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Table of Contents  
ORIGINAL ARTICLE
Year : 2019  |  Volume : 13  |  Issue : 4  |  Page : 663-668  

Large dose bupivacaine 0.5% versus small dose in elective cesarean section


Department of Anesthesia, Faculty of Medicine, Cairo University, Giza, Cairo, Egypt

Date of Submission26-Oct-2019
Date of Decision28-Oct-2019
Date of Acceptance16-Nov-2019
Date of Web Publication16-Dec-2019

Correspondence Address:
Hassan Mohamed Ali
Department of Anesthesia, Faculty of Medicine, Cairo University, Kasr Elaine Street, Giza, Cairo
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/aer.AER_131_19

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   Abstract 

Background and Aim: The spinal anesthesia in a cesarean section is still presenting a challenge to the anesthetist in the form of either severe hypotension from large bupivacaine dose or insufficient satisfactory anesthesia level conditions as a result of small bupivacaine dose. In this study, we tried to solve this challenge by increasing the dose of bupivacaine to achieve a proper spinal level accompanied by prolonged sitting up to avoid hypotension. Patients and Methods: We included 53 patients in this study whom were randomly divided into two groups, namely Group B and Group C. In Group B (25 patients), each patient received 3 mL of bupivacaine and left 5 min sitting up, whereas in Group C (28 patients), each patient received 2.5 mL of bupivacaine and was asked to lie supine immediately. Both groups were tested for hypotension, ephedrine dose, and sensory block level. Results: The present study showed a statistically significant lower dose of ephedrine which was given in Group B (7.2 ± 15.684 mg in Group B versus 27.86 ± 12.04 mg in Group C with P < 0.05). The proper anesthesia level was achieved equally in both groups. Conclusions: Large dose 15 mg of bupivacaine with the prolonged sitting position will lead to fewer incidences of hypotension and proper anesthesia block.

Keywords: Ephedrine, hypotension, spinal anesthesia


How to cite this article:
Ali HM, Ismail AA. Large dose bupivacaine 0.5% versus small dose in elective cesarean section. Anesth Essays Res 2019;13:663-8

How to cite this URL:
Ali HM, Ismail AA. Large dose bupivacaine 0.5% versus small dose in elective cesarean section. Anesth Essays Res [serial online] 2019 [cited 2020 Jul 11];13:663-8. Available from: http://www.aeronline.org/text.asp?2019/13/4/663/272975


   Introduction Top


Nowadays, spinal anesthesia is considered the standard technique in the cesarean sections. Similarly, the increased rate of cesarean sections, especially in Egypt, raises the concern about its problems and how to overcome.[1],[2]

Conventionally, the most frequent problem is the hypotension following intrathecal injection of bupivacaine, which ranges between 56% and 74% in the previous studies.[3],[4] To overcome this problem, many studies were directed to decrease the volume of bupivacaine, based on the fact that spinal anesthesia causing sympathectomy which subsequently will decrease the blood pressure. Unfortunately, all these studies were faced with the fact that decreasing the dose will lead to a lower block level and subsequently will lead to an unfavorable surgical condition along with the patient's discomfort. Moreover, it does not alter the incidence of hypotension raising the hypothesis that the hypotension cause is multi-factorial, and it may be greatly related to the great vessels compression by the uterus and increased intraabdominal pressure.[5],[6]

Other researchers have studied the effect of sitting posture to reduce the effect of hypotension relying on the second hypothesis of great vessel compression by the gravid uterus. Although they succeeded in reducing the incidence of hypotension, again on the cost of a low level of the spinal block that maybe not enough to a favorable surgical condition and may require supplementation with analgesia.[7]

Because of the above, we found that spinal anesthesia in an elective cesarean section depends on four pillars: the volume and dose of the local anesthetics, the level of the spinal block, the posture of the patient, and hypotension as a sequel of the spinal anesthesia and/or gravid uterus compression.

In this study, we hypothesized that a large dose of bupivacaine with prolonged sitting posture will achieve excellent surgical conditions (4th thoracic dermatome) with a lower incidence of hypotension.


   Patients and Methods Top


This is a prospective single-blindness randomized parallel study. Its registration number is NCT02937792 and its ethical committee approval number N36-2016. It is designed to include cases in two groups: one study Group B and one control Group C. Each group should have at least 25 female patients scheduled for an elective cesarean section with a total number of 50 cases.

