|
|
ORIGINAL ARTICLE |
|
Year : 2019 | Volume
: 33
| Issue : 3 | Page : 156-160 |
|
Comparative study of morphine or dexmedetomidine as intrathecal adjuvants to 0.5% hyperbaric bupivacaine in infraumbilical surgeries
Mamta Khandelwal, Harshita Rao, Pradeep Kumar, Usha Bafna, Sonali Beniwal
Department of Anaesthesia, Sawai Man Singh Medical College, Jaipur, Rajasthan, India
Date of Submission | 11-Apr-2019 |
Date of Decision | 22-Apr-2019 |
Date of Acceptance | 05-Aug-2019 |
Date of Web Publication | 5-Dec-2019 |
Correspondence Address: Dr. Pradeep Kumar S/o Sukh Dev Sevag, Ward No. 35, Behind Mangilal Bagri College, Nokhmandi, Bikaner - 334 803, Rajasthan India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/ijpn.ijpn_31_19
Background: Morphine and Dexmedetomidine have been used with subarachnoid block for postoperative pain relief, sedation and analgesia. In higher doses, it may produce adverse effect on haemodynamics. Aim and Objective: This study compares the block characteristics and side effects effects of morphine and intrathecal Dexmedetomidine, given with intrathecal bupivacaine. Materials and Methods: A prospective, randomised, double-blinded study was conducted in department of anaesthesiology at a tertiary referral hospital. Eighty patients with American Society of Anaesthesiologists Status I and II were randomly allocated to receive either dexmedetomidine (5 μg) or Morphine (200 mcg) with or 0.5% hyperbaric bupivacaine. Results: Time to first dose of rescue analgesia was significantly more with dexmedetomidine (386.75102.27 min) as compared to Morphine (232.5045.45 min). Duration of motor block was also significantly longer with dexmedetomidine (192.3836.50) than Morphine (155.488.66). There was no significant difference between the two groups in relation to onset of sensory or motor block, time to reach maximum level of sensory block, and the time for two segment regression. Conclusion: Intrathecal dexmedetomidine as compared to Morphine as an adjuvant to intrathecal bupivacaine prolonged the time to first rescue analgesia, without any significant adverse effect. Keywords: Bupivacaine, dexmedetomidine, intrathecal, morphine, spinal anesthesia
How to cite this article: Khandelwal M, Rao H, Kumar P, Bafna U, Beniwal S. Comparative study of morphine or dexmedetomidine as intrathecal adjuvants to 0.5% hyperbaric bupivacaine in infraumbilical surgeries. Indian J Pain 2019;33:156-60 |
How to cite this URL: Khandelwal M, Rao H, Kumar P, Bafna U, Beniwal S. Comparative study of morphine or dexmedetomidine as intrathecal adjuvants to 0.5% hyperbaric bupivacaine in infraumbilical surgeries. Indian J Pain [serial online] 2019 [cited 2023 Mar 31];33:156-60. Available from: https://www.indianjpain.org/text.asp?2019/33/3/156/272377 |
Introduction | |  |
Spinal anesthesia is the most frequently used method for lower abdominal surgeries as this technique is easy to administer as well as very economical. It has got the advantage of being cost-effective, easy administration technique, rapid onset of action, with relatively less adverse effects, and most importantly patient remaining aroused throughout the procedure.[1] Spinal anesthesia using short-duration local anesthetics poses difficulty in the management of postoperative pain; henceforth, the use of early analgesic is needed in the postoperative period. In recent years, different adjuvants such as opioids, gamma-aminobutyric acid agonist, α2-adrenoceptor (AR) agonist, calcium channel antagonist, and anticholinesterase have been used as adjuvant to prolong the duration of postoperative analgesia.
