|Year : 2016 | Volume
| Issue : 3 | Page : 166-171
Comparative study of the effect of dexmedetomidine and butorphanol as epidural adjuvants in abdominal hysterectomy under intrathecal levobupivacaine anesthesia
Nirmeen Fatima, Nongthombam Ratan Singh, Laithangbam Pradip Kumar Singh, Dhananjaya Bangalore Doddaiah, Takhelmayum Hemjit Singh, Yamini Taloh
Department of Anaesthesiology, Regional Institute of Medical Sciences, Imphal, Manipur, India
|Date of Web Publication||28-Sep-2016|
Nongthombam Ratan Singh
Department of Anaesthesiology, Regional Institute of Medical Sciences, Imphal - 795 004, Manipur
Source of Support: None, Conflict of Interest: None
Background: Combined spinal-epidural technique has become increasingly popular in the last few years for abdominal hysterectomies. Opioids or α-2 agonists are being increasingly used as epidural adjuncts. Aims: The aim of this study is to compare the clinical profile of dexmedetomidine and butorphanol when administered epidurally, following intrathecal levobupivacaine (heavy) in combined spinal and epidural anesthesia. Materials and Methods: Sixty adult patients aged 18-60 years, the American Society of Anesthesiologists Physical Status I and II undergoing abdominal hysterectomy were enrolled into the study and randomly divided into two groups: Group LD (n = 30) received 12.5 mg of 0.5% levobupivacaine (heavy) intrathecally plus dexmedetomidine 1 ΅g/kg in 10 ml saline epidurally and Group LB (n = 30) received 12.5 mg of 0.5% levobupivacaine (heavy) intrathecally plus butorphanol 10 ΅g/kg in 10 ml saline epidurally. The hemodynamics, block characteristics, and side effects were observed; the data were compiled and analyzed using Student's t-test and Chi-square test. P < 0.05 was considered statistically significant. Results: The demographic profiles of the patients were comparable between the two groups. The onset of sensory analgesia at T10 was significantly faster in the Group LD (92.80 ± 31.51 vs. 105.43 ± 42.04 s). The time to two-segmental regression in dexmedetomidine group was 184.23 ± 45.10 min versus 120.40 ± 33.03 min in butorphanol group (P < 0.001). Postoperative analgesia was prolonged in the Group LD (321.43 ± 60.68 vs. 205.03 ± 57.90 min, P < 0.001). Sedation scores were much better in the LD group and highly significant on statistical comparison (P < 0.001). Conclusions: Dexmedetomidine was a better alternative to butorphanol as an epidural adjuvant providing comparable stable hemodynamics, early onset, and establishment of sensory anesthesia, prolonged postoperative analgesia, and much better sedation.
Keywords: Adjuvants, butorphanol, combined spinal-epidural, dexmedetomidine, levobupivacaine
|How to cite this article:|
Fatima N, Singh NR, Singh LP, Doddaiah DB, Singh TH, Taloh Y. Comparative study of the effect of dexmedetomidine and butorphanol as epidural adjuvants in abdominal hysterectomy under intrathecal levobupivacaine anesthesia. J Med Soc 2016;30:166-71
|How to cite this URL:|
Fatima N, Singh NR, Singh LP, Doddaiah DB, Singh TH, Taloh Y. Comparative study of the effect of dexmedetomidine and butorphanol as epidural adjuvants in abdominal hysterectomy under intrathecal levobupivacaine anesthesia. J Med Soc [serial online] 2016 [cited 2020 Oct 31];30:166-71. Available from: https://www.jmedsoc.org/text.asp?2016/30/3/166/191183
| Introduction|| |
Regional anesthesia is the preferred mode of anesthesia  for major abdominal surgeries in present times. While epidural and spinal blockades are well-established regional anesthetic techniques, combined spinal-epidural technique has become increasingly popular in the last few years. The rationale for using a combination of the two techniques was to associate the advantages of each technique, minimizing specific disadvantages, namely, combines the efficacy of spinal anesthesia and flexibility of epidural anesthesia. 
Neuraxial adjuvants such as opioids, sodium bicarbonate, adrenaline, α-2 adrenoceptor agonists, N-methyl-D-aspartate antagonists, and GABA receptor agonists are used to improve, hasten, or prolong analgesia and decrease the adverse effects associated with high doses of the local anesthetic agent. 
Levobupivacaine is a long-acting local anesthetic which has a pharmacological structure similar to bupivacaine having a larger safety margin, reduced cardiotoxicity, neurotoxicity, and rapid recovery of motor functions. 
