The combined spinal-epidural technique is becoming

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1 Does the Baricity of Bupivacaine Influence Intrathecal Spread in the Prolonged Sitting Position Before Elective Cesarean Delivery? A Prospective Randomized Controlled Study Christian Loubert, FRCPC,* Stephen Hallworth, FRCA, Roshan Fernando, FRCA,* Malachy Columb, FRCA, Nisa Patel, FRCA,* Kavita Sarang, FRCA, and Vinnie Sodhi, FRCA BACKGROUND: Difficulties in inserting an epidural catheter while performing combined spinalepidural anesthesia for cesarean delivery may lead to undue delays between the spinal injection of the local anesthetic mixture and the adoption of the supine position with lateral tilt. We hypothesized that this delay may affect the intrathecal distribution of local anesthetic of different baricities such that hypobaric local anesthetic would lead to a higher sensory block level. METHODS: Healthy parturients with uncomplicated pregnancies undergoing elective cesarean delivery under combined spinal-epidural anesthesia were enrolled in this prospective doubleblind randomized controlled trial. The subjects were allocated to receive hyperbaric (hyperbaric group), isobaric (isobaric group), or hypobaric (hypobaric group) spinal bupivacaine 10 mg. After the spinal injection, the subjects remained in the sitting position for 5 minutes (to simulate difficulty in inserting the epidural catheter) before being helped into the supine lateral tilt position. The primary outcome was the sensory block level during the 25 minutes after the spinal injection. Other end points included motor block score, maternal hypotension, and vasopressor requirements. RESULTS: Data from 89 patients were analyzed. Patient characteristics were similar in all groups. The median [interquartile range] (95% confidence interval) sensory levels after spinal injection were significantly higher with decreasing baricity: hyperbaric T10 [T11-8] (T10-9), isobaric T9 [T10-7] (T9-7), and hypobaric T6 [T8-4] (T8-5) (P 0.001, Cuzick trend). All patients in the hypobaric group reached a sensory block level of T4 at 25 minutes after spinal injection compared with 80% of the patients in both the isobaric and hyperbaric groups (P 0.04; difference 20%, 95% confidence interval of difference 4% 33%). Significantly more patients in the hypobaric group had complete lower limb motor block (Bromage score 4) (hyperbaric 43%, isobaric 63%, and hypobaric 90%; P 0.001). The incidences of maternal hypotension and nausea and vomiting were similar among groups, although the ephedrine requirements were significantly increased in the isobaric and hypobaric groups by factors of 1.83 and 3.0, respectively, compared with the hyperbaric group (P 0.001, Cuzick trend). CONCLUSIONS: We demonstrated that when parturients undergoing cesarean delivery were maintained in the sitting position for 5 minutes after spinal injection of the local anesthetic, hypobaric bupivacaine resulted in sensory block levels that were higher compared with isobaric and hyperbaric bupivacaine, respectively, during the study period. (Anesth Analg 2011;113:811 7) The combined spinal-epidural technique is becoming increasingly popular to provide anesthesia for cesarean delivery. The epidural catheter can be used to provide additional anesthesia when the spinal component fails to achieve an adequate anesthetic level, or should the surgery be unexpectedly prolonged. 1,2 However, one of the From the *Department of Anesthetics, University College London Hospital; Department of Anesthetics, Royal London Hospital, London; Department of Anesthesia, University Hospital of South Manchester NHS Foundation Trust, Wythenshawe, Manchester; Department of Anesthetics, The Lister Hospital; and Department of Anaesthetics, Queen Charlotte s and Chelsea Hospital, Imperial College Healthcare NHS Trust, London, United Kingdom. Accepted for publication May 31, Study funding is listed at the end of the article. The authors declare no conflicts of interest. Reprints will not be available from the authors. Address correspondence to Roshan Fernando, FRCA, Department of Anesthetics, University College London Hospital, 235 Euston Rd., London, NW1 2BU, UK. Address to