|Year : 2015 | Volume
| Issue : 2 | Page : 96-100
Effect of intravenous dexmedetomidine on bupivacaine spinal analgesia
Stevie JN Sangma, Lourembam Kameshwar Singh, Nongthombam Ratan Singh, Langpoklakpam Chaoba Singh, Alem W Pongener, Dikila Bhutia
Department of Anaesthesiology, Regional Institute of Medical Sciences, Imphal, Manipur, India
|Date of Web Publication||20-Aug-2015|
Nongthombam Ratan Singh
Department of Anaesthesiology, Regional Institute of Medical Sciences, Imphal - 795 003, Manipur
Source of Support: None, Conflict of Interest: None
Background: Dexmedetomidine, a new α2 agonist, has been proven to prolong spinal anesthesia when administered through intrathecal route. This study was conducted to evaluate the effects of intravenous (IV) dexmedetomidine on spinal bupivacaine anesthesia. Materials and Methods: A prospective, randomized, double-blind, and placebo-controlled study was conducted on 80 female patients with the American Society of Anesthesiologists (ASA) grades I and II, aged 18-65 years undergoing abdominal hysterectomy under spinal anesthesia. After spinal anesthesia, patients in group D received a loading dose of 1 μg/kg IV dexmedetomidine over 10 min and followed by a dose of 0.2 μg/kg/h till the end of operative procedure, while patients in group C received the same calculated volume of normal saline. The time to reach peak sensory block level, time taken for two segment regression and maximum motor block, Ramsay sedation score, modified Bromage score, and visual analogue scale were recorded and were statistically analyzed using Statistical Package for Social Sciences (SPSS Inc. Chicago, IL, USA) Windows-based version 16.0. Results: Sensory regression to S1 was prolonged in the dexmedetomidine group compared to the control group (294 ± 18.2 min vs. 288 ± 24.3 min, P < 0.05). The time taken for motor block regression to modified Bromage score 6 in groups D and C were 263.73± 38.4 min and 251.7529.6 min, respectively (P = 0.008). Conclusion: IV infusion of dexmedetomidine significantly prolonged the duration of sensory and motor block of hyperbaric spinal bupivacaine with significant side effects.
Keywords: Bupivacaine, dexmedetomidine, infusion, intravenous (IV), spinal anesthesia
|How to cite this article:|
Sangma SJ, Singh LK, Singh NR, Singh LC, Pongener AW, Bhutia D. Effect of intravenous dexmedetomidine on bupivacaine spinal analgesia. J Med Soc 2015;29:96-100
|How to cite this URL:|
Sangma SJ, Singh LK, Singh NR, Singh LC, Pongener AW, Bhutia D. Effect of intravenous dexmedetomidine on bupivacaine spinal analgesia. J Med Soc [serial online] 2015 [cited 2020 Oct 20];29:96-100. Available from: https://www.jmedsoc.org/text.asp?2015/29/2/96/163199
| Introduction|| |
Postoperative pain relief is a challenging problem and it remains an elusive goal in anesthetic practice. Prolongation of spinal analgesia not only extends the duration of surgical anesthesia but also provides postoperative analgesia for a considerable duration. One of the methods for prolonging the duration of spinal bupivacaine analgesia is by the use of additives like opioids, benzodiazepines, epinephrine, neostigmine, α2 agonist, etc. Dexmedetomidine is the dextro-stereoisomer and active ingredient of medetomidine, an agent used for many years in veterinary anesthesia. Dexmedetomidine is the most recent α2 -adrenergic agonist, having selectively higher ratio for α2 than to α1 receptor (1600:1 as compared with 200:1 for clonidine). , Thus, it has attracted interest for its use in anesthetic procedures, mainly through the intravenous (IV) route due to its analgesic, sedative, and amnesic properties. 
This study was designed to evaluate the effects of IV dexmedetomidine on bupivacaine spinal analgesia, the characteristics of spinal block, and level of sedation after intrathecal bupivacaine.
| Materials and Methods|| |
After obtaining approval of the Institutional Ethics Committee and written informed consent from all the participants, a prospective, randomized, double-blind, placebo-controlled study was undertaken.
Assuming an α-value of 0.05 and β-value of 0.2 (power = 1 - β = 0.8, i.e., 80%) the sample size for this study was 40 in each group based on an earlier study. 
Eighty female patients, aged 18-65 years of ASA grade I or II,  scheduled to undergo abdominal hysterectomy under spinal anesthesia, were divided into two groups with 40 patients in each group by a computer-generated randomization table.
