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Perispinal analgesia for labour followed by patient-controlled infusion with bupivacaine and sufentanil: combined spinal-epidural vs. epidural analgesia alone

Vernis, L.; Dualé, C.; Storme, B.; Mission, J. P.; Rol, B.; Schoeffler, P.

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European Journal of Anaesthesiology: March 2004 - Volume 21 - Issue 3 - p 186-192


Epidural analgesia for labour has been routinely used for many years in most industrialized countries. Its popularity has been enhanced by the introduction of low-dose epidural analgesic techniques, in which a low dose of local anaesthetic is supplemented with an opioid to provide analgesia with minimal motor block [1]. However, this technique has certain disadvantages because the time of onset of effective analgesia may be up to 30 min, and inadequate pain relief occurs in 15-20% of patients [2]. Attempts have been made to avoid these problems with the use of combined spinal-epidural analgesia [3], which induces analgesia faster, lowers the doses of epidural local anaesthetics needed - and therefore the risk of toxicity - reduces the incidence of unilateral analgesia and improves satisfaction of the parturient [4,5]. Furthermore, low-dose spinal-epidural analgesia techniques may facilitate labour by increasing the rate of cervical dilation [6], and allowing ambulation [7], although these advantages have also been produced using the epidural route with low-dose drug combinations [8].

The advantages of the combined spinal-epidural technique are counterbalanced by the adverse effects linked to intrathecal analgesia, such as pruritus [5,7,9,10], nausea and vomiting [9], hypotension [9,11], fetal bradycardia [12], postdural puncture headache [2] and meningitis [13,14]. Conventional epidural and combined spinal-epidural techniques have been compared during labour by several investigators [5,7,9,15-18]. These articles criticize the use of combined spinal-epidural analgesia, as intrathecal opioids induce a high incidence of pruritus.

In the present study, bupivacaine was administered at low concentrations and patient-controlled epidural administration of bupivacaine and sufentanil was used to reduce the motor block, to avoid prolonging labour and to reduce the need for local anaesthesia [19]. Our hypothesis was that these conditions would be favourable to demonstrate the potentially beneficial effect of combined spinal-epidural analgesia on the characteristics of labour. The main hypothesis was that combined spinal-epidural analgesia would reduce the duration of labour.


After approval from the local Ethics Committee (CCPPRB d'Auvergne) and collection of written informed consent, 113 pregnant women, aged 18-40 yr, were enrolled in a prospective double-blind randomized study. Inclusion criteria were pregnancy without major complication, active labour (3-6 cm cervical dilation) at full term (>37 weeks of gestation) and singleton, vertex fetuses. Exclusion criteria were contraindication to spinal analgesia due to haemodynamic, infectious, allergic, neurological or haematological reasons, complicated pregnancy including pre-eclampsia, psychological reasons, previous intravenous (i.v.) opioid administration and labour judged to be unduly complicated at enrolment. Parturients who underwent initial epidural puncture for analgesia during an on-call period (overnight or on Sundays) were not recruited. However, patients who underwent epidural puncture before an on-call period were included and observed according to the protocol described.

When labour became active and analgesia was indicated, parturients were randomly included into one of two study groups, in a blind fashion. Anaesthesia was performed by one of the senior anaesthetists involved in the study, using standardized protocols, both of which were routinely performed prior to this study. In the first group, analgesia was performed with combined spinal-epidural anaesthesia. In the second group, epidural analgesia was performed alone. All parturients received an i.v. infusion of lactated Ringer's solution, 500 mL over 30 min, then 30 mL h−1. Parturients were monitored with a cardioscope, automatic sphygmodynamometer and pulse oximetry. Fetal heart rate (HR) and external topography were recorded throughout the labour. The initial epidural puncture was performed with the parturient in the sitting position after sterile preparation with chlorhexidine and intradermal local anaesthesia at a lumbar level (L3-4 or L4-5 interspace) and with an 18-G Tuohy needle (Perifix®; Braun, Melsungen, Germany). The epidural space was located using the loss-of-resistance to fluid technique.

