Summary We evaluated the effect of low-dose bupivacaine plus fentanyl administered intrathecally in elderly patients undergoing transurethral prostatectomy. Patients were randomly assigned to one of two groups. Group F received plain bupivacaine 4 mg with 25 µg of fentanyl and sterile water to a total of 1.5 ml, and Group B received only 0.5% plain bupivacaine 7.5 mg for spinal anaesthesia. Sensory block was adequate for surgery in all patients. The mean level of motor block was higher and the duration of motor block was longer in Group B (p < 0.0001). Hypotension and shivering were significantly more common in Group B (p < 0.05). The addition of fentanyl 25 µg to plain bupivacaine 4 mg provides adequate analgesia for transurethral prostatectomy with fewer side-effects in elderly patients when compared with the conventional dose of bupivacaine.
Spinal anaesthesia is the most frequently used anaesthetic for transurethral prostatectomy (TURP). The signs and symptoms of water intoxication, fluid overload and bladder perforation can be recognised early because patient is awake. However, many patients undergoing anaesthesia for TURP are elderly and have coexisting cardiac or pulmonary disease. It is important to limit the distribution of spinal block to reduce adverse haemodynamic and pulmonary effects in such patients. By using very small doses of local anaesthetic, one can limit the distribution of spinal block, but low dose bupivacaine cannot provide an adequate level of sensory block. Intrathecal opioids enhance analgesia from subtherapeutic dose of local anaesthetic and make it possible to achieve successful spinal anaesthesia using otherwise inadequate doses of local anaesthetic [1–4].
Beers et al.  reported that a spinal block higher than L1 was adequate during TURP when bladder pressure was monitored and kept low. By using bupivacaine 7.5 mg, they obtained this sensory block level in all patients. However, Biboulet et al.  demonstrated that the incidence of hypotension was 40% in geriatric patients even when the dose of intrathecal bupivacaine was 5 mg.
In this study, we compared the effects of low-dose bupivacaine (4 mg) with fentanyl (25 µg) and a conventional dose of bupivacaine (7.5 mg) in elderly patients undergoing TURP.
The approval of the institutional Human Studies Committee was given for the study, and signed written informed consent was obtained from all participating patients. Patients with a history of previous back surgery, infection at the injection site, uncontrolled hypertension, hypersensitivity to amide local anaesthetics or fentanyl, mental disturbance, or neurologic disease were excluded from the study. The patients were randomly allocated into two study groups according to a list of random numbers. Group F received an intrathecal injection of plain bupivacaine 4 mg with 25 µg fentanyl diluted to 1.5 ml with sterile distilled water. Group B received only 0.5% plain bupivacaine 7.5 mg.
No premedication was given. ECG, non-invasive blood pressure, and peripheral oxygen saturation were monitored. After an intravenous access was established, the patients were received 500 ml sodium chloride 0.9% solution over 30 min. The intravenous infusion was maintained at 8 ml.kg−1.h−1 during the intra-operative period. A combined spinal-epidural set (Espocan, B. Braun, Melsungen, Germany) was used. The epidural space was identified at the L2-3 or L3-4 interspace using an 18 gauge Tuohy needle and the loss of resistance to air technique. A 27-gauge spinal needle was passed through the epidural needle and 1.5 ml of the study solution injected intratechally over a period of 10 s. The study solution was prepared by another investigator and its content blinded to the anaesthetist who administered it. The direction of the needle aperture was cranial during the injection. The spinal needle was removed and an epidural catheter was inserted 2.5–3 cm into the epidural space and secured with tape, but no medication was injected via this catheter. The patients remained in the supine position until the sensory blockade reached the highest dermatomal level. Motor blockade was assessed at the time of reaching peak sensory level and this was considered the maximum motor blockade. All patients were then placed in the supine lithotomy position, and surgery was started. Oxygen was continuously given to the patients via a face mask. Sensory block was determined with a 22-gauge needle in the midlineand dermatomal levels tested every two minutes from injection until the level stabilised for four consecutive tests. Testing was then conducted every 10 minutes until two segment regression. Further testing was then performed at 20 minute intervals in the recovery room until recovery of the S2 dermatome. All times were recorded from the intrathecal injection. The highest dermatomal level of sensory blockade, the time to reach this level, motor blockade at the time of reaching peak sensory level, the time to two segment regression, the time to S2 sensory regression were recorded. Motor block was assessed with the Bromage scale (0 = no motor block; 1 = hip blocked; 2 = hip and knee blocked; and 3 = hip, knee and foot blocked). Duration of motor block was considered as the time when Bromage score returned to 0. Pain was assessed every 10 minutes from the beginning of surgery using a 10-cm visual analogue pain scale. In the event of a patient complaining of pain during surgery with a pain score over three then seven mls of 1% lidocaine would be administered epidurally.