Local anesthetic and opioid combination techniques have been studied in the subarachnoid block.[2] The local anesthetic works at nerve axons while the opioid works at the receptor site in the spinal cord. Opioid acts primarily as agonist at μ-opioid receptors to enhance spinal analgesia.[3],[4] Among the opioids, morphine is adjudged as the most effective due to its potent and prolonged effect. However, over the years, it is losing popularity due to dose-dependent side effects such as pruritus, nausea, vomiting, and the most feared risk of delayed respiratory depression.
Dexmedetomidine is a highly selective α2-AR agonist. When it is used as an adjuvant to bupivacaine, it provides stable hemodynamic conditions and good quality of intraoperative and prolonged postoperative analgesia with minimal side effects.[5],[6] The data comparing the efficacy of intrathecal morphine with intrathecal dexmedetomidine are very less in literature. Hence, this study was conducted with the aim to compare the analgesic efficacy of 5 μg of dexmedetomidine or 200 μg of morphine as an adjuvant to 0.5% hyperbaric bupivacaine in lower abdominal surgery.
Methodology | |  |
This prospective, randomized, double-blind study was conducted in the department of anesthesiology at one of the largest tertiary referral hospitals of North India, from October 2017 to November 2018, after approval by the institutional ethics committee. This study included 80 patients aged between 20 and 50 years, with American Society of Anesthesiologists (ASA) Grade I or II, scheduled for elective lower abdominal surgery under the subarachnoid block. Patients with any contraindication to spinal anesthesia or major systemic illness were excluded from the study. Informed written consent was obtained from all patients prior to recruitment into the study. Patients were randomized in two groups by computerized random number table.
- Group BD (n = 40) – Hyperbaric bupivacaine with dexmedetomidine
- Group BM (n = 40) – Hyperbaric bupivacaine with morphine.
After thorough preanesthetic examination day before the surgery, patients were kept nil by mouth overnight.
Spinal anesthesia was given at L3–L4 interspace with a 25G Quincke needle in sitting position under all aseptic precaution. Spinal anesthesia was given by the same researcher, under similar environment, using the same standard technique. Group BD patients received 3 ml of 0.5% hyperbaric bupivacaine and 1 ml of dexmedetomidine (5 μg) in spinal anesthesia, and Group BM received 3 ml of 0.5% hyperbaric bupivacaine and 1 ml (200 μg) of morphine. Researcher who recorded readings was different from researcher who gave spinal anesthesia and both were blinded to the groups to which the patient was allotted.
All patients were placed supine with head-low tilt. The level of sensory block was assessed at every 2 min till the highest level of block was achieved. Onset of motor block was defined as the time from intrathecal injection of the study drug to the time taken to achieve complete motor block (Grade 3) using Bromage scale.
Blood pressure, pulse rate, and SpO2 were monitored at every 5 min throughout the surgery. Any fall of mean arterial pressure (MAP) >20% from baseline or systolic blood pressure <90 mmHg was treated with intravenous fluid and incremental doses of ephedrine 5 mg intravenous. Bradycardia defined as heart rate (HR) <60/min was treated with injection atropine 0.6 mg intravenous. Pruritus was treated with injection promethazine 25 mg intramuscular which was repeated after 1 h, if needed.
Regression of sensory block was defined as the time taken for the sensory block to regress up to two segments of dermatome from the highest level achieved. The duration of motor block was assessed by recording the time elapsed from the maximum to the lowest Bromage score (3–0).
Postoperatively, the pain was assessed using the Visual Analog Pain Scale (VAS) between 0 and 10 (0 = no pain, 10 = most severe pain). It was assessed at every 30 min. Patients were given rescue analgesic on VAS score of 3. Intravenous injection diclofenac (75 mg) was given as rescue analgesic. Time from the intrathecal injection of study drug to the first administration of rescue analgesic (total duration of analgesia) was noted. This was the endpoint of the study. Patients were monitored for 24 h for any adverse effect.
“Four-Point Sedation Scale” was used to note postoperative sedation score. The incidence of adverse effects such as nausea, vomiting, bradycardia, respiratory depression, pruritus, urinary retention, and hypotension was recorded and managed accordingly.