Butorphanol is a lipid soluble narcotic with weak μ-receptor agonist and antagonist activity and strong k-receptor agonism.  Its use as an adjuvant in spinal anesthesia results in significantly faster onset of pain relief, prolonged duration of analgesia, and dose-sparing effect of local anesthetics.
Dexmedetomidine is a highly selective α-2 adrenergic agonist that acts on both pre- and post-synaptic sympathetic nerve terminal and central nervous system, thereby decreasing the sympathetic outflow causing sedative, antianxiety, analgesic, sympatholytic, and hemodynamic effects. ,
The aim of the study was to evaluate the effect of epidural supplementation with dexmedetomidine or butorphanol to intrathecal levobupivacaine in patients undergoing abdominal hysterectomy keeping the benefit of levobupivacaine in consideration.
| Materials and methods|| |
After the Institutional Ethics Committee's approval and written informed consent, sixty patients, the American Society of Anesthesiologists (ASA I and II)  of 18-60 years, undergoing abdominal hysterectomy were recruited in this randomized double-blinded study conducted in the Department of Anaesthesiology of a Tertiary Care Teaching Hospital in Imphal, Manipur.
The study drug was prepared by an anesthesiologist not involved in the study in a 10 ml syringe in equal volume. Based on a previous study,  using a web-based sample size calculator, the sample size in our study was 28 in each group, assuming α = 0.05 and β = 0.2 or power (1-β) = 0.8. Assuming a 5% drop out, in our study, we enrolled 30 patients in each group. Using computer-generated randomization, the patients were allocated into two groups:
- Group LD (n = 30): Received 12.5 mg of 0.5% levobupivacaine (heavy) intrathecally plus dexmedetomidine 1 μg/kg in 10 ml saline epidurally
- Group LB (n = 30): Received 12.5 mg of 0.5% levobupivacaine (heavy) intrathecally plus butorphanol 10 μg/kg in 10 ml saline epidurally.
The commercially available 0.5% solution levobupivacaine (isobaric) was made hyperbaric solution by adding 0.5 ml of 50% glucose. 
Patients with any contraindication to neuraxial anesthesia - previous spinal surgeries, spine abnormalities, local site infection, coagulation abnormalities, cardiopulmonary problems, neurological diseases, patients on tricyclic antidepressants, α-2 adrenergic agonists, opioids, antiarrhythmics, or β-blockers - were excluded from the study.
After preanesthetic evaluation, a day before the scheduled day of surgery, standard monitors were instituted in the operating room, namely, baseline noninvasive blood pressure, pulse rate, electrocardiograph, and pulse oximetry (SpO 2 ) were recorded and preloaded with Ringer's lactate solution.
Under strict aseptic and antiseptic precautions, with the patient in the left lateral decubitus position, the injection site in the lumbar region was infiltrated with local anesthetic and the epidural space between L2-3 was located using 18-gauge Tuohy needle (Perifix 401, B Braun Medical Melsungen, Germany) using midline approach and loss of resistance technique and a 20-gauge epidural catheter was placed in situ. After negative aspiration of blood and cerebrospinal fluid, a test dose of 3 ml of lignocaine with adrenaline 1:200,000 was injected through the catheter to exclude intrathecal or intravascular placement of the catheter. In the same position, dural puncture was performed in L3-4 interspace with 25-gauge Quincke needle (Spinocan, B Braun Medical Melsungen, Germany) 12.5 mg of 0.5% hyperbaric levobupivacaine. All durations were calculated considering the time of intrathecal injection as time "0" (zero). After securing the epidural catheter and making the patients supine, epidural adjuvants were administered depending on the group assigned.
Hypotension, defined as systolic blood pressure (SBP) <100 mm Hg or decrease in SBP <20% of baseline blood pressure, was corrected with fluids or injection mephentermine. Bradycardia (heart rate [HR] <50 bpm) was treated with injection atropine 0.3-0.6 mg intravenous. The incidence of adverse effects such as nausea, vomiting, shivering, pruritus, respiratory depression, sedation, hypotension, and bradycardia was recorded.
The sensory onset time (seconds) was taken as the first complaint of tingling and numbness in the lower limb after intrathecal injection. Sensory testing was assessed by loss of pinprick sensation along the midclavicular line bilaterally every minute until the highest level has been stabilized for four consecutive tests, until the point of two-segment regression of the block. Further testing was performed until the recovery of S2 dermatome was achieved.
