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Year : 2012  |  Volume : 6  |  Issue : 1  |  Page : 47-52  

Comparison of low doses of intrathecal bupivacaine in combined spinal epidural anaesthesia with epidural volume extension for caesarean delivery

1 Department of Anaesthesia, Teerthankar Mahaveer Medical College, Moradabad, Uttar Pradesh, India
2 Department of Anaesthesia, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India

Date of Web Publication14-Nov-2012

Correspondence Address:
Gaurav Jain
Assistant Professor, Department of Anaesthesia, Teerthankar Mahaveer Medical College, Delhi Road, Moradabad, Uttar Pradesh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0259-1162.103373

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Aims and Objectives: This study aims to compare relative efficacy of three different doses of intrathecal bupivacaine in combined spinal epidural anaesthesia (CSEA) for caesarean delivery.
Materials and Methods: In a double blinded manner, 204 cases were randomized into three groups: I, II, and III to receive a dose of 4, 5.5, and 7 mg of hyperbaric bupivacaine with a fixed dose of 25 μg fentanyl intrathecally, and Dextran 40 w/v 10 mL given for epidural volume extension (EVE), in CSEA. Our primary outcome was the number of effective doses. The block characteristics and side effects were also monitored.
Results: Out of 198 patients completing the study, 53, 63, and 65 in group I, II and III had effective doses. Mean P i (probability of an effective dose) in group I, II, and III, was 0.81, 0.95, and 0.97, respectively. The P b (superiority of one group over the other) of group II and III was higher than group I. The maximal sensory block height in group II and III (T 2 ) was higher than group I (T 3 ), with a shorter time required to achieve the same. Group I and II exhibited lesser motor blockade, lesser hypotension with early recovery as compared to group III. No significant adverse effects were observed between the groups.
Conclusion : The intermediate dose of bupivacaine (5.5 mg) provided safe and effective anaesthesia for caesarean delivery with an additional advantage of lesser episodes of hypotension and partial motor blockade in CSEA.

Keywords: Bupivacaine, combined spinal-epidural anaesthesia, Dextran 40, epidural volume extension (EVE), fentanyl

How to cite this article:
Jain G, Singh DK, Bansal P, Ahmed B, Dhama SS. Comparison of low doses of intrathecal bupivacaine in combined spinal epidural anaesthesia with epidural volume extension for caesarean delivery. Anesth Essays Res 2012;6:47-52

How to cite this URL:
Jain G, Singh DK, Bansal P, Ahmed B, Dhama SS. Comparison of low doses of intrathecal bupivacaine in combined spinal epidural anaesthesia with epidural volume extension for caesarean delivery. Anesth Essays Res [serial online] 2012 [cited 2022 Jul 3];6:47-52. Available from:

   Introduction Top

Epidural volume extension (EVE) is aimed at dose reduction of intrathecal bupivacaine, in the setting of combined spinal-epidural anaesthesia (CSEA). Though two earlier studies have failed to demonstrate any dose reduction by the use of saline in EVE, considerable dose reduction has been achieved by the use of colloid in the same. [1],[2],[3] This technique has an additional advantage of achieving a stable maternal haemodynamics, although the possibility of anaesthetic failure increases in parallel to a decrease in intrathecal dosage. [3],[4]

The low-dose intrathecal bupivacaine has a potential role in high-risk parturient, in whom maintenance of stable haemodynamics is imperative, provided the failure rates are minimal. [4] Previous studies done on CSEA were also not powered to analyze this secondary outcome. Extensive medline search did not revealed any published literature comparing the relative efficacy of low doses of intrathecal bupivacaine by the use of colloid for EVE. So, we conducted a trial to compare three different low doses of intrathecal bupivacaine, using 10 mL of Dextran 40 for EVE in the context of CSEA in patients undergoing caesarean delivery.

