|Year : 2013 | Volume
| Issue : 1 | Page : 76-82
Addition of intrathecal fentanyl to bupivacaine clonidine mixture effect on quality of subarachnoid block and postoperative analgesia
Marilyn Nazareth, Pabitra Ghoshal, Viraj Namshikar, Yogesh Gaude
Department of Anaesthesiology, Goa Medical College, Bambolim, Goa, India
|Date of Web Publication||26-Jun-2013|
Room No 323, GARD Hostel, Goa Medical College, Bambolim, Goa
Source of Support: Goa Medical College, Conflict of Interest: None
| Abstract|| |
Context: This study was undertaken in 100 patients scheduled for lower limb orthopaedic surgeries.
Aim: The objective of this study was to study the effect of addition of intrathecal fentanyl to bupivacaine clonidine mixture on the quality of subarachnoid block and compare it with intrathecal bupivacaine clonidine mixture without fentanyl.
Settings and Design: In this prospective and double blind randomized controlled study, one hundred patients, between 20-40 years of age, of either sex, weighing between 40-65 Kg, measuring more than 150 cm in height, of ASA Grade I and II who were undergoing orthopaedic lower limb surgeries were selected in order to study the quality of subarachnoid block and post-operative analgesia produced by a combination of bupivacaine clonidine and fentanyl in comparison with bupivacaine clonidine.
Materials and Methods: The patients were randomly divided in two groups of 50 each: Group BC: 2.4 ml of 0.5% hyperbaric bupivacaine (12 mg) + 0.2 ml (30 μg) clonidine + 0.4 ml of 0.9% NaCl. Group BCF: 2.4 ml of 0.5% hyperbaric bupivacaine (12 mg) + 0.2 ml (30 μg) clonidine + 0.4 ml (20 μg) of fentanyl. The total volume of solution in both the groups was 3.0 ml. The quality of subarachnoid block and post-operative analgesia were studied.
Statistical Analysis Used: The data thus obtained was statistically analysed using the following tests: Unpaired student's t-test. Average % change in data over baseline values to detect trends. A 'P' value of <0.05 was considered to be statistically significant.
Results: There was no significant difference in duration of sensory and motor blockade in group BCF compared to BC. The duration of analgesia as assessed by, either VAS score of >5 or demand of additional analgesia was > 524.6 ± 32.21 mins in group BC and > 774.4 ± 59.59 mins in group BCF. This prolongation of duration of analgesia in group BCF compared to group BC has statistical significance. Blood pressure and heart rate changes were not significantly different among groups, whereas sedation and pruritus were significantly more frequent in Group BCF.
Conclusions: In conclusion, this study has demonstrated that addition of 20 μg fentanyl to intrathecal 30 μg clonidine and 12 mg bupivacaine enhanced the duration of post-operative analgesia with moderately increased sedation and was not associated with hemodynamic instability or other complications.
Keywords: Bupivacaine, clonidine, fentanyl, intrathecal, post-operative analgesia
|How to cite this article:|
Nazareth M, Ghoshal P, Namshikar V, Gaude Y. Addition of intrathecal fentanyl to bupivacaine clonidine mixture effect on quality of subarachnoid block and postoperative analgesia. Anesth Essays Res 2013;7:76-82
|How to cite this URL:|
Nazareth M, Ghoshal P, Namshikar V, Gaude Y. Addition of intrathecal fentanyl to bupivacaine clonidine mixture effect on quality of subarachnoid block and postoperative analgesia. Anesth Essays Res [serial online] 2013 [cited 2020 Jul 8];7:76-82. Available from: http://www.aeronline.org/text.asp?2013/7/1/76/114003
| Introduction|| |
Spinal anesthesia with bupivacaine is administered routinely for lower abdominal and lower limb surgeries. The resulting nerve block is sufficient to ensure patient's wellbeing, while motor block facilitates the surgeon's work. It also provides effective pain relief in the initial post-operative period. When a patient is going to receive spinal anesthesia, with local anesthesia agents like bupivacaine, addition of an adjuvant drug intrathecally that will increase the efficacy of neuraxial block is a logical choice. Predictably, thus, a number of adjuvants have been added to spinal local anesthetics e.g., opioids like morphine, buprenorphine, pethidine, hydromorphone, fentanyl, sufentanil, and tramadol.  Other adjuvants like clonidine, ketamine, and neostigmine have been introduced recently.  Various studies have shown that intrathecal Clonidine along with opioids produce prolongation of spinal anesthesia and reduces the need of post-operative analgesic requirement. ,,, This would be beneficial in surgeries of long duration also. By using low dose clonidine and fentanyl the incidence of adverse effects of these drugs also could be reduced.  Therefore, we conducted a prospective, double blinded study to assess the effect of addition of intrathecal fentanyl to combination of bupivacaine clonidine on the quality of spinal anesthesia and post-operative analgesia and to study the effect of this combination on hemodynamic and vital parameters in Indian patients.
