|Year : 2017 | Volume
| Issue : 3 | Page : 589-593
Comparison of intrathecal clonidine and fentanyl as adjuvant to hyperbaric bupivacaine in subarachnoid block for lower limb orthopedic surgery
Sidharth Sraban Routray1, Khageswar Raut1, Amit Pradhan2, Abhilash Dash1, Mina Soren1
1 Department of Anaesthesiology and Critical Care, SCB Medical College and Hospital, Cuttack, Odisha, India
2 Department of Anaesthesiology, KIMS, Bhubaneswar, Odisha, India
|Date of Web Publication||21-Jun-2017|
Sidharth Sraban Routray
Department of Anaesthesiology and Critical Care, SCB Medical College and Hospital, Cuttack, Odisha
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Background: Many studies are there using adjuvants such as clonidine and fentanyl with bupivacaine in the subarachnoid block for prolonging postoperative analgesia. However, literature is divided regarding the dosage and efficacy of both intrathecal adjuvants. Furthermore, these adjuvants have their own side effects. Hence, search for ideal intrathecal adjuvant between clonidine and fentanyl to bupivacaine goes on. Aim: The aim of the present study was to compare the effect of intrathecal clonidine and fentanyl as adjuvant to bupivacaine in the subarachnoid block for lower limb orthopedic surgery. Materials and Methods: It was a prospective randomized study in which eighty patients posted for lower limb orthopedic surgery were divided into two groups of forty each. Group C – Received intrathecal hyperbaric bupivacaine (2.5 ml) +50 μg clonidine (diluted to 0.5 ml). Group F – Received intrathecal hyperbaric bupivacaine (2.5 ml) + fentanyl 25 μg (diluted to 0.5 ml). Duration of postoperative analgesia, sensory and motor block characteristics, hemodynamic parameters, and side effects were recorded and analyzed. Results: Time for first dose of rescue analgesic was delayed in Group C (510.84 ± 24.10 min) in comparison to Group F (434.95 ± 19.16 min) which was statistically significant (P < 0.001). Duration of sensory and motor block was significantly prolonged in Group C compared to Group F (P < 0.001). Sedation was more in Group C than Group F (P < 0.001). Other block characteristics, hemodynamic, and side effects were comparable in both groups. Conclusion: Intrathecal clonidine as adjuvant to hyperbaric bupivacaine provided prolonged postoperative analgesia with more sedation in comparison to intrathecal fentanyl.
Keywords: Analgesia, bupivacaine, clonidine, fentanyl, intrathecal
|How to cite this article:|
Routray SS, Raut K, Pradhan A, Dash A, Soren M. Comparison of intrathecal clonidine and fentanyl as adjuvant to hyperbaric bupivacaine in subarachnoid block for lower limb orthopedic surgery. Anesth Essays Res 2017;11:589-93
|How to cite this URL:|
Routray SS, Raut K, Pradhan A, Dash A, Soren M. Comparison of intrathecal clonidine and fentanyl as adjuvant to hyperbaric bupivacaine in subarachnoid block for lower limb orthopedic surgery. Anesth Essays Res [serial online] 2017 [cited 2020 Apr 3];11:589-93. Available from: http://www.aeronline.org/text.asp?2017/11/3/589/208683
| Introduction|| |
Local anesthetic like bupivacaine is commonly used in spinal anesthesia, but the duration of spinal anesthesia may be short and limited, and higher doses of rescue analgesics may be required in the postoperative period. This can be avoided by using higher doses of bupivacaine which again can produce cardiac toxicity. Studies have shown that duration of analgesia due to bupivacaine in spinal anesthesia can be prolonged by using adjuvants such as midazolam, opioids, neostigmine, dexmedetomidine, and clonidine. Almost all opioids have been used as adjuvants intrathecally.
