|Ahead of print publication
Randomized control trial with intravenous dexmedetomidine and intravenous clonidine using bupivacaine in spinal anesthesia in lower abdominal surgeries
M. S. Abhishek, T. K. Krishna Murthy
Department of Anaesthesia, Sri Siddhartha Medical College, Tumkur, Karnataka, India
|Date of Submission||20-Jan-2020|
|Date of Decision||04-Feb-2020|
|Date of Acceptance||20-Feb-2020|
T. K. Krishna Murthy,
Kuvempu Nagar, Gubbi, Tumkur - 572 216, Karnataka
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Background: In recent years, several adjuvants have been used to prolong the duration of the subarachnoid block. These adjuvants have either been used via intrathecal route or intravenous route. Dexmedetomidine and clonidine have been used as adjuvants to local anesthetic drugs by intrathecal, epidural, caudal, intravenous routes, and for peripheral nerve blocks. In this study, we endeavored at finding the efficacy of dexmedetomidine and clonidine in improving the analgesia quality and duration of the subarachnoid block. Setting and Design: A prospective double-blind randomized control trial comprising seventy patients posted for elective lower abdominal surgeries. Materials and Methods: Seventy patients were selected at random and were allocated to two groups of 35 each. In Group C, the patients received 0.5% hyperbaric bupivacaine with Clonidine 1.0 μg.kg−1 intravenously. In Group D, the patients received 0.5% hyperbaric bupivacaine with Dexmedetomidine 0.5 μg.kg−1 intravenously. Perioperatively, heart rate, systolic blood pressure, diastolic blood pressure, mean arterial pressure, and oxygen saturation were recorded and documented every 5 min till the end of surgery. Time of onset, level of sensory blockade, and duration of the sensory blockade were recorded. Motor block was assessed using the Modified Bromage scale. Data validation and analysis were carried out using the SPSS version 11. All the values ofP < 0.05 were considered statistically significant. Results: Time of onset of sensory blockade in the clonidine group was 3.46 ± 1.13 min and in the dexmedetomidine group was 2.93 ± 1.34 min (P < 0.05). The time of onset of motor block in the clonidine group was 4.17 ± 1.62 and in the dexmedetomidine group was 3.67 ± 1.51 min (P < 0.05). Time for two segment regressions of sensory block in clonidine group was 128.67 ± 14.53 min and in dexmedetomidine group was 136.31 ± 12.54 min (P < 0.05). Time of regression of motor block to the Modified Bromage Level 1 in clonidine group was 148.76 ± 19.65 min and in dexmedetomidine group was 145.76 ± 15.37 min (P < 0.05). Conclusion: The use of intravenous dexmedetomidine perioperatively prolongs the duration of sensory and motor block significantly when compared to intravenous clonidine.
Keywords: Adjuvants, bupivacaine, clonidine, dexmedetomidine, postoperative analgesia, rescue analgesia, spinal anesthesia
|How to cite this URL:|
Abhishek MS, Murthy TK. Randomized control trial with intravenous dexmedetomidine and intravenous clonidine using bupivacaine in spinal anesthesia in lower abdominal surgeries. Anesth Essays Res [Epub ahead of print] [cited 2020 Apr 6]. Available from: http://www.aeronline.org/preprintarticle.asp?id=281401
| Introduction|| |
Many techniques and drug regimens with partial or greater success have been tried from time to time to eliminate the anxiety component and to prolong the postoperative analgesia during regional anesthesia. Although beneficial in acute and chronic pain management, the use of local anesthetics is limited by its duration of action and the dose-dependent adverse effects on the cardiac and central nervous system. Adjuvants or additives are often used with local anesthetics for its synergistic effect by prolonging the duration of sensory – motor block and limiting the cumulative dose requirement of local anesthetics. α2 adrenergic agonists have both analgesic and sedative properties when used as an adjuvant to regional anesthesia. They potentiate the effect of local anesthetics and prolong the duration of both motor, sensory spinal blockade, and postoperative analgesia.
An adjuvant is a pharmacological agent which is added to a drug to increase or aid its effect. Opioids, first and foremost have attained an integral role as a spinal anesthetic adjuvant. However, research has supported a number of nonopioid adjuvants which prolong the duration of spinal anesthesia., Recently, α2 adrenoreceptor agonists have been used as adjuvants to local anesthetic agents because of their sedative, analgesic, and hemodynamic stabilizing effect. They have been found to prolong the duration of the spinal block following intrathecal administration.
