Randomized trial of anaesthetic interventions in external cephalic version for breech presentation.

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.

Randomized comparison of closed-loop feedback computer-controlled with manual-controlled infusion of phenylephrine for maintaining arterial pressure during spinal anaesthesia for caesarean delivery.

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.

Effects of different inspired oxygen fractions on lipid peroxidation during general anaesthesia for elective Caesarean section.

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.

Supplementary oxygen for emergency Caesarean section under regional anaesthesia.

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.

Randomised double-blinded comparison of phenylephrine vs ephedrine for maintaining blood pressure during spinal anaesthesia for non-elective Caesarean section*.

SUMMARY: In a randomised, double-blinded study, we compared boluses of phenylephrine 100 microg with ephedrine 10 mg for treating hypotension (systolic blood pressure < 100 mmHg) in 204 patients having non-elective Caesarean section under spinal anaesthesia. Umbilical arterial (UA) and venous (UV) pH and base excess were similar between groups. In the ephedrine group, UA lactate concentration was higher (median 2.6 [interquartile range 2.3-3.3] vs 2.4 [1.9-3.0] mmolxl(-1), p = 0.002) and UV lactate concentration was higher (2.5 [2.2-3.2] vs 2.3 [1.9-2.8] mmolxl(-1), p = 0.016) and more patients had nausea or vomiting (12.7% vs 3.9%, p = 0.02). Clinical neonatal outcome was similar. Of the protocol-compliant patients (n = 148), UA Po(2) and UV Po(2) were lower in the phenylephrine group although oxygen content was similar. We conclude that phenylephrine and ephedrine are both suitable vasopressors for use in non-elective Caesarean sections.

Closed-loop feedback computer-controlled infusion of phenylephrine for maintaining blood pressure during spinal anaesthesia for caesarean section: a preliminary descriptive study.

We describe the novel use of a closed-loop feedback computer-controlled infusion of phenylephrine for maintaining blood pressure in 53 patients having spinal anaesthesia for elective caesarean section. A simple on-off algorithm was used that activated an intravenous phenylephrine infusion at 100 microg.min(-1) when systolic blood pressure was less than or equal to baseline and stopped the infusion when systolic blood pressure exceeded baseline. Up to uterine incision, 94.6% of all systolic blood pressure measurements were within the range (baseline +/- 20%). Seven patients (13.2%) had one or more episodes of hypotension (systolic blood pressure < 80% of baseline) and 23 patients (37.7%) had one or more episodes of hypertension (systolic blood pressure > 120% of baseline). No patient had nausea or vomiting and in no case was umbilical arterial blood pH < 7.2. Calculated system performance parameters were comparable with those of previously published closed-loop systems and provide a reference for the potential development and comparison of more advanced algorithms.

Haemodynamic effects of glycopyrrolate pre-treatment before phenylephrine infusion during spinal anaesthesia for caesarean delivery.

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.

Comparison of phenylephrine infusion regimens for maintaining maternal blood pressure during spinal anaesthesia for Caesarean section.

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.

Metaraminol infusion for maintenance of arterial blood pressure during spinal anesthesia for cesarean delivery: the effect of a crystalloid bolus.

We randomly allocated women having elective cesarean delivery to receive either no bolus (Control Group, n = 31) or 20 mL/kg lactated Ringer's solution (Bolus Group, n = 35) IV before spinal anesthesia. An infusion of metaraminol started at 0.25 mg/min was titrated to maintain systolic arterial blood pressure in the target range 90%-100% of baseline. The total dose of metaraminol required up to the time of uterine incision was similar between the Control Group and the Bolus Group (3.62 +/- 1.20 vs 3.27 +/- 1.39 mg, P = 0.3). However, the Control Group required more metaraminol in the first 5 min (1.29 +/- 0.60 vs 0.96 +/- 0.58 mg, P = 0.025) and a faster maximum infusion rate (0.45 +/- 0.20 vs 0.32 +/- 0.13 mg/min, P = 0.002) compared with the Bolus Group. There was no difference between groups in regards to changes in systolic arterial blood pressure or heart rate over time, or maternal or neonatal outcome. We conclude that when metaraminol is used to maintain arterial pressure during spinal anesthesia for cesarean delivery, crystalloid bolus is not essential provided that sufficient vasopressor is given in the immediate postspinal period.

Synthesis and characterization of chiral N-O turns induced by alpha-aminoxy acids.

Chiral alpha-aminoxy acids of various side chains were synthesized with high optical purity starting from chiral alpha-amino acids. The conformations of diamides 13a-e, 15, and 16 were probed by using NMR, FT-IR, and CD spectroscopic methods as well as X-ray crystallography. The right-handed turns with eight-membered-ring intramolecular hydrogen bonds between adjacent residues (called the N-O turns) were found to be preferred for D-aminoxy acid residues, and they were independent of the side chains. The rigid chiral N-O turns should have great potential in molecular design.

Randomized controlled study of colloid preload before spinal anaesthesia for caesarean section.

We randomized women having elective Caesarean section to receive either no preload (control group, n=33) or 4% gelatin solution (Gelofusine) 15 ml kg(-1) (colloid group, n=35) i.v. before spinal anaesthesia. Intravenous metaraminol was titrated at 0.25-0.75 mg min(-1) to maintain systolic arterial pressure (SAP) in the target range 90-100% of baseline after the spinal injection. The control group required more vasopressor in the first 10 min [median 1.7 (range 0-2.9) mg vs 1.4 (0-2.8), P=0.02] at a greater maximum infusion rate [0.5 (0-0.75) vs 0.25 (0-0.5) mg min(-1), P=0.0005] and had a lower minimum SAP [90 (51-109) vs 101 (75-127) mm Hg, P=0.006] than the colloid group. Nausea was less frequent in the colloid group (6 vs 24%) but neonatal outcome was similar in the two groups. Colloid preload improved haemodynamic stability but did not affect neonatal outcome when arterial pressure was maintained with an infusion of metaraminol during spinal anaesthesia for Caesarean section.