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Background: Closed-loop feedback computer-controlled infusion has not been described for administering phenylephrine to maintain arterial pressure (AP) during spinal anaesthesia for caesarean delivery. We aimed to compare AP control using this automated system with a previously described manual infusion system.Methods: We randomly allocated 222 healthy subjects having spinal anaesthesia for scheduled caesarean delivery to have systolic AP maintained near baseline with phenylephrine (100 µg ml(-1)) by computer-controlled infusion utilizing a proportional algorithm or manual-controlled infusion utilizing an on-off algorithm. AP control was assessed by comparing the proportion of systolic AP measurements within ±20% of baseline and by performance error (PE) calculations.Results: A total of 212 subjects finished the study. In the computer-control group, 97% of systolic AP recordings fell within ±20% of baseline compared with 95% in the manual-control group (P=0.0004). For computer-control compared with manual-control, wobble was smaller [median 3.5 (inter-quartile range 2.5-4.8)% vs 4.2 (3.3-5.9)%, P=0.003], but there was no difference in the median PE [2.9 (0.3-4.7)% vs 1.9 (0-4.2)%], median absolute PE [4.7 (3.5-5.6)% vs 4.7 (3.8-6.7)%], or divergence [-0.01 (-0.03-0)% vs -0.06 (-0.26-0.08)%]. Fewer interventions per subject for controlling AP were required in the computer-control group [2 (2-2) vs 10 (8-13), P<0.001]. There were no differences in measured clinical outcomes.Conclusions: Within the constraints of the studied algorithms, closed-loop feedback computer-controlled phenylephrine infusion provided better AP control with fewer interventions required compared with manual-controlled infusion. [ABSTRACT FROM AUTHOR]

Background: During general anaesthesia (GA) for Caesarean section (CS), fetal oxygenation is increased by administering an inspired oxygen fraction (Fi(o(2))) of 1.0. However, it is unclear whether such high Fi(o(2)) will increase oxygen free radical activity.Methods: We randomized 39 ASA I-II parturients undergoing elective CS under GA to receive 30% (Gp 30), 50% (Gp 50), or 100% (Gp 100) oxygen with nitrous oxide and sevoflurane adjusted to provide equivalent minimum alveolar concentration. Baseline maternal arterial blood before preoxygenation and maternal arterial, umbilical arterial and venous blood at delivery were sampled for assays of the by-product of lipid peroxidation, isoprostane, and for measurement of blood gases and oxygen content.Results: Maternal and umbilical isoprostane concentrations were similar among the three groups at delivery, despite significantly increased maternal and fetal oxygenation in Gp 100. However, paired comparisons of maternal delivery vs baseline concentration of isoprostane showed an increase at delivery for all groups [Gp 30: mean 342 (sd 210) vs 154 (65) pg ml(-1), P=0.016; Gp 50: 284 (129) vs 156 (79) pg ml(-1), P=0.009; Gp 100: 332 (126) vs 158 (68) pg ml(-1), P<0.001]. The magnitude of increase was similar in all three groups and independent of the Fi(o(2)) or duration after induction.Conclusions: GA for CS is associated with a marked increase in free radical activity in the mother and baby. The mechanism is unclear but it is independent of the inspired oxygen in the anaesthetic mixture. Therefore, when 100% oxygen is administered with sevoflurane for GA, fetal oxygenation can be increased, without inducing an increase in lipid peroxidation. [ABSTRACT FROM AUTHOR]

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

BACKGROUND: Use of ephedrine in obstetric patients is associated with depression of fetal acid-base status. The authors hypothesized that the mechanism underlying this is transfer of ephedrine across the placenta and stimulation of metabolism in the fetus. METHODS: A total of 104 women having elective Cesarean delivery under spinal anesthesia randomly received infusion of phenylephrine (100 microg/ml) or ephedrine (8 mg/ml) titrated to maintain systolic blood pressure near baseline. At delivery, maternal arterial, umbilical arterial, and umbilical venous blood samples were taken for measurement of blood gases and plasma concentrations of phenylephrine, ephedrine, lactate, glucose, epinephrine, and norepinephrine. RESULTS: In the ephedrine group, umbilical arterial and umbilical venous pH and base excess were lower, whereas umbilical arterial and umbilical venous plasma concentrations of lactate, glucose, epinephrine, and norepinephrine were greater. Umbilical arterial Pco2 and umbilical venous Po2 were greater in the ephedrine group. Placental transfer was greater for ephedrine (median umbilical venous/maternal arterial plasma concentration ratio 1.13 vs. 0.17). The umbilical arterial/umbilical venous plasma concentration ratio was greater for ephedrine (median 0.83 vs. 0.71). CONCLUSIONS: Ephedrine crosses the placenta to a greater extent and undergoes less early metabolism and/or redistribution in the fetus compared with phenylephrine. The associated increased fetal concentrations of lactate, glucose, and catecholamines support the hypothesis that depression of fetal pH and base excess with ephedrine is related to metabolic effects secondary to stimulation of fetal beta-adrenergic receptors. Despite historical evidence suggesting uteroplacental blood flow may be better maintained with ephedrine, the overall effect of the vasopressors on fetal oxygen supply and demand balance may favor phenylephrine. [ABSTRACT FROM AUTHOR]

Background: Aortocaval compression (ACC) can result in haemodynamic disturbances and uteroplacental hypoperfusion in parturients. Its detection is difficult because in most patients, sympathetic compensation results in no signs or symptoms. However, profound hypotension may develop after sympathectomy during regional anaesthesia. In this prospective observational study, we aimed to detect ACC by analysing haemodynamic changes in term parturients who were positioned sequentially at different angles of lateral tilt.Methods: We studied haemodynamic changes in 157 non-labouring term parturients who were positioned in random order at 0°, 7.5°, 15°, and full left lateral tilt. Cardiac output (CO), stroke volume, and systemic vascular resistance were derived using suprasternal Doppler. Non-invasive arterial pressure (AP) measured in the upper and lower limbs was analysed to detect aortic compression.Results: CO was on average 5% higher when patients were tilted at ≥15° compared with <15°. In a subgroup of patients (n=11), CO decreased by more than 20%, without changes in systolic AP, when they were tilted to <15° which was considered attributable to severe inferior vena caval compression. Only one patient in the supine position had aortic compression with the systolic AP in the upper limb 25 mm Hg higher than the lower limb.Conclusions: Patients with ACC can be identified by the CO changes from serial measurements between supine, 15°, or full lateral tilt. Our findings suggest that in non-labouring parturients, ACC is asymptomatic and can be effectively minimized by the use of a left lateral tilt of 15° or greater. [ABSTRACT FROM AUTHOR]