Statistical analysis
In this study, 40 patients were taken in each group. The sample size was calculated at alpha error 0.05 and study power 80%, assuming a minimum difference of meantime for first rescue analgesic requirement to be 300 min, with a standard deviation of 460 min in intrathecal morphine and intrathecal dexmedetomidine in patients undergoing infraumbilical surgeries under spinal anesthesia.[7]
Categorical variables were summarized in terms of frequency and percentage and were analyzed using Chi-square test/Fisher's exact test as applicable. Continuous variables were expressed as mean and standard deviation and were analyzed using Student's t-test. P < 0.05 was considered statistically significant. All the statistical analyses were done using Epi Info version 7.2.1.0, CDC, USA.
Results | |  |
Spinal anesthesia was successful in all patients, and all patients completed the study. All groups were comparable with respect to age, ASA status, weight, type of surgery, and duration of the surgery [Table 1] and [Table 2]. There was no statistically significant difference between Group BD and Group BM in relation to the onset of sensory block, onset of motor block, time to reach the maximum level of sensory block, and time for two-segment regressions [Table 3]. In our study, time for onset of sensory block was 61.00 ± 31.79 s in Group BD and 66.25 ± 31.46 s in Group BM with no statistically significant difference (P = 0.460). Similarly, time for onset of motor block was 100.00 ± 44.3 s and 106.75 ± 34.76 s in Group BD and Group BM, respectively. It was also not statistically significant (P = 0.450). Time to reach the maximum level of sensory block was also not statistically significant (P = 0.056). It was 22.78 ± 7.47 min and 26.23 ± 8.46 min in Group BD and Group BM, respectively. The time for two-segment regressions was 99.50 ± 14.27 min in Group BD and 89.13 ± 19.93 min in Group BM. It was also found statistically insignificant (P = 0.009).
Time for first dose of rescue analgesia was more in Group BD (386.75 ± 102.27 min) as compared to Group BM (232.50 ± 45.45) with statistically significant difference (P< 0.001). The duration of motor block was significantly longer in Group BD than Group BM (P< 0.001). It was 192.38 ± 36.50 min and 155.48 ± 8.66 min in Group BD and Group BM, respectively [Table 3]. The VAS scores were lower in Group BD as compared to Group BM up to 5.0 h (P< 0.001) [Figure 1]. There was no significant difference between the mean HR and MAP in both the groups throughout the observation period [Figure 2] and [Figure 3]. The respiratory rate was always lesser, in Group BM compared to Group BD, at different time intervals, but none of the patients had respiratory depression. The incidence of bradycardia and hypotension was comparable in both the groups. The incidence of postoperative nausea, vomiting, pruritus, and urinary retention was not significantly different between the two groups [Table 4].
Sedation score was measured in both the groups which was statistically non significant [Table 5].
Discussion | |  |
Subarachnoid block with hyperbaric bupivacaine is an established technique for surgeries on the lower abdomen. However, its short duration of postoperative analgesia is a limitation. Numerous adjuvants have been used intrathecally to extend the duration of analgesia of the subarachnoid block. Co-administration of 3–15 μg dexmedetomidine with local anesthesia has a dose-dependent effect on anesthesia, analgesia, and hemodynamic stability. It has been shown in different studies.[8],[9] In case of intrathecal morphine till date, no consensus has been made regarding the optimal dose but appears to be 100–250 μg. Taking into account the ceiling dose for analgesic efficacy of intrathecal morphine, 200 μg of morphine was used in this study.[10],[11]
The present study was designed with aims of comparing the postoperative analgesic efficacy of intrathecal dexmedetomidine with intrathecal morphine in patients who underwent lower abdominal surgery.