r.fernando@btinternet.com. Copyright 2011 International Anesthesia Research Society DOI: /ANE.0b013e bf2 criticisms of the combined spinal-epidural technique is that it is more technically difficult than performing a single-shot spinal. This may be attributable to difficulty in threading the catheter into the epidural space, 2 to paresthesias, or to accidental intravascular insertion of the catheter into an epidural vein, requiring resiting of the epidural catheter. Because the sitting position is frequently used for induction of spinal anesthesia, hyperbaric solutions, under the influence of gravity, would be expected to spread caudally, whereas hypobaric solutions would be expected to distribute rostrally. 3 If there is undue delay in siting the epidural catheter, hyperbaric local anesthetic may fail to spread adequately in a timely manner and ultimately may result in inadequate surgical anesthesia. The aim of our study was to assess the effect of gravity on the spread of local anesthetic solutions of different baricities when a combined spinal-epidural technique performed in the sitting position is prolonged because of technical difficulties. We simulated difficulty in siting the epidural catheter by keeping the patient in the upright October 2011 Volume 113 Number

2 Influence of Baricity of Bupivacaine on Intrathecal Spread position for 5 minutes after the spinal injection. We hypothesized that hyperbaric local anesthetic would result in a significantly lower block level than isobaric or hypobaric local anesthetic. METHODS After receiving ethics committee (Royal Free Hampstead NHS Trust, London, UK) approval and written informed consent from all subjects, 90 ASA physical status I or II patients scheduled for elective cesarean delivery under neuraxial anesthesia were recruited, from June 2001 to March 2002, into this prospective randomized double-blind study. Exclusion criteria included age younger than 16 years, height 150 cm or 180 cm, weight 50 kg or 100 kg, bleeding disorders, pregnancy-related hypertensive disease, cardiovascular disease or cardiac medication, gestational age 36 weeks, active labor, and infection at the site of injection. The subjects were randomized by means of a computergenerated random number table into 1 of 3 groups. Preprinted sheets within sealed opaque envelopes contained information on group allocation. Patients were allocated to receive hyperbaric, isobaric, or hypobaric bupivacaine solutions (see below) with spinal anesthesia induced in the sitting position. The densities of the 3 solutions were determined at 37 C ( 0.01 C) using a density meter (DMA 450; Paar Scientific Ltd., London, UK) accurate to g/ml, which had been validated in a previous study. 4 The baricity of these solutions (spinal drug solution density relative to cerebrospinal fluid [CSF] density) were based on the results of a study by Richardson and Wissler 5 who found the mean (SD) density of term pregnant CSF to be ( ) g/ml. Three stock solutions were freshly prepared at the start of each day of the study. The hyperbaric solution was prepared by adding 8 ml of 0.5% wt/vol hyperbaric bupivacaine containing glucose 80 mg/ml (Marcain Heavy ; AstraZeneca, King s Langley, Herts, UK) to 1.2 ml (60 g) fentanyl (Evans, Leatherhead, Surrey, UK) and 0.8 ml of 5% wt/vol glucose (Macoflex ; Macopharma, Twickenham, Middlesex, UK). The isobaric solution was prepared by adding 8 ml plain bupivacaine 0.5% wt/vol (Antigen, Hillside, Southport, UK) to fentanyl 1.2 ml (60 g) and 0.8 ml of a solution taken from a mixture of 8 ml of 5% wt/vol dextrose solution and 2 ml of 0.9% saline. The hypobaric solution was prepared by adding 8 ml of 0.5% wt/vol plain bupivacaine to 1.2 ml (60 g) fentanyl and 0.8 ml of 0.9% saline. Each patient received an intrathecal injection of 2.5 ml of the allocated stock solution, which contained bupivacaine 10 mg and fentanyl 15 g. Before starting the study, the mean (SD) density of each stock solution was estimated using 5 separate density measurements, as described in a previous study. 