Background: Controversy still exists if the administration of supplementary oxygen to patients having emergency Caesarean section (CS) under regional anaesthesia is beneficial or potentially harmful. Therefore, in a prospective double-blinded study, we randomized patients having emergency CS under regional anaesthesia to receive either air or 60% oxygen until delivery and compared the effects on fetal oxygenation and lipid-peroxidation in the mother and baby.Methods: We recruited 131 women having emergency CS under regional anaesthesia. Either 21% (air group) or 60% oxygen (oxygen group) was administered using a Venturi-type facemask until delivery. We compared the oxygen exposure duration, umbilical arterial (UA) and venous (UV) blood gases and oxygen content, and plasma concentration of 8-isoprostane. Subanalysis was performed according to whether or not fetal compromise was considered present.Results: Data from 125 patients were analysed. For the oxygen group vs the air group, there were greater values for UA PO(2) [mean 2.2 (SD 0.5) vs 1.9 (0.6) kPa, P=0.01], UA O(2) content [6.6 (2.5) vs 4.9 (2.8) ml dl(-1), P=0.006], UV PO(2) [3.8 (0.8) vs 3.2 (0.8) kPa, P<0.0001], and UV O(2) content [12.9 (3.5) vs 10.4 (3.8) ml dl(-1), P=0.001]. There was no difference between the groups in maternal, UA, or UV 8-isoprostane concentration. Apgar scores and UA pH were similar between the groups. Similar changes were observed regardless of whether fetal compromise was considered present (n=37) or not (n=88).Conclusions: Breathing 60% oxygen during emergency CS under regional anaesthesia increased fetal oxygenation with no associated increase in lipid-peroxidation in the mother or fetus. [ABSTRACT FROM AUTHOR]

Study Objective: It is controversial whether local anesthetic dose requirement for spinal anesthesia for cesarean delivery differs between patients with singleton and patients with multiple gestation pregnancies. The aim of this study was to determine and compare the ED 50 and ED 90 for hyperbaric ropivacaine used for spinal anesthesia for cesarean delivery in patients with singleton pregnancies versus patients with twin pregnancies., Design: Prospective, randomized, comparative dose-finding study., Setting: Operating room, Women's Hospital, Zhejiang University School of Medicine., Patients: 100 patients with singleton pregnancies (Group S) and 100 patients with twin pregnancies (Group T) presenting for scheduled cesarean delivery under combined spinal-epidural anesthesia were enrolled in the study., Interventions: Patients in Group S or Group T were randomly allocated to receive 9.5, 11, 12.5, 14 or 15.5 mg of hyperbaric ropivacaine intrathecally. A dose was considered effective when it achieved a bilateral sensory block level at the T6 dermatome or above within 10 min after intrathecal injection, there was no numerical rating scale (NRS) pain score ≥ 3 intraoperatively, and there was no requirement for epidural supplementation at any time during anesthesia and operation. Values for ED 50 and ED 90 for ropivacaine were determined using probit regression. The difference in ropivacaine dose requirement between patients with singleton pregnancies and patients with twin pregnancies was assessed by calculating relative median potency., Measurements: Success rates for different intrathecal doses of ropivacaine, side effects and neonatal outcomes were recorded., Main Results: The estimated (95% confidence interval) values for ED 50 and ED 90 of intrathecal ropivacaine in patients with singleton pregnancies were 11.2 (10.2 to 12.0) mg and 15.7 (14.4 to 18.3) mg, respectively. The values for ED 50 and ED 90 in patients with twin pregnancies were 10.5 (9.5 to 11.3) mg and 14.8 mg (13.6 to 17.0) mg, respectively. The estimate of relative median potency for ropivacaine between patients with singleton and twin pregnancies was 0.94 (95% confidence interval 0.83 to 1.04)., Conclusion: Patients with singleton and twin pregnancies have similar dose requirement for hyperbaric ropivacaine used for spinal anesthesia for cesarean delivery in the setting of combined spinal-epidural (CSE) anesthesia, no opioids, low weight cohort, insertion with the patients in the right lateral position, and norepinephrine boluses., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Norepinephrine is an effective vasopressor during spinal anaesthesia for Caesarean delivery. However, before it can be fully recommended, possible adverse effects on neonatal outcome should be excluded. We aimed to test the hypothesis that umbilical arterial cord pH is at least as good (non-inferior) when norepinephrine is used compared with phenylephrine for treatment of hypotension., Methods: We enrolled 668 subjects having elective and non-elective Caesarean delivery under spinal or combined spinal-epidural anaesthesia in this randomised, double-blind, two-arm parallel, non-inferiority clinical trial. Arterial blood pressure was maintained using norepinephrine 6 μg ml -1 or phenylephrine 100 μg ml -1 according to the practice of the anaesthetist, either prophylactically or therapeutically, as an infusion or bolus. The primary outcome was umbilical arterial pH with a chosen non-inferiority margin of 0.01 units., Results: Of 664 subjects (531 elective and 133 non-elective) who completed the study, umbilical arterial cord blood was analysed for 351 samples from 332 subjects in the norepinephrine group and 343 samples from 332 subjects in the phenylephrine group. Umbilical arterial pH was non-inferior in the norepinephrine group (mean, 7.289; 95% confidence interval [CI], 7.284-7.294) compared with the phenylephrine group (mean, 7.287; 95% CI, 7.281-7.292) (mean difference between groups, 0.002; 95% CI, -0.005 to 0.009; P=0.017). Subgroup analysis confirmed the non-inferiority of norepinephrine for elective cases but was inconclusive for non-elective cases., Conclusions: Norepinephrine was non-inferior to phenylephrine for neonatal outcome assessed by umbilical arterial pH. These results provide high-quality evidence supporting the fetal safety of norepinephrine in obstetric anaesthesia., Clinical Trial Registration: ChiCTR-IPR-15006235., (Copyright © 2020 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Background: Ondansetron has been shown to reduce the incidence of hypotension and vasopressor requirement during spinal anesthesia for obstetric and nonobstetric surgery. However, the magnitude of this effect has not been fully quantified. In this parallel-group, randomized, double-blinded study, we determined the effective dose in 50% of subjects (ED50) of a prophylactic phenylephrine infusion for preventing hypotension in patients who received a single dose of intravenous ondansetron 4 mg or saline control before combined spinal-epidural anesthesia for elective cesarean delivery. ED50 values obtained were compared to estimate the effect of ondansetron versus placebo on vasopressor requirement., Methods: Sixty parturients were randomly assigned to receive ondansetron (group O) or saline control (group C) 10 minutes before positioning for induction of spinal anesthesia. A prophylactic phenylephrine infusion was used to prevent hypotension. The first patient in each group received a phenylephrine infusion at the rate of 0.5 µg/kg/min. The infusion rate for each subsequent patient was varied with increments or decrements of 0.05 µg/kg/min based on the response of the previous patient, and the effective dose of the phenylephrine infusion for preventing hypotension in 50% of patients (ED50) was calculated for each group and compared using up-down sequential analysis. Probit regression was applied as a backup and sensitivity analysis was used to compare ED50 values for phenylephrine between groups by comparing calculated relative mean potency., Results: The ED50 (mean [95% confidence interval (CI)]) of the rate of phenylephrine infusion was lower in group O (0.24 µg/kg/min [0.10-0.38 µg/kg/min]) compared with group C (0.32 µg/kg/min [0.14-0.47 µg/kg/min]) (P < .001). The total consumption of phenylephrine (mean ± standard deviation [SD]) until delivery was lower in group O (316.5 ± 25.9 µg) than in group C (387.7 ± 14.7 µg, P = .02). The estimate of relative median potency for phenylephrine for group O versus group C was 0.74 (95% CI, 0.37-0.95)., Conclusions: Under the conditions of this study, intravenous ondansetron 4 mg reduced the ED50 of a prophylactic phenylephrine infusion by approximately 26% in patients undergoing cesarean delivery under combined spinal-epidural anesthesia.