Systolic arterial pressure (SAP), diastolic arterial pressure (DAP), and heart rate (HR), were recorded every 3 min in the first 15 min after spinal anaesthesia, and then every 5 min until end of surgery. Hypotension (SAP < 90 or 30% decrease from the baseline) and bradycardia (HR < 45) were treated with intravenous bolus of ephedrine 5 mg and atropine 0.5 mg IV, respectively. Midazolam was given intravenously in 0.5 mg increments as indicated for anxiolysis. Adverse effects such as nausea, vomiting, shivering, pruritus, respiratory depression, and transient neurological symptoms were recorded. At the end of surgery, the amount of glycine used and the duration of surgery were recorded.
Statistical analysis was performed using the SPSS 9.0 (SPSS Inc., Chicago, IL, USA) for Windows. Sample size calculation was performed based on the results of Martyr et al. . In that study, when bupivacaine 7.5 mg used for spinal anaesthesia, the incidence of hypotension was 65%, and we were aiming at detecting a decrease to less than 20%. With a power of 80% and type 1 error of 5%, we calculated that 19 subjects were required per group. Incidence of pre-existing pathologies and adverse effects were tested with the Chi-squared test. The Student's t-test was used to analyse age, weight, height, duration of surgery, baseline and lowest blood pressure, recovery times of sensory and motor block, and volume of glycine. Inter-group differences of the amount of ephedrine used, peak sensory block level, and maximum motor block score were tested with the Mann–Whitney U-test. Data were expressed as mean (SD), median (interquartile range [range]) or number (proportion) as appropriate, and p-values < 0.05 were interpreted as statistically significant.
The two groups were comparable with respect to age, height, weight, and duration of surgery (Table 1).
Table 1. Patient characteristics and duration of surgery. Data are mean (SD).
Group F(n = 20)
Group B(n = 20)
Duration of surgery; min
There was no significant difference between the groups with regard to the level of dural puncture. In group F, intrathecal injection was made at L3-L4 interspace in 17 patients and at the L2-L3 interspace in three patients. In group B the L3-L4 interspace was used in 19 patients and the L2-L3 interspace in one patient.
The total amount of midazolam given in Group F and B was 6 mg and 5 mg, respectively. Study results are summarised in Table 2. In Group F, the spinal block provided a significantly less profound motor block (p < 0.0001). Duration of motor block was also shorter in Group F (p < 0.0001). Baseline and lowest blood pressures are shown in Fig. 1. Lowest systolic blood pressures in Group B were significantly lower than those of Group F (p = 0.015). Side-effects and complications are reported in Table 3. The incidence of hypotension and shivering was significantly higher in Group B (p = 0.024, p = 0.046). The total amount of the ephedrine used for treatment of hypotension was higher in Group B (50 mg) than that of Group F (0 mg) (p = 0.019). Pruritus not requiring any treatment occurred in Group F. Four patients in Group F had penile erection during surgery. Sensory block was adequate for surgery in all cases, and no patient required supplemental epidural lidocaine in both two groups.
Table 2. Study data. Values are median (interquartile range [range]) or mean (SD) ( * p < 0.0001).
