The use of ropivacaine for spinal anaesthesia has been described for obstetric [1,2] and nonobstetric patients [3-6]. Ropivacaine is a long-acting amide local anaesthetic with a high pKa and low lipid solubility . Previous studies with other local anaesthetics have shown that the addition of glucose improved the cephalic spread and reliability of anaesthesia and also shortened the duration of sensory and motor blocks [8,9]. For this reason, analgesia supplementation in the intraoperative period or early analgesic intervention in the postoperative period was often required [10-12]. Adding various opioids to the local anaesthetic solution administrated intrathecally improves the analgesic potency of local anaesthetics. In analgesia for caesarean section, it is important to use the smallest effective opioid dose to minimize potentially adverse maternal and neonatal risks .
There are few reports about the effects of fentanyl added to hyperbaric ropivacaine in caesarean delivery. The addition of fentanyl, a short-acting lipophilic opioid, to hyperbaric ropivacaine for caesarean delivery increases anaesthesia and analgesia of subarachnoid block without neonatal side-effects .
The purpose of this study was to evaluate the efficacy and safety of intrathecal fentanyl 10 μg added to 15 mg hyperbaric ropivacaine in patients undergoing caesarean section under spinal anaesthesia.
Thirty-seven healthy, full-term parturients, ASA I-II, scheduled for elective caesarean delivery under spinal anaesthesia, were included in this study. The study protocol was approved by the medical ethics committee of our hospital and a written informed consent was obtained from each patient. Patients who had obstetric complications, multiple gestation or suspected fetal abnormality were excluded.
This study was conducted in a randomized double-blind controlled fashion and an anaesthesiology nurse, who was not involved in the administration of spinal anaesthesia, prepared all drug solutions. Thus, the observer and the parturients were blinded to the drug solutions and patient groups. Patients were randomly assigned into two groups: Group S (saline group, n = 17) received 2.5 mL of 15 mg hyperbaric ropivacaine + 0.5 mL saline, in total 3 mL volume intrathecally; Group F (fentanyl group, n = 20) received 2.5 mL of 15 mg hyperbaric ropivacaine + 0.5 mL of saline containing 10 μg fentanyl, in total 3 mL intrathecally. The fentanyl solution was prepared by adding 2 mL of 50 μg mL−1 fentanyl to 3 mL saline and using 0.5 mL of the solution which contained 10 μg of fentanyl. The hyperbaric ropivacaine solution was prepared by adding 3 mL of 1% ropivacaine (Naropin, Astra Zeneca) to 2 mL of 20% dextrose and using 2.5 mL of the resulting solution which contained 15 mg of ropivacaine.
The patients were fasted overnight and received no medication preoperatively. After introduction of an intravenous (i.v.) cannula (>18-G), an infusion of lactated Ringer's solution 15 mg kg−1 was administered over approximately 15 min. Standard monitoring (pulse oximetry, non-invasive blood pressure (BP) and five lead electrocardiograms) was instituted before spinal anaesthesia. Both groups of patients received oxygen 4 L min−1 via a facemask. Spinal puncture was performed at the L3-4 interspace using a 25-G Quincke needle with patients in the right lateral decubitus position. After confirming free flow of clear cerebrospinal fluid, the study drug was injected over approximately 60 s. After the intrathecal injection, the patient was returned to the supine position with a left lateral tilt.
The assessments of sensory block to pinprick (bilateral mid-clavicular line using a short bevelled 27-G needle) were performed at every minute until it reached the T4 dermatome level after intrathecal injection and then every 15 min until regression to L5 level. Surgery was started when a sensory block ≥ the T4 dermatome was established. This time was noted as the onset of sensory block. Time to initial onset of anaesthesia, time for sensory block to reach the T7 dermatome, time for sensory block to reach the T4 dermatome, time to highest level of sensory block, time to regression of two segments from the maximum block height, time to regression of analgesic level to T10 and time to regression of analgesic level to L5 were recorded.
