|Year : 2014 | Volume
| Issue : 3 | Page : 149-154
Epidural 0.5% levobupivacaine with dexmedetomidine versus fentanyl for vaginal hysterectomy: A prospective study
Kumkum Gupta1, Bhawna Rastogi1, Prashant K Gupta2, Manish Jain1, Suneeta Gupta3, Deepti Mangla1
1 Department of Anaesthesiology and Critical Care, Netaji Subhash Chandra Bose Subharti Medical College, Swami Vivekananda Subharti University, Subhartipuram, Meerut, Uttar Pradesh, India
2 Department of Radio-diagnosis, Imaging and Interventional Radiology, Netaji Subhash Chandra Bose Subharti Medical College, Swami Vivekananda Subharti University, Subhartipuram, Meerut, Uttar Pradesh, India
3 Department of Obstetrics and Gynaecology, Netaji Subhash Chandra Bose Subharti Medical College, Swami Vivekananda Subharti University, Subhartipuram, Meerut, Uttar Pradesh, India
|Date of Web Publication||11-Aug-2014|
108, Chanakyapuri, Shastri Nagar, Meerut - 250 004, Uttar Pradesh
Source of Support: None, Conflict of Interest: None
Background: Epidural adjuvants enhance the quality and duration of surgical anesthesia. The present study was aimed to compare the hemodynamic, sedative, and analgesia potentiating effects of dexmedetomidine versus fentanyl with epidural 0.5% levobupivacaine for vaginal hysterectomy. Patients and Methods: Sixty consented females of ASA physical status I and II aged 35-65 years weighing 55-75 kg, were double blindly randomized into two treatment groups. Patients received epidural 0.5% levobupivacaine 15 ml either with of 25 μg dexmedetomidine (Group LD) or 50 μg fentanyl (Group LF) and the total volume of study solution was kept 16 ml. Onset of analgesia at T10, sensory and motor block levels and duration of analgesia were observed. Intra-operatively, they were assessed for sedation, hemodynamic changes, respiratory efficiency, and side effects. The data obtained, was compiled systematically and analyzed statistically using Chi-square test and ANOVA. Value of P < 0.05 is considered significant. Result: The demographic profile was comparable between groups. The onset of sensory analgesia at T10 (7.25 ± 2.3 versus 9.27 ± 2.79 min) and time to achieve complete motor blockade (19.27 ± 4.7 versus 22.78 ± 5.57 min) was significantly earlier in patients of LD Group. The intraoperative hemodynamic changes were comparable between groups. Ramsey Sedation score was better in LD group with statistically significance. Postoperative analgesia was significantly prolonged in LD Group. Incidence of nausea, vomiting, and pruritus was high in LF group. Conclusion: Dexmedetomidine was better than fentanyl as an epidural adjuvant for providing early onset of sensory analgesia, adequate sedation with no respiratory depression and prolonged postoperative analgesia.
Keywords: Dexmedetomidine, epidural anesthesia, fentanyl, hysterectomy, levobupivacaine
|How to cite this article:|
Gupta K, Rastogi B, Gupta PK, Jain M, Gupta S, Mangla D. Epidural 0.5% levobupivacaine with dexmedetomidine versus fentanyl for vaginal hysterectomy: A prospective study. Indian J Pain 2014;28:149-54
|How to cite this URL:|
Gupta K, Rastogi B, Gupta PK, Jain M, Gupta S, Mangla D. Epidural 0.5% levobupivacaine with dexmedetomidine versus fentanyl for vaginal hysterectomy: A prospective study. Indian J Pain [serial online] 2014 [cited 2019 Aug 20];28:149-54. Available from: http://www.indianjpain.org/text.asp?2014/28/3/149/138447
| Introduction|| |
Epidural anesthesia is performed to provide anesthesia for surgical procedures carried on lower abdomen, pelvis, and lower limbs. It offers superior pain relief and early mobilization especially when local anesthetic is combined with an adjuvant. Noxious impulses from damaged tissue evoke long lasting alterations in the central nervous system. Epidural anesthesia reduces the surgical stress by blocking the nociceptive impulses from the operative site and also reduces the blood loss, improve respiratory and bowel function and decreased incidence of deep vein thrombosis, but it is frequently associated with hemodynamic fluctuations due to use of large volumes of local anesthetic drug. ,
