Subarachnoid block is a widely used technique for elective and emergency Caesarean sections. Despite the excellent quality of analgesia and motor block that can be achieved solely by an intrathecal injection of hyperbaric bupivacaine, many patients require postoperative analgesia early after operation . The addition of lipophilic opioids (fentanyl and sufentanil) to local anaesthetics shortens the onset time of the block, improves the quality of surgical anaesthesia and prolongs the duration of analgesia [2-5]. Lipophilic opioids produce a lower incidence of side-effects, e.g. respiratory depression, due to less rostral spread in the subarachnoid space, compared with hydrophilic opioids . The addition of sufentanil 10-20 μg to hyperbaric bupivacaine in the subarachnoid space significantly prolongs the duration of complete and effective analgesia compared with bupivacaine alone. However, increasing the dose of subarachnoid sufentanil >10 μg does not achieve any corresponding increase in complete and effective analgesia .
Sufentanil in doses <10 μg added to hyperbaric bupivacaine for Caesarean section was evaluated in one study . The aim of the present study was to evaluate the comparative efficacy of bupivacaine combined with different doses of sufentanil using the subarachnoid route in pregnant women undergoing Caesarean section.
This prospective, double-blind, randomized, controlled trial was undertaken after the Institutional Ethics Committee approved the protocol and written informed consent was obtained from each patient. Eighty healthy, full-term parturients, ASA I-II, scheduled for elective Caesarean section under subarachnoid block were included in the study. Exclusion criteria were severe pre-eclampsia, ASA III or more, multiple gestation and prematurity. The parturients were fasted and did not receive premedication. The patients were randomly distributed according to a computer-generated random number list into four groups of 20 patients each. All groups were given hyperbaric bupivacaine 0.5% 12.5 mg (2.5 mL). Additionally, Groups 2-4 were given sufentanil 2.5 μg (0.5 mL), 5.0 μg (1 mL) or 7.5 μg (1.5 mL), respectively. Preservative-free physiological saline 0.9% was added to all the solutions to achieve a total volume of 4 mL. The dose of the study drug used was unknown to the anaesthesiologist administering the anaesthesia or to the anaesthesiologist who evaluated patients' responses.
In the operating room, each patient was continuously monitored with an electrocardiogram, a pulse oximeter and a non-invasive blood pressure device. Lactated Ringer's solution 500-750 mL was infused intravenously (i.v.) before the spinal block. With the patients in the sitting position, a 25-G Quincke needle was inserted at the L3-L4 interspace for induction of spinal anaesthesia. The anaesthetic solution was injected over 90 s. After the block was performed, the patients were placed in the supine position with left displacement of the uterus until birth. Oxygen (5 L min−1) by facemask was given until delivery. Fluid therapy was maintained with lactated Ringer's solution (10 mL kg−1 h−1). An experienced anaesthesiologist who was unaware of the drug given evaluated the spinal block and other physiological variables. Hypotension was defined as systolic arterial pressure <100 mmHg or >20% decrease from preanaesthetic values. Any hypotension was treated with a rapid infusion of crystalloids and, if persisting, a bolus of ephedrine (5 mg i.v.) was administered. Bradycardia was defined as heart rate <50 beats min−1 and treated with atropine (0.01-0.02 mg kg−1).
The following variables were evaluated: onset of the block - defined as the time between the injection of the intrathecal anaesthetic solution and the absence of pain at the T10 dermatome - assessed by pinprick; maximum level of sensory block - evaluated by pinprick every 3 min for 20 min after the end of the anaesthetic injection; degree of motor block - evaluated with the Bromage scale (0 = none; 1 = ability to flex knees, but not the hips; 2 = unable to flex knees, but no problems with ankle movement; 3 = no movement possible in any lower extremity) every 3 min for the first 20 min; duration of analgesia - defined as the time interval between the performance of the block and the patient's spontaneous request for pain relief. Maternal cardiovascular and respiratory variables: systolic (SBP) and diastolic arterial pressure (DBP), heart rate (HR), oxygen saturation (SPO2) were evaluated before the block, immediately after the block, every 5 min during surgery, at the end of procedure and during discharge from the postanaesthetic recovery ward.
The occurrence of maternal side-effects such as nausea, vomiting, pruritus, somnolence, respiratory depression (respiratory rate < 10 breaths min−1) were noted. Apgar scores at 1 and 5 min were also observed. To analyse the data, Fisher's exact test and ANOVA using Scheffe's test made comparisons between the groups. P < 0.05 was considered as statistically significant .
