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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]

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]

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: 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: 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.

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: 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.

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.

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.

Background: Phenylephrine and ephedrine are both used to maintain arterial blood pressure during spinal anesthesia for cesarean delivery. Usually, either drug is given alone but several previous studies have described combining the drugs. However, the effect of varying the proportion of vasopressors in such combinations has not been reported., Methods: One-hundred-twenty-five parturients having spinal anesthesia for elective cesarean delivery were randomized to receive an IV infusion of phenylephrine and ephedrine combined in one of five different concentration ratios. Assuming phenylephrine 100 microg to be approximately equipotent to ephedrine 8 mg, the groups contained the proportional potency equivalent of 100%, 75%, 50%, 25% or 0% of phenylephrine and 0%, 25%, 50%, 75% or 100%, respectively, of ephedrine. The infusions were adjusted to maintain systolic blood pressure (SBP) near baseline until uterine incision. Hemodynamic changes and umbilical cord blood gases were compared., Results: As the proportion of phenylephrine decreased and proportion of ephedrine increased among the groups, the following significant trends were detected: the incidences of hypotension and nausea/vomiting increased, the median magnitude of deviations of SBP above or below baseline and the bias for SBP to be above baseline increased, maternal heart rate was faster, fetal pH and base excess decreased, umbilical arterial oxygen content decreased and umbilical venous Po2 increased., Conclusions: When varying combinations of phenylephrine and ephedrine were given by infusion to maintain arterial blood pressure during spinal anesthesia for cesarean delivery, as the proportion of phenylephrine decreased and the proportion of ephedrine increased, hemodynamic control was reduced and fetal acid-base status was less favorable. Combinations of phenylephrine and ephedrine appear to have no advantage compared with phenylephrine alone when administered by infusion for the prevention of hypotension associated with spinal anesthesia for cesarean delivery.

Lumbar plexus block (LPB) is frequently used in combination with an ipsilateral sacral plexus or sciatic nerve block for lower limb surgery. This is traditionally performed using surface anatomical landmarks, and the site for local anaesthetic injection is confirmed by observing quadriceps muscle contraction to peripheral nerve stimulation. In this report, we describe a technique of ultrasound-guided LPB that was successfully used, in conjunction with a sciatic nerve block, for anaesthesia during emergency lower limb surgery. The anatomy, sonographic features, technique of identifying the lumbar plexus, and the potential benefits of using this approach are discussed.

Background: The dose-response relationship for spinal ropivacaine in patients undergoing surgery of the lower extremity has not been fully determined., Methods: We performed a prospective, randomized, double-blind study of 60 patients scheduled for lower limb surgery under combined spinal-epidural anesthesia. Patients were assigned to receive 1 of 5 doses of intrathecal ropivacaine: 2, 4, 7, 10, or 14 mg diluted to 2.8 mL with normal saline. A dose was considered successful if a sensory block to cold was achieved bilaterally at the T12 dermatome within 20 min and surgery proceeded without supplementation for at least 50 min., Results: Anesthesia was successful in 0, 0, 42, 83, and 100% of the 2, 4, 7, 10, and 14 mg groups, respectively. The derived value for ED(50) was 7.6 mg (95% CI: 6.2-8.7 mg) and for ED(95) was 11.4 mg (95% CI: 9.7-18.3 mg). The cephalic level of sensory block and the degree of motor block increased with larger doses of ropivacaine., Conclusion: The ED(50) and ED(95) for spinal ropivacaine in lower limb surgery of 50 min duration or less were 7.6 and 11.4 mg, respectively. This provides a useful guide for clinicians to choose the optimal dose of spinal ropivacaine under different clinical situations.

