Racemic bupivacaine is one of the most common local anaesthetics used for spinal analgesia and levobupivacaine is its S(−)-enantiomer. Clinical studies comparing levobupivacaine and racemic bupivacaine in epidural and spinal analgesia show that both are equally effective [1-6]. During epidural use, levobupivacaine and racemic bupivacaine have the same analgesic potency, however levobupivacaine is 13% less potent on a percentage weight per volume basis for motor block . Hence, in the epidural route, levobupivacaine has greater sensory-motor dissociation in blockade than racemic bupivacaine. It is likely that similiar sensory-motor dissociation is also present in the intrathecal use of levobupivacaine. Fentanyl is a lipophilic opioid which has been used as an adjunct to local anaesthetics, including racemic bupivacaine, for enhancement of analgesia without intensifying motor and sympathetic block in spinal analgesia [8,9]. It is possible that the addition of fentanyl to levobupivacaine may result in a mixture for spinal anaesthesia with minimal motor block and hypotension.
At the time this study was designed, no study had been published on the intrathecal use of 0.5% levobupivacaine with fentanyl. We performed this clinical study to compare the clinical efficacy, motor block and haemodynamic effects of using 2.3 mL of 0.5% levobupivacaine with fentanyl 15 μg (0.3 mL) and 2.6 mL of 0.5% levobupivacaine alone in spinal anaesthesia for urological surgery requiring sensory block to at least the tenth thoracic (T10) dermatome.
This prospective, randomized, double-blind study was approved by the Ethics Committee of Kwong Wah Hospital. After obtaining informed consent, 50 patients who were scheduled for elective transurethral resection of the prostate or bladder tumour were recruited into the study over a period of 9 months.
The inclusion criteria were aged between 50 and 75 yr, ASA I-III and body weight between 45 and 80 kg. The exclusion criteria were known hypersensitivity to amide local analgsics, contraindication to spinal analgesia or lack of understanding of English or Chinese.
The patients were then randomly assigned into two groups for spinal anaesthesia according to computer-generated random numbers inserted into sealed envelopes. Group L received 2.6 mL of 0.5% levobupivacaine (Antigen Pharmaceuticals Limited, Tipperary, Ireland for Abbott Laboratories) alone and Group LF received 2.3 mL of 0.5% levobupivacaine with fentanyl 15 μg (0.3 mL). Diazepam 5 mg was given orally as pre-medication on the morning of the operation and an intravenous (i.v.) infusion of 10 mL kg−1 of Hartmann's solution was given before initiation of the spinal anaesthesia. The anaesthesiologist who performed the intrathecal injection and assessment of the spinal block, was blinded to the group of study solution. The study solution was prepared by another anaesthesiologist who was not involved in the clinical care of the patient. Insertion of the spinal needle was undertaken in aseptic conditions using a 25-G Quincke needle at the lumbar L3-L4 interspace with midline or paramedian approach. The patient was in the left lateral position when the spinal needle was inserted. Upon completion of the intrathecal injection, the patient was immediately turned back to a supine position. All patients were given supplementary nasal oxygen of 2L min−1.
During the procedure electrocardiogram (ECG), heart rate (HR) and pulse oximetry were monitored continuously. Non-invasive blood pressure was taken before the conduct of spinal anaesthesia, every 2.5 min for 15 min after the initiation of spinal anaesthesia and every 5 min thereafter. Sensory blockade was monitored using loss of sensation to a cold spray of ethyl chloride, which was performed every 2.5 min for 15 min after the initiation of spinal anaesthesia and again at the end of the procedure. Motor blockade was assessed according to a modified Bromage Scale (0: no paralysis, able to flex hips, knees and ankles; 1: able to flex knees, unable to raise extended leg; 2: able to flex ankles, unable to flex knee; 3: unable to flex ankle, knee and hip) every 2.5 min for 15 min and at the end of the operation.
The operation was started 15 min after the initiation of spinal anaesthesia if the level of sensory block had reached T10 or above. If the level of sensory block was inadequate, then general anaesthesia was given.