Group D (N = 40) received a loading dose of 1 μg/kg dexmedetomidine intravenously over 10 min and followed by a dose of 0.2 μg/kg/h till the end of operative procedure.
Group C (N = 40) received the same calculated volume of normal saline.
Patients with a history of back surgery, infection at injection site, coagulopathy, hypovolemia, bradycardia, increased intracranial pressure, neurological disease, spinal deformities, hypersensitivity to local anesthetics or dexmedetomidine were excluded from the study.
On arrival in the operation theatre, a suitable peripheral vein was cannulated for administration of study drugs or control (placebo) and another for injection of IV fluids.
With patient in left lateral position, spinal analgesia was performed at the level of L3-L4 space through midline approach using a 25-gauge Quincke spinal needle with the bevel pointing upward. Then 0.5% hyperbaric bupivacaine (3 mL) was injected intrathecally in all patients. After spinal anesthesia with hyperbaric bupivacaine (15 mg), the patient allocated to group D received a loading dose of 1 μg/kg dexmedetomidine through IV infusion pump over 10 min followed by a dose of 0.2 μg/kg/h till the end of the operative procedure. Patients in group C also received the same calculated volume of normal saline as in group D till the end of surgery. The study drug was prepared by another anesthesiologist who was not involved in the study to achieve blinding and prevent bias.
After spinal anesthesia, the blood pressure was monitored by a noninvasive blood pressure (NIBP) monitor every 2 min for 10 minutes, then every 10 min till end of the surgery. Heart rate and peripheral oxygen saturation were recorded continuously. Peak sensory block level, time to reach peak sensory block level, time taken for segment regression and maximum motor block were recorded. Ramsay sedation score was recorded every 10 min intraoperatively, then postoperatively till a sensory regression to S1 along with the modified Bromage score and visual analogue scale were also recorded at 15 min, 30 min, 45 min, 60 min, 90 min, 120 min, 150 min, 180 min, 240 min, and 300 min.
In this study, hypotension was defined as a fall of blood pressure below 20% of the baseline and was corrected with fluids or vasoconstrictors (injection mephentermine) and bradycardia (heart rate <60 per min) was treated with injection atropine.
Ramsay sedation score  was used intraoperatively to assess the level of sedation:
- Patient anxious, agitated or restless, or both;
- Patient cooperative, oriented, and tranquil alert;
- Patient responds to commands;
- Asleep, but with brisk response to light glabellar tap or loud auditory stimulus;
- Asleep, sluggish response to light glabellar tap or loud auditory stimulus; and
- Asleep, no response.
Modified Bromage score  was used postoperatively for assessing the motor block level:
Bromage 1. Complete block (unable to move feet or knees)
Bromage 2. Almost complete block (able to move feet only)
Bromage 3. Partial block (just able to move knees)
Bromage 4. Detectable weakness of hip flexion (between score 3 and 5)
Bromage 5. No detectable weakness of hip flexion while supine (full flexion of knees)
Bromage 6. Able to perform partial knee bend
The collected data were analyzed using Statistical Package for Social Sciences (SPSS Inc. Chicago, IL, USA) Windows-based version 16.0. The parameters recorded were compared between the two groups using chi-square test and independent Student's t-test. A statistical value of P < 0.05 was considered as statistically significant.
| Results|| |
The demographic profiles with regard to age, weight, and height of the patients from the two study groups were comparable and were not statistically significant (P = 0.068) [Table 1].
Peak sensory block was found to be slightly higher in dexmedetomidine group when compared to the control group but it was not statistically significant. Time taken for the peak sensory block to achieve was also recorded, but its statistical analysis was found to be insignificant (P = 0.168). Independent t-test analysis was applied for time taken for two segment regression, and it was found that in group D, there was a decrease in regression time (min) when compared to the control group (134.639.70 vs. 130.757.12, P = 0.016), which was statistically found to be significant. Maximum motor block was also noted during the study period, but it was found to be insignificant (P = 0.091), when compared between the two groups. The sensory regression to S1 dermatome was prolonged in group D when compared to group C (294 ± 18.23 vs. 288 ± 24.31, P value 0.012) and was found to be statistically significant [Table 2].
The mean value of mean arterial blood pressure (MAP) during the first one and half hour after spinal anesthesia were comparable between the two groups [Figure 1]. The mean pulse rate decreased significantly in group D during the intraoperative period but was later comparable to group C [Figure 2].