4 The mean (SD) density of the hyperbaric, isobaric, and hypobaric solutions was ( ), ( ) and ( ) g/ml, respectively. To ensure that the procedure could be correctly blinded, one anesthesiologist (VS), blinded to treatment allocation, was responsible for performing the combined spinalepidural anesthesia and managing the anesthesia procedure. A technician opened the sealed envelope, distributed the appropriate anesthetic mixture to the blinded anesthesiologist, and then left the room. A second anesthesiologist, also unaware of patient group allocation, was responsible for preoperative and intraoperative data collection. All patients were unaware of group allocation. Each patient was premedicated with oral ranitidine 150 mg on the night before surgery, and ranitidine 150 mg with metoclopramide 10 mg orally 1 hour preoperatively. After initiation of routine monitoring, each patient was administered 1Lof0.9% saline via a 16-gauge cannula. Monitoring of electrocardiogram (initiated immediately after the combined spinal-epidural procedure), maternal heart rate, noninvasive arterial blood pressure, pulse oximetry, and cardiotocography was performed throughout the procedure. The combined spinal-epidural procedure was performed at the estimated L3-4 interspace using a midline approach in the sitting position; a 16-gauge Tuohy needle (Portex, Hythe, Kent, UK) was placed in the epidural space using the loss of resistance to saline technique (1 2 ml). A 27-gauge, 119-mm Whitacre spinal needle (Becton Dickinson, Franklin Lakes, NJ) was introduced through the epidural needle into the subarachnoid space and after observation of free CSF flow, 2.5 ml of the appropriate spinal solution was injected over 15 to 20 seconds. At the end of injection, CSF was aspirated to confirm accurate placement of the spinal needle in the subarachnoid space. The spinal needle was removed and an epidural catheter threaded through the Tuohy needle, such that 4 cm remained in the epidural space. The patient was kept in the sitting position for 5 minutes after the end of the spinal injection and then moved into the supine position with a 15 left lateral tilt. Oxygen at 4 L/min was administered if maternal hemoglobin saturation decreased below 96%. The primary outcome was the sensory block level to cold during the 25 minutes after the spinal injection. The block level was assessed bilaterally at the midclavicular line beginning from the feet in a cephalad direction. The lowest dermatome where the patient felt a cold sensation to ethyl chloride spray determined the sensory level. Secondary outcome measures included sensory block level to cold sensation at 10, 15, and 20 minutes after the spinal injection, and lower limb motor block assessed using a modified Bromage score (1 able to raise legs above table, 2 able to flex knees, 3 able to move feet only, and 4 no movement in legs or feet). The first assessments were made 5 minutes after the patient was placed in the supine position (10 minutes after spinal injection). All subsequent assessments were made at 5-minute intervals for a total of 20 minutes. Failure of block was defined as a maximal sensory level (using loss of cold sensation) below T4 at 25 minutes after spinal injection. In such cases, incremental 5-mL boluses of 0.5% wt/vol bupivacaine were administered through the epidural catheter. The first injection was given at 25 minutes after spinal injection and then at 10-minute intervals to achieve a sensory level to T4. The use of intraoperative supplementation for discomfort was noted and included treatment with incremental 5-mL boluses of bupivacaine 0.5% wt/vol via the epidural catheter, ANESTHESIA & ANALGESIA

3 incremental 25- g boluses of IV fentanyl, or induction of general anesthesia. Additional data collected included maternal blood pressure noted every 2.5 minutes from spinal injection to delivery of the fetus and the incidence of nausea and vomiting. Hypotension (a systolic blood pressure below 90 mm Hg or a 25% decrease below baseline values) or nausea and vomiting (not related to surgical stimulation) were treated with IV boluses of ephedrine 6 mg. Neonatal condition was assessed using Apgar scores and umbilical cord blood gases. The study ended at delivery of the fetus. Data are reported as mean (SD), median [interquartile range], and count as appropriate. The effect of baricity on sensory level during the study period (10 25 minutes after