Effect of intrathecal clonidine versus fentanyl on bupivacaine spinal block in transurethral resection of prostate surgeries.

AIMS: Our study aimed at comparing the onset, degree and recovery time of sensory and motor block, the hemodynamic effects and postoperative pain relief using intrathecal bupivacaine alone, bupivacaine along with fentanyl and clonidine.
MATERIALS AND METHODS: A total of 90 patients, undergoing transurethral resection of prostate (TURP) surgeries under spinal anesthesia were studied. Patients were randomly divided in a double-blind manner into three groups of 30 patients each. Group A (control) patients given subarachnoid block with 0.5% hyperbaric bupivacaine with 0.5 ml of normal saline. Group B patients were given subarachnoid block with 0.5% hyperbaric bupivacaine along with fentanyl 25 μg. Group C patients were given subarachnoid block with 0.5% hyperbaric bupivacaine 10 mg along with clonidine 30 μg and 0.3 ml of normal saline. After administering the subarachnoid block, vitals were recorded before and after surgery. Level of sensory block, the duration of motor block (DOMB), duration of sensory blockade (DOSB), the quality of postoperative analgesia using linear visual analog scale (VAS), and side effects were evaluated.
RESULTS: The time required to attain a maximum height of the block was significantly more in Group B as compared to Groups A and C, which was statistically significant. However, there was no statistically significant difference between Groups A and C. The mean DOSB in Groups A, B, and C were 90.83 ± 9.48 min, 135.33 ± 12.59 min, and 155.17 ± 17.49 min, respectively. The mean DOMB in Groups A, B, and C were 83.83 ± 6.52 min, 115.50 ± 14.70 min and 120.67 ± 11.50, respectively. Time of the first request of analgesia in Groups A, B and C in postoperative period were 132.50 ± 21.53 min, 296.00 ± 50.07 min, and 311.83 ± 65.34 min. patients had. VAS was significantly of higher value in Group A than Groups B and C.
CONCLUSIONS: Intrathecal clonidine in a combination of bupivacaine for TURP provides more satisfactory anesthesia and analgesia and has less side effects.

RCT Entities:   Population Interventions Outcomes

INTRODUCTION

Urological surgeries like transurethral resection of the prostate (TURP) are largely restricted to the geriatric population. They have a high incidence of anesthesia-related complications, especially hypotension increasing the risk of ischemia to various vital organs.[1] Bupivacaine, most commonly used the drug for subarachnoid block produces hypotension and bradycardia.[2] High doses of bupivacaine may lead to myocardial depression, heart blocks and dysrhythmias. The addition of certain adjuvants can counterbalance these side effects of the subarachnoid block with bupivacaine.

There are a number of studies on the use of intrathecal clonidine or fentanyl with bupivacaine in various lower abdominal surgeries.[345]

However, no study has been conducted to evaluate the efficacy of these additives in urological surgeries like TURP.

Our study aimed at using intrathecal bupivacaine alone, bupivacaine along with fentanyl and clonidine. The onset, degree and recovery time of sensory and motor block, the hemodynamic effects and postoperative pain relief were compared in the three groups.

MATERIALS AND METHODS

The present study was conducted after approval by the Hospital Ethics Committee. After obtaining a written informed consent a total of 90 patients, belonging to American Society of Anesthesiologists (ASA) physical status I and II scheduled for TURP surgeries under spinal anesthesia, were randomly divided in a double-blind manner into three groups of 30 patients each.

Group A (control)

Patients were given subarachnoid block with 2 ml of 0.5% hyperbaric bupivacaine with 0.5 ml of normal saline.

Group B

Patients were given subarachnoid block with 2 ml of 0.5% hyperbaric bupivacaine along with fentanyl 25 µg (0.5 ml).

Group C

Patients were given subarachnoid block with 2 ml of 0.5% hyperbaric bupivacaine along with clonidine 30 µg (0.2 ml) and 0.3 ml of normal saline.

The procedure of giving subarachnoid block was done by a senior anesthesiologist and data were collected by the investigator who was unaware of the nature of the drug given.

A routine preanesthetic check-up, comprising of general physical examination and systemic examination of all patients was conducted a day before surgery. Routine investigations such as hemoglobin, bleeding time, clotting time, urine routine, fasting blood sugar, blood urea, serum creatinine, and serum electrolytes were done in all patients.

After shifting patient to the operating table in the operation theatre, monitoring of heart rate (HR), noninvasive blood pressure (NIBP), respiratory rate (RR), and electrocardiography and oxygen saturation (SpO2) were done.