Background: Norepinephrine infusion has been suggested as an effective method for preventing hypotension during spinal anaesthesia for Caesarean delivery. However, optimal dosing regimens for norepinephrine have not been well established. This study aimed to determine the dose-response characteristics of a weight-adjusted fixed-rate infusion of norepinephrine to prevent hypotension during neuraxial anaesthesia for Caesarean delivery., Methods: In a double-blind, randomised controlled trial, 80 parturients having elective Caesarean delivery received a prophylactic norepinephrine infusion at 0.025 μg kg -1 min -1 (Group N1), 0.05 μg kg -1 min -1 (Group N2), 0.075 μg kg -1 min -1 (Group N3), or 0.10 μg kg -1 min -1 (Group N4), starting immediately after induction of combined spinal-epidural anaesthesia. The primary outcome was non-occurrence of hypotension, defined as a decrease in systolic arterial pressure ≥20% below baseline value or to ≤90 mm Hg, before delivery. Values for 50% effective dose (ED 50 ) and ED 90 were calculated using probit regression., Results: The incidence of hypotension was 11/20 (55%), 6/20 (30%), 2/20 (10%), and 1/20 (5%) in Groups N1, N2, N3, and N4, respectively (P<0.0001). The ED 50 and ED 90 (95% confidence interval) of norepinephrine infusions for preventing hypotension were 0.029 (-0.002 to 0.043) and 0.080 (0.065-0.116) μg kg -1 min -1 , respectively. The incidence of reactive hypertension increased with increasing norepinephrine dose (P=0.002). Other adverse effects were similar among groups., Conclusions: Under the conditions of this study, an infusion of norepinephrine 0.08 μg kg -1 min -1 was effective for preventing hypotension in 90% of patients. This information should provide a guide for initiating norepinephrine infusions., Clinical Trial Registration: ChiCTR1900022322 at the Chinese Clinical Trial Registry (http://www.chictr.org.cn/enindex.aspx)., (Copyright © 2019 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Background: The optimal choice of vasopressor drugs for managing hypotension during neuraxial anaesthesia for Caesarean delivery is unclear. Although phenylephrine was recently recommended as a consensus choice, direct comparison of phenylephrine with vasopressors used in other healthcare settings is largely lacking. Therefore, we assessed this indirectly by collating data from relevant studies in this comprehensive network meta-analysis. Here, we provide the possible rank orders for these vasopressor agents in relation to clinically important fetal and maternal outcomes., Methods: RCTs were independently searched in MEDLINE, Web of Science, Embase, The Cochrane Central Register of Controlled Trials, and clinicaltrials.gov (updated January 31, 2019). The primary outcome assessed was umbilical arterial base excess. Secondary fetal outcomes were umbilical arterial pH and Pco 2 . Maternal outcomes were incidences of nausea, vomiting, and bradycardia., Results: We included 52 RCTs with a total of 4126 patients. Our Bayesian network meta-analysis showed the likelihood that norepinephrine, metaraminol, and mephentermine had the lowest probability of adversely affecting the fetal acid-base status as assessed by their effect on umbilical arterial base excess (probability rank order: norepinephrine > mephentermine > metaraminol > phenylephrine > ephedrine). This rank order largely held true for umbilical arterial pH and Pco 2 . With the exception of maternal bradycardia, ephedrine had the highest probability of being the worst agent for all assessed outcomes. Because of the inherent imprecision when collating direct/indirect comparisons, the rank orders suggested are possibilities rather than absolute ranks., Conclusion: Our analysis suggests the possibility that norepinephrine and metaraminol are less likely than phenylephrine to be associated with adverse fetal acid-base status during Caesarean delivery. Our results, therefore, lay the scientific foundation for focused trials to enable direct comparisons between these agents and phenylephrine., (Copyright © 2019 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Background: Prophylactic IV infusion of phenylephrine has been recommended to prevent hypotension during spinal anesthesia for cesarean delivery. However, the optimal infusion dose is unknown. This study aimed to determine the infusion dose of phenylephrine that would be effective in preventing hypotension in 50% (ED50) and 90% (ED90) of patients when administered as a prophylactic infusion at a fixed rate based on the individual body weight., Methods: Eighty parturients scheduled for elective cesarean delivery were randomly allocated to receive IV infusion of prophylactic phenylephrine at 0.25, 0.375, 0.5, or 0.625 µg/kg/min (n = 20 per group) started immediately after intrathecal injection of 10 mg hyperbaric bupivacaine and 5 µg sufentanil using a combined spinal-epidural technique. An effective dose was defined by the occurrence of no hypotension (defined as a decrease in systolic blood pressure by ≥20% below baseline and to <90 mm Hg) during the interval from the initiation of spinal anesthesia to delivery of the infant. Values for ED50 and ED90 of prophylactic phenylephrine were calculated using probit analysis., Results: Hypotension occurred in 13/20, 8/20, 2/20, and 1/20 patients in the groups that received phenylephrine infusion at 0.25, 0.375, 0.5, or 0.625 µg/kg/min, respectively. The calculated values for ED50 and ED90 were 0.31 (95% CI, 0.24-0.36) and 0.54 (95% CI, 0.46-0.76) µg/kg/min, respectively. No difference was found in the incidence of adverse effects and neonatal outcomes among groups., Conclusions: Under the conditions of this study, when phenylephrine was given as a fixed-rate prophylactic infusion during spinal anesthesia for cesarean delivery to prevent hypotension, the values for ED50 and ED90 were 0.31 (95% CI, 0.24-0.36) and 0.54 (95% CI, 0.46-0.76) µg/kg/min, respectively.