| Materials and Methods|| |
In this prospective and double blind randomized controlled study, 100 patients, between 20-40 years of age, of either sex, weighing between 40-65 Kg, measuring more than 150 cms in height, of ASA Grade I and II who were undergoing orthopaedic lower limb surgeries were selected in order to study the quality of subarachnoid block and post-operative analgesia produced by a combination of bupivacaine clonidine and fentanyl in comparison with bupivacaine clonidine. After obtaining approval from the institutional ethics committee and ascertaining selection criteria, informed, valid written consent was obtained from each of the patients for participation in the study. One hundred patients, between 20-40 years of age, of either sex, weighing between 40-65 Kg, measuring more than 150 cms in height, of ASA grade I and II who were undergoing orthopaedic lower limb surgeries were selected. Exclusion criteria were: Patient refusal, patient on chronic analgesic therapy, patient with gross spinal deformity, patient with peripheral neuropathy, patient taking sympathomimetics or sympatholytic drugs, pregnancy/lactation, known allergy to local anesthetics, history of chronic headache or backache, local infection at the site, coagulation disorder, surgeries due to last longer than 3 h, ASA Grade III, IV, V, and history of alcohol or drug abuse. Preoperative evaluation was carried out in all patients with detailed history, general physical examination including height, weight, evidence of any spinal deformity or any neurological disease and mental status of the patient. Vital parameters [pulse, blood pressure, oxygen saturation in room air, respiratory rate] were noted and systemic examination was performed. The patients were randomly divided in two groups of 50 each using a computer generated random number list: Group BC: 2.4 ml of 0.5% hyperbaric bupivacaine (12 mg) +0.2 ml (30 μg) clonidine + 0.4 ml of 0.9% NaCl. Group BCF: 2.4 ml of 0.5% hyperbaric bupivacaine (12 mg) +0.2 ml (30 μg) clonidine + 0.4 ml (20 μg) of fentanyl. The total volume of solution in both the groups was 3.0 ml.
Preoperatively adequate fasting was confirmed and baseline heart rate and blood pressure were noted. Non-invasive monitoring was initiated including pulse oximeter, end tidal carbon dioxide, cardioscope and sphygmomanometer. A peripheral venous access was secured on non-dominant hand with 18 gauge cannula and preloading with lactated Ringer's solution was initiated at the rate of 8-10 ml/kg, 15 min prior to subarachnoid block. No sedatives or analgesics were administered preoperatively. Subarachnoid blockade was performed in sitting position with midline approach with strict aseptic precautions using 25 G Quincke needle. The drug combination was prepared by a different anesthesiologist. The anesthesiologist performing the block and later monitoring the patient was blinded to the nature of drug combination being injected intrathecally. Patients were immediately placed in supine position supporting the head and shoulders. The operation table was kept horizontal to the floor after institution of spinal block. Oxygen face mask was applied with flow rates 6 L/min.
The highest level of sensory block was checked by pin prick method, caudal to cephalad direction every 2 min after the procedure of the subarachnoid was complete and the time taken to achieve this was noted. Motor block was assessed by Modified Bromage scale (0: No motor block, 1: Inability to raise extended leg; able to move knees and feet, 2: Inability to raise extended leg and move knee; able to move feet, 3: Complete block of motor limb).  Intraoperative sedation score was graded (0: Wide awake. 1: Sleeping comfortably but responding to verbal commands. 2: Deep sleep but arousable. 3: Not arousable.)  Vital parameters like heart rate, arterial blood pressure, respiratory rate end tidal carbon dioxide and peripheral oxygenation saturation were noted immediately after injection and thereafter every 2 min for first 10 min, every 5 min for next 10 min, every 10 min for next 50 min, every 30 min for next 2 h, every 60 min for next 3 h and then at 12 h and 24 h after injection.
