|Year : 2017 | Volume
| Issue : 2 | Page : 59-64
Comparison between dexmedetomidine versus morphine added to bupivacaine in paravertebral block in patients scheduled for modified radical mastectomy
Ahmed R Morsy, Mervat M Abd-elmaksoud, Rehab A Abdel Aziz, Mohamed Metwally
Department of Anaethesia and Surgical Intensive Care, Faculty of Medicine, Alexandria University, Alexandria, Egypt
|Date of Submission||02-Feb-2016|
|Date of Acceptance||26-Feb-2016|
|Date of Web Publication||12-May-2017|
7 El-Mashtal, 2nd Street, Abu Yusef Al_Agamy, Alexandria
Source of Support: None, Conflict of Interest: None
The aim of the paper was to compare between dexmedetomidine (DM) versus morphine added to bupivacaine in paravertebral block (PVB) for perioperative analgesia in modified radical mastectomy in relation to hemodynamic stability, efficacy of pain relief, and possible complications.
Patients and methods
A randomized, double-blind, controlled trial was conducted on 45 American Society of Anesthesiologists I–II patients undergoing elective unilateral modified radical mastectomy. Patients were randomly allocated into three groups: group B (n=15) received 20 ml of 0.25% bupivacaine (as control group), group D (n=15) received 20 ml of 0.25% bupivacaine+100 μg DM, and group M (n=15) received 20 ml of 0.25% bupivacaine+2 mg morphine. Hemodynamic parameters, area of local anesthesia, postoperative oxygen saturation and respiratory rate, visual analog scale (VAS) score, shoulder restriction score, time to first dose, and total amounts of supplementary analgesia (meperidine hydrochloride) were recorded. Postoperative sedation was evaluated using Ramsay sedation scale, and postoperative nausea and vomiting were evaluated using postoperative nausea and vomiting impact scale score. Other side effects were also recorded.
There were no significant differences between the three studied groups at baseline regarding heart rate, mean arterial blood pressure, arterial oxygen saturation (SpO2), and respiratory rate. There was a significant reduction in heart rate in group D since the initiation of skin incision till the end of operation. There was a significant reduction in mean arterial blood pressure in the three groups from the starting of skin incision till the end of operation, but it was more evidenced in group D. Arterial oxygen saturation (SpO2) and respiratory rate were comparable between the three groups at all measuring times. There was significantly lower postoperative VAS score, longer time to first dose, and lower consumption of meperidine hydrochloride in group D than group B and group M. The present study did not show any serious intraoperative or postoperative complications in the three studied groups.
The addition of DM to bupivacaine in PVB provides a significant clinical benefit by decreasing VAS score, decreasing postoperative use of analgesics, and prolonging the onset of postoperative analgesic requirement without serious adverse effects and is superior to morphine as an adjuvant in PVB.
Keywords: bupivacaine, dexmedetomidine, modified radical mastectomy, morphine, paravertebral block
|How to cite this article:|
Morsy AR, Abd-elmaksoud MM, Abdel Aziz RA, Metwally M. Comparison between dexmedetomidine versus morphine added to bupivacaine in paravertebral block in patients scheduled for modified radical mastectomy. Res Opin Anesth Intensive Care 2017;4:59-64
|How to cite this URL:|
Morsy AR, Abd-elmaksoud MM, Abdel Aziz RA, Metwally M. Comparison between dexmedetomidine versus morphine added to bupivacaine in paravertebral block in patients scheduled for modified radical mastectomy. Res Opin Anesth Intensive Care [serial online] 2017 [cited 2017 Aug 22];4:59-64. Available from: http://www.roaic.eg.net/text.asp?2017/4/2/59/206147
| Introduction|| |
Breast cancer is the commonest cause of cancer deaths in women worldwide. Surgery, specially modified radical mastectomy (MRM), remains an important part of its management . Surgical pain is a universal phenomenon affecting all patients intraoperatively and postoperatively . Problems following MRM include chest wall pain, arm motion restriction, muscle strength, and edema. Pain, paresthesias, and strange sensations were reported by half of the patients . Hugo Sellhiem, in 1905, was probably the first to inject local anesthetic alongside the vertebral column, where the spinal nerves emerge from the spinal canal. Interest was reawakened in 1979 by the reappraisal of the paravertebral space, its structure, and percutaneous entry technique in the classic paper by Eason and Wyatt . The quality of the block at the dermatome site of injection is very high. Bathing of the ‘relatively naked’ spinal nerve in the intervertebral foramen mimics the technique of transforaminal sleeve nerve root blockade, which has known to produce very profound anesthesia of prolonged duration in chronic pain. Blockade of the rami communicans as well as the sympathetic chain results in a different and higher quality of block compared with neuraxial blocks . The addition of adjunctive analgesics to local anesthetics has been shown to enhance the quality and duration of sensory neural blockade and decrease the dose of local anesthetic and supplemental analgesia. Consequently, less doses of local anesthetic may be used and nontoxic plasma levels achieved .