Most commonly used opioid in regional anesthesia is fentanyl citrate which is a μ1- and μ2-receptor agonist. It is a highly potent drug because of its high lipophilicity. It is preferred as an adjuvant in spinal anesthesia because of its rapid onset and short duration of action with minimal cephalic spread., However, pruritus, nausea, vomiting, respiratory depression, and urinary retention are other common side effects for which search for ideal nonopioid adjuvants goes on. Clinical studies have suggested that intrathecal clonidine, an α2-receptor agonist, prolongs sensory and motor block in spinal anesthesia and provides prolonged postoperative analgesia. Clonidine has beneficial effects such as antiemesis, reduced postspinal shivering, anxiolysis, and sedation, thereby avoiding unwanted opioid-related side effects such as pruritus and respiratory depression.,
Literature is divided regarding efficacy of both intrathecal clonidine and fentanyl in providing prolonged postoperative analgesia. Studies by Khezri et al., Bajwa et al., Chhabra et al., and Sharan et al. opined that intrathecal clonidine was more potent in providing prolonged analgesia compared to intrathecal fentanyl. Study by Mahendru et al. concluded that intrathecal fentanyl and clonidine were comparable regarding requirement of first analgesia request. Another study by Bathari et al. concluded that intrathecal fentanyl was superior to intrathecal clonidine in knee arthroscopy. Hence, all the above studies differ in their postoperative sensory and motor block characteristics. Hence, the present study is being undertaken to evaluate and compare the effects of clonidine and fentanyl as intrathecal adjuvants to hyperbaric bupivacaine in patients undergoing lower limb orthopedic surgery. The primary objectives of this study were to evaluate and compare the effects of clonidine and fentanyl on time of request of first dose of rescue analgesic. Secondary objectives were to compare the effects of clonidine and fentanyl on time of onset and duration of sensory and motor block, hemodynamic status, and side effects.
| Materials and Methods|| |
This randomized controlled study was carried out from January 2016 to January 2017, after obtaining approval from the Hospital Ethics Committee and written informed consent from the patients. Eighty patients of the American Society of Anesthesiologists Classes I or II of either sex and of age 20–60 years of age posted for lower limb orthopedic surgery were randomly divided into two groups (n = 40) using computer-generated program. Assigned random group was enclosed in a sealed envelope to ensure concealment of allocation sequence. The anesthesiologist, who was not involved in the study, opened the envelope in operation theater and prepared the drug accordingly. The observation was done by the anesthesiologist who was blinded to the drug. Patients having severe systemic disorders such as diabetes mellitus, hypertension, heart disease, allergy to bupivacaine, spine deformity, increased intracranial pressure, neurological disorders, hemorrhagic diathesis, and infection at the puncture site were excluded from the study. Group C – Received hyperbaric bupivacaine (2.5 ml) +50 μg clonidine (diluted to 0.5 ml) administered intrathecally. Group F – Received hyperbaric bupivacaine (2.5 ml) + fentanyl 25 μg (diluted to 0.5 ml) administered intrathecally. Total volume of study drug was 3 ml. Preanesthetic checkup was done, and visual analog scale (VAS) was explained to all patients. All the patients were kept nil orally for 6 h before surgery. After shifting the patients to operation theater, intravenous (IV) cannula was inserted, and preloading was done with Ringer solution (10 ml/kg). Preoperative parameters such as pulse rate, oxygen saturation, and blood pressure were recorded. Under all aseptic precaution, spinal anesthesia was administered at the level of L3–L4 intervertebral space in sitting position using midline approach by 25-gauge Quincke spinal needle. The anesthesiologist