the spinal injection) was examined using Kruskal-Wallis 1-way analysis. Other outcome data, such as continuous Gaussian and categorical, were examined using 1-way analysis of variance and 2 tests for independence, respectively. Posttests included Dunn after Kruskal-Wallis analysis, Tukey-Kramer for continuous Gaussian data, Bonferroni corrections for categorical data, and Cuzick trend test. Significance was defined at P 0.05 (2-tailed). Analyses were performed using Number Cruncher Statistical Systems 2007 (NCSS, Inc., Kaysville, UT) and StatsDirect (StatsDirect Ltd., Altrincham, UK). The sample size estimates were based on detecting a difference of 2 (SD 2) dermatomes among groups at 80% power. Because there were 3 possible comparisons, a Bonferroni correction was applied (P 0.017) to keep the overall significance at P Table 1. Patient Characteristics Hyperbaric (n 30) Isobaric (n 30) Hypobaric (n 29) Age (y) Weight (kg) Height (cm) Gestational age (d) All values are expressed as mean SD. There are no differences among groups for all comparisons. A minimum of n 23 patients per group was required assuming a Gaussian distribution, and n 26 to allow for analysis using ranking methods. For the purposes of the study, n 30 were enrolled in each of the 3 groups. RESULTS The groups were similar regarding maternal age, height, weight, and gestational age (Table 1). One patient in the hypobaric group was excluded because she withdrew consent after induction of anesthesia (Fig. 1). Results for block characteristics, intraoperative supplementation, incidence of maternal hypotension, and vasopressor requirements are shown in Table 2. Figure 2 shows the evolution of the sensory block height in relation to time after spinal injection. There were significant effects (P 0.001, Kruskal- Wallis test) of baricity on sensory block heights during the study period. The median [interquartile range] (95% confidence interval [CI]) sensory levels after spinal injection were significantly higher with decreasing baricity: hyperbaric T10 [T11-8] (T10-9), isobaric T9 [T10-7] (T9-7), and hypobaric T6 [T8-4] (T8-5) (P 0.001, Cuzick trend). Hypobaric bupivacaine resulted in sensory block levels during the study period that were 2.5 (95% CI, ) and 3.6 (95% CI, ) dermatomes higher compared with isobaric and hyperbaric bupivacaine, respectively. At all time points, block height in the hypobaric group was significantly higher than in the 2 other groups (P 0.049). Sensory level was also significantly higher at 10 minutes after spinal injection in the isobaric than in the hyperbaric group, but there was no statistical difference between these 2 groups at any following time point. When considering only the time when the patients were in the supine position (from 10 to 25 minutes after injection), the sensory block spread over 11 segments in the hyperbaric group, 10 segments in the isobaric groups, and 4 segments in the hypobaric group (P 0.06, Kruskal-Wallis test). All patients (100%) in the hypobaric group reached a sensory block level of T4 (threshold for success rate) at 25 Figure 1. CONSORT (Consolidated Standards of Reporting Trials) 2010 flow diagram. October 2011 Volume 113 Number

4 Influence of Baricity of Bupivacaine on Intrathecal Spread Table 2. Block Characteristics and Side Effects Hyperbaric (n 30) Isobaric (n 30) Hypobaric (n 29) P values T4 level at 25 min after spinal injection* 24 (80%) 24 (80%) 29 (100%) 0.04 Cervical sensory block at 25 min after spinal injection 0 (0%) 3 (10%) 7 (24%) 0.01 Bromage score 4 at 25 min after spinal injection* 13 (43%) 19 (63%) 26 (90%) Intraoperative supplementation a 5 (17%) 5 (17%) 2 (7%) 0.41 Hypotension b 20 (67%) 24 (80%) 24 (83%) 0.09 Nausea or vomiting 7 (23%) 15 (50%) 14 (48%) 0.06 Hypotension, nausea or vomiting 19 (63%) 23 (77%) 24 (83%) 0.22 Ephedrine (mg) Data are presented as count (%) or median interquartile range and were analyzed using Kruskal-Wallis 1-way analysis or 2 test for independence, respectively, with Bonferroni corrections for group comparisons. a Intraoperative supplementation for discomfort included treatment with incremental 5-mL boluses of bupivacaine 0.5% wt/vol via the epidural catheter, incremental 25- g boluses of IV fentanyl