Bupivacaine is a local anesthetic drug that produces its effects through inhibition of the generation and/or dissemination of action potentials at the neuronal membrane, resulting in the blockade of afferent nociceptive barrage .
Dexmedetomidine (DM) is a potent and highly selective α2-adrenoceptor agonist with a selectivity ratio of 1600 : 1 (α2 : α1). It has a broad range of pharmacological properties, including sedation associated with arousability and orientation without respiratory depression. Additional properties include analgesia, anxiolysis, hemodynamic stability, antishivering effects, and reduced incidence of postoperative nausea and vomiting (PONV) .
Morphine is an opioid receptor agonist, and its main effect is binding to and activating the µ-opioid receptors in the central nervous system. Morphine is also a κ-opioid and δ-opioid receptor agonist. κ-Opioid’s action is associated with spinal analgesia and psychotomimetic effects. δ-Opioid is thought to play a role in analgesia .
| Aim|| |
The aim of this work was to compare between DM versus morphine added to bupivacaine in paravertebral block (PVB) for perioperative analgesia in MRM regarding hemodynamic stability, efficacy of pain relief, and possible complications.
| Patients and methods|| |
After approval of the study by the research ethics committee and obtaining written informed consents from patients, the present study was carried out in Alexandria Main University Hospital on 45 adult female patients with American Society of Anesthesiologists physical status I and II scheduled for elective unilateral MRM.
Patients with vertebral column anomalies, local infection or sepsis, coagulation disorders, refused to participate in the study, history of reaction to used drugs, or taking medications with α-adrenergic blocking effect were excluded from the study.
Evaluation of the patient was carried out through proper history taking and clinical examination and routine laboratory investigation.
Patients were randomly assigned to one of three groups according to the drug used for PVB: group B received 20 ml of 0.25% bupivacaine, group D received 20 ml of 0.25% bupivacaine+100 μg DM, and group M received 20 ml 0.25% bupivacaine+2 mg morphine.
Before the operation, all patients received instructions for using visual analog scale (VAS) scores (subjective measurement, with 0–no pain to 10–worst pain possible) . At the operating room, standard monitors were applied, including ECG, noninvasive blood pressure, and pulse oximetry [oxygen saturation and heart rate (HR)] using Dräger Infinity Vista XL (Draeger, Inc., Houston, TX 77085, USA).
An 18 G line was inserted, and 500 ml of 0.9% NaCl was infused preoperatively. Midazolam 2 mg was given as premedication. On the proposed side of operation, in sitting posture, under strict aseptic precautions, and after infiltration with local anesthetic, 2.5 cm lateral to the tip of spinous process of T3 vertebra, a Tuohy needle was advanced perpendicular to the skin in all planes to contact the transverse process of the vertebra, typically at a depth of 2–4 cm. After the transverse process identification, the needle was redirected cephalad and gradually advanced until loss of resistance was felt 1–1.5 cm distal to its superior edge. After negative aspiration for blood, cerebrospinal fluid, and air, anesthetic solution (according to the group assigned to) was injected. After 10 min of completion of block, the area of analgesia was tested using cotton-tipped applicator soaked in iced saline on the back of the patient. Induction of anesthesia was carried out with fentanyl citrate (1 μg/kg) intravenously; propofol 2 mg/kg intravenous was injected slowly till loss of verbal communication, and endotracheal intubation was facilitated by injection of rocuronium bromide 0.6 mg/kg intravenously. Anesthesia was maintained with 1.2% isoflurane in 100% oxygen, with intermittent boluses of rocuronium (0.1 mg/kg) intravenously every 30 min or as required. At the end of surgery, neuromuscular blockade was reversed with injection of neostigmine (40 μg/kg) with atropine (14 μg/kg), and then the patient was transferred to the postanesthesia care unit (PACU).