Background: It is commonly taught that patients with multiple gestation pregnancy are prone to more severe hypotension during spinal and epidural anesthesia compared to those with singleton pregnancy. However, few quantitative data are available to support this claim. In this study, we prospectively compared vasopressor requirement and hemodynamic changes in patients with multiple gestation versus singleton pregnancy during spinal anesthesia for elective cesarean delivery., Methods: Forty parturients with multiple gestation and 60 singleton controls who had identical anesthetic management during spinal anesthesia for elective cesarean delivery were enrolled. After IV prehydration, patients received intrathecal bupivacaine-fentanyl and were tilted to the left. A metaraminol infusion was titrated with the target of maintaining systolic blood pressure at 90%-100% of baseline. Vasopressor dose, minimum and maximum values for systolic blood pressure and the incidences of hypotension, hypertension, and nausea/vomiting were compared., Results: All outcome variables were similar between groups. The total dose of metaraminol required until uterine incision was similar in multiple gestation pregnancy (median 2.9 [interquartile range 2.0-3.7] mg) when compared with singleton pregnancy (median 3.1 [interquartile range 2.3-3.9] mg, P = 0.25; median difference 0.30 mg, 95% confidence interval of difference -0.20 to 0.90 mg). Neonatal outcome was similar between groups., Conclusion: Patients with multiple gestation pregnancy do not exhibit greater hemodynamic instability during spinal anesthesia for cesarean delivery compared to those with singleton pregnancy.

The original and modified Mallampati tests are commonly used to predict the difficult airway, but there is controversy regarding their accuracy. We searched MEDLINE and other databases for prospective studies of patients undergoing general anesthesia in which the results of a preoperative Mallampati test were compared with the subsequent rate of difficult airway (difficult laryngoscopy, difficult intubation, or difficult ventilation as reference tests). Forty-two studies enrolling 34,513 patients were included. The definitions of the reference tests varied widely. For predicting difficult laryngoscopy, both versions of the Mallampati test had good accuracy (area under the summary receiver operating characteristic (sROC) curve = 0.89 +/- 0.05 and 0.78 +/- 0.05, respectively). For predicting difficult intubation, the modified Mallampati test had good accuracy (area under the sROC curve = 0.83 +/- 0.03) whereas the original Mallampati test was poor (area under the sROC curve = 0.58 +/- 0.12). The Mallampati tests were poor at identifying difficult mask ventilation. Publication bias was not detected. Used alone, the Mallampati tests have limited accuracy for predicting the difficult airway and thus are not useful screening tests.

Background: Use of remifentanil during general anesthesia for cesarean delivery has been described, but its maternal and neonatal effects have not been investigated by a controlled study., Methods: In a randomized, double-blind, controlled study, patients undergoing elective cesarean delivery received an intravenous bolus of 1 microg/kg remifentanil (n = 20) or saline (n = 20) immediately before induction of general anesthesia. The authors compared maternal hemodynamic changes and neonatal condition and measured plasma concentrations of remifentanil., Results: The maximum increase in systolic arterial pressure from baseline after induction was smaller in the remifentanil group (median, 9 [range, -17 to 31] mmHg) compared with the control group (42 [6-73] mmHg, median difference, 33 mmHg; 95% confidence interval of difference, 23-45 mmHg; P < 0.0001). Maximum recorded values were smaller in the remifentanil group compared with the control group for systolic and mean arterial pressure and maternal heart rate. Apgar scores and time to sustained respiration were similar between groups. Two neonates in the remifentanil group were considered clinically depressed at birth and were given a single dose of naloxone. Remifentanil crossed the placenta with an umbilical venous/maternal arterial concentration ratio of 0.73 (SD, 0.17) and an umbilical arterial/umbilical venous concentration ratio of 0.60 (0.23)., Conclusions: A single bolus of 1 microg/kg remifentanil effectively attenuated hemodynamic changes after induction and tracheal intubation. However, remifentanil crosses the placenta and may cause mild neonatal depression and thus should be used for clear maternal indications when adequate facilities for neonatal resuscitation are available.