Ramsay sedation score was 3 in all the cases of group C, and ranged from 3 to 5 in group D, the maximum sedation score at 30 min was (4.15 ± 0.62) after the dexmedetomidine infusion [Figure 3]. The sedation score between group D and group C was statistically found to be very highly significant (P = 0.000).
[Figure 4] shows the modified Bromage score between the two groups at different time intervals; the motor block regression was much slower in group D than in group C and which was found to be statistically significant (P = 0.010).
The incidence of bradycardia (17/40 vs. 4/40) and hypotension (15/40 vs 5/40) were more in group D when compared to group C and was found to be statistically significant (P = 0.010) [Table 3].
| Discussion|| |
Effectiveness of α2 agonists like clonidine or dexmedetomidine as adjunct to bupivacaine hydrochloride given by intrathecal or extradural route in prolonging duration of block is well established. It has also been proved that IV clonidine prolongs spinal bupivacaine analgesia. We set out with the hypothesis that dexmedetomidine being an α2 agonist belonging to the same group as clonidine and having more selectivity for α2 adrenergic receptor should prolong spinal bupivacaine analgesia when given through IV route.
There was a statistically significant longer sensory and motor block in the dexmedetomidine group than in the control group in this study. In the dexmedetomidine group, time taken for two segment regression was increased, recovery of motor block was delayed, and side effects like hypotension and bradycardia were observed to be more, which was found to be statistically significant.
Our findings of prolongation of sensory and motor blocking effects of spinal bupivacaine when supplemented with IV dexmedetomidine given by the standard infusion technique of 1 μg/kg loading followed by 0.2 μg/kg/h continuously are in accordance with those of Whizar-Lugo et al.  who included clonidine in their study.
While our results are in agreement with those of Al-Mustafa et al.,  the duration of block is more in our groups: 294 18.2 min and 288 ± 24.3 min versus 261.5 ± 34.8 min and 165.2 ± 31.5 min for sensory and 263.73 ± 38.4 min and 251.75 ± 29.6 min versus 199 ± 42.8 min and 138.4 ± 31.3 min for motor block regression. The possible explanation may be the use of larger dose of bupivacaine. Moreover, clonidine may produce direct inhibition of impulse conduction in the large, myelinated A α fibers and the 50% effective concentration (EC50%) measured was found to be approximately fourfold of that in small, unmyelinated C fibers. The same process might be applied to dexmedetomidine, and it explains that the more sensory than motor block prolongation in group D as conduction of motor nerve fibers was less inhibited than sensory nerve fibers.  Harsoor et al.  also found prolongation in the sensory and motor blocking effects of spinal bupivacaine when supplemented with IV dexmedetomidine.
Although IV dexmedetomidine or clonidine was able to enhance the sensory blockade, it has been reported that spinal injection of these drugs produces a longer effect. Kanazi et al.  has concluded that adding 3 μg dexmedetomidine or 30 μg clonidine to 12 mg hyperbaric spinal bupivacaine prolonged regression time of sensory block to S1 segment to 300 ± 75 min and 272 38 min, respectively. Dexmedetomidine in a dose of 3-15 μg is usually added to local anesthetic solution as an adjuvant to prolong the spinal block. The sensory regression time of 300 ± 75 min in a study by Kanazi et al.  is comparable to 294 ± 18.2 min of our dexmedetomidine group though the drug was administered differently through IV route in our study. This implies that IV administration of dexmedetomidine may produce the same sensory blocking effect as intrathecal administration as an adjunct.
Sedation level starting at 10 min after the drug infusion was evaluated by using Ramsay sedation score, at every 10 min interval till the end of the operation. In group D, patients were sedated properly attaining Ramsay sedation score between 3 and 4 when compared with the control group in which the patients are well oriented, responding to verbal commands and scoring Ramsay sedation score 3, and it was found to be statistically significant. This observation was similar to the results found during the study conducted by Belleville et al. 
In our study, though the peak sensory block was slightly higher in group D (5.6 ± 1.2 thoracic segment vs 6.2 ± 1.1 thoracic segment) than group C, it was not found to be statistically significant. Likewise, time taken for the peak sensory block (for group D 6.1 ± 1.1 min vs 6.2 ± 0.9 min in group C) between the two study groups was not significant. These observations were found to be similar with the study conducted by Whizar-Lugo et al.  where they have inferred that dexmedetomidine- and clonidine-treated patients always maintained higher sensory block, without significant differences, when compared to placebo group. They also found that the mean time to reach the peak sensory block was similar in all the three groups, without any significant difference.