After approval of the faculty ethical committee, any full-term pregnant female who was indicated for an elective section with spinal anesthesia and had unremarkable medical history (not diabetic, cardiac, hypertensive, coagulopathy, or psychotic), ASA I or II, with full-term singleton pregnancy and aged between 18 and 45 years were included after signing informed consent over a period from December 12, 2016 to March 23, 2017 in the Department of Obstetrics at the Faculty of Medicine, Cairo University in Egypt.

The exclusion criteria included the urgent cases, emergency cases, psychotic cases, failed spinal cases, surgical complicated cases, patients with associated pregnancy complications, patients with adverse medical history, patients on anticoagulant treatment, and patients with allergy to any of the drugs which were planned to be given or patients refused to participate in the study.

Patients, who agreed to the study, were randomized divided into two groups: Group B patients who received an intrathecal injection of 3 mL of bupivacaine 0.5% and Group C patients who received an intrathecal injection of 2.5 mL of bupivacaine 0.5%. The method of randomization was by coin tossing.

The study was single blinded in which the investigator who gave the anesthesia was not blinded and then another one, who was blinded to the study, toke over after 5 min and followed up the patient. This was the blindness technique that we organized in the study. It is partial blindness as the former investigator stayed for the first 5 min, recorded the vitals, and managed the patients.

All patients were anesthetized by an expert anesthetist (at least 3 years of experience). They were given the anesthesia in the sitting position with a coload of crystalloid (ringer solution 500 cc), using a spinal needle 25G Quincke with the bevel directed laterally, midline approach, and in the lower lumbar region. An intrathecal dose of 3 mL hyperbaric bupivacaine 0.5% and 12.5 μg of fentanyl was administrated in the Group B patients. In the other Group (C), an intrathecal dose of 2.5 mL bupivacaine 0.5% and 12.5 μg of fentanyl were given. The patient was placed supine immediately with a left uterine displacement in the control Group C while left sitting for 5 min in Group B with continuous vital signs monitoring, routine monitoring was attached (noninvasive blood pressure, oxygen saturation, and electrocardiogram) and monitored continuously for 50 min with 5 min interval between the blood pressure reading. The level of the block was checked using cold water and the surgeon was allowed to start to work if a T6 level or above was achieved. Any hypotension (<100 mmHg systolic or decrease 20% of the baseline) was treated with ephedrine 9 mg increments, no sedation was given, and it was just reassurance.

After delivery, a dose of 20 IU/L oxytocin was commenced by intravenous infusion. Apgar score was assessed in the 1st min and after 5 min. Furthermore, the Neonatal Neurological and Adaptive Capacity Scoring was measured and recorded at 15 min.[8] The patient then was monitored for the following outcomes: heart rate, hypotension, nausea, vomiting, spinal block level, and ephedrine dose.

The patient then was referred to the postoperative care unit and monitored by a well-trained nurse, who was blinded to the study, for the following: patient satisfaction, using the Maternal Satisfaction Scale for cesarean section[9] and Bromage score (1 = unable to move feet or knees; 2 = able to move feet only; 3 = just able to move knees; 4 = full flexion of knees; 5 = no detectable weakness of hip flexion while supine; and 6 = able to perform partial knee bend).[10]

Statistical analysis

Data were statistically described in terms of mean ± standard deviation, median and range, or frequencies (number of cases) and percentages when appropriate. The comparison of numerical variables between the study groups was made using the Student's t-test for independent samples. For comparing categorical data, the Chi-square test was performed. The exact test was used instead when the expected frequency is <5. P <0.05 was considered statistically significant. All the statistical calculations were done using the computer program SPSS (Statistical Package for the Social Sciences; SPSS Inc., Chicago, IL, USA) release 15 for Microsoft Windows (2006).

Sample size

As considered the primary outcome, the sample size calculation was performed using the comparison of the incidence of hypotensive attacks between mothers experiencing an elective cesarean section treated with small-dose bupivacaine and those treated with large-dose bupivacaine. The calculation was done based on comparing two proportions from independent samples in a prospective study using the Chi-square test, the α-error level was fixed at 0.05, the power was set at 80%, and the intervention groups (case: control) ratio was set at 1. As previously published,[3],[4] 75% of cases treated with small-dose bupivacaine experience hypotensive attacks, whereas using a large dose is expected to decrease this incidence to 35% only. Accordingly, the minimum optimum sample size should be 23 participants in each arm, which increased to 25 to avoid dropouts. The sample size calculation was done using PS Power and Sample Size Calculations software, version 3.0.11 for MS Windows (William D. Dupont and Walton D. Vanderbilt, USA).