Background: The benefit of administering supplementary oxygen during elective Caesarean section under regional anaesthesia is controversial. It has been hypothesized that its use would improve fetal oxygenation in the event of a prolonged uterine incision-to-delivery (U-D) interval. Our aim was to test this hypothesis in a prospective, randomized, double-blinded, controlled study., Methods: We allocated randomly 204 women having elective Caesarean section under spinal anaesthesia to breathe 21, 40 or 60% oxygen. We recorded the U-D interval, umbilical arterial (UA) and venous (UV) blood gases and oxygen content and Apgar scores. Subgroup analysis was performed according to whether the U-D interval was prolonged (>180 s) or not., Results: The U-D interval was <180 s in 159 patients and >180 s in 45 patients. There were no differences in UV or UA blood gases, oxygen content or Apgar scores between cases with and without a prolonged U-D interval. In cases without a prolonged U-D interval, administering 60% oxygen increased UV PO(2) (mean 4.3 (SD 1.1) vs 3.7 (1.0) kPa, P=0.003) and oxygen content (14.4 (3.3) vs 12.9 (2.7) ml dl(-1), P=0.007) compared with air. In cases with a prolonged U-D interval, administering 60% oxygen increased UV PO(2) (4.6 (0.6) vs 3.9 (0.8) kPa, P=0.019) compared with air but there was no difference in UV oxygen content. There was no increase in the UV PO(2) or oxygen content when 40% oxygen was administered compared with air., Conclusions: Supplementary oxygen did not increase fetal oxygenation in cases where the U-D interval was prolonged. Our data do not support the routine administration of supplementary oxygen during elective Caesarean section for this purpose.

Background: During spinal anaesthesia for Caesarean section, the optimal phenylephrine regimen and the optimal blood pressure (BP) to which it should be titrated are undetermined. The ideal regimen would balance efficacy for maintaining uteroplacental perfusion pressure against potential for uteroplacental vasoconstriction, both of which may affect fetal acid-base status. We compared phenylephrine infusion regimens based on three different BP thresholds., Methods: After intrathecal injection, we infused phenylephrine 100 microg min(-1) for 2 min. Then, until delivery, we infused phenylephrine whenever systolic BP (SBP), measured every 1 min, was below a randomly assigned percentage of baseline: 100% (Group 100, n=25), 90% (Group 90, n=25) or 80% (Group 80, n=24). We compared umbilical blood gases, Apgar scores and maternal haemodynamics and symptoms., Results: Patients in Group 100 had fewer episodes [median 0 (range 0-8)] of hypotension (SBP <80% baseline) compared with Group 80 [5 (0-18)] and Group 90 [2 (0-7)] (P<0.001 in each instance). Total dose of phenylephrine was greater in Group 100 [median 1520 microg (interquartile range 1250-2130 microg)] compared with Group 90 [1070 (890-1360) microg] and Group 80 [790 (590-950) microg]. Umbilical arterial pH was greater in Group 100 [mean 7.32 (95% confidence interval 7.31-7.34)] than in Group 80 [7.30 (7.28-7.31)] (P=0.034). No patient had umbilical arterial pH <7.2. In Group 100, 1/24 (4%) patients had nausea or vomiting compared with 4/25 (16%) in Group 90 and 10/25 (40%) in Group 80 (P=0.006)., Conclusions: For optimal management, phenylephrine should be titrated to maintain maternal BP at near-baseline values.

Unlabelled: Studies have shown better obstetric outcome when ropivacaine 0.25% was used for labor epidural analgesia compared with bupivacaine 0.25%, but it is controversial whether there is any difference at smaller concentrations. In a prospective, double-blind trial, we randomized 350 ASA physical status I and II parturients with term cephalic singleton pregnancies to receive epidural labor analgesia using ropivacaine or bupivacaine. Analgesia was initiated with a 0.25% solution and maintained with a continuous infusion of a 0.1% solution with fentanyl 0.0002%. Supplementary boluses of 0.25% solution were given when requested. Labor was managed according to institutional standard labor ward protocols. Among patients who delivered vaginally, the duration of the first stage of labor was shorter in the ropivacaine group (median, 520 min; interquartile range, 377-745 min) compared with the bupivacaine group (645 min; interquartile range, 460-820 min; P = 0.009), but there was no difference in any other obstetric or neonatal outcomes. The mode of delivery was similar between groups, with operative (instrumental vaginal and cesarean) delivery rates of 61.8% (95% confidence interval, 54.4%-68.8%) in the ropivacaine group and 58.4% (95% confidence interval, 50.9%-65.5%) in the bupivacaine group (P = 0.72)., Implications: In a randomized-controlled study, we found no major outcome advantage of continuous epidural infusion of ropivacaine 0.1% with fentanyl 0.0002% over bupivacaine 0.1% with fentanyl 0.0002% for labor analgesia. Although ropivacaine was associated with a shorter first stage of labor, the relative difference is probably of limited clinical importance, and there was no difference in the mode of delivery.