If the duration of surgery prolongs, it has to be converted into general anesthesia, in which the patient is subjected to administration of intravenous drugs and inhalation agents along with its side effects and financial burden to the patient. Hence to improve the efficacy of the spinal anesthesia, adjuvants from different pharmacological classes of drugs are used to enhance the action of the drug, prolong anesthesia, to lower its dose requirements, and to reduce dose-dependent side effects.,,
Dexmedetomidine is a selective α2 adrenoreceptor agonist. It has α2/α1 selectivity ratio 8–10 times higher than that of clonidine. Analgesic and sedative properties were found when intrathecal, epidural, or intravenous dexmedetomidine was used as an adjuvant in previous studies. There are plenty of studies which have compared the dose equivalence of these two drugs; however, various studies have established that the dose of clonidine is 1.5–2 times higher than the dose of dexmedetomidine.,,
Clonidine is a partial α2 adrenergic agonist. It causes a decrease in the sympathetic tone and enhances the vagal tone. Stimulation of the α2 receptors in the vasomotor centers of medulla oblongata produces this effect. Clonidine is also used in the treatment of hypertension. Clonidine when added to local anesthetic for spinal and regional blocks has been shown to result in prolongation of the sensory blockade and reduction in the amount of concentration of local anesthetic required to produce postoperative analgesia.,,,
In this context, present research intends to compare the efficacy of intravenous dexmedetomidine and intravenous clonidine as an adjuvant to bupivacaine-induced spinal anesthesia.
Aim of the study
The aim of this study is to compare the efficacy of intravenous administration of dexmedetomidine and intravenous administration of clonidine as an adjuvant to bupivacaine-induced spinal anesthesia.
| Materials and Methods|| |
The present study was carried out as a prospective, randomized, double-blinded control trial. Written and informed consent was taken from seventy adult patients of age group 20–60 years of the American Society of Anesthesiologist's (ASA) Classification I and II. These patients were posted for elective lower abdominal surgeries under spinal anesthesia. Exclusion criteria were as follows: infection at the site of spinal anesthesia, patients with uncontrolled hypertension and diabetes, any neurological or psychiatric diseases and patients with coagulation disorders. Routine and detailed preanesthetic evaluations of all the patients were carried out and were randomly allocated into two groups as and when the cases were posted for elective surgery.
The patients were nil by mouth 8 h before the proposed procedure. Patients received tablet Ranitidine 150 mg at the night before the surgery at 10 p.m. and at 5.30 a.m. with a sip of water as premedication. Intravenous line was secured with 18G cannula. All the patients were preloaded with Ringer's Lactate 10 mL.kg−1, 15 min before the surgery. Standard monitoring, namely oxygen saturation (SpO2), heart rate (HR), noninvasive blood pressure, and electrocardiogram were attached and baseline hemodynamic values were recorded. Aseptic precautions were followed while administering spinal anesthesia. With 25G Quincke spinal needle, subarachnoid block was performed at L3–L4 inter – space in the midline with 0.5% hyperbaric bupivacaine (Neon Pharmaceuticals, India).
Group C received 4 mL of 0.5% hyperbaric bupivacaine with 1.0 μg.kg−1 of Clonidine intravenously. Group D received 4 mL of 0.5% hyperbaric bupivacaine with 0.5 μg.kg−1 of dexmedetomidine intravenously. The adjuvants were administered via a syringe pump. Systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), SpO2, and HR were recorded preoperatively and after performing the subarachnoid block, every 5 min till the end of the procedure. Time of onset of anesthesia was recorded. Sensory blockade was assessed and recorded using pinprick in the midclavicular line on both sides. Modified Bromage Scale was used to assess and record motor blockade. In the postanesthesia recovery room, the parameters were recorded every 15 min.
Simple randomization method was employed. The duration of the study was approximately 6 months. A pilot study was conducted and the sample size was arrived with the help of previous studies keeping in mind the caseload at our institution, the aforementioned number was arrived at.
The following formula was employed to arrive at the sample size.
Z = Z value (e.g. 1.96 for 95% confidence level).
p = percentage picking a choice, expressed as decimal.
(0.5 used for sample size needed).
c = confidence interval, expressed as decimal.
(e.g. 0.04= ±4).
The baseline, intraoperative, and postoperative hemodynamic changes at various time intervals were compared between the study groups using Chi-square test and unpaired t-test. Data validation and analysis were carried out using SPSS version 11.0 Statistical Package for the Social Sciences, IBM, USA. All the values of P < 0.05 were considered statistically significant.
| Results|| |
In the dexmedetomidine group, there were four patients in the age group of 20–25 years, seven patients in 25–30 years, six patients in 30–35 years, five patients in 35–40 years, ten patients in 40–45 years, and three patients in 45–50 years. In Clonidine group, there were three patients in the age group of 20–25 years, eight patients in 25–30 years, five patients in 30–35 years, six patients in 35–40 years, nine patients in 40–45 years, and four patients in 45–50 years [Table 1]. There were 18 males and 17 females in Dexmedetomidine group and 19 males and 16 females in Clonidine group. In our study, 27 patients in Dexmedetomidine group and 29 patients in Clonidine group were in the ASA Grade 1. Similarly, 8 patients in Dexmedetomidine group and 6 patients in Clonidine group were in ASA Grade 2 [Table 2].