In PACU, in all groups, if the VAS score became more than 3, meperidine hydrochloride 0.5 mg/kg intravenously was given, and any complication was managed.
The following parameters were measured.
Age, weight, and duration of anesthesia was documented. HR in beats per minute, mean arterial blood pressure (MABP), and ECG changes were monitored and recorded at the following periods: preoperative, after block, after induction of anesthesia, at skin incision, and then every 20 min till the end of the surgery. Postoperative HR (HR in beats per minute), MABP ECG changes, oxygen saturation of the room air, and respiratory rate were continuously monitored and recorded at the following periods: at PACU admission, every 2 h for the first 12 h, and then every 4 h for the next 12 h. Area of local analgesia was assessed using cotton-tipped applicator soaked in iced saline on the back of the patient to test the extent of dermatomes blocked 10 min after the block.
VAS during active movement of the ipsilateral arm, restriction of shoulder movement on the operative side (none − 0: full range of movement; mild − 1: slightly limited and able to abduct more than 90°; moderate − 2: unable to abduct more than 90°; and severe − 3: unable to move) was measured postoperatively at PACU admission, hourly for the first 12 h and then every 2 h for the next 12 h. Analgesic consumption (amount of analgesic consumed and time of first supplemental dose of analgesia) was recorded.
Sedation was assessed by Ramsay sedation score; hypotension (defined as systolic blood pressure less than 30% of its initial value or less than 90 mmHg), bradycardia (defined as HR <50 beat/min), respiratory depression (defined as respiratory rate <10 breaths/min), pruritus, and nausea and vomiting as assessed using PONV impact scale score were all assessed . Ondansterone was given as required. All these adverse effects were assessed at 1, 2, 4, 8, 16, and 24 h postoperatively.
| Results|| |
The demographic data of the three groups were similar. There were no statistical significant differences between the groups regarding age, weight of the patients, sex, and duration of surgery. There was an insignificant statistical difference in HR or MABP between the three groups in the preoperative period. There was a significant decrease in HR throughout the intraoperative period, and there was an insignificant decrease in postoperative measuring times from preoperative measurement in only group D, with significant statistical difference in HR between group D and group B and group M throughout the intraoperative and postoperative measuring times. No significant differences were found between group B and group M. Regarding HR, there was a significant decrease in MABP in group B in the intraoperative measurements at skin incision, 20, and 60 min after induction, with insignificant changes in the other intraoperative and postoperative measuring times; group D showed significant decrease in MABP throughout the intraoperative measuring times and insignificant changes in the postoperative measuring times; and group M showed significant decrease in MABP in the intraoperative measurements at skin incision, 60, 80, 100, and 120 min after induction, with insignificant changes in the other intraoperative and postoperative measuring times. There was a significant statistical difference in MABP in the intraoperative period between group D and group B at 20, 40, and 60 min intraoperatively and between group D and group M at 20, 40, 60, 80, and 140 min intraoperatively ([Figure 1]).
|Figure 1 Comparison between the three studied groups according to the mean heart rate (beat/min)|
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There was no statistical significant difference between groups regarding arterial oxygen saturation and respiratory rate.