Surgery was allowed after satisfactory subarachnoid block was established. Satisfactory block was defined as a sensory level of L1 and Modified Bromage score of 3. Duration of surgery was noted. At the end of surgery, no prophylactic pain relief was given and patients were transferred to post anesthesia care unit and monitoring was continued for vital parameters. Sedation score, level of sensory block, motor block and visual analogue scale (VAS), which were explained to patient prior, were noted every 15 min for the first 2 h, every 30 min for the next 4 h and thereafter every 6 h interval until 24 h. Duration of sensory block was defined as: From time of injection of subarachnoid drug till the level of regression to L5 - S1 level assessed by reappearance of sensation on heel and sole of foot. Duration of motor block was defined as: from the time of injection of subarachnoid drug until the time the patient was able to flex hip, knee and ankle (Modified Bromage scale 1) of non-operated limb. Both the durations were noted. Post operative pain was assessed by Visual Analogue Scale (VAS) using a plain scale measuring 10 cms with 1 mm markings. Duration of analgesia was considered as interval from time of intrathecal injection to the time of first analgesic demanded post-operatively or when VAS score was >5 whichever was first. We chose VAS score of 5 since, it depicts moderate pain and we wanted to asses till how long can the patient be comfortable only by virtue of neuraxial blockade. Injection Tramadol i.v. 100 mg was used as rescue analgesic. At that point, study was terminated with respect to analgesia. All the patients were observed for any side effects or complications in the post-operative period for 24 h.
To calculate the sample size, power analyses of α = 0.05 and α = 0.9, showed that 45 patients were required in each group. Hence, we chose a sample size of 100. The primary outcome variable was duration of analgesia and hemodynamic changes.
The data obtained was statistically analysed using the following tests: Unpaired student's t-test. Average % change in data over baseline values to detect trends. A 'P' value of < 0.05 was considered to be statistically significant.
| Results|| |
Consort flow diagram [Figure 1]. In this prospective study, both the groups were comparable in age weight, height and duration of surgery [Table 1]. Extent of sensory blockade was clinically similar in both groups [Table 2]. The highest level was T6 and lowest, T10. The time required for highest level in group BC was 7.46 ± 1.46 min and group BCF was 6.50 ± 1.29 min and this difference was statistically not significant (P = 0.14). There was no significant difference in duration of sensory blockade in group BCF compared to BC [Figure 2] (P = 0.96). All the patients in both the groups had complete motor blockade (modified Bromage scale 1) [Table 3]. There was no significant difference in the duration of motor blockade in both the groups [Figure 3] (P = 0.88). The duration of analgesia as assessed by, either VAS score of > 5 or demand of additional analgesia, was 524.6 ± 32.21 min in group BC and 774.4 ± 59.59 min in group BCF [Figure 4]. This prolongation of duration of analgesia in group BCF compared to group BC has statistical significance (P = 0.0001). The mean heart rate [Figure 5], systolic [Figure 6] and diastolic pressures [Figure 7] were comparable in both the groups preoperatively, intraoperatively and post-operatively. The incidence of hypotension and bradycardia were similar. The mean peripheral oxygen saturation was maintained in all cases perioperatively [Figure 8]. There were no instances of hypoxia. Hypoxia was defined as fall in peripheral oxygen saturation < 90%. In this study, highest sedation score was 2. In both groups all patients were calm, sleeping comfortably with 20% of the patients having sedation score of 2 and 80% of the patients having score of 1 in Group BC. Whereas, in Group BCF 70% of the patients had sedation score of 2 and 30% had a score of 1. No patient was excessively sedated. This was statistically significant [Figure 9] (P = <0.0001). The difference in incidence of hypotension (P = 0.3911), bradycardia (P = 0.4968) and nausea vomiting (P = 0.5354) are not statistically significant. The incidence of shivering in Group BC was 8% and in Group BCF it was 2% and this difference was statistically not significant. There were 2 incidences of dry mouth (P = 0.9956) in Group BC. In Group BCF, there were 2 incidences of urinary retention (P = 0.8965) and 4 incidences of pruritus (P = 0.9854) [Figure 10]. No neurological adverse events occurred during study.