|Table 1: Age profile: The subjects in both the groups were demographically similar|
Click here to view
Time of onset of sensory block in Dexmedetomidine group and Clonidine group was 2.93 ± 1.34 min and 3.46 ± 1.13 min, respectively (P = 0.021). Time of onset of motor block in Dexmedetomidine group and Clonidine group was 3.67 ± 1.51 min and 4.17 ± 1.62 min, respectively (P = 0.034) [Table 3]. Time for two segment regressions of sensory block in Dexmedetomidine group and Clonidine group was 136.31 ± 12.54 min and 128.67 ± 14.53 min, respectively (P = 0.047). Time of regressions of motor blockade to Bromage Scale 1 in Dexmedetomidine group and Clonidine group was 145.76 ± 15.37 min and 148.76 ± 19.65 min, respectively (P = 0.032) [Table 4].
In the Dexmedetomidine group, duration of analgesia was 202.81 ± 22.76 min, whereas in Clonidine group, it was 170.42 ± 37.32 min (P< 0.001). In the Dexmedetomidine group, the time for first rescue analgesic requirement was 226.64 ± 25.71 min, whereas in the Clonidine group, it was 186.73 ± 37.32 min (P< 0.001) [Table 5]. In Dexmedetomidine group, bradycardia was observed in six patients, hypotension was observed in five patients, Ramsey Sedation score of more than 3 was observed in six patients, nausea and vomiting were complained by two patients. In the Clonidine group, bradycardia was observed in two patients, hypotension was observed in two patients, Ramsey Sedation score of more than 3 was seen in four patients and one patient complained of nausea and vomiting. These were managed as per the study protocol. These differences were found to be statistically significant [Table 6].
In the Dexmedetomidine group, the intra operative Ramsey Sedation score was 2.43 ± 0.68 min, whereas in the Clonidine group, it was 1.42 ± 0.61 min (P< 0.05) [Graph 1]. The hemodynamic parameters were compared. The HR (P< 0.05) [Graph 2], SBP (P< 0.05) [Graph 3], DBP (P< 0.05) [Graph 4] and the MAP (P< 0.05) [Graph 5] were found to be statistically significant.
| Discussion|| |
Spinal anesthesia is a type of regional anesthesia technique where local anesthetic solution is injected into the subarachnoid space. It is widely preferred in urologic, cesarean, and lower limb procedures. Sedation is administered to allay the patient's anxiety of the surgical procedure. Sedation is administered via the intravenous route. Dexmedetomidine, an imidazole compound, is the pharmacologically active dextroisomer of medetomidine that displays specific and selective α2 adrenoceptor agonism. Activation of the receptors in the brain and spinal cord inhibits neuronal firing and results in sympatholytic effect, causing hypotension, bradycardia, and sedation.
In our study, it is clearly evident that both dexmedetomidine and clonidine prolong the duration of spinal anesthesia. Primary outcome of this study is that Dexmedetomidine is more preferred due to its longer duration of adjuvant action. Dexmedetomidine is known to cause bradycardia, which we found in our study and was clinically treated without any q.
In a study done by Kavya et al., it was found that the sensory recovery was significantly longer in the dexmedetomidine group when compared to the control group.
In a study conducted by Agrawal et al., it was observed that intravenous dexmedetomidine produces a better clinical profile compared to clonidine.
Motor and sensory block prolongation with the use of α2 agonists dexmedetomidine and clonidine occurs as a result of differential block of Aα and C fibers. Dexmedetomidine does not cause significant respiratory depression despite providing good sedation proving its high safety margin.,,
| Conclusion|| |
Premedication with intravenous dexmedetomidine significantly prolongs the duration of sensory and motor block, provides intraoperative sedation and postoperative analgesia. Both dexmedetomidine and clonidine cause hypotension and significant bradycardia which are transient and easily treatable. Dexmedetomidine provides a longer duration of sensory block, motor block, sedation, and postoperative analgesia than clonidine without significantly increasing the incidence of adverse effects.
Limitations of the study
On comparing with other study models, we had hoped for a higher sample size. This was limited by the low number of cases undergoing surgery at our institution within the given time frame. We hope to overcome this in future studies.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Cousins MJ, Bridenbaugh PO, Carr DB, Horlocker TT. Neural Blockade in Clinical Anaesthesia and Management of Pain. Mayo Clin Proc 2010;85:e51.