   Materials and Methods Top

After ethical committee approval and written informed consent, 204 cases of ASA Physical Status I or II, aged

20-40 years, height 145-165 cm, body mass index 25±10%, > 37 weeks of gestation, with a noncomplicated pregnancy booked to deliver by caesarean delivery in between Jan 2011 - Sept 2011, were enrolled in the study. Exclusion criteria included: Weight >100 kg, pregnancy-induced hypertension (PIH), end-organ disease, active labour, emergency caesarean section, or any contraindication to regional anaesthesia.

These patients were randomly allotted (using computer generated random numbers) to three groups (68 cases each): I, II, and III to receive 4 (0.8 mL), 5.5 (1.1 mL), and 7 mg (1.4 mL) hyperbaric bupivacaine, respectively. A fixed dose of fentanyl (25 μg) was added to above drug in all the groups. All the drug volumes were loaded through an insulin syringe to ensure accurate doses. The solution was then diluted to 2.5 mL volume with normal saline, to maintain the adequacy of blinding. A two-operator technique was employed to prevent the observer bias. Randomization was done by an anaesthetist intending to make the studied drug solution. Further interventions and monitoring was done by a second anaesthetist blinded to group allocation.

Patients received no premedication and were adequately fasted. Preloading was done with Hartmann's solution (10 mL/kg IV) and baseline parameters were recorded. Patients were placed in the right lateral decubitus position for the CSEA procedure. An 18-gauge Tuohy needle (Espocan, B. Braun, Germany) was inserted into the L 3-4 or L 4-5 interspace and epidural space was confirmed using loss of resistance to 2 mL of air. Thereafter, the intrathecal sac was punctured with a 27-gauge Whitacre spinal needle using a needle-through-needle technique. After confirming free flow of CSF, the prepared drug solution was injected via a spinal needle as per group allocation. The spinal needle was then withdrawn and EVE was performed with 10 mL of Dextran 40, injected via the same epidural needle. An epidural catheter was then inserted 4-5 cm in epidural space and having secured the catheter, the cases were immediately turned supine with a 10° left lateral tilt.

The level of dermatomal sensory block was tested bilaterally (defined as complete loss of sensation to pin-prick) after the induction of CSEA, in an ascending fashion starting from the T12 dermatome. The degree of lower limb motor block was assessed using modified Bromage scale (MBS): 1=complete block (unable to move feet or knees), 2=almost complete block (able to move feet only), 3=partial block (just able to move knees), 4=detectable weakness of hip flexion while supine (full flexion of knees), 5=no detectable weakness of hip flexion while supine, 6=able to perform partial knee bend. Surgery was allowed to commence once a bilateral T 5 sensory block was demonstrated. The block profile was evaluated at 5 min intervals for the first 20 min and at 10 min intervals thereafter, for the rest of the intraoperative period. An effective dose was defined as the one that resulted in a sensory block height to T 5 level within 20 min of the intrathecal injection with no epidural top-up requirements (maternal abdominal discomfort ≥5 on a 10-point numerical score or on maternal request for rescue) within 60 min of CSEA. All ineffective doses were managed by administering epidural top-ups of 4 mL plain bupivacaine (0.5%) and such cases were excluded from comparison of secondary variables. During the surgery, the operating surgeon was asked to evaluate the adequacy of muscle relaxation according to a four-point scale (1=excellent, 2=good, 3=fair, 4=poor).

Any episodes of hypotension (systolic blood pressure <100 mm Hg or <20% from baseline) were treated by administering the titrated IV boluses of ephedrine 5 mg. Rescue antiemetic was administered at the discretion of the anaesthesiologist. Bradycardia (HR <55/min or <25% of the baseline value) was treated by IV boluses of Atropine 0.6 mg. Shivering was treated by IV Tramadol 25 mg. The Apgar scores were recorded at 1 and 5 min. Postoperatively, epidural top-ups were given via epidural catheter on complain of the patient.