   Results Top


From December 2016 to March 2017 (December 12, 2016 to March 23, 2017), 65 patients were included according to the inclusion criteria. Five patients refused to share 60 patients were divided randomly into two groups; 7 cases excluded after that because of the shift to general anesthesia due to an early failed spinal anesthesia (before skin incision). Finally, Group C (control group) with 28 cases and Group B (study group) with 25 cases [Figure 1]. All patients had a detailed explanation about the study and their role, and all of them signed the consent.
Figure 1: Flow diagram

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Both groups have no statistical differences (P > 0.05) regarding the age, height, weight, and body mass index [Table 1].
Table 1: Demographic data of both groups

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There were no differences between both groups regarding the incidence of nausea and vomiting (6 cases (24.7%) in Group B versus 6 cases (21.42%) in Group C with a P > 0.05), but these data are misleading as all patients were received dexamethasone 8 mg and metoclopramide 10 mg routinely [Table 2]. Furthermore, the exact timing of nausea and vomiting concerning the surgery steps was not recorded. We did not know whether the cause was from hypotension, peritoneal traction, or something else.
Table 2: Sensory level, ephedrine, fluids, vomiting, Adaptive Capacity Scoring (Neurologic and Adaptive Capacity Score), and Apgar score distribution in both groups

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No cases in both groups were shifted to general anesthesia or experienced shortness of breathing [Table 2].

There was a marked reduction in ephedrine doses which were required to be given in Group B in comparison with Group C. It was 7.2 ± 15.684 mg in Group B versus 27.86 ± 12.04 mg in Group B with P < 0.05 (confidence interval [CI] 95%). Only 5 (20%) cases in Group B were indicated to have ephedrine, whereas 25 patients of 28 (89.2%) in Group C were indicated to support their blood pressure with ephedrine.

No analgesics or sedation was given to any patient, only reassurance, a detailed description of the procedure and intimate relation intraoperatively, especially for the patients with the first time spinal anesthesia [Table 2].

There were no differences between the two groups regarding the fluid intake (895 ± 125 mL in Group B versus 725 ± 213 mL in Group C with P > 0.05).

Neonatal Apgar score was 9 in the first 1 min and increased to 10 at 5 min.

The blood pressure and heart rate were within the accepted normal range all through the surgery after proper management with ephedrine in both groups, and there were no clinical differences [Table 2].

The satisfactory surgical sensory level was achieved in all cases in both groups with the following distribution: 26 (92.85%) cases were T4, and only 2 (7.14%) cases were T2 in Group C while all cases in Group B were at the T4 level [Table 2].

Neither sedation nor analgesics was given. All cases finished and recovered without any other complication.


   Discussion Top


This study shows that using a large dose of hyperbaric bupivacaine 0.5% with the prolonged sit-up straight of the patient for 5 min can lead to a satisfactory surgical spinal block with no need to add analgesics or to convert to general anesthesia.

The reason for choosing 5 min as an elapsing time between the injections of the medications and asking the patient to lie down is that the spinal anesthesia level will be settled up after 5 min. Moreover, 5 min is not a long time in the duration of an elective cesarean section surgery as it usually takes from 90 to 120 min from patient admission to the operating theater and till discharge, and so 5 min will represent around 3% from the total duration which is not an issue.

Any type of analgesia was not used, apart from intrathecal fentanyl, to decrease the liability of bias in this study and to decrease the other factors that may affect the reliability of the results. Furthermore, no sedation was used in any patient, and reassurance only was enough. Furthermore, this study is proving the hypothesis that aortocaval compression occurs during lying down after spinal anesthesia and causes and epidural venous congestion and compression of the dural sac which can force the local anesthetic toward the head and increase the level of sensory blockade. Therefore, allowing the patient to remain in the sitting position could delay the onset of anesthesia and decrease the incidence of hypotension.

Similarly, the classic problem of the unsatisfactory sensory block (low level), which is a sequel of prolonged sit up, was solved with the large bupivacaine dose.

Many studies were trying to find an optimum solution for the conflict among the four pillars: the dose/volume of the local anesthetics, the posture of the patient, the level of the block, and hypotension.

