The combined spinal-epidural (CSE) technique of providing regional anaesthesia for Caesarean section has been in widespread clinical use for over 15 yr. Subarachnoid injection of local anaesthetic provides rapid onset and reliable sacral block, while the presence of an epidural catheter allows flexibility in extending the block and provision of postoperative analgesia . Recently, this technique has undergone several modifications designed to increase its safety and efficacy. Administrations of epidural local anaesthetic or saline for epidural volume extension (EVE) are examples of these modifications [1-4]. The epidural injection, by causing compression of the subarachnoid space and promoting spread of the local anaesthetic, and the leakage of epidural local anaesthetic into the subarachnoid space are hypotheses as to why these modifications may improve the characteristics of the block [1-5].
Results of studies of EVE in spinal anaesthesia for Caesarean delivery are inconsistent [2-4]. Yamazaki and colleagues  found that the baricity of tetracaine solution did not affect the increase in analgesic levels after epidural saline injection. However, no studies in obstetric patients have examined the effect of baricity on EVE.
In this prospective, randomized, double-blind study we compared the effect of EVE on the extension of spinal anaesthesia with hyperbaric or plain bupivacaine in Caesarean section. The hypothesis was that in patients who underwent Caesarean section EVE, administered 5 min after spinal anaesthesia, would extend the maximal segmental spread of spinal anaesthesia regardless of hyperbaric or plain bupivacaine use. Thus, the primary outcome of this study was regarded as the maximum sensory block level.
This study was approved by local Ethics Committees from two university hospitals and written informed consent was obtained from each patient. We studied 240 parturients, American Society of Anaesthesiologists (ASA) physical status I or II, with a singleton uncomplicated pregnancy more than 37 weeks gestation who were undergoing elective Caesarean section under CSE. Parturients weighing more than 100 kg or with pre-eclampsia, pregnancy-induced hypertension, in active labour or presenting for emergency Caesarean section were excluded. This prospective, randomized, double-blind study was conducted by two different university hospitals with 120 patients each. Both centres included patients in all four groups. Randomization was stratified by the two study centers.
All participants received saline 1000 mL intravenously (i.v.) as a preload. Oxygen 4 L min−1 was administered through a simple face mask. Electrocardiogram (ECG), heart rate (HR) and peripheral oxygen saturation were monitored continuously.
The CSE blocks were performed by qualified anaesthetists having experience in CSE blockade. Each parturient received the CSE in the sitting position at the L3-4 or L4-5 vertebral level. After infiltrating the skin with 1% lidocaine, an 18-G Tuohy needle was introduced into the epidural space via a midline approach using the loss of resistance technique with <0.5 mL of saline. After the epidural space was identified, a 27-G, pencil point spinal needle was placed through the Tuohy needle into the subarachnoid space (CSEcure Portex Combined spinal/Epidural Minipack, SIMS Portex Limited, Hythe, Kent, UK). Needle aperture was oriented in a cephalad direction throughout intrathecal injection. After the flow of clear cerebrospinal fluid, patients taller than 163 cm received 9 mg of study drug and patients less than 163 cm received 8 mg of study drug over 15-20 s . Each study drug was combined with 20 μg fentanyl.
The spinal needle was removed and an epidural catheter was inserted 4 cm into the epidural space. After withdrawal of the Tuohy needle, the patients were placed supine with a 15° left lateral tilt. The supine position was adjusted by positioning the patient at the neutral level of the operation table, thereby assuring that the patient had the correct position.
The 240 patients were randomly allocated to one of four groups according to a computer-generated random numbers table:
- Group A (n = 60) received hyperbaric bupivacaine (Marcaine Spinal Heavy 0.5%, Astra Zeneca, Eczacıbaşı İstanbul, Turkey).
- Group B (n = 60) received hyperbaric bupivacaine and 10 mL saline epidurally 5 min after subarachnoid injection.