Statistical analysis was performed using SPSS 16.0 and Win BUGS (Bayesian Inference using Gibbs Sampling for Windows ( statistic software. Comparison of the primary variable, namely the number of effective doses, was assessed with probability assessment using Bayesian analysis. [5] It was assumed that number of effective doses across the groups is similar in some way. It was considered to be equivalent to specifying a random effect model for the true probability of having an effective dose (P) of intrathecal bupivacaine in different groups (i=I, II or III) as follows: Logit (Pi) = bi, bi~Normal (μ,τ), where bi=distribution of logit (Pi), μ=prior distribution for expected success rate of logit (Pi) and τ=prior distribution for precision of expected success rate of logit (Pi). To check the comparative performance of different groups, we calculated the probability of superiority of one group over the other (Pb). Patient demographics, baseline haemodynamics, time to maximal sensory block, time for sensory block regression to T 10 level, time to MBS of 6, ephedrine requirement, total IV fluid administered before delivery, duration of surgery, and estimated blood loss were measured and compared by one-way ANOVA test; post hoc intergroup comparisons done by Bonferonni's correction. The maximal sensory block level, minimum MBS after CSEA, and adequacy of muscle relaxation were measured and compared by Mann-Whitney U-test. The number of epidural supplement before and after delivery, APGAR score, number of episodes of hypotension, and side effects were measured and compared by Fisher's exact test/Chi square test whichever appropriate.

For calculating the sample size, the confidence interval approach was used. Since the true population proportion was unknown so we conducted a pilot study, and found that probability of having an effective dose was 80%, 94%, and 100% in group I, II, and III, respectively. Taking the least value as an estimation of true proportion, the sample size was calculated as 64 in each group. We selected 68 patients in each group to compensate for drop outs in our study.

   Results Top

Of the 204 cases recruited for study, six cases were excluded from data analysis because four cases complained of paresthesia at the moment of dural puncture mandating conversion of procedure to general anaesthesia, while protocol violation occurred in two other cases that were then given spinal anaesthesia. Thus, 66 patients in each group completed the study successfully. Patient demographics were similar in all the groups [Table 1]. There was no significant difference in IV fluid usage, estimated blood loss, duration of surgery and baseline haemodynamics between the groups [Table 1].
Table 1: Comparison of baseline characteristics

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Fifty-three cases in group I, Sixty-three in group II, and Sixty-five in group III had effective doses. We observed a mean Pi of 0.81, 0.95, and 0.97 in group I, II, and III, respectively. The Pb of group II (PII>PI=0.99) and III (PIII>PI=0.99) were better than group I (PI>PII=0.002, PI>PIII=0.006) [Table 2], [Figure 1]. The Pb of group III (PIII>PII=0.81) was also better than group II (PII>PIII=0.19). The probability of having an effective dose in the total population (P pop ) was 90% in a dose range of 4-7 mg of intrathecal bupivacaine [Table 2].
Figure 1: Box plot of probability of having an effective dose in different groups. Data expressed as mean ± interquartile range with 95% highest posterior density interval. Ppop=probability of having an effective dose in the total population at the dose range of 4– 7 mg of intrathecal bupivacaine. PI, PII, PIII= probability of having an effective dose in group I, II, and III respectively

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Table 2: Estimates of probability of effective dose at different doses of intrathecal bupivacaine between the groups (n=66)

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The maximum sensory block height achieved in group II and III (T 2 ) was higher than group I (T 3 ). Time required to achieve this height was significantly greater in group I, but these cases exhibited early sensory regression to T 10 and faster motor recovery as compared to group II to group III. More number of patients in group III (MBS 1) had complete motor blockade, as compared to group I (MBS 2) (P=0.058) and II (MBS 2) (P<0.001). Though there was no significant difference between group I and II in terms of MBS score, more patients in group I had partial motor blockade. Sensory block failed to achieve the desired height in nine cases in group I as compared to two cases in group II. There was no significant difference in the adequacy of muscle relaxation or epidural top up requirement between the groups [Table 3].
Table 3: Comparison of hemodynamic characteristics

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There were significantly lesser episodes of hypotension in group I as compared to group II, to group III, respectively. Ephedrine requirement was significantly higher in group III (4.2 mg) with no significant difference between group I and II (mean difference of 0.82 mg) [Table 4]. There was no difference in incidence of side effects between the groups. No adverse foetal outcome was observed [Table 5].
Table 4: Comparison of block characteristics.