Time to analgesic block at T10 dermatome, the peak sensory block level, the time to reach peak sensory block level, a two-segment dermatomal regression, and sensory regression to the S2 dermatome were recorded. The degree of motor block was assessed when cutaneous sensation was lost at T10 using Modified Bromage Scale,  and sedation scores were assessed using Modified Ramsay Sedation Scale. 
Duration of analgesia was recorded as the interval from the completion of anesthesia to the time of the first complaint of pain or visual analog pain >4. Rescue analgesia was provided by injection diclofenac 75 mg.
The data collected were analyzed using Statistical package for social sciences for windows (SPSS) version21.0 (Armonk, NY: IBM corp.) and compared using Student's t-test for parametric data and Chi-square test for nonparametric data and P < 0.05 was considered statistically significant.
| Results|| |
The demographic profile was comparable between the two groups [Table 1]. As shown in [Table 2], the time to onset of analgesia to reach T10 sensory level was 92.80 ± 31.51 s in Group LD and 105.43 ± 42.04 s in Group LB and statistically insignificant (P = 0.19); further, the time to reach maximum sensory block level in Group LD versus Group LB was 502.47 ± 284.5 versus 491.90 ± 269.42 s which was statistically insignificant (P = 0.88). Similarly, there was no significant difference in the time to achieve complete motor block between the two groups (P = 0.19). The time to two-segment dermatomal regression between Group LD versus Group LB was 184.23 ± 45.10 versus 120.40 ± 33.03 min which was statistically significant (P < 0.001). Similarly, time to S2 level sensory regression was more prolonged in the Group LD (373.50 ± 79.53 min) than in the Group LB (267.43 ± 64.30 min) and statistically significant, P < 0.001 [Table 2]. The difference between the maximum dermatome level achieved in the two groups was statistically significant (P < 0.001). Higher sensory block level was attained with dexmedetomidine-T4 in 96.66% patients. Dexmedetomidine group showed prolonged postoperative analgesia for 321.43 ± 60.68 min compared to butorphanol group where the time to rescue analgesic was 205.03 ± 57.90 min (P < 0.001).
The mean arterial pressure at various time intervals was comparable between the two groups and statistically not significant, but there was a fall in the HR from the 15 th min, which persisted but remained in the normal physiological range throughout the study period [Figure 1].
|Figure 1: The mean arterial pressure ± standard deviation and heart rate at different time points|
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The changes in the SBP and diastolic blood pressure [Figure 2] were comparable between the two groups and statistically not significant (P > 0.05).
|Figure 2: The mean systolic blood pressure ± standard deviation and diastolic blood pressure ± standard deviation between the two groups|
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Supplemental oxygen requirement was comparable and statistically not significant. The incidence of hypotension was comparable (P = 0.11), but bradycardia was more in Group LD (Group LD vs. Group LB: 7 vs. 1; P = 0.02) [Table 3]. Pruritus was not reported in any patient. The incidence of vomiting in Group LD versus Group LB was 15/30 versus 2/30, P < 0.001, which is statistically significant [Table 3]. The incidence of shivering was similar in both the groups (one in each group), and anxiety was comparable and statistically insignificant (P = 0.31) [Table 3]. Sedation scores were significantly higher in LD group with a score of 4 reported in 25/30 patients, i.e., 83.3%. No patients in LB group had a score of 4, where 24/30, i.e., 80% of patients had a sedation score of 2.
| Discussion|| |
Epidural analgesia was considered in conjunction with spinal anesthesia as it allows superior postoperative analgesia, leading to early patient mobilization.  Abdominal hysterectomies expected to last less than an hour were included in our study in an attempt to keep the intensity of postoperative pain nearly constant in both the groups and thereby avoiding bias due to surgical duration. The patients in both the groups were matched and comparable in age, body weight, ASA physical status, and duration of surgery with no significant statistical differences.
The rationale for comparing the two selected doses of dexmedetomidine (1 μ/kg) and butorphanol (10 μ/kg) was derived from earlier studies , which advocated the use of such doses to prolong the duration of analgesia without significant side effects.
The findings of the present study show that the addition of either epidural adjuvant following intrathecal levobupivacaine did not significantly affect the onset time of sensory block at T10 (P = 0.19), time to reach maximum sensory block level (P = 0.88), and time for complete motor block (P = 0.19). Our result is also supported by Jain et al.,  which may be because of the volume and the compressive effect of both the epidural adjuvants for increasing the height of block remained constant. However, in our study, we noticed a significant difference in the maximal dermatomal height of sensory level achieved in the dexmedetomidine group (P < 0.001). Maximum sensory dermatomal level being T4 in 29 out of 30 (96.6%) patients in dexmedetomidine group while 17 out of 30 (56.6%) in butorphanol group. This might be due to the synergistic action of α-2 adrenergic agonist with local anesthetics. Furthermore, since the associated sympathetic block is usually near-maximal with the doses used for spinal anesthesia,  the addition of epidural adjuvants does not further influence the near-maximal action of sympathetic block of levobupivacaine.