In the epidural analgesia group, a 20-G multihole catheter was inserted 3 cm into the epidural space, and the needle was then removed. An initial epidural injection of bupivacaine 0.125% with epinephrine 2.5 μg mL−1 plus sufentanil 7.5 μg was given. The volume injected was determined following the formula (0.2 × (patient height in cm − 100)). Four millilitres of local anaesthetic were injected initially, as a test dose, and then, if no signs of subarachnoid/i.v. injection appeared, the rest of the solution was injected. The upper sensory level of analgesia was assessed with a cold test. In case of failure of analgesia at the T10 level after 15 min, an additional 'top-up' of bupivacaine 0.125% 5 mL was injected through the catheter. In case of unilateral anaesthesia, this additional injection was performed following retraction of the catheter by 1 cm. When analgesia had been established, the epidural catheter was connected to a patient-controlled epidural analgesia device (IVAC, Rueil-Malmaison, France). The device allowed the parturient to self-administer bolus doses of bupivacaine 0.125% 4 mL plus sufentanil 0.25 μg mL−1. There was no continuous infusion. A 10 min lock-out time and a 12 mL h−1 maximal dose was programmed.

In the combined spinal-epidural group, after reaching the epidural space, a 120 mm, 27-G Whitacre needle (Braun, Melsungen, Germany) was inserted through the Tuohy needle to puncture the dura mater. When a flow of cerebrospinal fluid was observed, a single dose of bupivacaine 0.25% 1 mL (2.5 mg), plus sufentanil 5 μg - diluted in 1 mL of normal saline - was injected into the subarachnoid space. Then, after removal of the spinal needle, an epidural catheter was inserted as already described. When analgesia became insufficient, it was completed by the epidural route, following the same protocol as described, i.e. test dose, initial dose and patient-controlled epidural analgesia.

Spontaneous pain was assessed by the parturient using a visual analogue scale (VAS) (graduated from 0 to 100). A midwife recorded these data. Both midwife and parturient were blinded to the analgesic technique used. A pain score ≤30 was considered effective analgesia. The pain score was measured every 5 min until analgesia was obtained (the delay to first analgesia was noted), then every 30 min for 1 h, then hourly. Pain during the first hour was also assessed by calculating the area under the curve (AUC) for VAS values, as the sum of the values ((pain at tn+1 + pain at tn)/2) × (time (h) between tn and tn+1) calculated for each interval between the observations. For patients who had a vaginal delivery, pain scores on VAS were also noted at the time of delivery. Adverse effects of analgesia (pruritus, somnolence, nausea/vomiting and headache) were assessed by questioning the patient at each VAS observation. In case of persistent or unbearable opioid-related adverse effects, naloxone 40 μg was injected i.v. Headache was treated by i.v. propacetamol and, in case of persistence 1 day after delivery, an epidural blood patch was considered.

The degree of motor blockade induced by the perispinal analgesia was assessed clinically every hour, using the Bromage scale. Significant motor block was defined as a score <4 (full flexion of knees). At the time of delivery (or decision for Caesarean section), the consumption of bupivacaine and sufentanil, on the basis of additional boluses (self-administered or anaesthetist-administered), was calculated. Mean bupivacaine consumption was calculated for each patient as the ratio of total dose/duration of infusion. Maternal systolic, mean and diastolic arterial pressure, HR and SPO2 were recorded at the same observation times. Hypotension was defined as a decrease in mean arterial pressure of more than 30% of the initial value, or a value of systolic arterial pressure inferior to 100 mmHg. Any hypotensive incident, at any moment, was noted and treated with an i.v. bolus dose of ephedrine 3 mg or more if necessary, after the parturient had been positioned in the left lateral recumbent position. Fetal parameters were recorded throughout labour, and incidences were noted. Obstetric parameters, such as duration of first and second stage of labour (i.e. before and after complete cervical dilation), mode of delivery, indication for instrumental extraction and fetal presentation at the time of delivery, were recorded. Apgar scores at 1, 5 and 10 min after birth were noted.

The epidural catheter was removed after delivery. On day 3 after delivery, the patients were asked to reply to a simple written question (Were you satisfied with the pain relief you received during labour?) in order to establish a maternal satisfaction score concerning the quality of analgesia during labour (four-point Likert scale: excellent, satisfactory, somewhat unsatisfactory and unsatisfactory). Following completion, the patient was informed about the type of analgesia performed.

Data were collected using Microsoft Excel® 5.0 (Microsoft Corporation, USA). Data were expressed as mean ± standard deviation (SD). The t-test was used for comparisons of numerical data between the two groups (in the case of non-Gaussian distribution, data were expressed as median (CI25-CI75), and U-test was used). For comparison of the incidence of events (binary outcomes) between the two groups, the χ2-test was used. For comparisons of haemodynamic data at different times, one-way ANOVA for repeated measures was used, followed by a Dunnett's test for comparison to control (pre-analgesia) values. Statistical analysis was performed on Jandel Scientific SigmaStat® 2.0 (Jandel Scientific, San Rafael, CA, USA) and Microsoft Excel® 5.0.