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Table 5: Comparison of side effects and APGAR score

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   Discussion Top

In this study, although group II and III were comparable in terms of number of effective doses, Pb of group III was better than the other two groups. However, considering lesser incidence of hypotension, less vasopressor requirements, less intense motor blockade, faster sensory, and motor recovery together with a Pi of 95% in group II, a dose of 5.5 mg may be considered satisfactory. This dose may also be preferable for emergency caesarean delivery where rapid onset of block and consistency of the effect is highly desired.

In our study, nine (13.6%) cases in group I as compared to only two (3%) cases in group II, failed to achieve the required block height. Previous literature reports a failure rate of 4.5% with the use of 3.75 mg dose of bupivacaine. [4] The lower failure rate in that study could be due to use of the T 6 dermatomal level as a criterion for adequate anaesthesia, in place of T 5 level as in our study. Though the time required to achieve the maximum sensory blockade was significantly shorter in group III, the incidences of complete motor blockade were also unacceptably high, thus making this dose undesirable for routine recommendation. The time required for block regression (both sensory and motor) was significantly shorter in group I and II, allowing for early recovery of the patient during post operative period. [4] Thus, lower doses should be preferred for surgeries like caesarean delivery usually lasting for short duration.

Fentanyl is known to have a dose-sparing effect on intrathecal dose of bupivacaine. [6],[7],[8] It is also a useful help to combat intraoperative discomfort during caesarean delivery. [9] Similar dose reduction could also be achieved by the use of colloid for EVE. [3] We decided to include a colloid and fentanyl in our study taking this into consideration. Previous literature shows that significant hemodynamic stability could be achieved by the use of low doses of intrathecal hyperbaric bupivacaine in CSEA. [3],[4],[10],[11] This could have contributed to significantly less hypotension in group I and II as compared to group III with consequent less ephedrine usage. Although, the episodes of hypotension and ephedrine requirement increased in group II as compared to group I, it was not statistically significant.

With regard to epidural top-up requirements, only one patient in group I experienced abdominal discomfort before the delivery of foetus. In the remaining four cases (2, 1, 1 in group I, II, III respectively) it was after the delivery. It may be possible that epidural top ups may have been administered by the investigator, at a lower threshold of discomfort on request of the patient. It could be due to inter individual differences in the perception of discomfort by the patients during foetal extraction.

Despite apparent high thoracic sensory involvement in some cases in group II and III, there was no witnessed respiratory depression or bradycardia in any of the groups. These findings are quite comparable to a previous study, demonstrating no such side effects even on high cervical dermatomal involvement at a dose of 9 mg intrathecal bupivacaine. [4] The incidence of a PDPH is about 3-4% in our institute, but in our study only one patient in group III developed a PDPH. One possible explanation is that the prophylactic use of colloid in EVE may have prevented such an incidence of PDPH in CSEA. We however acknowledge that our study was not powered to measure this secondary outcome. There was no significant difference in the incidence of other adverse effects between the groups. [11] Neonatal outcome was good in all the cases irrespective of the group allocation.

Limitations of our study

Since the time for sensory regression to T 10 dermatome was <2 h in our study, these doses could not be utilized for surgeries of longer duration. This study was done in Indian subgroup of population. As their body size is comparatively small, the results of our study could not be extrapolated to other ethnic groups. Although Dextran 40 is routinely used via IV route, there are no recommendations by FDA regarding its safety in epidural space. In this study, Dextran 40 was chosen for EVE considering its safe use in our previous study and other case reports with no observed side effects. [12],[13],[14],[15] Parturient scheduled for caesarean section may have co-morbid illnesses (eg, PIH). As this subset of patients has been excluded from the current study, the results of this study cannot be extrapolated to all parturient requiring caesarean delivery.