The limitations of this study are that the study was single-blinded, and we found it is very difficult to make it double blinded as the patient will recognize.

Many studies were trying to reduce the volume or dose of bupivacaine claiming that the hypotension will be overcome.[11],[12],[13] Ginosar et al. studied the ED 95 of bupivacaine and found that 11.2 mg is enough to achieve a satisfactory sensory level and a pain-free surgery. They also found that the ED50 was 7.6 mg using a logistic regression model.[14]

Most practitioners use doses between 7.5 and 15 mg of hyperbaric bupivacaine. Those who use the lower dose, aiming to decrease the incidence of side effects such as hypotension or nausea, have faced a cost of patients' unsatisfaction and visceral pain. The studies showed an increased incidence of patients with an inadequate surgical sensory block when using doses <10 mg up to 71%.[15],[16]

Seljogi D et al.[17] did a retrospective study on 1252 patients receiving either 8 mg or 10 mg and found that there was a higher rate of conversion to general anesthesia in a group who received 8 mg (the relative risk was 4.88 [95% CI 1.41–16.85]).

Turhanoglu et al. found that using a low dose down to 4 mg of bupivacaine did not prevent hypotension regarding both severity and doses of ephedrine.[13]

In a review article done by Arzola and Wieczorek,[11] 15 reviewed articles concluded that doses <8 mg will result in more analgesic requirements such as a high rate of conversion to general anesthesia and less hypotension and nausea and vomiting. However, Nagata et al.[18] tried to compare a dose of 8 mg of hyperbaric bupivacaine versus 10 mg in the cesarean sections. The results were satisfactory with proper surgical conditions and less hypotension in 8 mg group (37%), while it was 71% in the 10 mg group in Japanese parturient with no data regarding the race and natural response in comparison with other races. The author himself announced that their frames (the Japanese) were smaller than that for the Caucasians.

It is clear that a low dose is not a practical solution and that is why we used big doses in this study to overcome this limitation. However, someone can claim that a conventional dose or even a low dose in a large volume can be the solution. Researchers tried to test this claim by using a regular dose or small dose in high volume. Jokinen et al.[19] revised 1368 cases that were received a big volume (mg/mL) of bupivacaine with volumes ranged between 8 mL and 12 mL, and they found that although it was a satisfactory dose for the surgery to be achieved, it did not decrease the incidence of hypotension (48%).

Some authors tried to use small doses with modifications, such as epidural volume extension using saline[20],[21] or to use isobaric bupivacaine,[22],[23] aiming to the more cephalic spread and subsequently proper sensory level and surgical conditions.

The former modification showed good results regarding hemodynamic and sensory level with a nonpractical technique as they inserted an epidural catheter and injected saline to increase the epidural space pressure and ensured more cephalic migration of the intrathecal bupivacaine. Practically, it is better to inject local anesthetics in the catheter slowly to achieve the same results and to save the patients from the complications of the intrathecal injection. Furthermore, the epidural catheter is costly and takes a long time to be inserted.

The latter, who tried isobaric bupivacaine,[22],[23] found disappointing results as there were no differences between both medications (isobaric and hyperbaric) regarding hemodynamic and the incidence of hypotension.

Positioning is another important factor that determines the sensory level and affects hemodynamic. Many types of research tried to study the effect of positioning on both hemodynamic changes and the level of the block.[7],[24],[25],[26],[27],[28],[29],[30]

They found that lateral or sitting decubitus for few minutes can avoid any movement of the intrathecal injected local anesthetics and subsequently will fix the level with no hypotension. However, this will be on the cost of the sensory level. This can help in surgeries for the lower limb and below the umbilicus that do not need either to manipulate the peritoneum or higher sensory level. This disadvantage limits the usage of this technique in cesarean sections. Xu et al.[28] tested different positions at the induction of spinal anesthesia and its effect on cephalad spread of the local anesthetics in the cesarean sections, and they found that there was a lower cephalad spread with the group that stayed 5 and 10 min in lateral position than the group of the patients that positioned immediately supine after intrathecal injection. This study did not mention the effect of this low level on surgical conditions and patient satisfaction.