who administered anesthesia was blinded to the group allocation. Pulse rate, respiratory rate, electrocardiogram, SpO2, and blood pressure were monitored. Pulse rate and blood pressure variations more than 20% of baseline were noted in both groups. Bradycardia and hypotension were treated with IV atropine and ephedrine, respectively. Sensory and motor block was monitored at 2, 4, 6, 8, 10, 15 min, and after that at 15 min interval. Sensory block was tested by pinprick method. The motor block was assessed according to the modified Bromage scale: Bromage 0: Patients able to move hip, knee, and ankle, Bromage 1: Patients unable to move hip but able to move the knee and ankle, Bromage 2: Patient unable to move hip and knee but able to move the ankle, Bromage 3: Patient unable to move hip, knee, and ankle. The onset of sensory block was taken from the time of intrathecal injection till loss of pin prick sensation at T10. Duration of sensory block was taken as time from maximum height of block till regression to Level 1. The onset of motor block was defined as time from intrathecal injection to motor blockade Level 2 in Bromage scale. Duration of motor blockade was taken as time from intrathecal injection till no motor weakness (Bromage 0). Duration of analgesia was defined as time from intrathecal injection till administration of first rescue analgesic. Any side effects such as nausea, vomiting, pain, shivering, pruritus, sedation, hypotension, bradycardia, and respiratory discomfort were noted. Patients were assessed for degree of sedation, and scoring was done with Campbell sedation score as: 1: Wide awake, 2: Awake and comfortable, 3: Drowsy and difficult to arouse, and 4: Not arousable. Postoperatively, the pain score was recorded by using VAS between 0 and 10 (0 = no pain, 10 = severe pain). Injection paracetamol (1 gm) was given intravenously as rescue analgesic when VAS was >5. Time of administering the first dose of rescue analgesia was noted.
Power analysis suggested that a sample size of forty patients per group was required to achieve a power of 80% and a level significance of 0.05 to be able to detect a difference in the mean duration of analgesia by 60 min between the groups. Interpretation of the data was carried out and analyzed using statistical package for social sciences (SPSS version 19, IBM Corp, NY, USA). Data was represented as mean ± standard deviation for continuous data and frequency (percentage) or median (range) for nonparametric (categorical) data. The two groups were compared using analysis of variance. The proportion of adverse effects was compared using Chi-square test. P < 0.05 was considered statistically significant. P < 0.001 was considered highly statistically significant.
| Results|| |
Both groups were comparable with respect to their demographic profile, baseline hemodynamic parameters, and duration of surgery [Table 1].
[Table 2] compares onset and duration of sensory and motor block and duration of postoperative analgesia. Time for first dose of rescue analgesic was delayed in Group C (510.84 ± 24.10 min) compared to Group F (434.95 ± 19.16 min) which was statistically significant (P < 0.001). Duration of sensory block in Group C was 250.52 ± 18.41 min compared to 205.16 ± 19.55 min in Group F which was statistically significant (P < 0.001). Duration of motor block was 190.19 ± 26.11 min in Group C in comparison to 171.31 ± 24.58 min in Group F which was statistically significant (P < 0.001). There was no statistical difference in onset of both sensory and motor block between the two groups (P > 0.05). There was also no significant difference regarding hemodynamic parameters such as systolic blood pressure, diastolic blood pressure, mean arterial pressure, and heart rate [Graph 1],[Graph 2],[Graph 3],[Graph 4].
In Group C, sedation score ≥3 was found in nine patients compared to none in Group F which was statistically significant (P < 0.001). There was no significant difference in both groups regarding other side effects [Graph 5].