According to previously published mean values (±SD) for the total duration of labour in a similar population [16,20-22], sample size for this study was based on an expected difference of 100 min (SD = 155). Thus, the initial sample size was set at 64 patients per group, with a risk α = 0.05 and β = 0.05 (two sided).


Although the desired sample size was initially set at 128 patients, this was reconsidered in the light of the incidence of adverse effects in the combined spinal-epidural analgesia group. The medical staff chose to end the study after inclusion of 113 parturients. However, as the sample size of 53 per group was sufficient to highlight differences using a one-sided test, the data could be used for analysis.

The analysis of the patient characteristics data (Table 1) revealed no significant differences between the two groups. At initial attempts to place the catheter, 20 patients required two punctures due to technical incidents (bleeding into the needle or catheter, insertion of the catheter impossible, intervertebal space not found). One parturient in the epidural group underwent a second puncture (combined spinal-epidural) after the initial analgesia had been given, and was excluded from the study. The different parameters of analgesia (i.e. ease of technique, effectiveness of pain relief, amount of the drugs needed to reach analgesia and maternal satisfaction) are shown in Table 2 and Figure 1. The combined spinal-epidural technique provided a faster onset of analgesia, allowed the use of a smaller quantity of perimedullar analgesic drugs and lowered the incidence of incomplete unilateral analgesia. Nevertheless, there was no difference in the score of maternal satisfaction. In the combined spinal-epidural group, the mean duration of analgesia following the first intrathecal injection (assessed with the time for first bolus demand) was 130.6 ± 24.7 min. Two parturients delivered before the end of intrathecal analgesia and were excluded from this calculation.

Table 1
Table 1:
Morphometric and patient characteristics.
Table 2
Table 2:
Quality of the analgesia for labour.
Figure 1
Figure 1:
Time course of pain during the first hour after induction of analgesia expressed as VAS score out of 100. □: Combined spinal-epidural analgesia; ▪: epidural analgesia. **P < 0.01; ***P < 0.001.

Table 3 shows that obstetrical and fetal parameters were not influenced by the technique used. There was a higher incidence of posterior fetal presentation in the combined spinal-epidural group.

Table 3
Table 3:
Obstetrical characteristics and newborn data.

Table 4 and Figure 2 show the possible inconveniences of each technique. Combined spinal-epidural analgesia induced more adverse effects such as pruritus and nausea. Hypotension was reported in the combined spinal-epidural group only; all episodes occurred within the first 10 min of the onset of analgesia. In one case, hypotension was associated with fetal bradycardia. In all eight cases, i.v. ephedrine, oxygen inhalation and adoption of the lateral decubitus position reversed the effects. A second case of fetal bradycardia occurred at the 30th min after induction of analgesia in the epidural group, without haemodynamic disturbance of the mother. It was reversed by i.v. nitroglycerin (100 μg) and oxygen.

Table 4
Table 4:
Adverse effects of perispinal analgesia.
Figure 2
Figure 2:
Time course of haemodynamic effects of perispinal analgesia. The percentage of the control value (i.e. the beginning of the procedure) is plotted against postoperative time (in hours). ○: combined spinal-epidural analgesia; ●: epidural analgesia. Data are expressed as mean values ± SEM. *P < 0.05, combined spinal-epidural analgesia vs. epidural analgesia. SAP: systolic arterial pressure; DAP: diastolic arterial pressure.

In one patient in the combined spinal-epidural group, the dura mater was accidentally punctured with the Tuohy needle. This patient suffered severe postdural puncture headache, requiring two consecutive epidural blood patches. In one 26-yr-old patient in the same group, severe headache appeared 14 h after delivery. It was first treated by i.v. propacetamol and an epidural blood patch. The patient then became hyperthermic (38.4°C), leading to a diagnostic lumbar puncture on the day 4 after puncture. The cerebrospinal fluid was turbid, and analysis revealed 1800 GB mm−3, no bacteria on direct examination, but Streptococcus mitis after culture. A diagnosis of meningitis was made and the condition rapidly cured using i.v. amoxycillin.


