Ephedrine versus phenylephrine as a vasopressor for spinal anaesthesia-induced hypotension in parturients undergoing high-risk caesarean section: meta-analysis, meta-regression and trial sequential analysis.

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.

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.

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.

Multi-dimensional response-probability-dose curves for bupivacaine and ropivacaine epidural labour analgesia.

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.

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.

Haemodynamic effects from aortocaval compression at different angles of lateral tilt in non-labouring term pregnant women.

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.

Sonoanatomy relevant for ultrasound-guided central neuraxial blocks via the paramedian approach in the lumbar region.

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.

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.

Fentanyl dosage and timing when inserting the laryngeal mask airway.

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.

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.

Ultrasound-guided lumbar plexus block through the acoustic window of the lumbar ultrasound trident.

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.

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.

Fentanyl dose-response curves when inserting the LMA Classic laryngeal mask airway.

Probit analysis was used to predict an optimal dose of fentanyl, co-administered with propofol 2.5 mg.kg(-1), when inserting the laryngeal mask airway. In all, 21 male and 54 female healthy Chinese patients, aged 18-63 years, requiring anaesthesia for minor surgery were recruited. They were assigned to one of five groups: placebo, 0.5, 1.0, 1.5 and 2.0 microg.kg(-1). Insertion was performed 90 s after administration and insertion conditions assessed using a six-category score. Dose-response curves could only be drawn for swallowing and movement categories, and only the ED(50) could be predicted with certainty. To provide optimal conditions in over 95% of patients, fentanyl doses well above the clinical range were required. A standard fentanyl dose of 1 mug.kg(-1), co-administered with propofol 2.5 mg.kg(-1), provided optimal conditions in 65% of cases. Ninety seconds may have been insufficient time for fentanyl to reach its peak effect.

A randomised double-blinded controlled trial of the effect of diluent volume on the efficacy of a single dose of epidural ropivacaine for labour analgesia.

BACKGROUND: Few studies have systematically investigated the effect of diluent volume on the efficacy of epidural local anaesthetics for labour analgesia and no data are available for ropivacaine. Our aim was to compare epidural ropivacaine given in three different volumes for labour analgesia. METHODS: In a double-blinded study, we randomly assigned 60 labouring parturients with cervical dilatation <5 cm to receive epidural ropivacaine 30 mg diluted to 5 mL (group 5, n=20), 10 mL (group 10, n=20) or 20 mL (group 20, n=20) for analgesia. We measured visual analogue scale pain scores at the peak of contraction for 30 min plus onset and duration of analgesia. RESULTS: Pain scores at 30 min were similar among group 5 (median 22 [interquartile range 0-44] mm), group 10 (9 [0-21] mm) and group 20 (37 [0-51] mm), P=0.35. The number of patients who achieved a decrease in pain score to < or =30% of baseline was similar among group 5 (12/20 (60%)), group 10 (17/20 (85%)) and group 20 (11/19 (58%)), P=0.13. Onset and duration of analgesia, the incidence of motor block and patient satisfaction were similar among groups. CONCLUSIONS: Under the conditions of this study, within the range of 5-20 mL, the volume and concentration were not significant factors influencing the efficacy of a single 30-mg bolus of epidural ropivacaine given for labour analgesia. This suggests that the most important factor influencing analgesic efficacy was drug mass.

Randomized double-blind comparison of ropivacaine-fentanyl and bupivacaine-fentanyl for spinal anaesthesia for urological surgery.

BACKGROUND: Early studies have suggested that ropivacaine causes less motor block than bupivacaine, which might be advantageous in spinal anaesthesia for short procedures. The aim of this study was to compare plain ropivacaine 10 mg and plain bupivacaine 10 mg, both with fentanyl 15 microg, for spinal anaesthesia in urological surgery. METHODS: This was a prospective randomized double-blind study. After written informed consent had been obtained, 34 ASA I-III patients scheduled for urological surgery were randomly assigned to receive intrathecal injection of either plain ropivacaine 10 mg with fentanyl 15 microg (ropivacaine group) or plain bupivacaine 10 mg with fentanyl 15 microg (bupivacaine group) using a combined spinal-epidural technique. RESULTS: All patients achieved sensory block to the T10 dermatome or higher at 15 min after intrathecal injection. One patient in the ropivacaine group was excluded because of unexpectedly prolonged surgery. The primary outcome, the duration of motor block, was shorter in the ropivacaine group (median, 126 min; interquartile range, 93-162 min) compared with the bupivacaine group (median, 189 min; interquartile range, 157-234 min; difference between medians, 71 min; 95% confidence interval, 28-109 min; P = 0.003). The duration of complete motor block was also shorter in the ropivacaine group compared with the bupivacaine group. There was no difference in the onset time of motor block. The characteristics of sensory block and the haemodynamic changes were similar between the groups. CONCLUSION: Plain ropivacaine 10 mg plus fentanyl 15 microg provided similar sensory anaesthesia, but with a shorter duration of motor block, compared with plain bupivacaine 10 mg plus fentanyl 15 microg when used for spinal anaesthesia in urological surgery.