Comparing the three groups, there was insignificant difference in the number of dermatomes anesthetized. VAS score was significantly lower in group D in comparison with group B and group M at PACU admission and up to 5 h postoperatively. There was a statistically insignificant difference in shoulder restriction between group D and groups B and M. Group D showed statistically significant longer latency period (577.33±201.69 min) before starting the analgesia regimen and less analgesia consumption (89±34.81 mg) than group B (244±76.14 min, P<0.001, and 157.33±34.53 mg, P<0.001, respectively) and group M (298.33±104.93 min, P<0.001, and 158±45.03 mg, P<0.001, respectively) ([Figure 2]).
|Figure 2 Comparison between the three studied groups according to the mean arterial blood pressure (MABP) (mmHg)|
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Sedation score was significantly higher in group D (2.5±0.5) in comparison with group B (2.1±0.3) and group M (2.1±0.4) at the first hour of postoperative period, with insignificant difference in postoperative sedation score all throughout the postoperative measuring times between the three groups. PONV impact scale score showed statistically insignificant difference between the three groups. There were three cases of nausea and two cases of vomiting in group B, four cases of nausea and one case of vomiting in group D, and three cases of nausea and two cases of vomiting in group M. Only one case in group D had bradycardia (HR 48) which was treated with 0.01 mg/kg atropine intravenously ([Figure 3] and [Figure 4]).
|Figure 3 Comparison between the three studied groups according to the mean postoperative visual analog scale (VAS) score|
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|Figure 4 Comparison between the three studied groups according to the rescue analgesia requirements|
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There was no incidence of hypotension, pruritus, and respiratory depression.
| Discussion|| |
In the present study, there was no statistical significant difference among the studied groups regarding the patients’ age, sex, and duration of the operation.
There was insignificant statistical difference in HR or MABP between the three groups in the preoperative period. There was statistical significant reduction in HR in group D starting at skin incision and up to 140 min intraoperatively. There was statistical significant reduction in HR between group D and groups B and M throughout the intraoperative and postoperative periods. Also there was insignificant statistical difference in MABP between the three groups in the preoperative period. There was statistical significant reduction in MABP in group D starting at skin incision and up to 140 min intraoperative, which was significantly lower in comparison with the reduction occurred in group B and group M, with insignificant changes in the postoperative period. The hemodynamic effect of DM on blood pressure is a centrally mediated sympatholytic effect and appears to be dose dependent 
This finding was in agreement with the one obtained by Mohamed et al.  who performed thoracic PVB with either 20 ml of bupivacaine 0.25% (group B) or 20 ml of bupivacaine 0.25%+1 µg/kg DM (groups B and D) and found that there was a significant reduction in pulse rate and MABP starting at 30 min in both groups, but more evidenced in groups B and D. A similar results was found by Jain et al.  and Bajwa et al. .
Our study finding was in disagreement with the one obtained by Kanazi et al.  who found that the mean values of HR and MABP were comparable between the three groups throughout the intraoperative and postoperative periods. This is probably because of the use of low dose of DM. The same was found in the study of Al-Mustafa et al.  and the study by Gupta et al.  who explained the absence of hemodynamic changes and comparable results between groups by the use of low dose of DM.
VAS score was significantly lower in group D in comparison with group B and group M at PACU admission and up to 5 h postoperatively.
Similarly, Mohta et al.  conducted randomized double-blind study on 45 female patients undergoing MRM or breast conservation surgery. Patients in group PB (paravertebral–bupivacaine) received PVB with 0.5% bupivacaine 0.3 ml/kg; those in the group PBD (paravertebral–bupivacaine–DM) received PVB with 0.5% bupivacaine 0.3 ml/kg and DM 1 µg/kg in a volume of 1 ml; whereas group C (control group) patients were given a sham block (subcutaneous injection with 2 ml normal saline) before receiving general anesthesia (GA). They found that VAS scores were lower in group PBD. Similar results was found by Sinha et al. .
In the present study, it was concluded that there was a significantly longer latency period to the request of postoperative analgesia given in the group D as compared with group B and group M; moreover, the total meperidine hydrochloride consumption was significantly lower in group D than in group B and group M (P<0.001).