Unlabelled: In a randomized, double-blinded, controlled trial, we investigated the prophylactic infusion of IV phenylephrine for the prevention of hypotension during spinal anesthesia for cesarean delivery. Immediately after intrathecal injection, phenylephrine was infused at 100 microg/min (n = 26) for 3 min. From that point until delivery, phenylephrine was infused at 100 microg/min whenever systolic arterial blood pressure (SAP), measured each minute, was less than baseline. A control group (n = 24) received IV bolus phenylephrine 100 microg after each measurement of SAP <80% of baseline. Phenylephrine infusion decreased the incidence (6 [23%] of 26 versus 21 [88%] of 24; P < 0.0001), frequency, and magnitude (median minimum SAP, 106 mm Hg; interquartile range, 95-111 mm Hg; versus median, 80 mm Hg; range, 73-93 mm Hg; P < 0.0001) of hypotension compared with control. Heart rate was significantly slower over time in the infusion group compared with the control group (P < 0.0001). Despite a large total dose of phenylephrine administered to the infusion group compared with the control group (median, 1260 microg; interquartile range, 1010-1640 microg; versus median, 450 microg; interquartile range, 300-750 microg; P < 0.0001), umbilical cord blood gases and Apgar scores were similar. One patient in each group had umbilical arterial pH <7.2. Prophylactic phenylephrine infusion is a simple, safe, and effective method of maintaining arterial blood pressure during spinal anesthesia for cesarean delivery., Implications: In patients receiving spinal anesthesia for elective cesarean delivery, a prophylactic infusion of phenylephrine 100 microg/min decreased the incidence, frequency, and magnitude of hypotension with equivalent neonatal outcome compared with a control group receiving IV bolus phenylephrine.

Unlabelled: We systematically reviewed available studies to determine the dose-response characteristics of prophylactic i.v. ephedrine for the prevention of hypotension during spinal anesthesia for cesarean delivery. We searched for randomized controlled trials (RCTs) or cohort studies-obtained through MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and reference lists of published articles-in which two or more different doses of prophylactic i.v. ephedrine were used to prevent hypotension during spinal anesthesia for cesarean delivery. Four RCTs and one cohort study were found (total n = 390). There was a significant dose-response relationship in the RCTs pooled for hypotension (slope = -0.0128; 95% confidence interval [CI], -0.0213 to -0.0044), hypertension (slope = 0.0563; 95% CI, 0.0235 to 0.0892), and umbilical arterial pH (slope = -0.03; 95% CI, -0.05 to 0.00). The efficacy of ephedrine for preventing hypotension was small. At 14 mg, the number-needed-to-treat was only 7.6 (95% CI, 4.8-21.1), and this was the same as the number-needed-to-harm (7.6; 95% CI, 3.7-23.4). At larger doses, the likelihood of causing hypertension was actually more than that of preventing hypotension, and there was also a minor decrease in umbilical arterial pH., Implications: The authors performed a systematic review of dose-response studies of i.v. bolus ephedrine for preventing hypotension during spinal anesthesia for cesarean delivery. Prophylactic ephedrine cannot be recommended. The efficacy is poor at smaller doses, whereas at larger doses, the likelihood of causing hypertension is actually more than that of preventing hypotension.

Objective: To examine the status of obstetric epidural analgesia services in Hong Kong public hospitals in 2001, and to compare findings with those from a similar survey conducted in 1995., Design: Postal questionnaire survey., Setting: Hospital Authority hospitals in Hong Kong offering an obstetric and delivery service., Participants: Chiefs of Service of departments of anaesthesia and coordinators of obstetric anaesthesia and analgesia service., Main Outcome Measures: The availability of an obstetric epidural analgesia service, specialist staff allocation to the service, existence of clinical protocols, rate of epidural analgesia, techniques of epidural administration, obstetric outcome or mode of delivery, and the incidence of adverse events associated with the use of epidural analgesia., Results: Between 1 January and 31 December 2001, all eight Hospital Authority hospitals with an obstetric service provided epidural analgesia for labour pain relief, but only six (75%) offered a 24-hour service. A dedicated anaesthetist provided obstetric anaesthesia and analgesia during office hours in all units, but after hours in only three. This level of service provision compared favourably with that available in 1995, when only 82% of public maternity units provided epidural analgesia and only 36% offered a 24-hour service. The median epidural analgesia rate was 15% (range, 8%-20%) compared with 10% in 1995. The incidence of adverse events and complications was very low. Formal written protocols for the conduct of epidural analgesia for labour were used in six units. All units used mixtures of local anaesthetic combined with opioid, administered as intermittent boluses, continuous epidural infusion, or patient-controlled epidural analgesia., Conclusions: Although there has been progress and improvement in the provision of obstetric epidural analgesia services in our public hospitals, the rate is still relatively low and the provision of services after hours is limited. Further progress will likely be hindered by current or future cutbacks in public hospital budgets.

