|Year : 2022 | Volume
| Issue : 3 | Page : 374-379
Comparison of onset of action of Intrathecal Clonidine vs Intrathecal Fentanyl as an adjuvant with hyperbaric Bupivacaine and Bupivacaine alone under spinal anesthesia for lower limb orthopedic surgeries
Aradhana Devi1, Amrita Santosh1, Archana Har1, Jessy Vennel1, Vikrant Gadkari2
1 Department of Anesthesiology, MGM Medical College and Hospital, Navi Mumbai-410209, Maharashtra, India
2 Department of Anesthesiology, Panagarh Military Hospital, Panagarh-713148, West Bengal, India
|Date of Submission||20-Jul-2022|
|Date of Acceptance||29-Aug-2022|
|Date of Web Publication||29-Sep-2022|
Dr. Aradhana Devi
Department of Anesthesiology, MGM Medical College and Hospital, Navi Mumbai-410209, Maharashtra
Source of Support: None, Conflict of Interest: None
Background: Adjuvants are added to a local anesthetic solution to prolong the duration of analgesia. There is a paucity of studies comparing the onset of action of adjuvants like Clonidine and Fentanyl. In this study, the time of onset of action of intrathecal clonidine and intrathecal fentanyl as adjuvants to bupivacaine and bupivacaine alone were compared in the subarachnoid block for lower limb orthopedic surgeries. Materials and Methods: 90 adult patients posted for orthopedic surgery of the lower limb were divided into three equal groups of 30 each. Group A being the control group was given hyperbaric Bupivacaine(3ml) +0.5ml of Normal saline, Group B was given Intrathecal hyperbaric Bupivacaine (3 ml) +30 μg Clonidine and Group C was given Intrathecal hyperbaric Bupivacaine (3 ml) + Fentanyl 25 μg. The primary objective was to compare the time of onset of block and duration of analgesia. The secondary outcomes were the duration of sensory and motor block, duration of analgesia, hemodynamic parameters, and side effects. Results: The time of onset of the sensory blockade was 4.83 ± 0.64, 1.72 ± 1.47, and 3.4 ± 1.43 mins in groups A, B, and C respectively. The time of onset of the motor blockade as estimated by the time to reach level 2 on the Bromage scale, was 6.07 ± 0.55, 2.38 ± 1.32, and 5.06 ± 1.28 mins in groups A, B, and C respectively. The duration of postoperative analgesia was prolonged in the Clonidine group compared to the Fentanyl group. Conclusion: The study reveals that the time of onset of action of sensory and motor block was faster and the duration of analgesia was prolonged with adjuvants like Clonidine when compared to Fentanyl when added to Bupivacaine.
Keywords: Analgesia, clonidine, fentanyl, intrathecal, onset of action, spinal anesthesia
|How to cite this article:|
Devi A, Santosh A, Har A, Vennel J, Gadkari V. Comparison of onset of action of Intrathecal Clonidine vs Intrathecal Fentanyl as an adjuvant with hyperbaric Bupivacaine and Bupivacaine alone under spinal anesthesia for lower limb orthopedic surgeries. MGM J Med Sci 2022;9:374-9
|How to cite this URL:|
Devi A, Santosh A, Har A, Vennel J, Gadkari V. Comparison of onset of action of Intrathecal Clonidine vs Intrathecal Fentanyl as an adjuvant with hyperbaric Bupivacaine and Bupivacaine alone under spinal anesthesia for lower limb orthopedic surgeries. MGM J Med Sci [serial online] 2022 [cited 2022 Nov 29];9:374-9. Available from: http://www.mgmjms.com/text.asp?2022/9/3/374/357484
| Introduction|| |
Spinal anesthesia is the commonly used regional technique for lower limb orthopedic surgeries. By adding a small dose of adjuvant to the local anesthetic solution the duration of anesthesia and analgesia can be significantly prolonged. Intrathecal opioids enhance the sensory blockade of the local anesthetics without affecting much of the sympathetic activity. Short-acting opioids like Fentanyl have been used intrathecally in the adult population to provide prolonged pain relief. Intrathecal Clonidine is a safe, non-opioid adjuvant to local anesthetics to prolong the duration of analgesia without any major side effects. Clonidine is an α2-adrenergic agonist. It blocks the conduction via Aδ and C fibers and prolongs the action of local anesthetics. When given intrathecally it activates the postsynaptic α2-receptors in substantia gelatinosa of the spinal cord and produces analgesia. Though both Clonidine and Fentanyl with intrathecal Bupivacaine provide prolonged analgesia, there is controversy in the literature regarding their onset and duration of analgesia. The present study aimed to compare the time of onset of action of Intrathecal Clonidine and Intrathecal Fentanyl to Bupivacaine as adjuvants in the subarachnoid block for lower limb orthopedic surgeries.