Background: Phenylephrine is the preferred vasopressor for the prevention and treatment of spinal anaesthesia-induced hypotension during caesarean section, because studies on low-risk elective patients found it to have a less detrimental effect on umbilical artery pH compared with ephedrine. However, limited data exist from high-risk parturients and parturients with uteroplacental insufficiency., Methods: We systematically searched for randomised, controlled, double-blinded trials of these two vasopressors in high-risk caesarean sections. We applied conventional meta-analysis, trial sequential analysis, computing the required information size that would exclude type I and II errors, contour-enhanced funnel plot testing for publication bias, meta-regression to assess the dose-response relationship, and the Grading of Recommendations Assessment, Development, and Evaluation system (GRADE). The incidence of fetal acidosis (umbilical arterial pH <7.2) was the primary outcome., Results: Eight trials (712 patients) with low risk of bias were identified. Pooling six studies of patients with preeclampsia and other reasons for fetal compromise, as well as subgroup analysis of the preeclampsia studies, revealed no significant differences in the incidence of fetal acidosis. Trial sequential analysis showed that the required information size was not reached. The funnel plot was not suggestive of publication bias. Meta-regression showed no dose-response relationship. The GRADE score was moderate quality., Conclusions: Despite several studies and a large number of patients there was insufficient evidence to make a recommendation for choice of vasopressor in high-risk caesarean section. Trials with adequate power to detect differences in the incidence of fetal acidosis between ephedrine and phenylephrine are required to provide evidence-based guidance., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: The use of norepinephrine for maintaining blood pressure (BP) during spinal anesthesia for cesarean delivery has been described recently. However, its administration by titrated manually controlled infusion in this context has not been evaluated., Methods: In a double-blinded, randomized controlled trial, 110 healthy women having spinal anesthesia for elective cesarean delivery were randomly allocated to 1 of 2 groups. In group 1, patients received an infusion of 5 µg/mL norepinephrine that was started at 30 mL/h (2.5 µg/min) immediately after intrathecal injection and then manually adjusted within the range 0-60 mL/h (0-5 µg/min), according to values of systolic BP measured noninvasively at 1-minute intervals until delivery, with the objective of maintaining values near baseline. In group 2, no prophylactic vasopressor was given, and a bolus of 1 mL norepinephrine 5 µg/mL (5 µg) was given whenever systolic BP decreased to <80% of the baseline value. The study protocol was continued until delivery. The primary outcomes of the study were the incidence of hypotension and the overall stability of systolic BP control versus baseline compared using performance error calculations. In addition, the incidence and timing of hypotension were further compared using survival analysis., Results: Three patients were excluded from the analysis. Nine patients (17%) in group 1 had 1 or more episodes of hypotension versus 35 (66%) in group 2 (P < .001). Performance error calculations showed that on average, systolic BP was maintained closer to baseline (P < .001) in group 1. Survival curve analysis showed a significant difference between groups (log-rank test P < .001). Four patients in each group had a recorded heart rate <60 beats/min (P = .98). Despite a much greater rate of administration of norepinephrine in group 1 (median, 61.0 [interquartile range, 47.0-72.5] µg) versus group 2 (5.0 [0-18.1] µg) (P < .001), there was no difference in neonatal outcome as assessed by Apgar scores and umbilical cord blood gas analysis., Conclusions: In patients having spinal anesthesia for elective cesarean delivery, a manually titrated infusion of 5 µg/mL of norepinephrine was effective for maintaining BP and decreasing the incidence of hypotension, with no detectable detrimental effect on neonatal outcome. Further investigation of the use of dilute norepinephrine infusions for routine use in obstetric patients is suggested.

Background: Norepinephrine has been investigated as a potential alterative to phenylephrine for maintaining blood pressure during spinal anesthesia for cesarean delivery with the advantage of less depression of maternal heart rate and cardiac output. However, the relative potencies of these two vasopressors have not been fully determined in this context., Methods: In a random-allocation, graded dose-response study, 180 healthy patients undergoing spinal anesthesia for elective cesarean delivery received a single bolus of norepinephrine in one of six different doses ranging from 4 to 12 µg or phenylephrine in one of six different doses ranging from 60 to 200 µg to treat the first episode of hypotension. The magnitude of response was measured as the percentage of full restoration of systolic blood pressure to the baseline value. Dose-response analysis was performed using nonlinear regression to derive four-parameter logistic dose-response curves, which were compared to determine relative potency., Results: Data were analyzed for 180 patients. The estimated ED50 values (dose giving a 50% response) were norepinephrine 10 µg (95% CI, 6 to 17 µg) and phenylephrine 137 µg (95% CI, 79 to 236 µg). The estimated relative potency ratio for the two drugs was 13.1 µg (95% CI, 10.4 to 15.8 µg)., Conclusions: Comparative dose-response analysis was completed for norepinephrine and phenylephrine given as a bolus to treat the first episode of hypotension in patients undergoing spinal anesthesia for cesarean delivery. The estimated dose equivalent to phenylephrine 100 µg was norepinephrine 8 µg (95% CI, 6 to 10 µg). These results may be useful to inform the design of future comparative studies.