In agreement with finding of the present study, Mohta et al.  found that the time to first analgesic request was significantly longer and total morphine consumption was lower in group PBD. Similar results were found by Mohamed et al. , Bajwa et al. , Jain et al.  and Abdallah and Brull .
In our study, shoulder restriction score in the immediate postoperative period showed mild restriction and ranged from mild to moderate restriction thereafter. Severe restriction was not recorded in any patient. There was no significant difference between groups owing to rescue analgesia given if VAS score was more than 3.
Khai et al.  showed similar findings in a study where single-injection thoracic paravertebral technique was applied with 20 ml of ropivacaine 1% with adrenaline (5 µg/ml) in 32 cases scheduled for elective breast cancer surgery with axillary dissection. Shoulder restriction score in the immediate postoperative period ranged from none to mild restriction in 26 patients and moderate in six patients, with no patients with severe restriction.
In peripheral nerve blocks, DM acts on α2-adrenoceptors located on primary afferent terminals of peripheral nerve endings. Activation of these receptors in vitro has been shown to block conduction along C and A-δ pain fibers, increase potassium conductance, and intensify the conduction block produced by local anesthetics .
The present study also demonstrates significant increase in sedation score at 1 h postoperatively among group D, with a mean value of 2.5±0.5; group B, with a mean value of 2.1±0.3; and group M, with a mean value of 2.1±0.4, with insignificant difference between the three groups in all other postoperative measuring times.
The significance in sedation score at 1 h postoperatively is attributed to the sedative effect of DM by acting on locus coeruleus, which is an important modulator of wakefulness, has one of the highest concentrations of the α2-receptor, and may be a critical site for the hypnotic–sedative effects of α2-adrenoceptor activation .
Similar to our study, Bajwa et al.  found that sedation scores were much better in the RD (ropivacaine +DM) group and significant on statistical comparison (P<0.001) in the intraoperative period. A similar effect was found by Jain et al .
The sedative effect is because of action on the locus coeruleus, which is associated with a wide variety of physiologic regulatory processes, including regulation of sleep and wakefulness and is inhibited by α2-adrenergic agonists (e.g. DM). Sedation after epidural administration of α2-adrenergic agonists likely reflects systemic absorption and vascular redistribution to higher centers. Although it is conceivable that cephalad migration of α2-adrenergic agonists in cerebrospinal fluid could result in delayed onset of sedation, such delayed-onset sedation has not been observed nor has delayed-onset hypotension .
In disagreement with the present study, Kanazi et al.  found no sedative effect with groups using DM. Al-Mustafa et al  and Gupta et al  found similar results.
There was no significant difference between the three groups regarding other adverse effects such as nausea and vomiting, bradycardia, hypotension, pruritus, and respiratory depression.
A similar result was found by Mohamed et al. , Gupta et al. , Al-Mustafa et al. , Kanazi et al. , and Jain et al. .
| Conclusion|| |
- PVB with bupivacaine is a safe and effective modality for pain management in breast surgeries.
- The addition of DM to bupivacaine for PVB provides a significant clinical benefit by decreasing the postoperative pain and VAS score, decreasing postoperative use of analgesics, and prolonging the onset of postoperative analgesic requirement without causing additional serious adverse effects and is superior to morphine as an adjuvant in PVB.
- The addition of morphine to bupivacaine for PVB at the dose of 2 mg, as an adjuvant, does not produce significant benefit in comparison with bupivacaine alone.
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Conflicts of interest
There are no conflicts of interest.
| References|| |
Key TJ, Verkasalo PK, Banks E. Epidemiology of breast cancer. Lancet Oncol. 2001; 2:133–140.
American Academy of Pediatrics, Committee on Psychosocial Aspects of C, Family H, Task Force on Pain in Infants C, Adolescents. The assessment and management of acute pain in infants, children, and adolescents. Pediatrics 2001; 108:793–797.
Gerber L, Lampert M, Wood C, Duncan M, D’Angelo T, Schain W et al.
Comparison of pain, motion, and edema after modified radical mastectomy vs. local excision with axillary dissection and radiation. Breast Cancer Res Treat 1992; 21:139–145.