| Discussion|| |
Spinal anesthesia is a popular anesthesia technique for lower limb surgeries. Though it provides effective analgesia in initial postoperative period, this effect is very short lasting. In the context of "Augmentation strategies" for intrathecal analgesia, the discovery of opioid receptors and the subsequent development of the technique of epidural and intrathecal opioid administration is undoubtedly one of the most significant advances in pain management in the last three decades. Plethora of studies has shown that intrathecal opioids can provide profound post-operative analgesia with fewer central and systemic adverse effects than with opioids administered systemically. A wide variety of non-opioids have also been used in epidural or subarachnoid space to achieve pain relief without the risk of respiratory depression. , Segmental analgesia induced by spinal administration of opioids and non-opioids have been used successfully to treat intraoperative pain, post-operative pain, traumatic pain, obstetric pain, chronic pain and cancer pain. Clonidine is a selective partial agonist for α2 adrenoreceptors. It is known to increase both sensory and motor block of local anesthetics.  The rationale behind intrathecal administration of clonidine is to achieve a high drug concentration in the vicinity of α2 adrenoreceptors in the spinal cord and it works by blocking the conduction of C and Ad fibers, increases potassium conductance in isolated neurons in vitro and intensifies conduction block of local anesthetics. , Opioid receptors were identified in the central nervous system in 1971  later, in 1977; these receptors were precisely localized in the posterior horn of the spinal cord.  The effectiveness of intrathecal opioids depends on their bioavailability. Penetration into medullary tissue is influenced by their molecular weight, degree of ionization, and lipophilicity. Fentanyl and meperidine are absorbed more rapidly than morphine for these reasons. They bind more solidly to neural tissue. Clearance depends on diffusion along the neuraxis, as well as vascular absorption. The drug reaches the cerebellomedullary cistern via diffusion where it is absorbed by the arachnoid granulations. This is particularly true in the case of morphine. The more lipophilic products are reabsorbed at the site through spinal vasculature. 
In our study, it was found that duration of sensory and motor blockade remained same after addition of fentanyl. The maximal extension of the sensory blockade was T6. The upper level of sensory blockade level attained was similar in both the groups. Time taken to achieve highest level of sensory block in Group BCF was quicker than that in Group BC. A complete motor blockade of lower extremities was observed in all patients. The duration of analgesia in group BCF was significantly higher. Thus, patients receiving clonidine and fentanyl as adjuvant to bupivacaine were pain free and comfortable for longer duration after surgery compared to patients receiving bupivacaine clonidine.
| Conclusions|| |
In our study, we observed that, in both groups all patients were calm, sleeping comfortably. No patient was excessively sedated. Sedation is a well known side effect of clonidine and fentanyl notwithstanding the fact that the patients who received clonidine and fentanyl were more sedated than those in the control group, no excessive sedation or respiratory depression was noted in our study. This underlies the safety of low dose intrathecal clonidine plus fentanyl. The hemodynamic parameters viz. Heart rate and blood pressure were monitored perioperatively. The data obtained from our study shows that the baseline heart rate was well maintained, except for slight reduction in both the groups at 5-30 min after subarachnoid block. The incidence of hypotension and bradycardia were similar in both groups and they responded to standard doses of ephedrine and atropine. There was no significant difference in systolic and diastolic pressures between the groups. We found that the incidence of pruritus increased with addition of fentanyl. Urinary retention, a typical side effect of opioids was reported in two patients in the group receiving fentanyl. There was no significant change in respiratory rate end tidal carbon dioxide and peripheral oxygen saturation from baseline in both the groups (P > 0.05), and supplemental oxygen or any other form of airway management was not needed.
| Acknowledgment|| |
Department of Anesthesiology, Department of Orthopaedics, Goa Medical College.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8], [Figure 9], [Figure 10]
[Table 1], [Table 2], [Table 3]