Background and Objectives: Bupivacaine, levobupivacaine, and ropivacaine are often given intrathecally for labor analgesia, but limited data are available for their dose-response properties in this context. The objective of this study was to describe the dose-response curves of these local anesthetics when given intrathecally for labor analgesia, to determine values for D50 (dose producing a 50% response) and to compare the calculated values of D50 for levobupivacaine and ropivacaine with those for bupivacaine., Methods: With ethics approval and written consent, we randomized 270 nulliparous laboring patients requesting neuraxial analgesia at 5-cm cervical dilation or less to receive a single dose of intrathecal local anesthetic without opioid as part of a combined spinal-epidural technique. Patients received either bupivacaine, levobupivacaine, or ropivacaine at a dose of 0.625, 1.0, 1.5, 2.5, 4.0, or 6.25 mg (n = 15 per group). Visual analog scale pain scores were measured for 15 minutes, after which further analgesia and management were at the clinician's discretion. The primary end point was percentage reduction of pain score at 15 minutes. Logistic sigmoidal dose-response curves were fitted to the data using nonlinear regression, and D50 values were calculated for each drug., Results: Data were analyzed from 270 patients. Patient characteristics were similar between groups. The calculated D50 and 95% confidence interval values were as follows: bupivacaine, 1.56 mg (1.25-1.94 mg); ropivacaine, 1.95 mg (1.57-2.43 mg); and levobupivacaine, 2.20 mg (1.76-2.73 mg)., Conclusions: The results of this study support previous work showing that intrathecal levobupivacaine and ropivacaine are less potent than bupivacaine., Clinical Trial Registration: Chinese Clinical Trial Registry (identifier: ChiCTR-TRC-09000773) and Centre of Clinical Trials Clinical Registry of the Chinese University of Hong Kong (identifier: CUHK&#95;CCT00245).

Background: The use of phenylephrine as the first-line agent for prevention and treatment of maternal hypotension during cesarean delivery (CD) may reduce cardiac output, posing a theoretical risk to mother and fetus. Norepinephrine has been suggested as a potential alternative, because its β-adrenergic effects might result in greater heart rate and cardiac output than phenylephrine. The use of norepinephrine to prevent and treat hypotension during CD is new, and its use as a bolus has not been fully determined in this context. The purpose of this study was to determine the effective norepinephrine dose, when given as intermittent intravenous (IV) boluses, to prevent postspinal hypotension in 90% of women undergoing elective CD (ED90)., Methods: This was a prospective, double-blind sequential allocation dose-finding study, using the biased coin up-and-down design. Forty-term pregnant women undergoing elective CD under spinal anesthesia received a set intermittent norepinephrine bolus of either 3, 4, 5, 6, 7, or 8 µg every time their systolic blood pressure (SBP) fell to below 100% of baseline. The primary outcome was the success of the norepinephrine regimen to maintain SBP at or above 80% of baseline, from induction of spinal anesthesia to delivery of the fetus. Secondary outcomes included nausea, vomiting, hypertension (SBP > 120% of baseline), bradycardia (<50 bpm), upper sensory level of anesthesia to ice cold and umbilical artery and vein blood gases. The ED90 and 95% confidence intervals (CIs) were estimated using both truncated Dixon and Mood and isotonic regression methods., Results: The estimated ED90 of norepinephrine was 5.49 µg (95% CI, 5.15-5.83) using the truncated Dixon and Mood method and 5.80 µg (95% CI, 5.01-6.59) using the isotonic regression method., Conclusions: The use of intermittent IV norepinephrine boluses to prevent spinal-induced hypotension in elective CD seems feasible and was not observed to be associated with adverse outcomes. Practically, we suggest an ED90 dose of 6 µg. Further work is warranted to elucidate the comparative effects of intermittent IV bolus doses of phenylephrine and norepinephrine, in terms of efficacy and safety.

Background: We previously described the use of closed-loop feedback computer-controlled infusion of phenylephrine for maintaining blood pressure (BP) during spinal anesthesia for cesarean delivery. In this study, we report a modified system in which phenylephrine is delivered by intermittent boluses rather than infusion. We hypothesized that the use of computer-controlled boluses would result in more precise control of BP compared with infusions., Methods: Two hundred fourteen healthy patients having spinal anesthesia for elective cesarean delivery were randomized to have their systolic BP maintained by phenylephrine administered by computer-controlled continuous infusion or computer-controlled intermittent boluses. From induction of anesthesia until the time of uterine incision, a noninvasive BP monitor was set to cycle at 1-minute intervals. In the infusion group, the infusion rate was automatically adjusted after each BP measurement using a previously described algorithm. In the bolus group, the algorithm was modified so that the mass of drug that would have been delivered over 1 minute was instead injected as a rapid intravenous bolus after each BP measurement. The precision of BP control was assessed using performance error calculations and compared between groups, with the primary outcome defined as median absolute performance error, and the latter being a measure of inaccuracy showing an average of the magnitudes of the differences of measured BP values above or below the target values., Results: The precision of BP control was greater, as shown by smaller values for median absolute performance error, in the bolus group (median 4.38 [quartiles 3.22, 6.25] %) versus the infusion group (5.39 [4.12, 7.04] %, P = .008). In the bolus group, phenylephrine consumption was smaller; this was associated with smaller values for median performance error compared with the continuous infusion group (P < .001), which indicates that values for systolic BP, averaged over time, were slightly lower in the bolus group. There were no differences in cardiac output, nausea or vomiting, or neonatal outcome between groups., Conclusions: We confirmed the hypothesis that BP control was more precise when computer-controlled phenylephrine was delivered using intermittent boluses rather than continuous infusion. However, the difference between groups was small and was not associated with any difference in clinical outcomes. In the infusion group, greater doses of phenylephrine were delivered, which was related to the time taken for the noninvasive BP monitor to complete measurements. The use of intermittent boluses may be a useful alternative in the design of closed-loop vasopressor systems.

Closed-loop feedback computer-controlled vasopressor infusion has been previously described for maintaining blood pressure during spinal anaesthesia for caesarean section but there are limited data available comparing the relative performance of different vasopressors. The aim of this study was to compare the performance of norepinephrine versus phenylephrine in this system. Data from a randomized, two-arm parallel group, double-blinded controlled trial were reanalyzed. 104 patients scheduled for elective caesarean section under spinal anaesthesia were randomized to receive computer-controlled closed-loop infusion of either norepinephrine 5 µg ml -1 or phenylephrine 100 µg ml -1 . This was started immediately after induction of spinal anaesthesia and used an algorithm designed to maintain systolic blood pressure near baseline until fetal delivery. Performance error calculations were used to compare the performance of the two vasopressors. The primary outcome was defined as the median absolute performance error. Median performance error, wobble and divergence were also compared. Median absolute performance error was smaller in the norepinephrine group (median 3.79 [interquartile range 2.82-5.17] %) versus the phenylephrine group (4.70 [3.23-6.57] %, P = 0.028). In addition, median performance error was smaller (0.75 [-1.56-2.52] %) versus 2.61 [0.83-4.57] %, P = 0.002) and wobble was smaller (2.85 [2.07-5.17] %) versus 3.39 [2.62-4.90] %, P = 0.028) in the norepinephrine group versus the phenylephrine group. Divergence was similar between groups. The precision of the control of blood pressure was greater with norepinephrine compared with phenylephrine at the drug concentrations used.