There were no significant differences among the groups with respect to physical characteristics and parity of the women (Table 1). The onset time of the block was significantly shorter in patients who received sufentanil. There were no differences among the groups in the highest level of sensory block or in motor block. Analgesia was significantly prolonged in Groups 3 and 4 (Table 2). With respect to the duration of analgesia, determination of the statistical power of the study for a between-group difference using the four groups and their mean differences using ANOVA was estimated as 93% (β = 0.07, d.f. = 3). Pruritus and somnolence were observed in the groups receiving sufentanil. These effects increased significantly in the group given sufentanil 7.5 μg (P < 0.01) compared with the other groups (Table 3).
All the patients maintained respiratory rate >10 breaths min−1 and peripheral O2 saturation between 95 and 100%. No significant differences among the groups were observed in SBP, DBP and HR at any time. All Apgar scores were satisfactory.
Our results were similar to those of others [4,7] and demonstrate that the addition of sufentanil 5.0 and 7.5 μg to hyperbaric bupivacaine significantly prolonged the duration of analgesia in comparison with that provided by bupivacaine alone or combined with a lower dose of sufentanil (2.5 μg). In the group receiving the lowest dose of sufentanil, there was a slight but insignificant increase in the duration of analgesia compared with the control group. These findings are similar to those of others , who studied the combination of bupivacaine and different doses of fentanyl. They emphasized that the optimal dose of fentanyl was 6.25 μg, since higher doses did not produce a corresponding increase in the duration of analgesia. Although we observed a significantly longer duration of analgesia in Group 4 (i.e., those who received the highest dose of sufentanil, 7.5 μg) than in Groups 1 and 2 (control and lowest dose, 2.5 μg), there was no difference between Groups 3 and 4 (given intermediate dose, 5 μg). In addition, it has been estimated that the differences between the duration of analgesia produced by sufentanil 5.0 and 7.5 μg is 7 min, which is not statistically significant. Nevertheless, the simultaneous 95% confidence interval associated with this difference −44.9 to 58.9 min, i.e., the estimate is not precise enough considering that the interval is relatively wide. A more precise comparison between the duration of analgesia produced by sufentanil 5.0 and 7.5 μg would therefore require a much larger sample size. This needs to be addressed in future studies.
These results indicate that increasing the dose of sufentanil >5 μg significantly increases the incidence of pruritus without any advantage in terms of postoperative analgesia, and has already been reported . In addition to pruritus, opioids delivered by the spinal route may produce nausea, vomiting, urinary retention and respiratory depression mainly due to opioid action at the μ- and κ-receptors . In this study, the primary side-effects were nausea and pruritus, which were mild and brief not requiring medication. Coinciding with data from the literature [4,7], the pruritus was dose-dependent. It was also the most frequently observed side-effect occurring in 80% of the group receiving the highest dose (7.5 μg) of sufentanil. Similar results were also found in patients receiving analgesia during labour with spinal anaesthesia sufentanil 10 μg . Somnolence occurred more frequently in patients who had received the highest dose of opioid. However, according to Courtney and colleagues , the respiratory rate was never <10 breaths min−1, despite the occurrence of somnolence. However, we are aware that the respiratory rate is not the most reliable means to detect respiratory depression and that the number of patients included in our study is not large enough to detect this side-effect. The optimal indicator of a drug's potential to cause respiratory depression is still a subject of controversy. Although the ventilatory response to CO2 and PaCO2 are considered the most sensitive indicators of respiratory compromise , nevertheless because of its simplicity, respiratory rate is the most frequently employed variable to evaluate respiratory status.
Haemodynamic changes during Caesarean section under spinal anaesthesia with hyperbaric bupivacaine can be worsened by the changes inherent in pregnancy [12,13]. Hypotension - defined as systolic arterial pressure < 100 mmHg or a 30% decrease from baseline values - has the highest potential for causing detrimental effects to the fetus. Its incidence and severity depend on the spread of the block, the circulating blood volume and aortocaval compression . In our study, these changes were not seen, despite the levels of sensory block (T4) achieved. This may have been attributed to prophylactic fluid therapy before and during block performance, as well as continuous left uterine displacement until the birth. In the doses used, maternal sufentanil did not affect the neonate as demonstrated by 1 and 5 min Apgar scores (>7). These results had already been observed . Although the level of sensory block in all groups was recommended and considered adequate for the performance of Caesarean section, episodes of nausea were common. This side-effect, which has been documented before, may be a sign of subclinical visceral pain and occurs during uterine manipulation and peritoneal traction and closure . In this study, the incidence of nausea during the intraoperative period was lower in those groups that received sufentanil (n.s.). The reduction in intraoperative nausea by the addition of fentanyl and sufentanil to hyperbaric bupivacaine has been reported [7,15]. The lack of any need for i.v. analgesic supplementation confirmed that intraoperative analgesia was adequate and may have been potentiated by the subarachnoid opioid [3,4,7,15].