Motor block in the lower limb was assessed by using a modified Bromage scale (0: able to lift extended leg and hip; 1: able to flex the knee but not lift extended leg; 2: able to move the foot only; 3: unable to move even the foot). This test was performed every minute until complete motor block and then every 30 min until the return of normal motor function. The times to complete motor block and complete recovery were recorded.
Baseline maternal heart rate (HR) and arterial BP were recorded before induction, every 2 min before delivery and then every 5 min until discharge from recovery room. Hypotension, defined by a decrease in systolic BP to less than 100 mmHg or <80% of baseline, was treated with i.v. ephedrine 5-10 mg and additional lactated Ringer's solution. Bradycardia, defined as HR <60 beats min−1, was treated with i.v. atropine 0.5 mg. Nausea and vomiting were treated with metoclopropamide 10 mg and pruritus with diphenhydramide 20 mg both i.v.
Time intervals of spinal puncture, delivery and surgery were recorded. After delivery, blood samples were collected from the umbilical artery and vein for blood gas analyses. Apgar scores were assessed at 1 and 5 min by the attending paediatrician.
At the end of surgery, the investigator judged the quality of intraoperative analgesia as excellent (no discomfort or pain), good (mild pain or discomfort, no need for additional analgesics), fair (pain that required additional analgesics) or poor (moderate or severe pain that required more than fentanyl 100 μg or general anaesthesia).
Time to first feeling of pain (complete analgesia) and time to first request of analgesics (visual analogue score (VAS) ≥ 3) were recorded postoperatively. On the first postoperative day, patients were evaluated regarding possible side-effects including pruritus, nausea and vomiting, headache, back pain and other neurological symptoms.
Statistical analyses were performed using SPSS (version 10; SPSS Inc., Chicago, IL, USA). Data were analysed using paired or unpaired t-test, U-test or χ2-test, as appropriate. Data are shown as mean ± standard deviation (SD). A value of P < 0.05 was regarded as statistically significant.
The mean age, weight, height, spinal puncture-delivery time and duration of surgery were comparable between the groups (Table 1). Successful spinal anaesthesia was performed in all patients.
There was no significant difference between the two groups with respect to achieving sensory block to T7 and T4 dermatomal level, to the highest level of sensory block or in time to reach peak level. All patients developed sensory block to the T4 dermatome or higher. Regression of sensory block to L5 was significantly prolonged in the fentanyl group compared with the saline group (P = 0.001; Table 2). Times of complete motor block, the recovery of complete motor block and the degree of motor block were also similar between the two groups (Table 2).
The overall quality of spinal anaesthesia was similar in both groups. No patients in the fentanyl group required supplementary intraoperative analgesics, whereas one patient did in the saline group. Time to the first feeling of pain and the first analgesic requirement were significantly shorter in the saline group compared with the fentanyl group (Table 3).
The incidence of bradycardia, dyspnoea, hypotension, nausea, pruritus, shivering and the mean doses of ephedrine required during surgery were not different between the two groups (Table 4).
No patients required antipruritic or antiemetic treatments during the postoperative period and postural headache or neurological symptoms were not observed. Two patients in the saline group and four patients in the fentanyl group suffered from moderate backache localized at the injection site.
The newborn infants had a gestational age of 38 ± 2 week and a birth weight of 2980 ± 550 g, which were comparable between the groups. Umbilical arterial and venous blood gases did not differ between the groups (Table 5). Apgar scores were similar in both groups. One infant in the saline group had an Apgar score of <7 at 1 min. No infants had an Apgar score of >7 at 5 min.
In this study, we have shown that the addition of fentanyl to hyperbaric ropivacaine for spinal anaesthesia provides similar sensory and motor blocks, Apgar scores, umbilical pH values and side-effects but increases the duration of complete analgesia and effective analgesia in the early postoperative period in patients undergoing caesarean section.