Unlabelled: The addition of epinephrine to ropivacaine has not been recommended because ropivacaine has intrinsic vasoconstrictor properties. However, few pharmacokinetic data are available on the addition of epinephrine to epidural ropivacaine in humans. In this prospective, double-blinded study, we randomized patients having elective abdominal hysterectomy to receive epidural ropivacaine 1.5 mg/kg, diluted in 15 mL, either with (epinephrine group, n = 12) or without (plain group, n = 12) epinephrine 5 microg/mL and then measured arterial and venous plasma concentrations of ropivacaine at intervals up to 180 min. We found that arterial and venous plasma ropivacaine concentrations were smaller in the epinephrine group compared with the plain group in the first 60 min after the drug administration (P < 0.01). Mean (+/- SD) maximum total plasma ropivacaine concentration was smaller in the epinephrine group (arterial, 0.92 +/- 0.32 microg/mL; venous, 0.82 +/- 0.33 microg/mL) compared with the plain group (1.31 +/- 0.39 microg/mL and 1.31 +/- 0.50 microg/mL, respectively; P = 0.01). Time to maximum total plasma ropivacaine concentration was not significantly different between groups (mean +/- SD; arterial, 16 +/- 2 min; venous, 23 +/- 2 min in the epinephrine group versus 9 +/- 2 min and 12 +/- 3 min, respectively, in the plain group; P = 0.08). Arterial plasma ropivacaine concentrations were larger than venous concentrations during the first hour (P < 0.01); the arterio-venous difference decreased exponentially, and the rate and magnitude of this decrease was unaffected by epinephrine. We conclude that the addition of epinephrine 5 microg/mL to ropivacaine reduced the early systemic plasma concentrations of ropivacaine after epidural injection and may be useful for decreasing the risk of toxicity from systemic absorption of epidural ropivacaine., Implications: The addition of epinephrine 5 microg/mL to epidural ropivacaine reduced the systemic arterial and venous plasma concentrations of ropivacaine in the first hour and the maximum plasma concentration of ropivacaine. Epinephrine may be a useful additive for reducing the risk of systemic toxicity when large doses of ropivacaine are given epidurally.

Background: The optimal inspired oxygen fraction FI(O(2)) for fetal oxygenation during general anaesthesia for Caesarean section is not known., Methods: We randomized patients having elective Caesarean section to receive one of the following: FI(O(2)) 0.3, FI(N(2))(O) 0.7 and end-tidal sevoflurane 0.6% (Group 30, n=20); FI(O(2)) 0.5, FI(N(2))(O) 0.5 and end-tidal sevoflurane 1.0% (Group 50, n=20), or FI(O(2)) 1.0 and end-tidal sevoflurane 2.0% (Group 100, n=20) until delivery. Neonatal outcome was compared biochemically and clinically., Results: At delivery, for umbilical venous blood, mean PO(2) was greater in Group 100 (7.6 (SD 3.7) kPa) compared with both Group 30 (4.0 (1.1) kPa, P<0.0001) and Group 50 (4.7 (0.9) kPa, P=0.002) and oxygen content was greater in Group 100 (17.2 (1.6) ml dl(-1)) compared with both Group 30 (12.8 (3.6) ml dl(-1), P=0.0001) and Group 50 (13.8 (2.6) ml dl(-1), P=0.0001). For umbilical arterial blood, PO(2) was greater in Group 100 (3.2 (0.4) kPa) compared with Group 30 (2.4 (0.7) kPa, P=0.003), and in Group 50 (2.9 (0.8) kPa) compared with Group 30 (2.4 (0.7) kPa, P=0.04); oxygen content was greater in Group 100 (10.8 (3.5) ml dl(-1)) than in Group 30 (7.0 (3.0) ml dl(-1), P<0.01). Apgar scores, neonatal neurologic and adaptive capacity scores, and maternal arterial plasma concentrations of epinephrine and norepinephrine before induction and at delivery were similar among groups. No patient reported intraoperative awareness., Conclusions: Use of FI(O(2)) 1.0 during general anaesthesia for elective Caesarean section increased fetal oxygenation.