- Group C (n = 60) received plain bupivacaine (Marcaine 0.5%, Astra Zeneca, Eczacıbaşı, Istanbul, Turkey); and
- Group D (n = 60) received plain bupivacaine and 10 mL saline epidurally 5 min after subarachnoid injection.
Following measurement of baseline systolic blood pressure (BP) and HR in the supine position, spinal anaesthesia was performed with the patient in the sitting position. After obtaining the baseline haemodynamic variables, BP and HRs were measured at 1 min intervals for 10 min and subsequently every 5 min for 30 min. All measurements were performed by an anaesthetist blinded to the treatment groups. Hypotension was defined as systolic BP <100 mmHg or a reduction of more than 20% from baseline. Hypotension was treated with ephedrine boluses of 5 mg. Intraoperative pain was assessed using a verbal rating scale from 0 to 10 (0 = no pain at all, 10 = maximum imaginable pain). The level of sensory block, defined as the loss of sharp sensation (Hollmen Grade I) by using a pinprick induced by a 25-G hypodermic needle, was assessed bilaterally at the midclavicular line. We also measured the maximal segmental spread of analgesia by assessing loss of pinprick (Hollmen Grade I) [7,8]. Motor block was assessed by modified Bromage score (0 = able to move hip, knee and ankle; 1 = unable to move hip, able to move knee and ankle; 2 = unable to move hip and knee, able to move ankle; 3 = unable to move hip, knee and ankle).
Sensory block, motor block and pain scores were recorded by an anaesthetist blinded to the patient group at 5, 10, 15, 20, 25 and 30 min after subarachnoid injection and subsequently (during the recovery period) every 15 min for 135 min.
Surgery was allowed to commence as soon as the sensory block height reached the fourth thoracic dermatome. Oxytocin 5 IU and ergometrine were given with slow i.v. injection after delivery of the infant followed by infusion of oxytocin 30 IU in 500 mL saline over 1 h.
Patients were observed for intraoperative nausea and vomiting, and were treated with metoclopramide 10 mg if needed as a rescue antiemetic. If the patient experienced intraoperative pain (score > 3), analgesia was supplemented with epidural injections of 3 mL 2% lidocaine, and if this rescue epidural administration was not sufficient conversion to general anaesthesia was undertaken . It was planned that if the patient would have needed general anaesthesia or rescue epidural lidocaine, the patient would have been dropped from further analysis.
A paediatrician assessed the condition of the baby at 1 and 5 min (Apgar score) after delivery. The duration of surgery and total administered fluid during surgery was recorded and patients were transported to the recovery room where they were monitored. The time intervals for sensory recovery to the tenth thoracic dermatome (T10) and motor recovery to modified Bromage score 0 were assessed by a blinded anaesthetist at 15 min intervals. A 24 h postoperative review was also conducted in which the time to the first request of epidural analgesia was noted.
Prospective power analysis was based on the primary outcome, which we defined as the maximal segmental spread of sensory block. The size of the sample was based on the results of previous studies [6,10] investigating the effect of EVE on the spread of anaesthesia, to detect a clinically significant difference in the extension of maximal segmental spread of sensory block of two dermatomes, with an α risk at 0.05 and a β risk at 0.20. The power analysis revealed that 52 patients would be required in each of four groups. Data are presented as mean ± SD, number of patients or median (range) where appropriate. Statistical analyses were performed using the SPSS version 11.0 for windows (SPSS Inc., Chicago, IL, USA). Comparisons between groups were performed by using one-way analysis of variance (ANOVA), Scheffe multiple comparisons, χ2 and Fisher's exact test when appropriate. ANOVA with repeated measures was used to detect intergroup difference and intragroup changes overtime. Statistical significance was set at P < 0.05.
Seven patients had insufficient analgesia (3 in Group A, 1 in Group B and 3 in Group D). Six patients received 3 mL 2% lidocaine because of insufficient spinal analgesia and were not included in further analysis. One patient from Group D required general anaesthesia and was also withdrawn from the study.