Side effects of the drugs such as dizziness, bradycardia, hypotension, anxiety, pruritus, and dry mouth were studied during intraoperative period. The incidence of bradycardia was 17/40 (42.5%) in group D and 4/40 (10%) in group C (P value = 0.001); incidence of hypotension was 15/40 (37.7%) in group D and 5/40 (12.5%) in group C (P value <0.05). This significant difference observed in occurrence of hypotension is contrary to the study done by Al-Mustafa et al.  , which might be due to the different dose of hyperbaric bupivacaine (15 mg vs 12.5 mg). The decrease in pulse rate and MAP was more in group D in comparison to group C, which might be explained by the decreased sympathetic outflow and circulating levels of catecholamines caused by dexmedetomidine.  The hemodynamic changes in this study are in agreement with the findings of Arain and Ebert,  who compared dexmedetomidine with propofol for sedation during surgery under regional anesthesia. However, significant difference was not observed in regard to other side effects like dizziness, anxiety, pruritus, and dry mouth.
Limitations in our study include the absence of any standardized preloading or coloading technique. Further studies with different loading and maintenance dose with different infusion rates are needed.
| Conclusion|| |
It can be concluded from the present study that IV infusion of dexmedetomidine significantly prolongs the duration of sensory and motor block of spinal bupivacaine anesthesia. The time taken for two segment regression was prolonged with statistically significant incidence of hypotension and bradycardia.
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Conflicts of interest
There are no conflicts of interest.
| References|| |
Ebert TJ, Hall JE, Barney JA, Uhrich TD, Colinco MD. The effects of increasing plasma concentrations of dexmedetomidine in humans. Anesthesiology 2000;93:382-94.
Glick DB. The autonomic nervous system. In: Miller RD, editor. Miller′s Anesthesia. 7 th
ed. Philadelphia: Churchill Livingstone Elsevier; 2010. p. 284.
Hall JE, Uhrich TD, Barney JA, Arain SR, Ebert TJ. Sedative, amnestic, and analgesic properties of small-dose dexmedetomidine infusion. Anesth Analg 2000;90:699-705.
Kaabachi O, Zarghouni A, Ouezini R, Abdelaziz AB, Chattaoui O, Kokki H. Clonidine 1 microg/kg is safe and effective adjuvant to plain bupivacaine in spinal anesthesia in adolescents. Anesth Analg 2007;105:516-9.
Fischer SP, Bader AM, Sweitzer B. Perioperative evaluation. In: Miller RD, editor. Miller′s Anesthesia. 7 th
ed. Philadelphia: Churchill Livingstone Elsevier; 2010. p. 1002.
Ramsay MA, Savege TM, Simpson BR, Goodwin R. Controlled sedation with alphaxalone-alphadolone. Br Med J 1974;2:656-9.
Breen TW, Shapiro T, Glass B, Foster-Payne D, Oriol NE. Epidural anesthesia for labor in an ambulatory patient. Anesth Analg 1993;77:919-24.
Whizar-Lugo V, Gümez-Ramírez IA, Cisneros-Corral R, Martinez-Gallegos N. Intravenous dexmedetomidine vs intravenous clonidine to prolong bupivacaine spinal anesthesia. A double blind study. Anestesia en México 2007;19:143-6.
Al-Mustafa MM, Badran IZ, Abu-Ali HM, Al-Barazangi BA, Massad IM, Al-Ghanem SM. Intravenous dexmedetomidine prolongs bupivacaine spinal analgesia. Middle East J Anaesthesiol 2009;20:225-31.
Harsoor S, Rani DD, Yalamuru B, Sudheesh K, Nethra S. Effect of supplementation of low dose intravenous dexmedetomidine on characteristics of spinal anaesthesia with hyperbaric bupivacaine. Indian J Anaesth 2013;57:265-9.
Kanazi GE, Aquad 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.
Belleville JP, Ward DS, Bloor BC, Maze M. Effects of intravenous dexmedetomidine in humans. I. Sedation, ventilation, and metabolic rate. Anesthesiology 1992;77:1125-33.
Arain SR, Ebert TJ. The efficacy, side effects, and recovery characteristics of dexmedetomidine versus propofol when used for intraoperative sedation. Anesth Analg 2002;95:461-6, table of contents.
[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2], [Table 3]