The results of the present study showed that the supplementation of spinal bupivacaine with 5 μg of dexmedetomidine produced a prolonged analgesic effect and motor blockade as compared to 200 μg of intrathecal morphine. VAS score was significantly lower in Group BD till 300 min. Patients were hemodynamically stable in both the groups, and none of the patients had respiratory depression.
In the current study, there was no statistically significant difference between Group BD and Group BM in relation to the onset of sensory block, onset of motor block, time to reach maximum level of sensory block, and time for two-segment regressions. The results of the present study are in accordance with the studies done by Kurhekar et al.[7] and Qi et al.[12]
Time to first request for analgesia was significantly prolonged in Group BD than Group BM. Intrathecal dexmedetomidine acts by the inhibition of nociceptive neurons by stimulation of α-ARs at the substantia gelatinosa of the dorsal horn in the spinal cord. Activation of both α2C- and α2A-receptors reduces pain transmission by reducing the release of pronociceptive transmitter, substance P, and glutamate from primary afferent terminals and by hyperpolarizing spinal interneurons through G-protein-mediated activation of potassium channels.[13] Prolongation of the duration of analgesia in the dexmedetomidine group may be due to an additive or synergistic effect secondary to the different mechanisms of action of local anesthetic and α2-AR agonist.
Five micrograms of dexmedetomidine used with hyperbaric bupivacaine resulted in prolonged anesthesia and analgesia with reduced need of rescue analgesics.[14],[15],[16] The study comparing 2.5 μg of intrathecal dexmedetomidine with 250 μg of intrathecal morphine as an adjuvant to 15 mg of hyperbaric bupivacaine, did not find any difference in first analgesic demand time and total analgesic requirement.[7]
Group BD attained a significantly longer duration of motor block than Group BM. The binding of α2-AR agonists to motor neurons in the dorsal horn causes prolongation of the motor block of spinal anesthetics, or prolonged motor blockade might be caused by the direct impairment of excitatory amino acids from the spinal interneurons. The study comparing intrathecal dexmedetomidine with morphine found prolonged motor blockade with intrathecal dexmedetomidine.[7],[13]
Intrathecal morphine and dexmedetomidine both cause hypotension by action on ARs.[17] Regarding hemodynamic variables measured during the intraoperative and postoperative periods, there was no significant difference in HR, systolic blood pressure, diastolic blood pressure, and MAP among both the groups. The incidence of bradycardia and hypotension was not significant in a study done by Qi et al.[12] The previous study has demonstrated that intrathecal dexmedetomidine at doses of 5 and 10 μg has no significant effect on blood pressure or HR.[18]
Opioid is a traditional analgesic for postoperative pain control but has drawbacks such as respiratory depression, vomiting, nausea, and pruritus in terms of adverse effects; the most obvious benefit of dexmedetomidine is that this drug does not cause pruritus. In our study, four patients in Group BM developed pruritus. Respiratory rate was less in Group BM than Group BD at different time intervals during the intraoperative and postoperative periods, but none of the patients had respiratory depression, so no active intervention was required in any patient. The incidence of respiratory depression at low doses of intrathecal morphine (<0.3 mg) is negligible which is confirmed by our study.[19],[20] Patients were easily arousable and cooperative in both the groups.
Intrathecal dexmedetomidine provides prolonged postoperative analgesia as compared to intrathecal morphine without undesirable side effects. Thus, these findings suggest that intrathecal dexmedetomidine can be used as an adjuvant to hyperbaric bupivacaine.
The limitation of the present study is that the total analgesic requirement during 24 h was not noted in this study.