Stereoisomers of the local anesthetics are coming up instead of the isomers, in order to avoid the toxic effects as much as possible. Levobupivacaine, an amide local anesthetic, showed a profile close to bupivacaine in terms of onset, quality, and duration of sensory block, but with lesser cardiac and neurotoxic adverse effects. The clinical data showed its efficacy and safety for regional anesthetic techniques with minimal hemodynamic fluctuations. Its low lipid solubility leads to greater sensory-motor differentiation by blocking sensory nerve fibers more readily than motor fiber. Early recovery of motor function is associated with decreased incidences of venous thrombo-embolism. ,
The addition of adjuvants like opioids or α-2agonist provide a dose-sparing effects of local anesthetics and would accelerate the onset of sensory blockade of epidural anesthesia and decrease the effective dose of local anesthetic. Sedation, stable hemodynamic and an ability to provide prolonged postoperative analgesia are the main desirable qualities of an epidural adjuvant. Fentanyl acts as agonist at μ-opioid receptors to enhance the analgesia, while dexmedetomidine acts on pre and post-synaptic sympathetic nerve terminal and central nervous system to decrease the sympathetic outflow and nor-epinephrine release causing sedation, analgesia, sympatholytic and hemodynamic effects. Motor blockade tends to be denser with dexmedetomidine. Dexmedetomidine is also devoid of respiratory depression, pruritus, nausea, and vomiting.
The synergism between epidural local anesthetic and opioids is well established but evidence regarding combination of local anesthetic with dexmedetomidine through epidural route is scarce in literature. There is no such study which compared the dose equivalence of these drugs. Considering the merits of levobupivacaine and adjuvants, this prospective double-blind randomized study was aimed to evaluate the clinical efficiency of dexmedetomidine and fentanyl when used as an adjuvant to epidural levobupivacaine for vaginal hysterectomy.
| Patients and Methods|| |
After approval by the Institutional Ethical Committee and written informed consent, 60 female patients of American Society of Anaesthesiologist (ASA) physical status I and II, aged 35-65 years weighing 55-75 kg, scheduled for elective vaginal hysterectomy under epidural anesthesia from December 2012 to November 2013, were enrolled for this prospective double-blind randomized study. Patients with history of diabetes mellitus, pre-existing severe cardiac or pulmonary disease, hypertension, renal or hepatic disease, spinal deformity, skin infection or local cellulitis at the site, coagulation or bleeding disorders, allergy to local anesthetic, history of opioid dependence or neurological disorders and patient's refusal to technique were excluded from the study. Before enrolment for the study, patients were explained on the method of sensory and motor assessments. All patients were given oral ranitidine 150 mg and alprazolam 0.25 mg, night before surgery.
Patients were randomized according to computer-generated number, into two groups of 30 patients each. Group LD patients received epidural study solution of 15 ml of levobupivacaine 0.5% with 25 μg dexmedetomidine and Group LF patients received epidural study solution of 15 ml of levobupivacaine 0.5% with fentanyl 50 μg keeping the total volume of 16 ml in both the groups. The volume of the local anesthetic given was estimated as to provide anesthesia upto T 7 dermatome. The drug was prepared by an anesthesiologist who was blinded to study protocol and was not involved in further data collection and assessment of patient.
After arrival of patient into operation theater, routine monitoring of non-invasive blood pressure, heart rate, electrocardiogram (ECG), and finger pulse oximetry was started. An intravenous line was established to preload the patient with Ringer lactate solution at rate of 10 ml kg -1 before the initiation of epidural block. Under all aseptic condition, epidural anesthesia was administered in the lateral decubitus position at L3-4 or L4-5 interspace with an 18-G Tuohy needle by loss of resistance technique. With the bevel of the Tuohy needle in cephalic direction, an epidural catheter was inserted 5 cm into epidural space and secured. The position of catheter was checked by aspiration for blood or CSF. A test dose of 60 mg lidocaine containing 1:200,000 epinephrine, was administered to detect intrathecal or intravenous injection and patients turned to supine position. After 3 minutes the patients received study solution according to randomization schedule at rate of 3 ml/10 seconds by epidural catheter.