Purpose of Review: Hypotension remains one of the most researched subjects in obstetric anaesthesia. The purpose of this study is to review the most recent published articles on the use of vasopressors during spinal anaesthesia for caesarean section., Recent Findings: Despite continued research indicating advantages of phenylephrine over ephedrine, practitioners in some countries continue to favour ephedrine. Recent research has continued to compare the two drugs with some work emerging on high-risk patients. Concern about reflexive bradycardia during phenylephrine use has led to consideration of alternatives. Norepinephrine which has mild β-adrenergic activity has been shown to have equivalent pressor activity but with less depressant effect on heart rate and cardiac output versus phenylephrine. Research continues to focus on methods of vasopressor administration. Prophylactic infusions of phenylephrine have been shown to be effective and may require less physician intervention compared with intermittent boluses. Automated computer-controlled systems have been further investigated using multiple agents and continuous noninvasive blood pressure monitoring., Summary: Evidence continues to support phenylephrine as the first-line vasopressor in obstetrics. However, recent research is emerging to suggest that low-dose norepinephrine may be a better alternative. Prophylactic infusions are effective and automated systems have potential for the future.

Background: Successful external cephalic version (ECV) for breech presenting fetus reduces the need for Caesarean section (CS). We aimed to compare the success rate of ECV with either spinal anaesthesia (SA) or i.v. analgesia using remifentanil., Methods: In a double-phased, stratified randomized blinded controlled study we compared the success rates of ECV, performed under spinal anaesthesia (SA), i.v. analgesia (IVA) using remifentanil or no anaesthetic interventions. In phase I, 189 patients were stratified by parity before randomization to ECV, performed by blinded operators, under SA using either hyperbaric bupivacaine 9 mg with fentanyl 15 µg, i.v. remifentanil infusion 0.1 µg kg min(-1), or Control (no anaesthetic intervention). Operators performing ECV were blinded to the treatment allocation. In phase 2, patients in the Control group in whom the initial ECV failed were further randomized to receive either SA (n=9) or IVA (n=9) for a re-attempt. The primary outcome was the incidence of successful ECV., Results: The success rate in Phase 1 was greatest using SA [52/63 (83%)], compared with IVA [40/63 (64%)] and Control [40/63 (64%)], (P=0.027). Median [IQR] pain scores on a visual analogue scale (range 0-100), were 0 [0-0] with SA, 35 [0-60] with IVA and 50 [30-75] in the Control group (P<0.001). Median [IQR] VAS sedation scores were highest with IVA [75 (50-80)], followed by SA, [0 (0-50)] and Control [0 (0-0)]. In phase 2, 7/9 (78%) of ECV re-attempts were successful with SA, whereas all re-attempts using IVA failed (P=0.0007). The incidence of fetal bradycardia necessitating emergency CS within 30 min, was similar among groups; 1.6% (1/63) in the SA and IVA groups and 3.2% (2/63) in the Control group., Conclusions: SA increased the success rate and reduced pain for both primary and re-attempts of ECV, whereas IVA using remifentanil infusion only reduced the pain. There was no significant increase in the incidence of fetal bradycardia or emergency CS, with ECV performed under anaesthetic interventions. Relaxation of the abdominal muscles from SA appears to underlie the improved outcomes for ECV., (© The Author 2015. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: During spinal anesthesia for cesarean delivery, phenylephrine can cause reflexive decreases in maternal heart rate and cardiac output. Norepinephrine has weak β-adrenergic receptor agonist activity in addition to potent α-adrenergic receptor activity and therefore may be suitable for maintaining blood pressure with less negative effects on heart rate and cardiac output compared with phenylephrine., Methods: In a randomized, double-blinded study, 104 healthy patients having cesarean delivery under spinal anesthesia were randomized to have systolic blood pressure maintained with a computer-controlled infusion of norepinephrine 5 μg/ml or phenylephrine 100 μg/ml. The primary outcome compared was cardiac output. Blood pressure heart rate and neonatal outcome were also compared., Results: Normalized cardiac output 5 min after induction was greater in the norepinephrine group versus the phenylephrine group (median 102.7% [interquartile range, 94.3 to 116.7%] versus 93.8% [85.0 to 103.1%], P = 0.004, median difference 9.8%, 95% CI of difference between medians 2.8 to 16.1%). From induction until uterine incision, for norepinephrine versus phenylephrine, systolic blood pressure and stroke volume were similar, heart rate and cardiac output were greater, systemic vascular resistance was lower, and the incidence of bradycardia was smaller. Neonatal outcome was similar between groups., Conclusions: When given by computer-controlled infusion during spinal anesthesia for cesarean delivery, norepinephrine was effective for maintaining blood pressure and was associated with greater heart rate and cardiac output compared with phenylephrine. Further work would be of interest to confirm the safety and efficacy of norepinephrine as a vasopressor in obstetric patients.