or induction of general anesthesia. b Hypotension defined as a systolic blood pressure 90 mm Hg or a 25% decrease below baseline values. *Hypobaric group different from isobaric and hyperbaric groups. Hypobaric group different from hyperbaric group. Figure 2. Box plot of sensory block dermatomes. The solid line represents median sensory block height, the box represents the interquartile range, and the dots represent values outside the interquartile range. The dashed line indicates the defined threshold for successful sensory block level (T4). Table 3. Neonatal Data Hyperbaric (n 30) Isobaric (n 30) Hypobaric (n 29) P value Umbilical artery ph Umbilical ph min Apgar score min Apgar score Data are expressed as mean SD or median interquartile range and were analyzed using 1-way analysis of variance or Kruskal-Wallis 1-way analysis, respectively. minutes after spinal injection, compared with 80% of the patients in both the isobaric and hyperbaric groups (P 0.04, 2 test; difference 20%, 95% CI of difference 4% 33%). Adequate surgical anesthesia was successfully provided with 1 to 2 epidural boluses in all patients and no general anesthetic was required. Median sensory block level at 25 minutes after spinal injection reached the cervical dermatomes in 24% of patients in the hypobaric group as compared with 10% and 0% of those in the isobaric group and hyperbaric groups, respectively (P 0.01, 2 test), but no patient reported breathing discomfort or upper extremity motor block as a result of these blocks. The incidences of hypotension, nausea and vomiting, and the combined incidence of hypotension and nausea and vomiting were similar among groups. Median ephedrine dose requirements were significantly (P 0.001, Cuzick trend) increased in the isobaric and hypobaric groups by factors of 1.83 and 3.0, respectively, compared 4 with the hyperbaric group (Table 2). The Apgar scores were similar among the groups (Table 3). One neonate in the hyperbaric group and 2 neonates in the isobaric group had 1-minute Apgar scores 7, but all newborns recovered rapidly (Apgar score 9 at 5 minutes) ANESTHESIA & ANALGESIA

5 DISCUSSION To assess the effect of gravity on the distribution of bupivacaine solutions of different baricities, the subjects in our study were maintained in the sitting position for 5 minutes after the spinal injection before being placed in the supine lateral tilt position. The important finding of this study was that there was a significant trend toward higher cephalad spread of local anesthetic with lower baricity. This prolonged upright position most likely favored the migration of hyperbaric bupivacaine caudally in contrast to the cephalad migration of hypobaric bupivacaine. Our results also show that all patients in the hypobaric group reached a sensory block level of T4 (threshold for success rate) at 25 minutes after spinal injection, compared with 80% of the patients in both the isobaric and hyperbaric groups. Interestingly, when the patients were in the supine position, the extent of the cephalad progression was greater in the hyperbaric group than in the 2 other groups, although this difference was not statistically significant. However, because the progression of the block started from a lower median height at 10 minutes in the hyperbaric group, the sensory block level in these subjects remained lower at 25 minutes after injection. These observations may be explained by 3 main factors. First, the interaction between patient position and local anesthetic baricity at the time of spinal injection is significant. Hallworth et al. 6 and Richardson et al. 7 demonstrated that when pregnant women are sitting during spinal injection, the spread of the local anesthetic solutions behaved as described by Stienstra et al., 3 that is, solutions of higher baricity tend to follow gravity whereas those of lower baricity migrate in the opposite direction. In their studies, the authors did not observe a difference in sensory block height between hyperbaric and hypobaric solutions when injected in patients lying in the lateral position during the spinal anesthesia induction. Second, in pregnancy, adopting the supine position, even with left lateral tilt, causes inferior vena caval compression, which in turn results in an engorgement of the epidural venous plexus. 