The onset of sensory blockade with maximal cephalic spread was assessed by bilateral pin prick method along the midclavicular line using a short bevelled 26-G hypodermic needle. The modified Bromage scale (0 = no power impairment and able to raise straight leg; 1 = unable to raise straight leg but able to flex knee; 2 = unable to flex knee; 3 = unable to flex ankle and foot- no movements) was used to measure the motor blockade effect at 5, 10, 15, 20, 25, and 30 minutes intervals after epidural administration of the drugs. The end points were onset of sensory analgesia at T10, the complete establishment of motor blockade, the time to two segmental dermatome regressions of analgesic level and time to complete recovery.
Grading of sedation was evaluated by using Ramsey sedation scale (1 = awake, conscious, no sedation; 2 = calm and compose; 3 = awake on verbal command; 4 = brisk response to gentle tactile stimulation; 5 = awake on vigorous shaking; 6 = unarousable). Sedation score were recorded just before the initiation and at every 20 minutes during the hysterectomy.
Cardio-respiratory parameters of heart rate, blood pressure, and SpO 2 were monitored continuously and recorded before (baseline) and every 5 min after epidural block performance until the end of surgery. Intraoperatively supplemental oxygen was given. For the present study, hypotension was defined as a fall in systolic blood pressure of more than 20% of baseline value or less than 100 mm Hg and was treated with volume expansion and if required, by incremental doses of mephenteramine 3-6 mg. Bradycardia (heart rate <55/min) was treated with 0.3 mg of intravenous atropine. During the hysterectomy, pruritus, nausea, vomiting, respiratory depression, and post-epidural shivering were carefully observed, recorded, and managed symptomatically.
Surgical technique of vaginal hysterectomy was also standardized. Adrenaline in dose of 1 mg (1:100,000) was infiltrated in vesicovaginal space to separate the anterior vaginal wall mucosa from pericervical fascia.
In the postoperative room, all the vitals and hemodynamic parameters were observed and postoperative pain was managed with 3 ml of 0.5 % levobupivacaine with 1 ml of tramadol (50 mg), diluted with 6 ml of normal saline (10 ml) through epidural catheter. All patients were followed up for any side effects till their hospital stay.
The sample size was based in order to detect a 30-minute difference in mean duration of sensory and motor blockade between the groups to ensure statistically significant results. The recorded data are compiled systematically and was analysed using Stat Graphic Centurion (Stat point Technology Inc). The parametric data were analyzed using Student's t-test and nonparametric data using Chi-square test. Block characteristics were compared using Mann-Whitney U test. A P-value of <0.05 was considered statistically significant.
| Results|| |
Sixty female patients were successfully operated for hysterectomy under epidural levobupivacaine anesthesia. There was no preoperative or intraoperative protocol deviation and all patients were co-operative with subsequent assessment. The demographic profile was comparable between groups and did not show any statistical significant difference [Table 1].
The baseline heart rate was 73.4 ± 11.6 beats per minute and systolic blood pressure was 133.7 ± 9.2 mmHg. The intraoperative mean values of heart rate and systolic blood pressure did not show statistically significant decline from the base values. The episodes of hypotension and bradycardia were negligible thus atropine and vasopressor was not required [Figure 1] and [Figure 2].
The sensory and motor blockade characteristics of both groups are shown in [Table 2]. The mean onset time of adequate sensory analgesia at T 10 dermatome was 7.25 ± 2.3 min in patients of group LD and 9.27 ± 2.79 min in patients of group LF. The difference was not clinically significant. The mean time to achieve maximal sensory block showed statistically significant difference with P- value of 0.045. The mean time taken to achieve complete motor block was 19.27 ± 4.7 min in patients of group LD while it took 22.78 ± 5.5 min in patients of group LF. The difference was clinically significant with P-value of 0.038. The difference in mean duration of sensory analgesia between groups was statistically highly significant (187.7 min in group LD versus 146.7 min in group LF). Bromage scale 3 was observed in 96% of patients. The total duration of motor blockade was less than sensory analgesia in all patients with statistical significant difference between groups.