Hypotension was defined as a decrease in the systolic blood pressure of more than 30% from the baseline or <100 mmHg. This was treated with i.v. infusion of Hartmann's solution or i.v. boluses of ephedrine 5 mg. Bradycardia was defined as a heart rate of <50 beats min−1 and was treated with i.v. injection of atropine 0.3-0.6 mg.
The onset of adequate sensory block was defined as the achievement of a sensory block level of T10 dermatome or higher. The addition of any sedative drugs, if required, was recorded. Patient satisfaction was assessed as good, fair or poor at the end of the operation. Adequacy of anaesthesia was assessed by the attending anaesthesiologist as good, fair or poor.
Sample size was calculated to provide 80% power to detect a 25% reduction in the incidence of complete motor block in the LF group compared with the L group. Statistical analyses were performed using student t-test (for parametric data), U-test (for non-parametric data) and χ2-test or Fisher's exact tests (for frequency data such as incidence). P < 0.05 was considered statistically significant.
Twenty-five patients were recruited in each group. There were no significant differences between the two groups for patient characteristic data, ASA classification and type of operation (Table 1). The baseline and intraoperative haemodynamic parameters were similar in both groups (Table 2). The onset time for adequate level of sensory block, the highest level of sensory block and degree of motor block were also similar in both groups (Table 3).
The efficacy of both levobupivacaine alone and levobupivacaine with fentanyl was good. Anaesthesia was adequate and patient satisfaction was good in all cases. Two patients, one in each group, required supplementary sedation with i.v. midazolam 1 mg and 2 mg, respectively.
Side-effects of anaesthesia with these two regimes were minor and infrequent. Three patients (12%) in the Group L had shivering. Hypotension occurred in four patients (16%), one in Group L and three in Group LF. No patient had nausea, vomiting or pruritus.
This study found that 2.3 mL of 0.5% levobupivacaine with fentanyl 15 μg was an effective mixture for spinal anaesthesia in urological surgery that required a sensory block to the T10 dermatome. The onset time, level of sensory block, degree of motor block and haemodynamic effects were similar between 2.6 mL of 0.5% levobupivacaine alone and 2.3 mL of 0.5% levobupivacaine with fentanyl 15 μg.
Levobupivacaine has been found to be as effective as racemic bupivacaine in spinal anaesthesia [5,6]. The effect of adding fentanyl to bupivacaine for spinal anaesthesia has been studied. Ben-David and colleagues (1997) compared the use of 0.17% bupivacaine 3 mL with and without fentanyl 10 μg in spinal anaesthesia for arthroscopy . The sensory blockade was significantly more intense with a lower failure rate in the group with fentanyl. Ben-David and colleagues (2000) compared the use of bupivacaine 4 mg with fentanyl 20 μg and bupivacaine 10 mg in spinal anaesthesia for surgical repair of hip fracture in geriatric patients . Both regimes were effective with less hypotension in the group with fentanyl. It was suggested that the intrathecal use of fentanyl had a synergistic effect with the low-dose bupivacaine in the achievement of a functional sensory blockade for surgical anaesthesia. The use of a low dose of bupivacaine was associated with a less sympathetic blockade resulting in lower incidence of hypotension. Choi and colleagues (2000) found that the intrathecal use of hyperbaric bupivacaine 8 mg with 10 μg of fentanyl was as effective as hyperbaric bupivacaine 12 mg in Caesarean section . The addition of fentanyl had the advantage of a low incidence of excessively high block. Martyr and Clark (2001) compared the use of 7.5 mg hyperbaric bupivacaine with fentanyl 20 μg and 12.5 mg hyperbaric bupivacaine alone . Both groups were equally effective with no differences in the incidence or severity of hypotension. Korhonen and colleagues (2003) found that 3 mg of hyperbaric bupivacaine with 10 μg of fentanyl was as effective as 4 mg of hyperbaric bupivacaine for knee arthroscopy . The recovery of motor function was faster in the group with fentanyl. These studies confirmed the local anaesthetic dose-sparing effect of fentanyl when it was added to bupivacaine for intrathecal use. This might be associated with less hypotension during spinal anaesthesia.