8,9 The consequent dural sac compression may facilitate bulk movement of drugs injected into the CSF and could explain the cephalad progression of not only the isobaric bupivacaine, but of the hypobaric and hyperbaric solutions as well. 10,11 Indeed, our results show that all 3 solutions of different baricities migrated in the same direction (cephalad) from the first to the last time points. Third, Hirabayashi et al. 12 have shown that when term pregnant women are lying in the supine position, the natural lordosis of the spine is displaced in a caudad direction, and the thoracic kyphosis is reduced. However, the maximum angle of decline of the lumbar spinal canal is similar in the pregnant and nonpregnant populations (12.4 vs 13.4, respectively), with the highest point being at the lumbar level and the lowest point at the thoracic level. When the patients are in the supine position, this angle favors the cephalad spread of the hyperbaric bupivacaine as opposed to the hypobaric and isobaric solutions. This may explain the trend toward extension from the lumbar to high thoracic dermatomes of the sensory level of the hyperbaric solution from 10 to 25 minutes after spinal injection. The influence of baricity on the sensory block level may have clinical implications when patients are kept upright after the intrathecal injection. We defined failure of block as an absence of sensory block to cold sensation at the level of T4 at 25 minutes after the spinal injection. We found that all patients in the hypobaric group were successfully blocked whereas the failure rate was 20% in both the hyperbaric and isobaric groups. Moreover, at all time points, a significantly larger proportion of patients in the hypobaric groups than in the 2 other groups reached a sensory block to T4. These results suggest that patients in the hypobaric group were ready earlier for surgical incision. A corollary of this higher success rate in the hypobaric group lies in the greater number of high (cervical) blocks in these patients, indicating a high spread of local anesthetic within the subarachnoid space. In contrast, the hyperbaric solution did not result in cervical sensory levels, but was associated with a higher failure rate at 25 minutes after spinal injection. It is noteworthy that no patient who demonstrated cervical anesthesia developed breathing difficulties, discomfort, or upper extremity motor block as a result of the high block. One should bear in mind, however, that our study is underpowered to identify potential adverse events associated with cervical level blocks. Significantly more patients in the hypobaric group presented with complete motor block (Bromage score of 4) than in the isobaric and hyperbaric groups. This corroborates previous results from Hallworth et al. 6 who observed the same trend between the baricity of bupivacaine and motor block. Several authors, however, have not demonstrated such an association. It is possible that low local anesthetic doses, such as those studied by Vercauteren et al. 13 (bupivacaine 6.6 mg with sufentanil 3.3 g) would fail to result in a complete motor block, regardless of the baricity of the local anesthetic. We also hypothesize that maintaining patients in the sitting position for 5 minutes leads to a pooling of a significant amount of hyperbaric bupivacaine in the sacral region of the dural sac. Upon assuming the wedged supine position, it is possible that a significant proportion of this local anesthetic is entrapped in the sacral area because of the lordotic curvature of the lumbar spine. Consequently, a smaller amount of hyperbaric versus iso- or hypobaric bupivacaine would migrate rostrally and contribute to sensory and motor blockade. Not only might this pooling phenomenon explain the lower incidence of complete motor block in the hyperbaric group (and to a lesser extent in the isobaric group), it could also partly contribute to the observed failure to reach an adequate sensory block in 20% of our patients in the hyperbaric and isobaric groups. It should be noted that the dose of bupivacaine used in our study was 10 mg. Ginosar et al. 17 found the 95% effective dose of hyperbaric bupivacaine with fentanyl 10 g and morphine 200 g injected as part of a combined spinal-epidural technique to be 11 mg. Carvalho et al. 18 found the 95% effective dose of isobaric bupivacaine to be 13 mg (plain bupivacaine combined with fentanyl 10 g and morphine 200 g, which results in a slightly hypobaric October 2011 Volume 113 Number