Swain A, Nag DS, Sahu S, Samaddar DP. Adjuvants to local anesthetics: Current understanding and future trends. World J Clin Cases 2017;5:307-23.
Höhener D, Blumenthal S, Borgeat A. Sedation and regional anesthesia in the adult patient. Br J Anaesth 2008;100:8-16.
Nayagam HA, Singh NR, Singh HS. A prospective randomised double blind study of intrathecal fentanyl and dexmedetomidine added to low dose bupivacaine for spinal anaesthesia for lower abdominal surgeries. Indian J Anaesth 2014;58:430-5.
] [Full text]
Eid H, Shafie M, Youssef H. Dose-related prolongation of hyperbaric bupivacaine spinal anaesthesia by dexmedetomidine. Ain Shams J Anaesthesiol 2011;4:83-95.
Sudheesh K, Rao RR, Kavya M, Aarthi J, Rani DD, Nethra SS. Comparative study of two doses of intrathecal dexmedetomidine as adjuvant with low dose hyperbaric bupivacaine in ambulatory perianal surgeries: A prospective randomised controlled study. Indian J Anaesth 2015;59:648-52.
] [Full text]
Shaikh SI, Dattatri R. Dexmedetomidine as an adjuvant to hyperbaric spinal bupivacaine for infra-umbilical procedures: A dose related study. Anaesth Pain Intensive Care 2014;18:180-85.
Gupta R, Bogra J, Verma R, Kohli M, Kushwaha JK, Kumar S. Dexmedetomidine as an intrathecal adjuvant for postoperative analgesia. Indian J Anaesth 2011;55:347-51.
] [Full text]
Zhang Y, Shan Z, Kuang L, Xu Y, Xiu H, Wen J, et al
. The effect of different doses of intrathecal dexmedetomidine on spinal anaesthesia: A meta analysis. Int J Clin Exp Med 2016;9:18860-86.
Coskuner I, Tekin M, Kati I, Yagmur C, Elcicek K. Effects of dexmedetomidine on the duration of anaesthesia and wakefulness in bupivacaine epidural block. Eur J Anaesthesiol 2007;24:535-40.
Dobrydnjov I, Axelsson K, Thörn SE, Matthiesen P, Klockhoff H, Holmström B, et al
. Clonidine combined with small-dose bupivacaine during spinal anesthesia for inguinal herniorrhaphy: A randomized double-blinded study. Anesth Analg 2003;96:1496-503.
Grandhe RP, Wig J, Yaddanapudi LN. Evaluation of bupivacaine-clonidine combination for unilateral anesthesia in lower limb orthopaedic surgery. J Anaesthesiol Clin Pharmacol 2008;24:155-8. [Full text]
Kanazi GE, Aouad MT, Jabbour-Khoury SI, Al Jazzar MD, Alameddine MM, Al-Yaman R, et al
. Effect of low-dose dexmedetomidine or clonidine on the characteristics of bupivacaine spinal block. Acta Anaesthesiol Scand 2006;50:222-7.
Elia N, Culebras X, Mazza C, Schiffer E, Tramèr MR. Clonidine as an adjuvant to intrathecal local anesthetics for surgery: Systematic review of randomized trials. Reg Anesth Pain Med 2008;33:159-67.
De Cassai A, Boscolo A, Tonetti T, Ban I, Ori C. Assignment of ASA-physical status relates to anesthesiologists' experience: A survey-based national-study. Korean J Anesthesiol 2019;72:53-9.
Kavya UR, Laxmi S, Ramkumar V. Effect of intravenous dexmedetomidine administered as bolus or as bolus-plus-infusion on subarachnoid anesthesia with hyperbaric bupivacaine. J Anaesthesiol Clin Pharmacol 2018;34:46-50.
] [Full text]
Agrawal A, Agrawal S, Payal YS. Comparison of block characteristics of spinal anesthesia following intravenous dexmedetomidine and clonidine. J Anaesthesiol Clin Pharmacol 2016;32:339-43.
] [Full text]
Apkarian AV, Bushnell MC, Treede RD, Zubieta JK. Human brain mechanisms of pain perception and regulation in health and disease. Eur J Pain 2005;9:463-84.
Terman GW, Bonica JJ. Spinal mechanisms and their modulation. In: Loeser JD, Butler SH, Chapman CR, Turk DC, editors. Bonica's Management of Pain. 3rd
ed., Vol. 73. Philadelphia, Pennsylvania, USA: Lippincott Williams and Wilkins; 2003.
Basbaum AI, Bautista DM, Scherrer G, Julius D. Cellular and molecular mechanisms of pain. Cell 2009;139:267-84.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]