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

Background: Phenylephrine given during spinal anaesthesia for caesarean delivery often induces a decrease in heart rate which may decrease cardiac output. Anticholinergic drugs may be given to attenuate this effect but may also cause more labile blood pressure. This study evaluated the effects of glycopyrrolate pre-treatment on non-invasively measured cardiac output and accuracy of blood pressure control., Methods: At induction of spinal anaesthesia for caesarean delivery, 104 patients randomly received intravenous glycopyrrolate 4μg/kg or saline placebo. Systolic blood pressure, measured at 1-min intervals, was maintained near baseline using closed-loop feedback computer-controlled phenylephrine infusion with crystalloid cohydration. Cardiac output and stroke volume were measured using suprasternal Doppler ultrasonography at baseline and 5-min intervals for 20min. Blood pressure control was assessed using performance error calculations., Results: Eleven patients were excluded. Patients who received glycopyrrolate (n=45) had greater cardiac output over time (P<0.001), greater heart rate over time (P<0.001), similar stroke volume over time (P=0.95), and lower median phenylephrine infusion rate (P=0.006) compared with control (n=48). There was no difference in the incidence of hypotension between groups. Analysis of blood pressure control showed greater positive bias, greater inaccuracy and greater wobble in the glycopyrrolate group (all P<0.05). Neonatal outcome was similar between groups., Conclusions: Glycopyrrolate 4μg/kg given at the start of a phenylephrine infusion increased heart rate and cardiac output but also decreased accuracy of blood pressure control, increased the incidence of hypertension and caused an increased incidence of dry mouth postoperatively compared with control., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

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

Objectives: The use of ultrasound to guide peripheral nerve blocks is now a well-established technique in regional anaesthesia. However, despite reports of ultrasound guided epidural access via the paramedian approach, there are limited data on the use of ultrasound for central neuraxial blocks, which may be due to a poor understanding of spinal sonoanatomy. The aim of this study was to define the sonoanatomy of the lumbar spine relevant for central neuraxial blocks via the paramedian approach., Methods: The sonoanatomy of the lumbar spine relevant for central neuraxial blocks via the paramedian approach was defined using a "water-based spine phantom", young volunteers and anatomical slices rendered from the Visible Human Project data set., Results: The water-based spine phantom was a simple model to study the sonoanatomy of the osseous elements of the lumbar spine. Each osseous element of the lumbar spine, in the spine phantom, produced a "signature pattern" on the paramedian sagittal scans, which was comparable to its sonographic appearance in vivo. In the volunteers, despite the narrow acoustic window, the ultrasound visibility of the neuraxial structures at the L3/L4 and L4/L5 lumbar intervertebral spaces was good, and we were able to delineate the sonoanatomy relevant for ultrasound-guided central neuraxial blocks via the paramedian approach., Conclusion: Using a simple water-based spine phantom, volunteer scans and anatomical slices from the Visible Human Project (cadaver) we have described the sonoanatomy relevant for ultrasound-guided central neuraxial blocks via the paramedian approach in the lumbar region.

Background: Brachial plexus block (BPB) causes vasodilatation and an increase in blood flow to the ipsilateral upper limb. However, no reports have comprehensively evaluated the regional hemodynamic changes after a BPB., Methods: Eight healthy adult patients who were scheduled for elective hand surgery had an ultrasound-guided axillary BPB for anesthesia. Regional hemodynamic parameters were measured in the ipsilateral brachial artery, using pulsed-wave Doppler (PWD) ultrasound before the block (0 minute) and at regular intervals for 30 minutes after the block. Skin temperature on the dorsum of the ipsilateral hand was also recorded at the same time intervals. Regional hemodynamic parameters that were measured in the brachial artery included peak systolic velocity (PSV, cm/s), end-diastolic velocity (EDV, cm/s), mean velocity (Vmean) and time-averaged mean velocity (TAVM, cm/s), ratio of PSV and EDV (S/D), diameter (d, cm), resistance index (RI), and pulsatility index (PI). Brachial artery blood flow (Q) was calculated as the product of TAVM and cross-sectional area., Results: The ultrasound-guided axillary BPB was successful in all the patients studied. The earliest change after the BPB was a change in the morphology of the PWD spectral waveform from a triphasic to a monophasic waveform and an elevation in the diastolic blood flow velocity. Over time, there was also a significant increase in PSV, EDV, Vmean, TAVM, d, brachial artery blood flow, and skin temperature and a decrease in S/D ratio, RI, and PI. Most of these changes were seen as early as 5 minutes after the block. The increase in EDV (3.7-fold) was the most notable change, and it was greater (P < 0.05) than the increase in PSV (1.5-fold) and Vmean (2.8-fold)., Conclusions: Regional hemodynamic changes that occur after an axillary BPB include a change in the morphology of the PWD spectral waveform, arterial vasodilatation, an increase in blood flow velocity, and an increase in blood flow through the ipsilateral brachial artery.

Background: Previous work demonstrated that maternal haplotypes of the β₂-adrenoceptor gene (ADRB2) influence ephedrine requirements during cesarean delivery. The use of ephedrine versus a pure α-adrenergic agonist such as phenylephrine has been associated with lower umbilical artery (UA) pH, thought to be secondary to increased fetal metabolism. There are no data evaluating the effect of fetal/neonatal genotypes on the metabolic response to maternally administered vasopressors. We hypothesized that neonatal ADRB2 genotype would affect the extent of neonatal acidemia. We also examined the effect of maternal ADRB2 and the endothelial nitric oxide synthase gene (NOS3) on ephedrine and phenylephrine requirements for treatment of maternal hypotension., Methods: The study was performed on 104 Chinese women scheduled for cesarean delivery under spinal anesthesia who were participating in a double-blind randomized clinical trial evaluating the maternal and neonatal effects of ephedrine versus phenylephrine infusions. Blood samples were drawn from the UA, umbilical vein, and maternal radial artery to measure blood gas values and lactate, ephedrine, and phenylephrine concentrations, and to determine maternal and neonatal genotype at nonsynonymous single nucleotide polymorphisms at codons 16 (rs1042713) and 27 (rs1042714) of ADRB2 and codon 298 (rs1799983) of NOS. Clinical variables (UA pH, UA lactate, and dose of vasopressors) among genotypes were compared, and regression models were created to assess the effect of genotype on vasopressor dose and fetal acid-base status., Results: Maternal ADRB2 genotype did not affect the ephedrine dose. Neonatal genotype at codon 16 influenced fetal acid-base status. UA pH was higher in Arg16 homozygous neonates (7.31 ± 0.03 in p.16Arg/Arg vs. 7.25 ± 0.11 in p.16 Arg/Gly and p.16 Gly/Gly; P < 0.001, 95%confidence interval (CI) of difference 0.03 ~ 0.09) and UA lactate was lower (2.67 mmol/L ± 0.99 in p.16Arg/Arg vs 4.28 mmol/L ± 2.79 in. p.16 Arg/Gly and p.16 Gly/Gly; P < 0.001, 95% CI of difference -2.40 ~ -0.82). In neonates born to mothers receiving ephedrine, the magnitude of the difference among genotypes was even greater (pH 7.30 ± 0.02 in p.16Arg/Arg vs. 7.19 ± 0.10 in p.16 Arg/Gly and p.16 Gly/Gly; P < 0.001, 95% CI of difference 0.07 ~ 0.14) and UA lactate was lower (3.66 mmol/L ± 1.30 in p.16Arg/Arg vs. 5.79 mmol/L ± 2.88 in p.16 Arg/Gly and p.16 Gly/Gly; P = 0.003, 95% CI of difference -3.48 ~ -0.80). In a multiple linear regression model (R² = 63.6%; P = 0.03), neonatal ADRB2 genotypes (p.16Arg/Arg and p.27Gln/Glu) and lower neonatal birth weight predicted lower UA lactate concentrations. Phenylephrine dose was not affected by maternal ADRB2 or NOS3 genotypes, and neonatal NOS3 genotype did not affect UA pH or UA lactate., Conclusion: In contrast to previous findings in a North American cohort, maternal ADRB2 genotype did not affect ephedrine requirements during elective cesarean delivery in a Chinese cohort. However, our findings suggest that neonatal ADRB2 p.Arg16 homozygosity confers a protective effect against developing ephedrine-induced fetal acidemia.