Unlabelled: This quantitative systematic review compared the efficacy and safety of ephedrine with phenylephrine for the prevention and treatment of hypotension during spinal anesthesia for cesarean delivery. Seven randomized controlled trials (n = 292) were identified after a systematic search of electronic databases (MEDLINE, EMBASE, The Cochrane Controlled Trials Registry), published articles, and contact with authors. Outcomes assessed were maternal hypotension, hypertension and bradycardia, and neonatal umbilical cord blood pH values and Apgar scores. For the management (prevention and treatment) of maternal hypotension, there was no difference between phenylephrine and ephedrine (relative risk [RR] of 1.00; 95% confidence interval [CI], 0.96-1.06). Maternal bradycardia was more likely to occur with phenylephrine than with ephedrine (RR of 4.79; 95% CI, 1.47-15.60). Women given phenylephrine had neonates with higher umbilical arterial pH values than those given ephedrine (weighted mean difference of 0.03; 95% CI, 0.02-0.04). There was no difference between the two vasopressors in the incidence of true fetal acidosis (umbilical arterial pH value of <7.2; RR of 0.78; 95% CI, 0.16-3.92) or Apgar score of <7 at 1 and 5 min. This systematic review does not support the traditional idea that ephedrine is the preferred choice for the management of maternal hypotension during spinal anesthesia for elective cesarean delivery in healthy, nonlaboring women., Implications: Phenylephrine and ephedrine to manage hypotension during spinal anesthesia for elective cesarean delivery were compared in this systematic review. Women given ephedrine had neonates with lower umbilical cord blood pH values compared with those given phenylephrine. However, no differences in the incidence of fetal acidosis (pH value of <7.2) or neonatal Apgar scores were found.

Unlabelled: We compared, in this prospective, randomized, double-blinded study, the characteristics of spinal anesthesia with plain and hyperbaric ropivacaine for elective cesarean delivery. We hypothesized that the addition of glucose would change the onset, offset, and extent of motor and sensory block from intrathecal ropivacaine. Forty ASA physical status I--II women were given 25 mg of either ropivacaine (n = 20) or ropivacaine in 8.3% glucose (n = 20) intrathecally, via a combined spinal/epidural technique in the right lateral position. Sensory changes to ice and pinprick and motor block (Bromage score) were recorded at 2.5-min intervals. Adequate anesthesia for surgery was achieved in all patients in the Hyperbaric group, whereas in the Plain group, five (25%) patients required epidural top-up because of insufficient rostral spread (P < 0.05). With hyperbaric ropivacaine, we found the following: higher cephalic spread (median [range] maximum block height to pinprick, T1 [T4 to C2] versus T3 [T11 to C3], P < 0.001); lower coefficient of variation of maximum block height (17.7% vs 21.9%); faster onset to T4 dermatome (mean [SD] 7.7 [4.9] vs 16.4 [14.1] min, P = 0.015); and faster recovery to L1 (189.0 [29.6] vs 215.5 [27.0] min, P = 0.01). The onset of complete motor block (9.9 [5.3] vs 13.8 [5.4] min, P = 0.027) and complete recovery (144.8 [28.4] vs 218.5 [56.8] min, P < 0.001) was also faster. No neurologic symptoms were found at 24 h., Implications: We compared hyperbaric and plain ropivacaine for combined spinal/epidural analgesia in the lateral position in patients undergoing elective cesarean delivery. Hyperbaric ropivacaine produced more rapid block with faster recovery and less requirement for epidural supplementation compared with plain ropivacaine.