6 Influence of Baricity of Bupivacaine on Intrathecal Spread solution). It is possible that, had we used a higher bupivacaine dose, our sensory block failure rate might have been lower and, as described by Ginosar et al., 17 the block speed of onset anesthesia might have been faster. The time taken to perform the combined spinal-epidural procedure, to wait until an adequate level of analgesia was achieved, and then top up the epidural catheter was 30 minutes in 20% of our patients in the hyperbaric and isobaric groups. Although most clinicians would not wait 25 minutes after inadequate spinal anesthesia before injecting supplemental local anesthetics in the epidural space, difficult or even impossible catheter placement might delay the adoption of the supine position and preclude presurgical supplementation. In this instance, if the anesthesiologist had injected a hypobaric solution, he or she might feel more inclined to abandon the epidural component of a combined spinal-epidural technique and rely on what is effectively a single-shot spinal anesthetic. Indeed, our results suggest that in such a situation, hypobaric local anesthetic might provide a higher success rate in a shorter time interval than hyperbaric or isobaric bupivacaine. Hypotension is common after spinal anesthesia. The significant difference in ephedrine usage but not in the incidence of hypotension is explained by the fact that we treated the symptoms of hypotension (usually nausea and vomiting) immediately, sometimes even before we were able to obtain a blood pressure measurement. By the time the blood pressure was measured, the ephedrine had been administered. The apparent greater influence of hypobaric bupivacaine on maternal hypotension (reflected by a larger ephedrine requirement) observed in our study was likely the result of more cephalad blockade in the hypobaric group compared with the 2 other groups. Indeed, spinal block height is a well-recognized risk factor for hypotension. 19,20 In conclusion, we demonstrated that when parturients undergoing cesarean delivery under combined spinalepidural anesthesia were maintained in the sitting position for 5 minutes after spinal injection of the local anesthetic, hypobaric bupivacaine resulted in a higher sensory block level at 25 minutes and a higher rate of successful sensory block (minimum T4 level) than isobaric or hyperbaric bupivacaine. However, this benefit was obtained at the cost of an increased incidence of cervical dermatome blockade and higher consumption of ephedrine, reflecting an increased incidence of maternal hypotension. These results may have clinical implications in patients in whom there is difficulty siting the epidural catheter during initiation of combined spinal-epidural anesthesia in the sitting position. STUDY FUNDING Dr. Fernando was supported by the University College London Hospitals/University College London Comprehensive Biomedical Research Centre, which receives a proportion of funding from the United Kingdom Department of Health s National Institute of Health research (NIHR) Biomedical Research Center s funding scheme. Dr. Vinnie Sodhi and Dr. Steve Hallworth were supported by a research fellowship grant from Portex UK, Ltd., Hythe, Kent, UK. Dr. Vinnie Sodhi also acknowledges the support of the UK NIHR Comprehensive Biomedical Research Centre Scheme. Dr. Nisa Patel was supported by a research fellowship grant from the Obstetric Anaesthetists Association, London, UK (registered charity ). DISCLOSURES Name: Christian Loubert, FRCPC. Contribution: This author helped analyze the data and write the manuscript. Attestation: Christian Loubert has seen the original study data and approved the final manuscript. Name: Stephen Hallworth, FRCA. Contribution: This author helped design the study, conduct the study, analyze the data, and write the manuscript. Attestation: Stephen Hallworth has seen