| Discussion|| |
Clonidine is an α2-agonist which block the conduction of Aδ and C fibers, thereby prolongs the action of local anesthetics. When used intrathecally, it activates the postsynaptic α2-receptors in substantia gelatinosa of spinal cord and produces analgesia., We have used intrathecal clonidine with bupivacaine to see whether it provides prolonged analgesia, avoiding side effects of fentanyl. In our study, we found that intrathecal clonidine as adjuvant to bupivacaine provided prolonged analgesia compared to intrathecal fentanyl. Khezri et al. in their study concluded that intrathecal clonidine 75 μg with bupivacaine prolonged the time to first analgesia request compared to fentanyl which was similar to our study. Bajwa et al. in their study concluded that addition of clonidine (50 μg) to intrathecal bupivacaine provided prolonged postoperative analgesia in comparison to fentanyl (25 μg), but clonidine provided more sedation. We have found similar finding in our study. Chhabra et al. in their study concluded that clonidine 60 μg has advantage over fentanyl and it prolonged the duration of the subarachnoid block and postoperative analgesia, similar to our study. Sharan et al. compared intrathecal clonidine 30 μg with fentanyl 25 μg and concluded that clonidine had advantage over fentanyl which is in agreement with our study. However, Mahendru et al. in their study opined that intrathecal 30 μg clonidine is comparable to 25 μg fentanyl regarding sensory and motor block characteristics which was not in agreement with our study. Bathari et al. in their study concluded that intrathecal fentanyl 30 μg was superior to intrathecal clonidine15 μg in knee arthroscopy which was not in agreement with our study. This may be due to the use of low dose of intrathecal clonidine and high dose of intrathecal fentanyl. Benhamou et al. demonstrated higher spread and prolonged postoperative analgesia in lower limb surgery by adding 75 μg of clonidine to intrathecal bupivacaine, and the side effects were not increased with this dose. In our study, intrathecal addition of 50 μg clonidine to bupivacaine produced longer duration of postoperative analgesia with minimal side effects. Lavand'homme et al. showed higher incidence of hypotension and sedation with intrathecal clonidine 150 μg than clonidine 75 μg. The dose of clonidine was limited to 50 μg in our study to decrease the side effects. Kothari et al. compared different doses of clonidine as an adjuvant to intrathecal bupivacaine for spinal anesthesia in patients undergoing cesarian section aiming to find out the lowest possible effective dose and found that the incidence of both hypotension and bradycardia more in bupivacaine group than in bupivacaine with clonidine group which was not in agreement with our study. Bhure et al. demonstrated that addition of clonidine, fentanyl, and midazolam to bupivacaine significantly improves the onset and duration of sensory and motor block with relative hemodynamic stability, prolongs the duration of analgesia, and reduces the consumption of systemic analgesics in comparison to bupivacaine alone. They concluded that clonidine is an excellent additive to bupivacaine in spinal anesthesia and provides prolonged duration of analgesia without any deleterious effects on the mother and baby. Tilkar et al. conducted a prospective study to differentiate between the effects of fentanyl versus clonidine when added to intrathecal bupivacaine in spinal anesthesia. They concluded that addition of intrathecal clonidine to hyperbaric bupivacaine was more advantageous than fentanyl with special regard to its analgesic properties. Singh et al. evaluated the effect of addition of intrathecal clonidine to hyperbaric bupivacaine on postoperative pain after caesarean section and has shown that the duration of postoperative analgesia increases significantly on adding 75 μg clonidine to 2 ml of hyperbaric bupivacaine without any increase in maternal side effects. There was no effect on neonatal outcome. Finding of this study was similar to ours. Shidhaye et al. concluded that intrathecal addition of 25 μg fentanyl to bupivacaine provides good analgesia with less sedation and is a better option when sedation is not desirable. However, intrathecal addition of 60 μg clonidine to bupivacaine provides longer duration of postoperative analgesia than 25 μg of fentanyl and is a preferred option when sedation is acceptable. Bhattacharjee et al. concluded from their study that perioperative analgesia for cesarean section was prolonged by the addition of 75 μg of clonidine and 25 μg fentanyl to bupivacaine. However, prolongation of postoperative analgesia was more with fentanyl compared to clonidine, and side effects such as nausea, vomiting, and hypotension were more with clonidine. This study is not in agreement with our study. Kaur et al. evaluated intrathecal bupivacaine-clonidine combination in lower abdominal surgeries and concluded that intrathecal clonidine 150 μg added to bupivacaine not only fastens onset of sensory and motor block but also prolongs the duration of the same, thereby decreasing the rescue analgesic requirement which is in agreement with our study. However, sedation and bradycardia were more with clonidine 150 μg. Several other studies had opined that intrathecal clonidine is an ideal adjuvant which provided prolonged analgesia with minimal side effects.,,, These are in agreement with findings in our study. Singh et al. in their study in patients posted for transurethral resection of prostate concluded that intrathecal clonidine in a combination with bupivacaine provides more satisfactory anesthesia and analgesia and has less side effects compared to fentanyl which was similar to our finding. All above studies have used intrathecal clonidine in doses from 15 μg to 150 μg, but use of intrathecal clonidine in dose of 50 μg provided prolonged postoperative analgesia with minimum side effects compared to fentanyl and other different doses of clonidine.