Wang et al.[29] tried the lateral position for 15 min; they gave the patients the spinal anesthesia in the lateral position and keep them for around 15 min comparing them with another group lying supine immediately. They found that the lateral position for 15 min can achieve a satisfactory level with a less incidence of hypotension. However, the methodology was not clear regarding the duration of the lateral position and the needle insertion. Besides, they used ropivacaine, not bupivacaine, which will make the comparison difficult. El-Hakeem et al.[30] added another maneuver to overcome the hypotensive effect of the spinal anesthesia and at the same time achieving a satisfactory anesthesia block level. They gave the conventional bupivacaine dose and asked the patient to sit up for 5 min and then to put her supine. They found that the blood pressure was maintained with less incidence of hypotension and a lower dose of ephedrine. Although the level was lower in the group that used sitting up position for 5 min, the surgery went smoothly without patient discomfort or pain. In this study, the researcher used fentanyl intrathecal and fentanyl intravenous routinely which may explain the smooth surgical course.

Many authors studied the effect of posture, intraabdominal pressure, and inferior vena cava diameter and compressibility in the parturient and their hemodynamics.[5],[6] They found a tight relation and a guide for expectations for those how will experience hypotension after the induction of spinal anesthesia.

Based on the above short review, we can notice the following facts; there is a significant relationship between the patient position and hypotension during the 1st min of the spinal anesthesia in any type of patient whether doing a cesarean section or not and this also will affect the level. The second fact is the presence of a strong relationship between a pregnant patient's position and hypotension either she will have spinal anesthesia or not.


   Conclusions Top


We can conclude that a large dose of hyperbaric bupivacaine in the spinal anesthesia for a cesarean section with prolonged sitting up straight will lead to perfect surgical conditions with minimal hypotension. Moreover, prolonged sitting up in a parturient can allow the anesthetist to consider the patients as a nonparturient.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
   References Top

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Betrán AP, Ye J, Moller AB, Zhang J, Gülmezoglu AM, Torloni MR. The Increasing Trend in Caesarean Section Rates: Global, Regional and National Estimates: 1990-2014. PLoS One 2016;11:e0148343.  Back to cited text no. 1
    
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Shaaban MM, Sayed Ahmed WA, Khadr Z, El-Sayed HF. Rising cesarean section rates, a patient's perspective: experience from a high birth rate country. Clin Exp Obstet Gynecol 2014;41:436-9.  Back to cited text no. 2
    
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Chumpathong S, Chinachoti T, Visalyaputra S, Himmunngan T. Incidence and risk factors of hypotension during spinal anesthesia for cesarean section at Siriraj hospital. J Med Assoc Thai 2006;89:1127-32.  Back to cited text no. 3
    
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Ohpasanon P, Chinachoti T, Sriswasdi P, Srichu S. Prospective study of hypotension after spinal anesthesia for cesarean section at Siriraj hospital: Incidence and risk factors, Part 2. J Med Assoc Thai 2008;91:675-80.  Back to cited text no. 4
    
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Chun R, Baghirzada L, Tiruta C, Kirkpatrick AW. Measurement of intra-abdominal pressure in term pregnancy: A pilot study. Int J Obstet Anesth 2012;21:135-9.  Back to cited text no. 5
    
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Kundra P, Arunsekar G, Vasudevan A, Vinayagam S, Habeebullah S, Ramesh A. Effect of postural changes on inferior vena cava dimensions and its influence on haemodynamics during caesarean section under spinal anaesthesia. J Obstet Gynaecol 2015;35:667-71.  Back to cited text no. 6
    
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Jeon YT, Hwang JW, Kim MH, Oh AY, Park KH, Park HP, et al. Positional blood pressure change and the risk of hypotension during spinal anesthesia for cesarean delivery: An observational study. Anesth Analg 2010;111:712-5.  Back to cited text no. 7
    
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Brockhurst NJ, Littleford JA, Halpern SH. The neurologic and adaptive capacity score: A systematic review of its use in obstetric anesthesia research. Anesthesiology 2000;92:237-46.  Back to cited text no. 8
    
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Morgan PJ, Halpern S, Lo J. The development of a maternal satisfaction scale for caesarean section. Int J Obstet Anesth 1999;8:165-70.  Back to cited text no. 9
    
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Breen TW, Shapiro T, Glass B, Foster-Payne D, Oriol NE. Epidural anesthesia for labor in an ambulatory patient. Anesth Analg 1993;77:919-24.  Back to cited text no. 10
    
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Arzola C, Wieczorek PM. Efficacy of low-dose bupivacaine in spinal anaesthesia for Caesarean delivery: Systematic review and meta-analysis. Br J Anaesth 2011;107:308-18.  Back to cited text no. 11
    