Under strict aseptic condition, lumbar puncture was performed in sitting position at the level of L3–4 or L4–5 intervertebral space using 26-gauge Quinke's spinal needle after infiltrating skin with 0.5–1 ml of 2% lidocaine. After obtaining a free flow of cerebrospinal fluid, study drug was injected intrathecally at approximately 0.25 ml/s. After administering the subarachnoid block, the spinal needle was taken out, and the patient was made to lie in the supine position and the position of operating table was kept horizontal.

We recorded various parameters such as; HR, NIBP, RR, and SpO2 were recorded at 2 min interval for the first 20 min from the time of subarachnoid block and then after every 15 min till the completion of surgery. Episodes of perioperative hypotension (systolic blood pressure [BP] <90 mm Hg or fall in systolic BP >20% of baseline value) and bradycardia (HR <50 beats/min) was also recorded. Hypotension was treated with an incremental dose of mephentermine (3 mg) intravenously, and bradycardia was treated with injection atropine intravenously.

The level of sensory block was determined by temperature test every 2 min until the level was established. The maximum upper level of sensory block (MUSLB) and the time taken to attain maximum upper level was recorded.

The duration of motor block (DOMB) of the lower extremities was measured according to the modified Bromage scale every 2 min till achievement of Bromage score 3 or up to maximum of 15 min, whichever was earlier.

Postoperative assessment included the duration of sensory blockade (DOSB) which was noted by assessing the level of the sensory block after every 15 min until the time of regression to T 12 level. Motor block was assessed and graded at the end of surgery and then at 15 min interval using the modified Bromage scale. Time until full return of lower extremity motor function (score = 0) was noted.

The quality of postoperative analgesia was assessed using a 0–10 linear visual analog scale (VAS) every 15 min until the first request of supplement analgesia.

HR, NIBP RR, and SpO2 were recorded after every 15 min for the 1st h and then half hourly till the time of analgesia request.

Side effects which as nausea, vomiting, pruritus, respiratory depression (RR <10 breaths/min or SpO2<90%) and hypotension or any other complication were noted.

Statistical analysis

A sample size of 25 patients per group was adequate to detect the difference and median duration of analgesia between the groups using the Mann–Whitney U-test, with a power of 0.9 and an α = 0.05. We included 30 patients in each group to allow for dropouts and protocol violations. The data collected for various parameters was statistically analyzed using the SPSS (SPSS 15.0, SPSS Inc., Chicago, IL, USA). Mean and standard deviations were individually compiled. The comparisons were done by analysis of variance.

RESULTS

Patient characteristics including age, weight, and height were compared in all the three groups. All the groups were statistically comparable with P values more than 0.05.

Most patients belonged to ASA grades I and II. Distribution of patients as per ASA grade was comparable among all the three groups' patients with a P > 0.05 which was statistically insignificant.

Preoperative HR, mean BP and RR were 77.03 ± 13.24, 100.5 ± 12.00, and 15.19 ± 2.12 in Group A, respectively. It was 76.07 ± 13.44, 98.6 ± 11.5, and 16.23 ± 2.56 in Group B, and 77.67 ± 9.77, 97.4 ± 10.6, and 16.53 ± 2.29 in Group C which were comparable with a P > 0.05 which was statistically insignificant.

The time required to attain MUSLB (time of onset of the maximum sensory block) in Groups A, B, and C were 10.43 ± 1.97 min, 12.03 ± 2.59 min, and 9.26 ± 1.43 min, respectively. The time required to attain a maximum height of the block was significantly more in Group B as compared to Groups A and C, which was statistically significant (P < 0.05). However, there was no statistically significant difference between Groups A and C [Table 1].

Table 1

Value of various variables in the three groups

The mean DOSB in Groups A, B, and C were 90.83 ± 9.48 min, 135.33 ± 12.59 min, and 155.17 ± 17.49 min, respectively. The DOSB was statistically significant in all groups.

The mean DOMB in Groups A, B, and C were 83.83 ± 6.52 min, 115.50 ± 14.70 min, and 120.67 ± 11.50 min, respectively. The DOMB was statistically significant.

Time of the first request of analgesia in Groups A, B, and C in postoperative period were 132.50 ± 21.53 min, 296.00 ± 50.07 min, and 311.83 ± 65.34 min. TOAR was later in Groups B and C and was statistically significant as compared to Group A. Group C has meant time of analgesia request even later than in Group B, which was statistically insignificant.

There was a significant difference between all the three groups in achieving the highest level of sensory block [Figure 1]. In intra-group comparison, 36.66% patients in Group A had MUSLB as T8, which was the most common MUSLB. In Groups B and C, most common MUSLB was T10 (36.66% of a patient of Group B and 53.33% patients in Group C) [Figure 1].