The use of racemic bupivacaine with fentanyl in spinal anaesthesia for urological surgery is effective. Kuusniemi and colleagues (2000) studied the effect of adding fentanyl 25 μg to bupivacaine for spinal anaesthesia . They found that the addition of fentanyl 25 μg to 5 mg of bupivacaine resulted in effective anaesthesia with motor block of short duration. While the addition of fentanyl 25 μg to 10 mg of bupivacaine increased the intensity and duration of motor block in comparison to bupivacaine 10 mg alone. The incidence of pruritus in all patients with fentanyl was 30%. Goel and colleagues (2003) studied the addition of fentanyl to bupivacaine 5 mg in spinal anaesthesia . It was concluded that the addition of fentanyl 12.5 μg provided better surgical anaesthesia and improved the reliability of block than fentanyl 7.5 or 10 μg. Haemodynamic stability was good in all patients. The incidence of pruritus was 33%. Kararmaz and colleagues (2003) compared the intrathecal injection of bupivacaine 4 mg with fentanyl 25 μg (Group F) and bupivacaine 7.5 mg (Group B) . The density and duration of motor block were more in Group B. Both groups had adequate sensory block for surgery. Hypotension was more significant in the Group B (25% vs. 0%). The incidence of pruritus was 75% in Group F. These studies showed that the addition of fentanyl to bupivacaine for spinal anaesthesia would augment the effect of bupivacaine. This would allow the reduction in the dose of bupivacaine used and would increase the reliability of lower dose of bupivacaine used for spinal anaesthesia. This might result in less intensity of motor block and less hypotension. However, the use of intrathecal fentanyl was associated with significant incidence of pruritus.
The addition of fentanyl to levobupivacaine has been found to have a dose-sparing effect on the requirement of levobupivacaine for epidural analgesia in labour . Intrathecal use of levobupivacaine has been studied. Our previous study with 2.6 mL of 0.5% levobupivacaine and that of Glaser and colleagues both found that 0.5% levobupivacaine and 0.5% bupivacaine have similar clinical effects, including sensory and motor block [5,6]. Intrathecal injection of an opioid with levobupivacaine had been studied by Vercauteren and colleagues . They used 2 mL of 0.125% levobupivacaine or racemic bupivacaine with sufentanil 0.75 μg mL−1 and epinephrine 1: 800 000 as the initial intrathecal injection for combined spinal-epidural analgesia in labour. They found that the levobupivacaine produced no motor block in comparison with 34% of patients in the bupivacaine group had motor block of Bromage Score 1. Our study found that 2.3 mL of 0.5% levobupivacaine with fentanyl 15 μg was as effective as 2.6 mL of 0.5% levobupivacaine alone in spinal anaesthesia. The haemodynamic effects, the characteristics of sensory and motor block were similar. Hence, the addition of fentanyl had a dose-sparing effect with levobupivacaine in spinal anaesthesia. Nevertheless, the potential advantages of less motor block and less hypotension were not unveiled in the dose used in our study. The potential side-effects of spinal fentanyl such as the pruritus, nausea and vomiting did not occur in our patients.
The potency ratio of levobupivacaine to racemic bupivacaine was 0.98 for epidural analgesia in labour pain . Their potency ratio in intrathecal use has not been determined. Our choice of comparing 2.6 mL of levobupivacaine with 2.3 mL of levobupivacaine and fentanyl 15 μg was based on our previous study on the efficacy of 2.6 mL of levobupivacaine in spinal anaesthesia for urological surgery and published result in the use of fentanyl with bupivacaine [6,14]. Further studies can be directed to find the optimal combination of levobupivacaine and opioid with maximal haemodynamic stability and least motor block, which may be useful for spinal anaesthesia in ambulatory surgery.
In conclusion, the haemodynamic effects and the characteristics of sensory and motor blockade are similar between 2.6 mL of 0.5% levobupivacaine alone and 2.3 mL of 0.5% levobupivacaine with fentanyl 15 μg in spinal anaesthesia for urological surgery requiring sensory block to at least T10 dermatome. The addition of fentanyl has a dose-sparing effect with 0.5% levobupivacaine in spinal anaesthesia. Both regimes are effective with minimal side-effects.
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