Patient characteristics and duration of surgery were comparable between the groups (Table 1). No technical difficulty was encountered. After EVE, no significant difference in block characteristics was found between Groups A and B or between Groups C and D at any time. In the whole intraoperative period, maximum sensory block levels were always significantly higher in Group C than in Group A (Table 2). Time to reach T4 was significantly shorter in Groups C and D when compared with Groups A (P = 0.003 and 0.017) and B (P = 0.006 and 0.048, respectively; Table 3). Time to reach the highest level of sensory block in Group A was significantly longer compared with Groups C and D (P = 0.017 and 0.048, respectively; Table 3). There was no difference in the Bromage scores between the groups in the intraoperative period and all patients reached a score of 3.
Significant decreases in systolic BP occurred in all groups after intrathecal injection and they became significant after 5 min in Groups C and D compared to baseline values. The number of patients who developed hypotension at 5 min was significantly higher in Groups C and D than in Groups A and B (P = 0.001; Table 4). The number of parturients requiring ephedrine was also higher in these groups (P = 0.008). Recovery in terms of sensory and motor block and first analgesic requirements were similar in all groups (Tables 3 and 5). There were no differences in APGAR scores between the groups.
Intraoperative nausea and vomiting occurred in 46.6% of patients in Group A, 36.6% in Group B, 46.6% in Group C and 56.6% in Group D. Five patients (one in Group A, two in Group C and two in Group D) had moderate backache with minor local tenderness at the injection site.
The main finding of our study is that EVE with saline did not result in an extension of spinal block with hyperbaric or plain bupivacaine for Caesarean delivery. In this study, EVE did not offer any advantage to extend spinal analgesia with hyperbaric or plain bupivacaine. Furthermore, neither an increase in sensory and motor block nor a faster recovery profile of spinal anaesthesia in parturients was achieved by EVE.
It has been reported that height would be a significant variable in adjusting the spinal dose of local anaesthetic and predicting the final level of the block [11,12]. In our study, parturients received two different doses of intrathecal bupivacaine according to their height. Consequently, this methodology would be expected to demonstrate a reliable extension of the block height with EVE.
Blumgart and colleagues  reported that bupivacaine 0.5% 10 mL given epidurally 5 min after an intrathecal injection of hyperbaric bupivacaine resulted in similar increase in sensory block compared with saline 0.9% 10 mL. In that study, increased sensory block with saline has been explained by an epidural volume effect. Similarly, Takiguchi and colleagues  demonstrated clinical and myelographic extension of sensory block with 10 mL saline 0.9%. This was the reason for using 0.9% saline 10 mL as a volume extender in our study rather than local anaesthetics.
Using volumes of 5 and 10 mL, Stienstra and colleagues  reported an increase in maximal sensory block height with both epidural bupivacaine 0.5% and saline 0.9%. However, in a magnetic resonance imaging study, 5, 10 and 15 mL saline, given into the epidural space, did not result in an increase in maximal sensory block height . Although a large number of parturients were included in our study, we could not find any extending effect of EVE on spinal anaesthesia with either hyperbaric or plain bupivacaine.
As the ideal volume or time to epidural injection of saline is yet to be found to provide an extension in spinal anaesthesia, choice of ideal volume or time to epidural injection to achieve the desired clinical effect may be important. In a myelographic study, an augmented effect of EVE with 10 mL saline has been demonstrated and confirmed by other studies using 6, 7, 8 and 10 mL [3,5,9,13,15]. Our choice was to use 10 mL EVE 5 min after subarachnoid injection [2,4]. Some authors injected the epidural volume just after subarachnoid injection and some after 5, 10 and 20 min [3,4,15]. In our study, epidural saline was injected 5 min after spinal block and this was consistent with the previous studies investigating the time effect of EVE [3,4,15].
