnant and pregnant patients.

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.

The potencies for motor block after intrathecal ropivacaine and bupivacaine

Objective To determine the median effective doae (ED50) for motor block after intrathecal ropivacaine and bupivacaine. Methods Sixty ASA Ⅰ or Ⅱ patients, aged 18-64, weighing 46-75 kg, undergoing elective urological surgery under combined spinal-epidural anesthesia, were randomized into 2 groups ( n = 30each) receiving intrathecal 0.5% ropivacaine and 0.5% bupivacaine respectively. The ED50 was determined by up-down sequential allocation. The initial dose was 4 mg. Each time the dose increased/decreased by 1 mg. Efficacy was determined by the occurrence of any motor block in either lower extremity (modified Bromage scale > 0)within 5 or 10 min after the spinal injection. Results The intrathecal ED50 for motor block was 6.68 mg for ropivacaine (95% confidence interval 6.27-7.13 mg) and 4.07 mg for bupivacaine (95% confidence interval 3.56-4.47mg) . The relative motor blocking potency ratio was ropivacaine/bupivacaine 0.61. Conclusion The potency of intrathecal ropivacaine is lower than that of bupivacaine for motor block. Key words: Anesthesia, spinal; Anesthetics, local; Motor block