The maximum Ramsey sedation scores were higher (>3) in patients of dexmedetomidine group while it was less than 2 in patients of fentanyl group. No patient needed any supplemental sedation during surgery. Mild pruritus was observed only in seven patients of group LF which required no treatment. The ventilatory frequency and peripheral oxygen saturation were comparable between groups. No patients suffered from post-epidural shivering, nausea or vomiting, and urinary retention and the bowel recovery was not altered. There were no transient neurological symptoms in any patient.
| Discussion|| |
Epidural levobupivacaine with dexmedetomidine and fentanyl for vaginal hysterectomy was evaluated in the present study. The study demonstrated the adequate surgical anesthesia with comparable intraoperative hemodynamic changes in both groups. No episodes of hypotension, nausea and vomiting, headache, post-epidural shivering, and urinary retention occurred in any patients during the study. Only seven patients of levobupivacaine with fentanyl suffered with mild pruritus.
The indications for hysterectomy are varied and greatly influenced by the patient's age, pathological diagnosis and reproductive status. The anesthetic management must be congruent with the gynecological diagnosis and associated comorbidities of chronic obstructive pulmonary disease (COPD), diabetes mellitus, obesity, hypertension, coronary artery disease, or cancer.
Many techniques and drug regimens have been tried to eliminate the anxiety and to facilitate the early recovery after hysterectomy. Continuous supine position for a prolonged duration and the inability to move the body during regional anesthesia causes discomfort and phobia in many patients. Alpha 2 adrenergic agonists and opioids have both analgesic and sedative properties when used as adjuvant in regional anesthesia. Sedation, stable hemodynamic, and prolonged postoperative analgesia are the main desirable qualities of an adjuvant to epidural anesthesia. 
Epidural blockade reduces the surgical stress response and postoperative dynamic pain due to central sensitization and permits analgesic dosing through the catheter for postoperative pain management. Selection of exclusive epidural route during this study was done deliberately to avoid invasive dural penetration technique as well as to provide postoperative analgesia. The patients are not rendered unconsciousness thus retain spontaneous reflexes and cognitive responsiveness with early mobilization. 
Equal doses of levobupivacaine and bupivacaine provide similar onset of sensory block, maximum cephalic spread, and duration of analgesia but the onset of motor block is delayed and less dense. Levobupivacaine has a wider margin of safety and showed greater differentiation between duration of sensory and motor blockade. It can be safely used for regional anesthesia for hysterectomy. The onset of sensory anesthesia begins at 10-25 minutes after epidural administration with 2-4 hour duration. 
The potency and duration of levobupivacaine can be altered by adjuvants due to their synergistic interaction. Local anesthetics block propagation and generation of neural action potential by a selective effect on sodium channels. Fentanyl acts primarily as agonist at μ-opioid receptors to enhance the analgesia. The dorsal roots (primary afferent tissues) contain opioid-binding sites and fentanyl either acts directly on the spinal nerve or by penetrating the duramater to act at the spinal roots. , Casimiro et al., compared levobupivacaine with fentanyl and bupivacaine with fentanyl and concluded that both groups showed similar anesthetic effects but higher proportion of patients receiving levobupivacaine lacked dense motor block. 
Dexmedetomidine acts on pre and post-synaptic sympathetic nerve terminal and central nervous system thereby decreasing the sympathetic outflow and nor-epinephrine release to cause sedation, analgesia and hemodynamic effects. It acts peripherally by blocking conduction through Aa and C fibers to enhance the effects of local anesthetics without increasing the incidence of side effects. ,,
In the present study, the dexmedetomidine showed an earlier onset of sensory and motor blockade as compared to fentanyl during epidural anesthesia. Honoura et al. concluded in their study that addition of dexmedetomidine to bupivacaine and fentanyl has improved intraoperative condition and quality of postoperative analgesia without significant maternal or neonatal significant.  Selim et al., found in their study that epidural dexmedetomidine and bupivacaine provided better maternal satisfaction for labor pain in comparison to bupivacaine-fentanyl combination without deleterious effect on newborns. 
Hemodynamic stability was one of the most remarkable features observed with addition of dexmedetomidine or fentanyl to epidural levobupivacaine. Decrease in heart rate is known clinical effects of opioids but in the present study similar negative chronotropic effect was also exhibited by dexmedetomidine approximately 30-35 minutes after epidural injection of drug. Thereafter, the heart rate remained stable in range of 57-64 beats/min in both groups. Similarly mean arterial blood pressure was decreased from baseline in both groups with maximum decline at 30-35 minutes after the epidural injection but it never went beyond acceptable physiological limit of 65 mmHg. Postoperative heart rate and blood pressure remained stabilized in both groups.