Conclusion | |  |
The present study concludes that the addition of 5 μg dexmedetomidine as an adjuvant to 0.5% hyperbaric bupivacaine intrathecally can be a better alternative to provide satisfactory and longer duration of analgesia as compared to addition of 200 μg of morphine.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
References | |  |
1. | Paul C, Barasch G, Collen Bruce F. Clinical Anaesthesia. 6 th ed. Lippincort: Williams and Wilkins; 2006. p. 700-6. |
2. | Brill S, Gurman GM, Fisher A. A history of neuraxial administration of local analgesics and opioids. Eur J Anaesthesiol 2003;20:682-9. |
3. | Fields HL, Emson PC, Leigh BK, Gilbert RF, Iversen LL. Multiple opiate receptor sites on primary afferent fibres. Nature 1980;284:351-3. |
4. | Ozgurel O. Comparison of fentanyl added to ropivacaine or bupivacaine in spinal anesthesia. Reg Anesth Pain Med 2003;5 Suppl 1:23. |
5. | Kaya FN, Yavascaoglu B, Turker G, Yildirim A, Gurbet A, Mogol EB, et al. Intravenous dexmedetomidine, but not midazolam, prolongs bupivacaine spinal anesthesia. Can J Anaesth 2010;57:39-45. |
6. | Venn RM, Bradshaw CJ, Spencer R, Brealey D, Caudwell E, Naughton C, et al. Preliminary UK experience of dexmedetomidine, a novel agent for postoperative sedation in the intensive care unit. Anaesthesia 1999;54:1136-42. |
7. | Kurhekar P, Kumar SM, Sampath D. Comparative evaluation of intrathecal morphine and intrathecal dexmedetomidine in patients undergoing gynaecological surgeries under spinal anaesthesia: A prospective randomised double blind study. Indian J Anaesth 2016;60:382-7.  [ PUBMED] [Full text] |
8. | 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.  [ PUBMED] [Full text] |
9. | Al-Mustafa MM, Abu-Halaweh SA, Aloweidi AS, Murshidi MM, Ammari BA, Awwad ZM, et al. Effect of dexmedetomidine added to spinal bupivacaine for urological procedures. Saudi Med J 2009;30:365-70. |
10. | Sultan P, Gutierrez MC, Carvalho B. Neuraxial morphine and respiratory depression: Finding the right balance. Drugs 2011;71:1807-19. |
11. | Rathmell JP, Lair TR, Nauman B. The role of intrathecal drugs in the treatment of acute pain. Anesth Analg 2005;101:S30-43. |
12. | Qi X, Chen D, Li G, Huang X, Li Y, Wang X, et al. Comparison of intrathecal dexmedetomidine with morphine as adjuvants in cesarean sections. Biol Pharm Bull 2016;39:1455-60. |
13. | Ishii H, Kohno T, Yamakura T, Ikoma M, Baba H. Action of dexmedetomidine on the substantia gelatinosa neurons of the rat spinal cord. Eur J Neurosci 2008;27:3182-90. |
14. | Schulz KF, Altman DG, Moher D; CONSORT Group. CONSORT 2010 statement: Updated guidelines for reporting parallel group randomised trials. BMC Med 2010;8:18. |
15. | 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.  [ PUBMED] [Full text] |
16. | Gupta M, Shailaja S, Hegde KS. Comparison of intrathecal dexmedetomidine with buprenorphine as adjuvant to bupivacaine in spinal anaesthesia. J Clin Diagn Res 2014;8:114-7. |
17. | Solomon RE, Gebhart GF. Intrathecal morphine and clonidine: Antinociceptive tolerance and cross-tolerance and effects on blood pressure. J Pharmacol Exp Ther 1988;245:444-54. |
18. | Weinbroum AA, Ben-Abraham R. Dextromethorphan and dexmedetomidine: New agents for the control of perioperative pain. Eur J Surg 2001;167:563-9. |
19. | Gehling M, Tryba M. Risks and side-effects of intrathecal morphine combined with spinal anaesthesia: A meta-analysis. Anaesthesia 2009;64:643-51. |
20. | Meylan N, Elia N, Lysakowski C, Tramèr MR. Benefit and risk of intrathecal morphine without local anaesthetic in patients undergoing major surgery: Meta-analysis of randomized trials. Br J Anaesth 2009;102:156-67. |
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]
|