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Dyer RA, Joubert IA. Low-dose spinal anaesthesia for caesarean section. Curr Opin Anaesthesiol 2004;17:301-8.  Back to cited text no. 12
    
13.
Turhanoglu S, Kaya S, Erdogan H. Is there an advantage in using low-dose intrathecal bupivacaine for cesarean section? J Anesth 2009;23:353-7.  Back to cited text no. 13
    
14.
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;100:676-82.  Back to cited text no. 14
    
15.
Pedersen H, Santos AC, Steinberg ES, Schapiro HM, Harmon TW, Finster M. Incidence of visceral pain during cesarean section: The effect of varying doses of spinal bupivacaine. Anesth Analg 1989;69:46-9.  Back to cited text no. 15
    
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KIran S, Singal NK. A comparative study of three different doses of 0.5% hyperbaric bupivacaine for spinal anaesthesia in elective caesarean section. Int J Obstet Anesth 2002;11:185-9.  Back to cited text no. 16
    
17.
Seljogi D, Wolff AP, Scheffer GJ, van Geffen GJ, Bruhn J. Correlation of bupivacaine 0.5% dose and conversion from spinal anesthesia to general anesthesia in cesarean sections. Acta Anaesthesiol Belg 2016;67:36-42.  Back to cited text no. 17
    
18.
Nagata E, Yoshimine K, Minoda Y, Kawaguchi Y, Sakamoto M, Takehara A. Comparison of 8 mg and 10 mg hyperbaric bupivacaine during spinal anesthesia for cesarean section in Japanese parturients. Masui 2004;53:131-6.  Back to cited text no. 18
    
19.
Jokinen J, Adametz V, Kredel M, Muellenbach RM, Hönig A, Wöckel A, et al. Spinal anesthesia in high-volume, low-concentration technique for Caesarean sections: Retrospective analysis. Anaesthesist 2015;64:108-14.  Back to cited text no. 19
    
20.
Fabris LK, Belci D, Zdravčević KŠ, Hrgović Z, Šakić L. Do we need cephalic spread of spinal anaesthesia for caesarean section? A different approach to CSE-EVE for reducing hypotension. Z Geburtshilfe Neonatol 2013;217:130-8.  Back to cited text no. 20
    
21.
Sitkin SI, Ronenson AM, Savel'eva YV. New technique of spinal anesthesia with epidural volume extension for caesaren section in pregnant women with concomitant cardiac pathology. Anesteziol Reanimatol 2015;60:58-61.  Back to cited text no. 21
    
22.
Sng BL, Siddiqui FJ, Leong WL, Assam PN, Chan ES, Tan KH, et al. Hyperbaric versus isobaric bupivacaine for spinal anaesthesia for caesarean section. Cochrane Database Syst Rev 2016;9:CD005143.  Back to cited text no. 22
    
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Punshi GD, Afshan G. Spinal anaesthesia for caesarean section: Plain vs. hyperbaric bupivacaine. J Pak Med Assoc 2012;62:807-11.  Back to cited text no. 23
    
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Rafaniello C, Ianniello B, De Vizia M, Mercogliano A, Lettieri B, Rinaldi B, et al. Cardiorespiratory effects of change in posture after spinal anesthesia with hyperbaric bupivacaine. Minerva Med 2011;102:501-4.  Back to cited text no. 26
    
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Han G, Zhao GY, Li L, Zhao P. Comparison of hemodynamics after combined spinal-epidural anesthesia between decubitus and sitting positions in aged patients undergoing total hip replacement. Pharmacology 2014;93:193-6.  Back to cited text no. 27
    
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Xu F, Qian M, Wei Y, Wang Y, Wang J, Li M, et al. Postural change from lateral to supine is an important mechanism enhancing cephalic spread after injection of intrathecal 0.5% plain bupivacaine for cesarean section. Int J Obstet Anesth 2015;24:308-12.  Back to cited text no. 28
    
29.
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30.
El-Hakeem EE, Kaki AM, Almazrooa AA, Al-Mansouri NM, Alhashemi JA. Effect of sitting up for 5 min versus immediately lying down after spinal anesthesia for cesarean delivery on fluid and ephedrine requirement; a randomized trial. Can J Anaesth 2011;58:10839.  Back to cited text no. 30
    


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