   Conclusion Top

Intrathecal hyperbaric bupivacaine 5.5 mg with colloid induced EVE in the context of CSEA used in our study provided rapid and successful anaesthesia for caesarean delivery with an additional advantage of stable maternal hemodynamics and faster recovery. However epidural top-ups need to be supplemented for surgeries lasting for longer duration. Understanding the individual advantage with each dose allows for better planning of anaesthesia, and selection of an intrathecal dose should be done by weighing out expected surgical duration against the chances of maternal hypotension.

   References Top

1.Tyagi A, Kumar A, Sethi AK, Mohta M. Epidural volume extension and intrathecal dose requirement: Plain versus hyperbaric bupivacaine. Anesth Analg 2008;107:333-8.  Back to cited text no. 1
2.Beale N, Evans B, Plaat F, Columb MO, Lyons G, Stocks GM. Effect of epidural volume extension on dose requirement of intrathecal hyperbaric bupivacaine at Caesarean section. Br J Anaesth 2005;95:500-3.  Back to cited text no. 2
3.Jain G, Singh DK. Effect of colloid induced epidural volume extension on dose reduction of intrathecal bupivacaine in caesarean delivery. ASEAN J Anaesthesiol 2010;11:1-12.  Back to cited text no. 3
4.Teoh WH, Thomas E, Tan HM. Ultra-low dose combined spinal-epidural anesthesia with intrathecal bupivacaine 3.75 mg for cesarean delivery: A randomized controlled trial. Int J Obstet Anesth 2006;15:273-8.  Back to cited text no. 4
5.Ntzoufras I. Bayesian Modeling using Win BUGS. 1 st ed. New Jersey: John Wiley and Sons, Inc.; 2009.  Back to cited text no. 5
6.Choi DH, Ahn HJ, Kim MH. Bupivacaine sparing effect of fentanyl in spinal anesthesia for cesarean delivery. Reg Anaesth Pain Med 2000;25:240-5.  Back to cited text no. 6
7.Ben-David B, Solomon E, Levin H, Admoni H, Goldik Z. Intrathecal fentanyl with small dose dilute bupivacaine: Better anesthesia without prolonging recovery. Anesth Analg 1997;85:560-5.  Back to cited text no. 7
8.Wang C, Chakrabarti MK, Whitwam JG. Specific enhancement by fentanyl of the effects of intrathecal bupivacaine on nociceptive afferent but not on sympathetic efferent pathways in dogs. Anesthesiology 1993;79:766-73.  Back to cited text no. 8
9.Hughes SC, Levinson G, Rosen MA. Anesthesia for caesarean section. In schidner's and levinson's anesthesia for obstetrics, 4 th ed, Philadelphia: Lippincott Williams and Wilkins; 2006. p. 201-36.  Back to cited text no. 9
10.Balestrieri PJ. Combined spinal epidural anesthesia for cesarean delivery: The dose dependent effects of hyperbaric bupivacaine on maternal hemodynamics. Anesth Analg 2007;104:453.  Back to cited text no. 10
11.Ben David B, Miller G, Gavriel R, Gurevitch A. Low dose bupivacaine-fentanyl spinal anesthesia for cesarean delivery. Reg Anesth Pain Med 2000;25:235-9.  Back to cited text no. 11
12.Chiron B, Laffon M, Ferrandière M, Pittet JF. Postdural puncture headache in a parturient with sickle cell disease: Use of an epidural colloid patch. Can J Anesth 2003;50:812-4.  Back to cited text no. 12
13.Lander CJ, Korbon GA. Histopathologic consequences of epidural blood patch and epidurally administered Dextran 40. Anesthesiology 1988;69: A410.  Back to cited text no. 13
14.Souron V, Hamza J. Treatment of Postdural Puncture Headaches with Colloid Solutions: An Alternative to Epidural Blood Patch. Anesth Analg 1999;89:1333.  Back to cited text no. 14
15.Salvador L, Carrero E, Castillo J, Villalonga A, Nalda MA. Prevention of post dural headache with epidural-administered dextran 40. Reg Anaesth 1992;17:357-8.  Back to cited text no. 15


  [Figure 1]

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]

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