| Materials and methods|| |
It is a prospective randomized study. 90 adult patients in the age group of 20–60 years of either sex belonging to ASA I and II classes posted for lower limb orthopedic surgery in MGM Hospital Navi Mumbai were enrolled for the present study. Patients were interviewed and examined one day before the scheduled surgery. Informed consent along with proper pre-operative evaluation and relevant investigations were done. Patients having co-morbidities such as diabetes mellitus, hypertension, heart disease, allergy to Bupivacaine, spine deformity, raised intracranial pressure, neurological disorders, bleeding disorders, and infection at the puncture site were excluded from the study. A pre-anesthetic checkup was done, and the visual analog scale (VAS) was explained to all the patients. All patients were kept nil by mouth (NBM) as per protocol. Patients were divided into three groups of 30 each using a computer-generated program. The assigned random group was kept in a sealed envelope to ensure the concealment of the allocation sequence. The anesthesiologist who was not involved in the study was assigned to open the envelope in the operation theater and prepared the drug accordingly. After the patient was shifted to the operation theatre, ASA standard monitors were attached and vitals were noted. Two IV cannulas were secured in a peripheral vein one for giving drugs and the other for administering fluids. Under all aseptic precautions, L3–L4 intervertebral space was palpated in a sitting position using a midline approach and spinal anesthesia was administered by a 25-gauge Quincke spinal needle. Group A received 15 mg hyperbaric Bupivacaine plain + 0.5 ml of normal saline, Group B Received intrathecal hyperbaric Bupivacaine (3 ml) +30 μg Clonidine, Group C – Received intrathecal hyperbaric Bupivacaine (3 ml) + Fentanyl 25 μg. A total volume of 3.5 ml was made in all groups. The observation was done by the anesthesiologist who was blinded to the drug. The respiratory rate, electrocardiogram, SpO2, pulse rate, and blood pressure were monitored. The blood pressure and pulse rate variations of more than 20% of baseline were noted in all three groups. IV atropine and ephedrine were given to treat bradycardia and hypotension. The primary objective was to compare the time of onset of block and duration of analgesia. The secondary outcomes were the duration of sensory and motor block, duration of analgesia, hemodynamic parameters, and side effects. The time of onset of sensory and motor block was monitored at an interval of 2, 4, 6, 8, 10, and 15 min, and after that at 15 min intervals still 1 hour. Sensory block was tested by light touch cold swab test and pinprick method. The sensory level was tested by the three-point scale:0=Absent, 1= Reduced, 2= Normal face was taken as control. The motor block was assessed according to the Modified Bromage scale.
- Grade 1: Free movement of legs and feet.
- Grade II: Just able to flex knees with free movement of feet.
- Grade III: Unable to flex knees but with free movement of feet.
- Grade IV: Unable to move legs or feet.
The onset of motor block was defined as the time from intrathecal injection to motor blockade Level 2 on the Bromage scale. The motor block duration was taken as the time from intrathecal injection till no motor weakness. The sensory block onset was taken as the time from intrathecal injection till the loss of pinprick sensation at T10. Duration of sensory block was taken as time from a maximum level of block till regression to L1. Duration of analgesia was noted as the time from intrathecal injection to the administration of the first rescue analgesia. Any side effects such as nausea, vomiting, pain, shivering, pruritus, sedation, hypotension, bradycardia, and respiratory discomfort were noted. These patients were observed in the post-anesthesia recovery room and then later shifted to the ward. Postoperatively, the pain score was recorded by using a visual analog scale (VAS) between 0 and 10 (0 denotes no pain, 10 denotes severe pain). Injection Paracetamol (1gm) intravenous was administered as rescue analgesia when VAS was greater than 5. The time of administration of the first dose of rescue analgesia was noted.