There was a significant difference in time to reach T4 between Groups A and C and Groups B and D. We found a faster onset time and higher sensory block level in Groups C and D. In the literature, only a small number of randomized controlled trials, comparing plain and hyperbaric bupivacaine, have been published and mostly in non-obstetric patients. Logan and colleagues  reported that plain bupivacaine is unpredictable in its behaviour often spreading to different dermatomal levels in obstetric and non-obstetric patients. Factors affecting the spread of plain bupivacaine are complex, but it has been postulated that epidural venous engorgement in the lumbosacral region that occurs on movement may displace cerebrospinal fluid (CSF) in a cranial direction [16,17]. Russell and colleagues  suggested that pregnancy has a more marked effect on the spread of plain than hyperbaric solution when the differences between non-pregnant and pregnant patients are compared. In our study, the difference in sensory block levels between Groups A and C was thought to be related with the baricity of the local anaesthetic. These findings were consistent with the study investigating the effect of EVE on spinal anaesthesia with hyperbaric or plain tetracaine in non-obstetric patients . Beale and colleagues  studied the effect of EVE (7 mL) on the dose requirement of intrathecal hyperbaric bupivacaine and failed to demonstrate any advantage of EVE over intrathecal hyperbaric bupivacaine. The use of insufficient (7 mL) volume for epidural injection and the use of heavy bupivacaine instead of plain bupivacaine were claimed as reasons for the failure by the authors. Similarly, Yamazaki and colleagues  reported that the reinforcement of spinal anaesthesia by an epidural injection of saline is not affected by the baricity of the spinal anaesthetic solution used.
It is already known that the height of spinal anaesthesia is affected by the baricity of local anaesthetic [11,12]. However, so far, published studies evaluating the effect of EVE in obstetric patients are too small in size to address the issue and are inconsistent. Sarvela and colleagues  reported that sensory block levels were not different between hyperbaric and plain spinal bupivacaine. In that study, recovery from motor block was faster in the hyperbaric group. Similarly, Khaw and colleagues  stated that onset and recovery times of sensory and motor block were faster in a hyperbaric ropivacaine group than in a plain ropivacaine group. Vercauteren and colleagues  did not find any difference in sensory and motor block levels between hyperbaric and plain bupivacaine in Caesarean section. In our study, after EVE, we could not find any difference in the segmental spread of spinal anaesthesia with either hyperbaric or plain bupivacaine.
The incidence of hypotension in our study is less than that reported in other studies [2,9]. The characteristics of the block during spinal anaesthesia are influenced by the interaction among baricity, gravity and patient position. It was observed previously that when intrathecal injection was performed with patients in the lateral position, hyperbaric solutions tended to give a higher cephalic spread whereas plain solutions frequently resulted in insufficient cephalic spread of anaesthesia [21-24]. We performed the subarachnoid block with the patients in the sitting position, which may have affected our results and differences in block height might explain the difference in the incidence of hypotension.
The time interval to the first request for postoperative analgesic treatment was similar between the groups. Likewise, Karaman and colleagues , using similar subarachnoid medication, but with epidural bupivacaine top up, achieved similar pain-free time intervals. Additionally, similar intervals have also been reported in the literatures with higher doses . Parturients in the study group of Lew and colleagues  received 9 mg hyperbaric subarachnoid bupivacaine and had a very long pain-free time interval at 563±451 min. However, they did not discuss the reason for the prolonged time interval and high variance to the first analgesic requirement.
In our study, the incidence of intraoperative nausea and vomiting ranging between 36.6% and 56.6% suggested that the density of the block did not differ significantly between groups. The incidence of nausea and vomiting has been reported to be as high as 50% under both spinal and epidural anaesthesia during Caesarean section .
In conclusion, in patients undergoing Caesarean section under spinal anaesthesia with fentanyl and bupivacaine, the addition of EVE (10 mL) given after 5 min did not offer an enhancement in the segmental spread of spinal block.
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