The main advantage of the combined spinal-epidural technique was rapid and effective analgesia (Fig. 1). This is in accordance with previous observations [5,18], where complete pain relief in all patients 5 min after intrathecal injection of bupivacaine and fentanyl was noted. The analgesia induced by the intrathecal injection was effective for at least 1 h (Fig. 1). The mean time of first demand for supplemental analgesia (130 min) was very close to that observed by Kartawiadi and colleagues [15] after bupivacaine 0.125% 1 mL plus sufentanil 10 μg injected intrathecally (137 min). Thus, the reduced need for bupivacaine and sufentanil observed here can be explained by the effectiveness of the initial spinal analgesia in the combined spinal-epidural group. However, this beneficial effect seemed to be short lived only, as pain at delivery was the same for the two groups.

Another beneficial effect of the combined spinal-epidural technique, highlighted by the results of our study, is the significant reduction in the incidence of incomplete unilateral analgesia. This may be explained by the fact that the active drugs spread towards the spinal sites of action after they are injected intrathecally, contrary to the epidural route. Furthermore, there was no difference in motor block between the two groups. This was not surprising as the concentration of intrathecal bupivacaine was intentionally kept low compared to previous studies [3,16]. Maternal satisfaction was not influenced by technique.

As the combined spinal-epidural technique allowed a significant reduction in the dose of local anaesthetic, it could in theory have a beneficial impact on obstetric dynamics. However, we failed to observe this because the duration of labour and the mode of delivery were not influenced by the technique used. Furthermore, there was a higher incidence of posterior fetal presentation in the combined spinal-epidural group. However, there is no clear explanation for this, even if the role of the faster onset of analgesia could be evoked [23].

Intrathecal injection of bupivacaine and sufentanil brings some significant disadvantages that must be emphasized. Some of these are minor and are related to sufentanil, such as pruritus, which is reported for about half of parturients [5,7,15], even when no local anaesthetic is injected intrathecally [9]. The increased incidence of nausea and somnolence can also be explained by this mechanism.

There was a slight tendency to hypotension in the combined spinal-epidural group, because systolic arterial pressure was lower in this group during the first hour of analgesia, and more hypotensive episodes occurred. However, if systolic arterial pressure were affected in the combined spinal-epidural group, neither diastolic arterial pressure nor HR was differently impaired. This indicates that the lower systolic arterial pressure in the combined spinal-epidural group could be explained by more effective analgesia produced rather than by bradycardia or vasoplegia. The possible role of intrathecal sufentanil (either by direct vascular effect or by reducing the pain-induced stress response) is suggested, as it can induce hypotension when injected alone [11]. Similarly, fetal bradycardia noted during 25% of the hypotensive events can be related to sufentanil, as previously reported [12]. As sufentanil 5 μg appears in the literature as the smallest efficient dose [24], we cannot expect to reduce hypotensive events by further lowering the dose of the opioid. This indicates that arterial pressure must be monitored frequently after intrathecal induction, and that hypotension must be immediately managed, as in general anaesthetic situations.

Finally, one case of meningitis was observed in this study, which can be considered as a major complication. This has been previously reported [13,14]. It must be noted that the rules of cross infection control and aseptic technique were fully respected during this clinical trial, as in daily practice.

In conclusion, this study showed that combined spinal-epidural analgesia for labour offered only few advantages over epidural analgesia, even when analgesia was maintained with patient-controlled boluses of bupivacaine. Another study to compare combined spinal-epidural analgesia with epidural analgesia alone has recently been published, using fentanyl as the additional opioid rather than sufentanil. These authors also concluded that combined spinal-epidural analgesia provided no advantage [16]. In the present study, the overall drug requirements were reduced in the combined spinal-epidural group compared to the epidural group, and the onset of analgesia was faster. However, combined spinal-epidural analgesia may be of benefit in particular cases, such as patients undergoing painful advanced labour [25,26] or patients with a previous experience of unilateral spread of epidural analgesia. The theory that combined spinal-epidural analgesia might facilitate the advance of labour was not supported. Adverse effects in the combined spinal-epidural group (pruritus, nausea, somnolence, headache, hypotension and meningitis) must be considered by the practitioner who wishes to use this technique routinely, and parturients must be informed about both the benefits and risks.


This paper was presented in part at the 2000 Annual Meeting of the Société Française d'Anesthésie et de Réanimation (Paris). The authors thank Agnès Barrière, Franck Bolandard, Philippe Duband and Claude Dubray for their technical assistance, and Denise Faulks for correction of the English manuscript.


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