Power analysis suggested that a sample size of 28 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 onset of analgesia by 5 min between the groups. We have included 30 patients in each group anticipating possible dropouts. Data are expressed as the mean ± sd and median (range) as appropriate. Statistical analysis was performed by SPSS 20.0 software. ANOVA and χ2 tests were used for analyzing standard characteristics, degree of motor block, sensory block level, and postoperative analgesia. Data that were distributed non-normally were analyzed by a Mann-Whitney U test. Categorical variables were analyzed using Fisher’s exact test if the number of subjects in any cell of the contingency table was expected to be less than five. The analysis of variance for repeated measures was used to compare hemodynamic characteristics. P < 0.05 was considered statistically significant. [Figure 1]
| Results|| |
A hundred patients scheduled to undergo lower limb surgery were evaluated for inclusion in this study. Two patients for coagulopathy, three for infection at the block site, two for chronic renal failure, two for BMI>30kg/m2, and one patient for refusal were excluded from the study. [Figure 2]
|Figure 2: shows the time of onset of sensory blockade was faster in Group B(bupivacaine+clonidine) when compared tong Group C(bupivacaine+fentanyl)|
Click here to view
It has been observed that the demographic profile (age, sex, height, weight) were comparable in the control group (hyperbaric bupivacaine with saline) as well as the two other groups clonidine and fentanyl as an adjuvant to hyperbaric bupivacaine [Table 1].
The time of onset of the sensory blockade as estimated by cold sensation and pinprick method was 4.83 ± 0.64,1.72 ± 1.47 and 3.4 ± 1.43 mins in groups A, B, and C respectively, the difference being statistically significant. [Table 2], [Figure 2] The time of onset of the motor blockade as estimated by the time to reach level 2 on the Bromage scale, was6.07 ± 0.55, 2.38 ± 1.32, and 5.06 ± 1.28mins in groups A, B, and C respectively the difference being statistically significant. [Table 2], [Figure 3]The onset of the sensory block as well as the motor block was faster where clonidine was the adjuvant compared to fentanyl. [Figure 4] Duration of sensory block was prolonged in the clonidine group compared to the statistically significant fentanyl group. Duration of motor block was prolonged in the clonidine group compared to the statistically significant fentanyl group. There was also no significant difference regarding hemodynamic parameters like SBP, DBP, MAP, and heart rate among the three groups. There was no significant difference in all three groups regarding side effects [Table 3].
|Figure 3: shows time of onset of motor blockade was faster in group B( Bupivacaine+clonidine) compared to Group C(Bupivacaine + fentanyl)|
Click here to view
|Figure 4: Shows the time of sensory and motor blockade was faster in group B (bupivacaine+clonidine) than Group C (bupivacaine+fentanyl)|
Click here to view
| Discussion|| |
Many investigators have used adjuvant drugs to prolong the duration of analgesia without increasing the side effects. This is a new study that compares the onset of action of hyperbaric Bupivacaine alone, hyperbaric Bupivacaine with Clonidine, and hyperbaric Bupivacaine with Fentanyl used intrathecally as a subarachnoid block for lower limb surgeries. In our study, we found that the time of onset of action sensory and motor block was faster in the Clonidine group when compared to Fentanyl and control group without significant side effects. Clonidine is an α2 receptor agonist, which when used in spinal anesthesia, prolongs sensory and motor blockade and prolongs postoperative analgesia. Fentanyl is an opioid µ1 and µ2 receptor agonist, which when used as an adjuvant in spinal anesthesia has a rapid onset and short duration of action with minimal cephalic spread. Clonidine acts by blocking the conduction of A§ and C fibers thus prolonging the action of the local anesthetic. Chhabra et al. observed that intrathecal Clonidine 60 µg prolonged the duration of subarachnoid block compared to Fentanyl which was similar to our study. Khezri et al. in their study found that intrathecal Clonidine75 