the original study data, reviewed the analysis of the data, and approved the final manuscript. Name: Roshan Fernando, FRCA. Contribution: This author helped design the study, conduct the study, analyze the data, and write the manuscript. Attestation: Roshan Fernando has seen the original study data, reviewed the analysis of the data, approved the final manuscript, and is the author responsible for archiving the study files. Name: Malachy Columb, FRCA. Contribution: This author helped design the study and analyze the data. Attestation: Malachy Columb has seen the original study data, reviewed the analysis of the data, and approved the final manuscript. Name: Nisa Patel, FRCA. Contribution: This author helped design the study and conduct the study. Attestation: Nisa Patel has seen the original study data, reviewed the analysis of the data, and approved the final manuscript. Name: Kavita Sarang, FRCA. Contribution: This author helped design the study and conduct the study. Attestation: Kavita Sarang has seen the original study data and approved the final manuscript. Name: Vinnie Sodhi, FRCA. Contribution: This author helped design the study, conduct the study and write the manuscript. Attestation: Vinnie Sodhi has seen the original study data and approved the final manuscript. This manuscript was handled by: Cynthia A. Wong, MD. REFERENCES 1. Crowhurst JA, Birnbach DJ. Small-dose neuraxial block: heading toward the new millennium. Anesth Analg 2000;90: Ranasinghe JS, Steadman J, Toyama T, Lai M. 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7 7. Richardson MG, Thakur R, Abramowicz JS, Wissler RN. Maternal posture influences the extent of sensory block produced by intrathecal dextrose-free bupivacaine with fentanyl for labor analgesia. Anesth Analg 1996;83: Hirabayashi Y, Shimizu R, Fukuda H, Saitoh K, Igarashi T. Effects of the pregnant uterus on the extradural venous plexus in the supine and lateral positions, as determined by magnetic resonance imaging. Br J Anaesth 1997;78: Takiguchi T, Yamaguchi S, Tezuka M, Furukawa N, Kitajima T. Compression of the subarachnoid space by the engorged epidural venous plexus in pregnant women. Anesthesiology 2006;105: Higuchi H, Hirata J, Adachi Y, Kazama T. Influence of lumbosacral cerebrospinal fluid density, velocity, and volume on extent and duration of plain bupivacaine spinal anesthesia. Anesthesiology 2004;100: Russell IF. Spinal anaesthesia for caesarean section: the use of 0.5% bupivacaine. Br J Anaesth 1983;55: Hirabayashi Y, Shimizu R, Fukuda H, Saitoh K, Furuse M. Anatomical configuration of the spinal column in the supine position. II. Comparison of pregnant and non-pregnant women. Br J Anaesth 1995;75: Vercauteren MP, Coppejans HC, Hoffmann VL, Saldien V, Adriaensen HA. Small-dose hyperbaric versus plain bupivacaine during spinal anesthesia for cesarean section. Anesth Analg 1998;86: Russell IF, Holmqvist EL. Subarachnoid analgesia for caesarean section: a double-blind comparison of plain and hyperbaric 0.5% bupivacaine. Br J Anaesth 1987;59: Kucukguclu S, Unlugenc H, Gunenc F, Kuvaki B, Gokmen N, Gunasti S, Guclu S, Yilmaz F, Isik G. The influence of epidural volume extension on spinal block with hyperbaric or plain bupivacaine for caesarean delivery. Eur J Anaesthesiol 2008;25: Gunaydin B, Tan ED. Intrathecal hyperbaric or isobaric bupivacaine and ropivacaine with fentanyl for elective caesarean section. J Matern Fetal Neonatal Med 2010;23: Ginosar Y, Mirikatani E, Drover DR, Cohen SE, Riley ET. ED50 and ED95 of intrathecal hyperbaric bupivacaine coadministered with opioids for cesarean delivery. Anesthesiology 2004;100: Carvalho B, Durbin M, Drover DR, Cohen SE, Ginosar Y, Riley ET. The ED50 and ED95 of intrathecal isobaric bupivacaine with opioids for cesarean delivery. Anesthesiology 2005;103: Brenck F, Hartmann B, Katzer C, Obaid R, Bruggmann D, Benson M, Rohrig R, Junger A. Hypotension after spinal anesthesia for cesarean section: identification of risk factors using an anesthesia information management system. J Clin Monit Comput 2009;23: Carpenter RL, Caplan RA, Brown DL, Stephenson C, Wu R. Incidence and risk factors for side effects of spinal anesthesia. Anesthesiology 1992;76: October 2011 Volume 113 Number