Figure 1

Distribution of groups according to maximum upper level of sensory block

There was no statistically significant difference in baseline HR in all the groups. The baseline HR in Group A was 77.03 ± 13.24 per min. After 20 min of the subarachnoid block, there was an initial decrease in HR of 7.79% which further dropped to 9.09% in 20 min after subarachnoid block. Similar trends of decrease in HR were also observed in Groups B and C [Figure 2]. At the same point of time fall in HR was similar in all the three groups and there was no significant difference between the three groups at various time intervals.

Figure 2

Comparison of intraoperative heart rate trends

There was no statistically significant difference in the baseline mean BP in all groups. The baseline mean BP in Group A was 100.49 ± 10.92 mm Hg. Maximum fall of 10.7% in systolic BP was observed 15 min after giving subarachnoid block. The baseline means BP in Group B was 98.63 ± 10.36 mm Hg. In Group B, maximum fall of 9.28% in mean BP observed 25 min after giving subarachnoid block. The baseline means BP in Group C was 98.78 ± 9.27 mm Hg. Fall in mean BP of 9.06% in mean BP was observed 20 min after giving subarachnoid block.

The baseline RR in all the groups was comparable. The baseline RR in Group A was 16.23 ± 2.55 per min. The baseline RR in Group B was 16.30 ± 2.56 per min. The baseline RR in Group C was 16.53 ± 2.29 per min.

The baseline saturation in all the groups was comparable. The baseline saturation in Group A was 98.93 ± 1.08 per min, in Group B it was 98.93 ± 1.08 per min in Group C it was 98.77 ± 1.14 per min. In no patient, fall in saturation was <90%.

The mean postoperative HR in Group A varied from 68.37 to 72.50. It was between 69.87 and 71.90 in Group B and 69.57 to 71.00 in Group C. The change in mean postoperative HR at all-time was statistically insignificant in all groups.

Comparing the three groups there was in clinically and statistically insignificant change in the mean BP.

The mean RR varied between 16.20 and 16.73 in Group A, in Group B it varied from 16.20 to 17.27 and in Group C it varied from 15.63 to 16.80.

The mean postoperative SpO2 in Groups A and B varied between 98.70 and 98.97. In Group C, it varied from 97.69 to 98.57. On inter-group comparison trends in postoperative saturation was statistically significant with P < 0.05 but fall in saturation was clinically insignificant.

Postoperatively, patient's pain was graded was graded according to VAS score. The quality of analgesia was assessed until the first request of analgesia. On intergroup comparison, VAS was significantly of higher value in Group A than Groups B and C. The trend of increase in VAS was significantly earlier in Group A as compared to Groups B and C. No significant difference in VAS scores was observed in between Groups B and C (P < 0.05).

Nausea and vomiting were seen in 6.67% patients of Group A, and none in Groups B and C. Pruritus was seen in 46.66% Group B patients while in Groups A and C [Figure 3].

Figure 3

Comparison of perioperative side effects

DISCUSSION

Spinal anesthesia is commonly used the technique for various urological procedures like TURP. Most of such patients are elderly, and the majority of them have coexisting cardiac and pulmonary comorbidity. The duration of TURP ranges from 60 to 75 min, and the level of the sensory blockade is required at T10 dermatome during most of the transurethral surgeries.[6]

Common complications associated with spinal anesthesia are hypotension, bradycardia, post-dural puncture headache, backache, urinary retention, and inadequate, or failed block requiring supplementation of general anesthesia.[78] Opioids and local anesthetics administered together intrathecally have potent synergistic analgesic effects. Intrathecal fentanyl enhances the sensory block without altering the degree of sympathetic blockade.[9] Neuraxial administration of opioids in conjugation with local anesthetic not only improves the quality of intraoperative analgesia but also prolongs the duration of postoperative analgesia.[1011] The side effects such as respiratory depression, pruritus, urinary retention, however, have prompted further research to develop non-opioid analgesics with less worrisome side effects.

Clonidine is a direct actin alpha adrenergic agonist which increases both sensory and motor block of local anesthetics.[12] Neuraxial clonidine does not cause respiratory depression.

Opioids and clonidine in conjunction with local anesthetics help in decreasing their dose thereby reducing side effects and prolonging the duration of postoperative analgesia.[13] In our study, we evaluated the effects of addition of fentanyl 25 µg and clonidine 30 µg with 0.5% hyperbaric bupivacaine (10 mg) for TURP surgeries.

Onset of sensory block

It is the time was taken to reach the maximum level of sensory block. In our study, it was 10.43 ± 1.97 min, 12.03 ± 2.59 min, and 9.26 ± 1.43 min in Groups A, B, and C, respectively. The onset of sensory block was earliest in Group C. There was statistically significant delay in onset of the block in Group B as compared to Groups A and C, which was statistically significant. However, there was no statistically significant difference between Groups A and C. Our study results are in accordance with previous study conducted by Sia[14] in which onset of sensory block was rapid in patients receiving clonidine with bupivacaine and sufentanyl as compared to patients who received bupivacaine and sufentanyl.