In rats, epidural sufentanil has been compared with other routes of administration including subcutaneous and subarachnoid administration. In terms of onset analgesia, the order of latency is subarachnoid < epidural < subcutaneous . Sufentanil exerts a certain local anaesthetic effect, which has been proven in an isolated nerve preparation, resulting in nerve conduction block not susceptible to reversal by naloxone [16,17]. The local anaesthetic activity of opioids, albeit weak, may increase the antinociceptive effect when these agents are applied intrathecally. In the groups where opioid was added to bupivacaine, onset of the block (absence of pain at T10 dermatome) was faster than in the control group and was not dose-related. Our results differ from those described by others who did not observe a reduction in time of onset, even when higher doses of subarachnoid opioids were used [4,7], although latency was evaluated considering the absence of pain at the T4 dermatome. Therefore, the results from this study should be interpreted with care because of methodological differences compared with other studies [4,7], and the small number of patients, which could be a major risk of making a Type II error.
In summary, the combination of sufentanil with hyperbaric bupivacaine for subarachnoid block in Caesarean section proved advantageous, leading to a more rapid onset of analgesia and prolonged postoperative pain relief without maternal-fetal repercussions. These findings demonstrated the advantage of using opioids in conjunction with local anaesthetic. Intrathecal 5.0 and 7.5 μg sufentanil increased the duration of analgesia compared with sufentanil 2.5 μg and placebo. Pruritus, the most common side-effect, has a significantly higher incidence when doses of 7.5 μg were used.
1. Dahl JB, Jeppesen IS, Jorgensen H, Wetterslev J, Moiniche S. Intraoperative and postoperative analgesic efficacy and adverse effects of intrathecal opioids in patients undergoing cesarean section with spinal anesthesia. A qualitative and quantitative systematic review of randomized controlled trials. Anesthesiology
2. Van Steenberger A. Epidural and subarachnoid opioids in labor and delivery: European view. In: Van Zundert A, Ostheimer GW, eds. Pain Relief Anesthesia in Obstetrics.
New York, USA: Churchill Livingstone, 1996: 225-228.
3. Hunt CO, Naulty JS, Bader AM, et al.
Perioperative analgesia with subarachnoid fentanyl bupivacaine for cesarean delivery. Anesthesiology
4. Courtney MA, Bader AM, Hartwell B, Hauch M, Grennan MJ, Datta S. Perioperative analgesia with subarachnoid sufentanil administration. Reg Anesth
5. Shende D, Cooper GM, Bowden MI. The influence of intrathecal fentanyl on the characteristics of subarachnoid block for caesarean section. Anaesthesia
6. Cousins MJ, Mather LE. Intrathecal and epidural administration of opioids. Anesthesiology
7. Dahlgren G, Hultstrand C, Jakobsson J, Norman M, Eriksson EW, Martin H. Intrathecal sufentanil, fentanyl, or placebo added to bupivacaine for cesarean section. Anesth Analg
8. Montgomery D. Design and Analysis of Experiments,
3rd edn. New York, USA: Wiley, 1991: 649.
9. Snyder SH. Opiate receptors and internal opiates. Sci Am
10. Camann WR, Minzter BH, Denney RL, Datta S. Intrathecal sufentanil for labor analgesia. Effects of added epinephrine. Anesthesiology
11. Takki S, Aromaa U, Kauste A. The validity and usefulness of end tidal PCO2
during anesthesia. Ann Clin Res
12. Van Gessel EF, Foster A, Schweizer A, Gamulin Z. Comparison of hypobaric, hyperbaric and isobaric solutions of bupivacaine during continuous spinal anesthesia. Anesth Analg
13. Kestin IG. Spinal anaesthesia in obstetrics. Br J Anaesth
14. Gomar C, Fernandez C. Epidural analgesia-anaesthesia in obstetrics. Eur J Anaesthesiol
15. Randalls B, Broadway JW, Browne DA, Morgan BM. Comparison of four subarachnoid solutions in a needle-through-needle technique for elective caesarean section. Br J Anaesth
16. Power I, Brown DT, Wildsmith JAW. The effect of fentanyl, meperidine, and diamorphine on nerve conduction in vitro. Reg Anesth
17. Gissen AJ, Gugino LD, Datta S, Miller J, Covino BG. Effects of fentanyl and sufentanil on peripheral mammalian nerves. Anesth Analg