µg with Bupivacaine decreased the onset time and increased the time to first rescue analgesia compared to intrathecal Fentanyl which was similar to our study.Bajwa et al. observed that the addition of Clonidine 50 µg to intrathecal hyperbaric bupivacaine provided late onset of the block along with prolonged postoperative analgesia as well as more sedation compared to Fentanyl 25 µg which was in disagreement with our study. In a similar study, Sharan et al.compared Clonidine 30 µg with fentanyl 25 µg intrathecally as an adjuvant to Ropivacaineand observed a faster onset of the block with Clonidine compared to Fentanyl which was similar to our study. Conversely, Mahendru et al. observed in their study that Clonidine 30 µg produced similar onset of block compared to Fentanyl 25 µg when given intrathecally. This may be due to the use of a low dose of intrathecal Clonidine. Singh R, et al observed that the onset of action comparing 4 groups of Bupivacaine 7.5 mg plus normal saline 0.5 mg, Bupivacaine 7.5 mg plus Fentanyl 25 µg, Bupivacaine 7.5 mg plus Clonidine 75 µg and Bupivacaine 7.5 mg, Clonidine 37.5 µg and Fentanyl 12.5 µg when given intrathecally, the time of onset of sensory block was earlier in the Bupivacaine and Clonidine group which was similar to our study. In the same way, the onset of motor block was also earlier in the Clonidine group. Routray et al. in their study observed that intrathecal Clonidine had a faster onset of action than Fentanyl as an adjuvant to hyperbaric Bupivacaine in the subarachnoid block for lower limb surgeries which was similar to our study. Studies by Li Z et al., Paech et al and Tilkar et al were also in agreement with our study. The duration of block and postoperative analgesia was prolonged in the Clonidine group compared to Fentanyl which was similar to other studies. As our sample size was small, more studies need to be done to validate our study findings.
| Conclusion|| |
It may be concluded that the time of onset of action of sensory and motor block was faster with Clonidine when compared to Fentanyl with intrathecal Bupivacaine without significant side effects.
The Institutional Ethics Committee of MGM Medical College, Navi Mumbai, Maharashtra, India reviewed and approved the research study entitled “Comparison of onset of action of Intrathecal Clonidine vsIntrathecal Fentanyl as an adjuvant with hyperbaric Bupivacaine and Bupivacaine alone under spinal anesthesia for lower limb orthopedic surgeries” in the IEC meeting held on 09 December 2021 vide letter no. N-EC/2021/12/95 dated 30th December 2021.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Giovannitti JA Jr, Thoms SM, Crawford JJ Alpha-2 adrenergic receptor agonists: A review of current clinical applications. Anesth Prog 2015;62:31-9.
Sethi BS, Samuel M, Sreevastava D Efficacy of analgesic effects of low dose intrathecal clonidine as an adjuvant to bupivacaine. Indian J Anaesth 2007;51:415-9.
Shidhaye RV, Shah BB, Joshi SS, Deogaonkar SG, Bhuva AP Comparison of clonidine and fentanyl as an adjuvant to intrathecal bupivacaine for spinal anaesthesia and postoperative analgesia in patients undergoing caesarian section. Sri Lankan J Anaesthesiol 2013;22:15-20.
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.
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.
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.
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.
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.
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.
Singh R, Kundra S, Gupta S, Grewal A, Tewari A Effect of clonidine and/or fentanyl in combination with intrathecal bupivacaine for lower limb surgery. J Anaesthesiol Clin Pharmacol 2015;31:485-90.
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.
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.
Paech MJ, Banks SL, Gurrin LC, Yeo ST, Pavy TJ A randomized, double-blinded trial of subarachnoid bupivacaine and fentanyl, with or without clonidine, for combined spinal/epidural analgesia during labor. Anesth Analg 2002;95:1396-401, table of contents.
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 SciPublic Health 2015;4:458-62.
[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2], [Table 3]