This report describes the preparation of a gelatin-agar spine phantom that was used for spinal sonography and to practice the hand-eye coordination skills required to perform sonographically guided central neuraxial blocks. The phantom was prepared by embedding a lumbosacral spine model into a mixture of gelatin and agar in a plastic box. Cellulose powder and chlorhexidine were also added to the mixture, after which it was allowed to solidify. Sonography of the osseous elements of the lumbosacral spine in the phantom was then performed, and their sonographic appearances were compared to those in volunteers. Simulated real-time sonographically guided paramedian spinal needle insertions were also performed in the phantom. The texture and echogenicity of the phantom were subjectively comparable to those of tissue in vivo. The osseous elements of the spine in the phantom were clearly delineated, and their sonographic appearances were comparable to those seen in vivo in the volunteers. During the simulated sonographically guided spinal injections, the needle could be clearly visualized, but the phantom provided little tactile feedback. In conclusion, the gelatin-agar spine phantom is a simple and inexpensive sonographic spine model that has a tissuelike texture and echogenicity. It can be used to study the osseous anatomy of the lumbar spine and practice the skills required to perform sonographically guided central neuraxial blocks.

Objective: To review the perinatal outcome of monochorionic twin pregnancies treated by fetoscopic laser coagulation for twin-twin transfusion syndrome., Design: Retrospective study., Setting: A university teaching hospital in Hong Kong., Patients: Thirty consecutive cases of fetoscopic laser coagulation of placental anastomoses for twin-twin transfusion syndrome performed in a single centre., Main Outcome Measures: Operative complications and perinatal survival rates., Results: The median gestational age at initial presentation, laser photocoagulation, and delivery were 22 (range, 16-27) weeks, 23 (18-28) weeks, and 32 (21-37) weeks, respectively. To improve the visualisation, in three cases amnio-exchange was undertaken; the procedure was abandoned in two due to poor visualisation. The overall fetal survival rate, the double infant survival rate, and survival rate for at least one twin were 72% (43/60), 60% (18/30), and 83% (25/30), respectively. The most common peri-operative complication was bleeding from the uterine wall into the amniotic cavity, which affected three (10%) patients., Conclusions: Our results of fetoscopic laser surgery for twin-twin transfusion syndrome were similar to those in specialised centres in other countries.

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

Purpose of Review: Hypotension during regional anaesthesia for caesarean section remains a common clinical problem, particularly for spinal anaesthesia. The purpose of this review is to evaluate recent research in this area with a focus on English language papers from the past 1-2 years., Recent Findings: Risk factors for hypotension include increased sympathetic tone, increasing age, obesity, higher blocks and higher birthweight, but not multiple gestation. Methods aimed at countering effects of aortocaval compression do not reliably prevent hypotension. Intravenous crystalloid prehydration has poor efficacy, and focus has changed toward cohydration and use of colloids. Phenylephrine is established as a first-line vasopressor, although there are limited data from high-risk patients. Initial phenylephrine bolus dose requirement may be surprisingly large. Phenylephrine infusions can be conveniently titrated to maintain blood pressure and prevent maternal symptoms. Ephedrine crosses the placenta more than phenylephrine and direct fetal effects of ephedrine may explain associated depression of fetal pH and base excess., Conclusion: Recent research supports decreased use of crystalloid prehydration and ephedrine and increased use of cohydration, colloids, smaller spinal doses and phenylephrine. Further research is required to investigate these techniques in high-risk patients and to evaluate novel monitoring techniques.

Background: Intrathecal anesthesia is commonly used for lower limb surgery. Bupivacaine, levobupivacaine, and ropivacaine have all been used as intrathecal drugs, but their relative potency in this context has not been fully determined. In this study, we determined the median effective dose (ED(50)) of these three local anesthetics for intrathecal anesthesia in lower limb surgery and hence their relative potencies., Methods: Seventy-five patients scheduled for lower limb surgery under combined spinal-epidural anesthesia were randomly allocated to one of three groups receiving intrathecal bupivacaine, levobupivacaine, or ropivacaine. The dose of local anesthetic was varied using up-down sequential allocation technique. The dose for the first patient in each group was 8 mg, and the dosing increment was set at 1 mg. Subsequent doses in each group were determined by the outcome in the previous patient using success or failure of the spinal anesthesia as the primary end point. A success was recorded if a bilateral T12 sensory block to cold was attained within 20 min after intrathecal injection, and the surgery proceeded successfully until at least 50 min after the intrathecal injection without supplementary epidural injection. The ED(50) was calculated using the method of Dixon and Massey., Results: The ED(50)s were 5.50 mg for bupivacaine (95% confidence interval [CI]: 4.90-6.10 mg), 5.68 mg for levobupivacaine (95% CI: 4.92-6.44 mg), and 8.41 mg for ropivacaine (95% CI: 7.15-9.67 mg) in intrathecal anesthesia. The relative anesthetic potency ratios are 0.97 (95% CI: 0.81-1.17) for levobupivacaine/bupivacaine, 0.65 (95% CI: 0.54-0.80) for ropivacaine/bupivacaine, and 0.68 (95% CI: 0.55-0.84) for ropivacaine/levobupivacaine., Conclusion: This study suggests that in intrathecal anesthesia for lower limb surgery, ropivacaine is less potent than levobupivacaine and bupivacaine, whereas the potency is similar between levobupivacaine and bupivacaine.