Eason MJ, Wyatt R. Paravertebral thoracic block-α reappraisal. Anaesthesia 1979; 34:638–642.
Richardson J, Jones J, Atkinson R. The effect of thoracic paravertebral blockade on intercostal somatosensory evoked potentials. Anesth Analg 1998; 87:373–376.
Liu SS, Salinas FV. Continuous plexus and peripheral nerve blocks for postoperative analgesia. Anesth Analg 2003; 96:263–272.
Becker DE, Reed KL. Essentials of local anesthetic pharmacology. Anesth Prog 2006; 53:98–108.
Khan ZP, Ferguson CN, Jones RM. Alpha-2 and imidazoline receptor agonists. Their pharmacology and therapeutic role. Anaesthesia 1999; 54:146–165.
Trescot AM, Datta S, Lee M, Hansen H. Opioid pharmacology. Pain Physician 2008; 11(2 Suppl):S133–S153.
Wewers ME, Lowe NK. A critical review of visual analogue scales in the measurement of clinical phenomena. Res Nurs Health 1990; 13:227–236.
Mohamed SA, Fares KM, Mohamed AA, Alieldin NH. Dexmedetomidine as an adjunctive analgesic with bupivacaine in paravertebral analgesia for breast cancer surgery. Pain Physician 2014; 17:E589–E598.
Penttila J, Helminen A, Anttila M, Hinkka S, Scheinin H. Cardiovascular and parasympathetic effects of dexmedetomidine in healthy subjects. Can J Physiol Pharmacol 2004; 82:359–362.
Jain D, Khan R, Kumar D, Kumar N. Perioperative effect of epidural dexmedetomidine with intrathecal bupivacaine on haemodynamic parameters and quality of analgesia. South Afr J Anaesth Analg 2012; 18:105–109.
Bajwa SJS, Arora V, Kaur J, Singh A, Parmar S. Comparative evaluation of dexmedetomidine and fentanyl for epidural analgesia in lower limb orthopedic surgeries. Saudi J Anaesth 2011; 5:365–370. [Full text]
Kanazi G, Aouad M, Jabbour‐Khoury S, Al Jazzar M, Alameddine M, Al‐Yaman R et al.
Effect of low‐dose dexmedetomidine or clonidine on the characteristics of bupivacaine spinal block. Acta Anaesthesiol Scand 2006; 50:222–227.
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; 30:365–370.
Gupta R, Bogra J, Verma R, Kohli M, Kushwaha JK, Kumar S. Dexmedetomidine as an intrathecal adjuvant for postoperative analgesia. Indian J Anaesth 2011; 55:347–351.
] [Full text]
Mohta M, Kalra B, Sethi AK, Kaur N. Efficacy of dexmedetomidine as an adjuvant in paravertebral block in breast cancer surgery. J Anesth 2016; 30:252–260.
Sinha S, Mukherjee M, Chatterjee S, Vijay MK, Hazra A, Ray M. Comparative study of analgesic efficacy of ropivacaine with ropivacaine plus dexmedetomidine for paravertebral block in unilateral renal surgery. Anesth Pain Intensive Care 2012; 16:38–42.
Abdallah F, Brull R. Facilitatory effects of perineural dexmedetomidine on neuraxial and peripheral nerve block: a systematic review and meta-analysis. Br J Anaesth 2013; 110:915–925.
Khai Darren Koh Liang. The use of single-injection thoracic paravertebral block in breast cancer surgeries in our Asian population: The Singapore general hospital experience. Proceedings of Singapore Healthcare 2013; 22.2:107–113.
Louis WJ, Jarrott B, Conway EL. Sites of actions of alpha 2 agonists in the brain and periphery. Am J Cardiol 1988; 61:15D–7D.
French N. Alpha 2-adrenoceptors and I2 sites in the mammalian central nervous system. Pharmacol Ther 1995; 68:175–208.
Eisenach JC, De Kock M, Klimscha W. Alpha sub 2-adrenergic agonists for regional anesthesia: a clinical review of clonidine (1984–1995). Anesthesiology 1996; 85:655–674.
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