The requirement of vasopressor for maintenance of stable hemodynamic parameters did not reveal any significant difference between both the groups on statistical comparison. The stable hemodynamic can possibly be explained on the basis of lower volume of local anesthetic used and infiltration of vesicovaginal space with adrenaline in dose of 1 mg (1:100,000) during vaginal hysterectomy. The absence of respiratory depression in the present study can be explained on the basis that we used fentanyl in a lower dosage and dexmedetomidine does not exhibit respiratory depression.
The faster onset of action of local anesthetic agents, rapid establishment of both sensory and motor blockade, prolonged duration of analgesia into the postoperative period and stable cardiovascular parameters makes these agents very effective adjuvants in regional anesthesia.
| Conclusion|| |
Epidural levobupivacaine with dexmedetomidine provided better sedation, adequate surgical anesthesia and stable cardiorespiratory parameters with prolonged postoperative analgesia for vaginal hysterectomy but no difference was elicited as far as the level of sensory block is concerned between dexmedetomidine and fentanyl. Both adjuvants reduced the epidural dose of levobupivacaine and potentiated its efficacy for vaginal hysterectomy.
| References|| |
|1.||Richards JT, Read JR, Chambers WA. Epidural anesthesia as a method of pre-emptive analgesia for abdominal hysterectomy. Anesthesia 1998;53:296-8. |
|2.||Rigg JR, Jamrozik K, Myles PS, Silbert BS, Peyton PJ, Parsons RW, et al.; MASTER Anaethesia Trial Study Group. Epidural anesthesia and analgesia and outcome of major surgery: A randomized trial. Lancet 2002;359:1276-82. |
|3.||Stewart J, Kellert N, Castro D. The central nervous system and cardiovascular effects of levobupivacaine and ropivacaine in healthy volunteers. Anesth Anal 2003;97:412-6. |
|4.||Foster RH, Markham A. Levobupivacaine. A review of its pharmacology and use as a local anaesthetic. Drugs 2000;59:551-79. |
|5.||Gabriel JS, Cordin V. Alpha 2 agonists in regional anaesthesia and analgesia. Curr Opin Anaesthesiol 2001;14:751-3. |
|6.||Hohener D, Blumenthal S, Borgeat A. Sedation and regional anesthesia in the adult patients. Br J Anaesth 2008;100:8-16. |
|7.||Ozgurel O. Comparison of fentanyl added to ropivacaine or bupivacaine in spinal anesthesia. Reg Anesth Pain Med 2003;28:23. |
|8.||Cherng CH, Yang CP, Wong CS. Epidural fentanyl speeds the onset of sensory and motor blocks during epidural ropivacaine anesthesia. Anesth Anal 2005;101:1834-7. |
|9.||Casimiro C, Rodrigo J, Mendiola MA, Rey F, Barrios A, Glisanz F. Levobupivacaine plus fentanyl versus racemic bupivacaine plus fentanyl in epidural anesthesia for lower limb surgery. Minerva Anestesiologica 2008;74:381-91. |
|10.||Bajwa SJ, Bajwa SK, Kaur J, Singh G, Arora V, Gupta S, et al. Dexmedetomidine and clonidine in epidural anaesthesia: A comparative evaluation. Indian J Anaesth 2011;55:116-21. |
|11.||Oriol-Lopez SA, Maldonado-Sanchez KA, Hernandez-Bernal CE, Castelazo-Arredondo JA, Moctezuma IR. Epidural dexmedetomidine in regional anesthesia to reduce the anxiety. Anesthesiologia 2008;31:271-7. |
|12.||Riberio RN, Naseimento JP. The use of dexmedetomidine in anesthesiology. Rev Bras Anesthesiol 2003;53:97-113. |
|13.||Hanoura SE, Hassanin R, Singh R. Intraoperative condition and quality of postoperative analgesia after adding dexmedetomidine to epidural bupivacaine and fentanyl in elective cesarean section using combined spinal-epidural anesthesia. Anesthesia 2013;7:168-72. |
|14.||Selim MF, Elnabtity AM, Hasan AM. Comparative evaluation of epidural bupivacaine-dexmedetomidine and bupivacaine-fentanyl on Doppler velocimetry of uterine and umbilical arteries during labor. J Prenat Med 2012;6:47-54. |
[Figure 1], [Figure 2]
[Table 1], [Table 2]