| Conclusion|| |
Intrathecal clonidine (50 μg) when added to bupivacaine in spinal anesthesia provides prolonged duration of postoperative analgesia than 25 μg of fentanyl but with higher degree of sedation. Fentanyl (25 μg) may be recommended as a better option when sedation is not desirable.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Gupta A, Saha U. Spinal anesthesia in children: A review. J Anaesthesiol Clin Pharmacol 2014;30:10-8.
] [Full text]
Singh H, Yang J, Thornton K, Giesecke AH. Intrathecal fentanyl prolongs sensory bupivacaine spinal block. Can J Anaesth 1995;42:987-91.
Unal D, Ozdogan L, Ornek HD, Sonmez HK, Ayderen T, Arslan M, et al.
Selective spinal anaesthesia with low-dose bupivacaine and bupivacaine fentanyl in ambulatory arthroscopic knee surgery. J Pak Med Assoc 2012;62:313-8.
van Tuijl I, van Klei WA, van der Werff DB, Kalkman CJ. The effect of addition of intrathecal clonidine to hyperbaric bupivacaine on postoperative pain and morphine requirements after caesarean section: A randomized controlled trial. Br J Anaesth 2006;97:365-70.
Belzarena SD. Clinical effects of intrathecally administered fentanyl in patients undergoing cesarean section. Anesth Analg 1992;74:653-7.
Bonnet F, Buisson BV, Francois Y, Catoire P, Saada M. Effects of oral and subarachnoid clonidine on spinal anesthesia with bupivacaine. Reg Anesth 1990;15:211-4.
Khezri MB, Rezaei M, Delkhosh Reihany M, Haji Seid Javadi E. Comparison of postoperative analgesic effect of intrathecal clonidine and fentanyl added to bupivacaine in patients undergoing cesarean section: A prospective randomized double-blind study. Pain Res Treat 2014;2014:513628.
Bajwa BS, Singh AP, Rekhi AK. Comparison of intrathecal clonidine and fentanyl in hyperbaric bupivacaine for spinal anesthesia and postoperative analgesia in patients undergoing lower abdominal surgeries. Saudi J Anaesth 2017;11:37-40.
] [Full text]
Chhabra AR, Jagtap SR, Dawoodi SF. Comparison of clonidine versus fentanyl as an adjuvant to intrathecal ropivacaine for major lower limb surgeries: A randomized double blind prospective study. Indian J Pain 2013;27:170-4. [Full text]
Sharan R, Verma R, Dhawan A, Kumar J. Comparison of clonidine and fentanyl as adjuvant to ropivacaine in spinal anesthesia in lower abdominal surgeries. Anesth Essays Res 2016;10:526-31.
] [Full text]
Mahendru V, Tewari A, Katyal S, Grewal A, Singh MR, Katyal R. A comparison of intrathecal dexmedetomidine, clonidine, and fentanyl as adjuvants to hyperbaric bupivacaine for lower limb surgery: A double blind controlled study. J Anaesthesiol Clin Pharmacol 2013;29:496-502.
] [Full text]
Bathari R, Bhalotra A, Anand R, Kumar V. A randomised trial to compare the effect of addition of clonidine and fentanyl to hyperbaric ropivacaine for spinal anaesthesia for knee arthroscopy. S Afr J Anaesth Analg 2016;22:14-8.
Giovannitti JA, Thoms SM, Crawford JJ. Alpha-2 adrenergic receptor agonists: A review of current clinical applications. Anesth Prog 2015;62:31-8.