Height of sensory block

In prostatic surgeries, the sensory blockade level produced by regional anesthetic technique should be approximately T9–T10 to prevent the discomfort of bladder distension. A sensory level above T9 is undesirable as pain due to perforation of the prostatic capsule will not be apparent to the patient if a complication occurs. Lower level of the block in elderly patients also has a better hemodynamic stability. In our study, there was a significant difference in all the three groups in achieving the MULSB). Group A had MUSLB (T8). In Group B, the maximum MULSB was T10 in 36.66% of patients in Group C MULSB was 53.33%. In our study, Group C had more satisfactory level achieved for urological surgeries.

Duration of sensory block

In our study, block regression was significantly slower with the addition of intrathecal clonidine and fentanyl. The mean DOSB was statistically significant in Groups B and C as compared to Group A. The DOSB was longest in Group C (155.17 ± 17.49 min as compared to 90.83 ± 9.48 min in Group A and 135.33 ± 12.59 min in Group B). Our study was consistent with clinical reviews of clonidine for regional anesthesia by Eisenach et al.[15]

Motor block

Our study demonstrated statistically significant difference regarding the DOMB the between Group A as compared and Groups B and C. Motor blockade in all the three groups was determined using modified Bromage score. In our study, the mean DOMB in different group was 83.83 ± 6.52 min, 115.50 ± 14.70 min, and 120.67 ± 11.50 min in Groups A, B, and C, respectively. It was prolonged in Groups B and C as compared to Group A with Group C having the maximum DOMB. The studies conducted by Niemi.[16] and Merivirta et al.[17] showed similar results.

Perioperative hemodynamic

Hemodynamic parameters studies in both intraoperative and postoperative period included HR, NIBP, RR, and SpO2.

Heart rate

There was no statistically significant difference in baseline HR in all the groups. At the same point of time fall in HR was similar in all the three groups and there was no significant difference between the three groups are various time intervals.

Blood pressure

There was no significant difference in baseline mean systolic BP in all groups. Fogarty et al.,[18] van Tuijl et al.[19] observed similar results.

Respiratory rate

The baseline RR in all the groups was comparable. None of the patients in any group developed respiratory depression.

Oxygen saturation

The baseline saturation in all the groups was comparable. In no patient fall in saturation was <90%.

Postoperatively also on intergroup and intragroup comparison at all-time intervals there was no clinically significant change in hemodynamic. Niemi[16] van Tuijl et al.[19] Dobrydnjov and Samarütel[20] also observed similar results.

Postoperative analgesia

In our study, the postoperative analgesia was graded according to VAS score. The quality of analgesia was assessed until the first request of analgesia. On inter-group comparison; VAS was significantly of higher values in Group A than Groups B and C. The trend of increase in VAS was significantly earlier in Group A as compared to Groups B and C. Group C has longest mean time of analgesia request. Improved perioperative analgesia following co-administration of fentanyl or clonidine and bupivacaine can be explained by a synergistic inhibitory action of these agents on A delta and C fiber conduction. Niemi,[16] van Tuijl et al.,[19] also reported similar finding.

Perioperative side effects

Nausea and vomiting was seen in 6.67% patients of Group B none in Groups A and C. Our results were similar to results observed by Fogarty et al.,[18] and Grace et al.[21]

Pruritus was seen in 46.66% Group B patients while not in Groups A and C. similar results have been observed by Benhamou et al.,[22] where the addition of fentanyl increased the incidence of pruritus.

In our study, only one additive that is, fentanyl or clonidine was administered to the patients, however studies are currently being published where authors have shown that a combination of clonidine and fentanyl with bupivacaine gives better results.[6] The ideal additive can be decided only after randomized control trials using a greater number of patients.

CONCLUSIONS

Our study favors the use of intrathecal clonidine (30 µg) in combination of hyperbaric bupivacaine (10 mg) in elderly patients undergoing TURP in spinal anesthesia because

It provides more satisfactory sensory level of T10 for patients

This combination has shorter onset of sensory block

This combination has slightly greater DOSB and postoperative analgesia with minimal difference in DOMB as compared to fentanyl group

Hemodynamic stability is maintained perioperatively

Clonidine has the advantage of not having pruritus, nausea and vomiting as side effects.

The combination of intrathecal clonidine or fentanyl as adjuvants to bupivacaine in spinal anesthesia is although equally acceptable clinically in terms of DOSB; motor block, duration of analgesia and hemodynamic stability as compared to bupivacaine alone. The advantage of shorter onset and more appropriate level of sensory block for TURP surgeries and not having pruritus, nausea and vomiting as side effects with intrathecal clonidine favor its use as adjuvant to bupivacaine in spinal anesthesia for TURP surgeries in geriatric patients.