The results of our study clearly indicate that dexmedetomidine has a visible edge over butorphanol as it prolonged the time to two-segment dermatomal regression and sensory block regression to S2 (P < 0.001) similar to the previous study.  Wapang et al.  compared the effects of intrathecal dexmedetomidine and magnesium sulfate on the characteristics of bupivacaine spinal block and observed a similar delay in the two-segmental regression in the dexmedetomidine group (132.33 ± 12.51 min, P < 0.001). The mechanism of action by which intrathecal α-2 adrenergic agonists prolong the block of local anesthetics is not well-known. , The local anesthetics act by blocking sodium channels, whereas α-2 adrenoceptor agonist acts by binding to presynaptic C-fiber and postsynaptic dorsal horn neurons.  It may be an additive or synergistic effect secondary to the different mechanisms of action of the local anesthetics and the α-2 adrenoceptor agonist as studied by Salgado et al. 
In our study, we found that the analgesic effect of intrathecal levobupivacaine was potentiated by epidural dexmedetomidine. Similarly, several workers ,, concluded that the use of dexmedetomidine either intrathecally or epidurally when compared with fentanyl or saline significantly improved the analgesic efficacy and prolonged the postoperative analgesia. The prolongation of analgesic effect may be due to an additive or synergistic effect of different mechanisms of action of local anesthetic and α-2 adrenoceptor agonists. The complementary action of local anesthetics and α-2 adrenoceptor agonists accounts for their profound analgesic properties.
The sedation scores were significantly higher in dexmedetomidine group compared to butorphanol group (P < 0.001), which are in agreement with previous studies.  These sedative effects of α-2 adrenoceptor agonists are mediated by the activation of presynaptic α-2 adrenoceptors in the locus coeruleus, which inhibit the release of norepinephrine.
Hemodynamic stability was one of the most remarkable features observed with the addition of epidural dexmedetomidine and butorphanol to intrathecal levobupivacaine. The cardiovascular parameters suggest that changes in systolic, diastolic, and mean blood pressure in the two groups were comparable and not statistically significant. Decrease in HR is a known clinical effect of opioids; however, in the present study, similar negative chronotropic effect was exhibited by dexmedetomidine. Similar findings were observed by Jain et al.  and Gupta et al.  The decrease in HR caused by α-2 agonist can be explained on the basis of their central action, whereby the decrease in sympathetic outflow and norepinephrine release. , Although hypotension was found in 15 patients in dexmedetomidine group and nine patients in butorphanol group, requiring treatment, the overall difference between the two groups was statistically insignificant (P = 0.11). The reason could be an additive hypotensive effect of the combination of these epidural adjuvants with intrathecal levobupivacaine. We noticed a significantly higher incidence (P = 0.02) of bradycardia in the dexmedetomidine similar to other studies. ,
Nausea and vomiting occurred in 50% of the patients in butorphanol group as compared to 6.7% in dexmedetomidine group (P < 0.001). This higher incidence of nausea and vomiting, a known side effect of opioids, was observed despite a low dose of butorphanol used epidurally. The α-2 adrenergic agents also have antishivering property as observed by Talke et al.  Bansal and Jain  also noted the antishivering effect of butorphanol because of agonist action at μ and k receptors. However, we found one case of shivering in each group. The absence of pruritus in our study which was observed in few patients in previous studies  may be due to the use of lower dosage of butorphanol.
We also reported a single patient experiencing anxiety in butorphanol group and none in dexmedetomidine group which may be attributed to the anxiolytic property of dexmedetomidine.
| Conclusions|| |
Epidural dexmedetomidine supplementation is a better alternative than epidural butorphanol when used as an adjuvant to intrathecal levobupivacaine anesthesia in abdominal hysterectomy.
The presence of ceiling effect and any significant effect at a higher dose range was not determined; the study could have been investigated with other physical status.
Thus, further studies with varied doses of epidural adjuncts plus varied intrathecal local anesthetic and a larger sample size are recommended to come to a definitive conclusion.
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Conflicts of interest
There are no conflicts of interest
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[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3]