Sethi BS, Samuel M, Sreevastava D. Efficacy of analgesic effects of low dose intrathecal clonidine as adjuvant to bupivacaine. Indian J Anaesth 2007;51:415-9. [Full text]
Benhamou D, Thorin D, Brichant JF, Dailland P, Milon D, Schneider M. Intrathecal clonidine and fentanyl with hyperbaric bupivacaine improves analgesia during Cesarean section. Anesth Analg 1998;87:609-13.
Lavand'homme PM, Roelants F, Waterloos H, Collet V, De Kock MF. An evaluation of the postoperative antihyperalgesic and analgesic effects of intrathecal clonidine administered during elective cesarean delivery. Anesth Analg 2008;107:948-55.
Kothari N, Bogra J, Chaudhary AK. Evaluation of analgesic effects of intrathecal clonidine along with bupivacaine in Cesarean section. Saudi J Anaesth 2011;5:31-5.
] [Full text]
Bhure A, Kalita N, Ingley P, Gadkari CP. Comparative study of intrathecal hyperbaric bupivacaine with clonidine, fentanyl and midazolam for quality of anaesthesia and duration of postoperative pain relief in patients undergoing elective caesarean section. Peoples J Sci Res 2012;5:19-23.
Tilkar Y, Bansal SA, Agnihotri GS. Effect of adding clonidine versus fentanyl to intrathecal bupivacaine on spinal block characteristics in orthopedic procedures: A double blind controlled study. Int J Med Sci Public Health 2015;4:458-62.
Singh R, Gupta D, Jain A. The effect of addition of intrathecal clonidine to hyperbaric bupivacaine on postoperative pain after lower segment caesarean section: A randomized control trial. Saudi J Anaesth 2013;7:283-90.
] [Full text]
Shidhaye RV, Shah BB, Joshi SS, Deogaonkar SG, Bhuva AP. Comparison of clonidine and fentanyl as adjuvant to intrathecal bupivacaine for spinal anaesthesia and postoperative analgesia in patients undergoing caesarean section. Sri Lankan J Anaesthesiol 2013;22:15-20.
Bhattacharjee A, Singh NR, Singh SS, Debberma P, Debberma P, Singh T, et al
. A comparative study of Intrathecal clonidine and fentanyl along with bupivacaine in spinal anesthesia for caesarean section. J Med Soc 2015;29:145-9. [Full text]
Kaur U, Sidhu J, Aggarwal S. Evaluation of intrathecal bupivacaine-clonidine combination in lower abdominal surgeries: A double blind randomized control study. Sch J Appl Med Sci 2015;3:379-86.
Thakur A, Bhardwaj M, Kaur K, Dureja J, Hooda S, Taxak S. Intrathecal clonidine as an adjuvant to hyperbaric bupivacaine in patients undergoing inguinal herniorrhaphy: A randomized double-blinded study. J Anaesthesiol Clin Pharmacol 2013;29:66-70.
] [Full text]
Nasr IA, Elokda SA. Safety and efficacy of intrathecal adjuvants for Cesarean section: Bupivacaine, sufentanil, ordexmedetomidine. Ain Shams J Anaesthesiol 2015;8:388-95.
Shrivastava S, Sinha D, Shrivastava S. Effect of intrathecal clonidine on duration of spinal analgesia. J Evol Med Dent Sci 2015;4:7777-84.
Li Z, Tian M, Zhang CY, Li AZ, Huang AJ, Shi CX, et al.
A randomised controlled trial to evaluate the effectiveness of intrathecal bupivacaine combined with different adjuvants (fentanyl, clonidine and dexmedetomidine) in caesarean section. Drug Res (Stuttg) 2015;65:581-6.
Singh G, Aulakh GS, Aulakh NK, Singh RM, Bose A, Katayal S, et al.
Effect of intrathecal clonidine versus fentanyl on bupivacaine spinal block in transurethral resection of prostate surgeries. Anesth Essays Res 2016;10:65-70.
] [Full text]
[Table 1], [Table 2]