The administration of local anaesthetics with opioids has become a well-accepted practice in the management of spinal anaesthesia for surgical procedures. Prolonging effective postoperative analgesia after caesarean delivery is considered to be an advantage of spinal anaesthesia. In the study of Chung and colleagues , hyperbaric ropivacaine 18 mg produced adequate spinal anaesthesia for caesarean delivery. However, intraoperative analgesic supplementation was required in 10% of patients. Due to the short duration of ropivacaine, it may be insufficient for the entire duration of surgery and additional analgesic requirement in the intraoperative period is generally required. However, in our study, hyperbaric ropivacaine 15 mg produced adequate spinal anaesthesia for caesarean delivery, and only one patient in saline group required analgesic supplementation in the intraoperative period.
Adding an opioid to the local anaesthetic may reduce the intraoperative pain which occurs with small doses of local anaesthetic despite apparently adequate spread of sensory anaesthesia . The addition of small-dose intrathecal fentanyl (10-25 μg) to local anaesthetics during spinal anaesthesia enhances sensory analgesia and increases its duration without intensifying the motor block or prolonging recovery [17-19]. It is accepted that ropivacaine has specific effects on sensory nerves rather than motor nerves . In our study, the onset time and the highest level of sensory block were not different in the two groups; however, intrathecal fentanyl prolonged the recovery of sensory block when compared with plain hyperbaric ropivacaine. These effects of intrathecal fentanyl with hyperbaric ropivacaine seem similar to those reported with hyperbaric ropivacaine or bupivacaine [13,14, 20,21].
The addition of fentanyl 10 μg to hyperbaric bupivacaine 8 mg has been reported to increase the intraoperative and early postoperative analgesic quality of spinal anaesthesia in patients undergoing caesarean section [22,23]. It has also been reported that fentanyl has a dose-dependent effect on duration of analgesia . Chung and colleagues  have shown that the addition of fentanyl 10 μg to 18 mg hyperbaric ropivacaine for spinal anaesthesia improved the quality of intraoperative analgesia and prolonged its duration by approximately 40 min and that of effective analgesia by approximately 70 min in the early postoperative period at caesarean delivery when compared with the control group. Our results were in agreement with those reported by these authors; in our study, the duration of complete analgesia was prolonged by approximately 24 min and the time to the first dose of analgesic administration by approximately 52 min in the fentanyl group.
Previous studies have reported the use of hyperbaric ropivacaine for spinal anesthesia [3,4,14,24]. It was shown that the incidence of hypotension was more frequent when using hyperbaric ropivacaine compared with plain ropivacaine . In another study, Chung and colleagues have demonstrated that the incidence of hypotension was frequent in 18 mg hyperbaric ropivacaine (67%) or 12 mg hyperbaric bupivacaine (80%) administered intrathecally in caesarean section . Based upon previous experience , we chose to use fentanyl 10 μg with 15 mg hyperbaric ropivacaine. In our study, the incidence of hypotension did not differ between the groups and all hypotensive episodes were of short duration and promptly corrected. We observed that i.v. prehydration was not so effective and better control of BP could be achieved with ephedrine.
Side-effects associated with use of intrathecal lipophilic opioids may include nausea, vomiting, urinary retention and dose-dependent respiratory depression. However, even in elderly patients, fentanyl 25 μg  intrathecally has been shown to provide peroperative analgesia without respiratory depression.
Addition of fentanyl to intrathecal local anaesthetics has also been reported to decrease the incidence of nausea and vomiting , although other studies have not confirmed this effect [21,23,26]. In our study, the incidence of nausea and vomiting were not significantly different between the groups. We observed a higher incidence of pruritus in the fentanyl group similar to those reported previously [13,23,26]. However, it was of mild intensity and lasted for a short duration, requiring no treatment. Umbilical blood pH values and unsatisfactory Apgar scores were similar in both groups.
In conclusion, this study shows that the addition of fentanyl 10 μg to hyperbaric ropivacaine 15 mg for spinal anaesthesia increased duration of complete analgesia and effective analgesia in the early postoperative period in patients undergoing caesarean delivery, without increasing maternal or neonatal side-effects.
We thank Professor Saim Yilmaz, Department of Radiology, Akdeniz University, for his helpful suggestions in the writing of this manuscript. This study was supported by Akdeniz University Medical Research Unit, Antalya, Turkey.
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