This study showed that the use of plain bupivacaine 4 mg with 25 µg of fentanyl provided adequate spinal anaesthesia for TURP, and better haemodynamic stability than conventional dose. The synergism between intrathecal opioids and local anaesthetics may allow a reduction in the dose of local anaesthetic and reduce hypotension, while still maintaining adequate anaesthesia. Our results are consistent with those studies demonstrating that intrathecal opioids enhance analgesia without altering the degree of sympathetic blockade when added to subtherapeutic doses of local anaesthetics [8,9]. Although Beers et al.  reported that a mid-lumbar block level provided adequate anaesthesia for TURP when bladder pressure kept low, sensory block extending to the T10 is necessary to provide adequate analgesia, since monitoring of intravesical pressure is not available always . However, the sensory block was frequently higher than this level even when bupivacaine 5 mg combined with 25 µg of fentanyl was used for spinal anaesthesia . In addition, there is the risk of hypotension when bupivacaine 5 mg is used for spinal anaesthesia in elderly patients .
Spinal anaesthesia is often used in elderly patients undergoing urologic surgery, but intra-operative hypotension is a common and sometimes deleterious event in elderly patients [9,11]. Moreover, the high incidence of coronary disease in this population increases the risk of myocardial ischaemia secondary to hypotension . The incidence of coronary artery disease is 23% in our study. In order to avoid hypotension, a preloading dose of 500 ml of NaCl 0.9% solution was administered, followed by continuous infusion of 8 mg.kg−1.h−1 throughout the operation as the recommended in the review by Critchley . Nevertheless, the incidence of hypotension was 20% in the patients administered bupivacaine 7.5 mg. Fluid loading has not always been effective since the reduced physiological reserve of the elderly makes them less able to increase their cardiac output in response to fluid loading [13,14]. Hypotensive episodes were treated with ephedrine, and no complications related to further myocardial ischaemia were observed during the intra- and postoperative period. Martyr and Clark  have claimed that a dose of isobaric bupivacaine less than 10 mg is necessary to avoid hypotension in elderly patients. In view of our findings we believe that it may be necessary to reduce this figure to 7.5 mg.
Boucher et al.  suggested that fentanyl did not change the characteristics of the spinal block with spinal procaine. Ben-David et al.  showed that fentanyl added to bupivacaine did not affect median block level, but it intensified sensory blockade and increased duration of sensory block. In our study, intrathecal fentanyl increased dermatomal spread without affecting motor function. These results are consistent with those studies in which it has been demonstrated that fentanyl added to small dose of local anaesthetics improve the quality of block, and increase duration of sensory block [17,18].
Spinal opioids carry the risk of respiratory depression in elderly patients. Varrassi et al.  showed that 25 µg of fentanyl did not cause respiratory depression, but 50 µg did. Fernandez-Galinski et al.  suggested that 25 µg of spinal fentanyl induced oxygen desaturation, but benzodiazepines used during pre- and per-operative period was responsible from this depression. In view of this we used minimal doses of benzodiazopines intra-operatively in this study. Marthry and Clark  suggested that intrathecal fentanyl in combination with small doses of intravenous midazolam can be safely administered to elderly patients provided they are given oxygen and observed closely.
Pruritus was the most common adverse effect in patients who received intrathecal fentanyl as previously reported by other investigators [18,21]. However, none of the patients needed treatment. No patients suffered the vomiting, but one patient in Group F complained of nausea that did not required treatment. Interestingly, the incidence of penile erection was higher in Group F. Surgery can continue in most of these patients, but one of these patients was treated with intracavernous injection of epinephrine 10 µg. Perhaps, low-dose bupivacaine inhibited pain sensation but might not affect touch sensation and lead to penile erection. Shivering during spinal anaesthesia is a common complication in patients undergoing TURP. Shivering is known to increase oxygen consumption, ventilation and cardiac output, which can result in morbidity to patients with limited cardiopulmonary reserves . Our results confirmed that the addition of fentanyl to low dose bupivacaine decreased incidence of shivering during spinal anaesthesia in elderly patients [22,23].
In conclusion, we believe that intrathecal bupivacaine 4 mg combined with fentanyl 25 µg provides adequate anaesthesia for TURP in elderly patients and is associated with a lower incidence of hypotension of shivering than a conventional dose of bupivacaine (7.5 mg).