Year : 2018 | Volume
| Issue : 4 | Page : 548-554
Comparative evaluation of analgesic sparing efficacy between dexmedetomidine and clonidine used as adjuvant to ropivacaine in thoracic paravertebral block for patients undergoing breast cancer surgery: A prospective, randomized, double-blind study
Anindya Mukherjee1, Anjan Das2, Nairita Mayur2, Chiranjib Bhattacharyya3, Hirak Biswas2, Tapobrata Mitra4, Sandip Roybasunia4, Subrata Kumar Mandal2
1 Department of Anaesthesiology, NRS Medical College, Kolkata, West Bengal, India
2 Department of Anaesthesiology, College of Medicine and Sagore Dutta Hospital, Kolkata, West Bengal, India
3 Department of Anaesthesiology, IPGMER, Kolkata, West Bengal, India
4 Department of Anaesthesiology, Murshidabad Medical College, Berhampore, West Bengal, India
Dr. Anjan Das
174, Gorakshabashi Road, Royal Plaza Apartment (4th Floor, Flat No 1), Nagerbazar, Kolkata - 700 028, West Bengal
Source of Support: None, Conflict of Interest: None
|Date of Web Publication||4-Oct-2018|
Introduction: Thoracic paravertebral block (TPVB) is an effective method for intra- and post-operative pain management in thoracic surgeries. For a long time, various adjuvants have been tried for prolonging the duration of TPVB.
Objective: In this prospective study, we have compared the analgesic sparing efficacy of dexmedetomidine and clonidine, two α2 adrenergic agonists, administered along with ropivacaine for TPVB for breast cancer surgery patients.
Materials and Methods: Forty-four breast cancer surgery patients undergoing general anesthesia (GA) were randomly divided into Group C and Group D (n = 44 each) receiving preoperative TPVB at T3-5 level with 0.5% ropivacaine solution admixture with clonidine and dexmedetomidine, respectively. Cancer surgery was performed under GA. Intraoperative fentanyl and propofol requirement was compared. Visual analogue scale was used for pain assessment. Total dose and mean time to administration of first rescue analgesic diclofenac sodium was noted. Side effects and hemodynamic parameters were also noted.
Results: Intraoperative fentanyl and propofol requirement was significantly less in dexmedetomidine group than clonidine. The requirement of diclofenac sodium was also significantly less and later in Group D than Group C. Hemodynamics, and side effects were comparable among two groups.
Conclusion: Dexmedetomidine provided better intraoperative as well as postoperative analgesia than clonidine when administered with ropivacaine in TPVB before breast cancer surgery patients without producing remarkable side effects.
Keywords: Clonidine; dexmedetomidine; general anesthesia; thoracic paravertebral block; visual analog scale
|How to cite this article:|
Mukherjee A, Das A, Mayur N, Bhattacharyya C, Biswas H, Mitra T, Roybasunia S, Mandal SK. Comparative evaluation of analgesic sparing efficacy between dexmedetomidine and clonidine used as adjuvant to ropivacaine in thoracic paravertebral block for patients undergoing breast cancer surgery: A prospective, randomized, double-blind study. Saudi J Anaesth 2018;12:548-54
|How to cite this URL:|
Mukherjee A, Das A, Mayur N, Bhattacharyya C, Biswas H, Mitra T, Roybasunia S, Mandal SK. Comparative evaluation of analgesic sparing efficacy between dexmedetomidine and clonidine used as adjuvant to ropivacaine in thoracic paravertebral block for patients undergoing breast cancer surgery: A prospective, randomized, double-blind study. Saudi J Anaesth [serial online] 2018 [cited 2019 Aug 17];12:548-54. Available from: http://www.saudija.org/text.asp?2018/12/4/548/242670
| Introduction|| |
Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage. Patients with breast cancer have pain either at the time of diagnosis or mostly at advanced stages. Breast cancer is one of the most common cancers affecting women and surgery is often the mainstay treatment. Although few patients reported chronic pain, most of women experienced moderate-to-severe intensity acute postoperative pain in the 1st week after breast cancer surgery. If postoperative excruciating pain is properly managed, then it will reduce the percentage of women suffering from chronic postsurgical pain.
General anesthesia (GA) has been widely accepted as the gold standard technique over the past years and thoracic paravertebral block (TPVB) has emerged as an analgesic modality for the patients undergoing GA since major breast cancer surgeries are associated with a high incidence of postoperative pain.
TPVB was found to be safe and an excellent analgesic modality for intra- and post-operative pain management in thoracotomy, gastrectomy, open cholecystectomy, and nephrectomy  operations with no opioid and nonsteroidal anti-inflammatory drugs like side effects.
In patients receiving TPVB, immediate- and long-term analgesia is superior to systemic analgesia, and more importantly, typical adverse effects of systemic opioid such as nausea and vomiting are decreased. TPVB includes both effective short-term pain control, reduction in burden of chronic pain, and potential for early discharge. The commonly used drugs for TPVB are bupivacaine, lignocaine, levobupivacaine, ropivacaine, and combination of these drugs.
Many adjuvants have been tried along with the above-mentioned local anesthetic agents such as epinephrine, dexamethasone, opioids, and magnesium.
In our study, we had added dexmedetomidine (1 mcg/kg) and clonidine (1 mcg/kg) to local anesthetic ropivacaine to achieve desired block.
Clonidine is, centrally acting, a selective α2 adrenergic agonist with some α1 agonist properties (220:1 is α2:α1). In clinical studies, the addition of clonidine to local anesthetic solutions when used in caudal block, brachial plexus block, causes a faster onset time, prolonged duration of sensory block during surgery, and extended postoperative analgesia is obtained.
Dexmedetomidine is much more selective (ten times more selective than clonidine), and potent α2-adrenergic agonist having sedative, antihypertensive, analgesic, and anesthetic-sparing effects when used in systemic route. Adding dexmedetomidine has also been proven to prolong the duration of analgesia when added to local anesthetics in various peripheral nerve blockade  and regional blocks.
The objective of this study was to compare the efficacy of dexmedetomidine and clonidine as adjuvant in TPVB in addition to conventional local anesthetic solution (ropivacaine) for pain management in breast cancer surgeries. A visual analog scale (VAS) was used to assess postoperative pain up to 48 h.
| Materials and Methods|| |
After Ethical Committee approval, written informed consent was obtained from each of 88 breast cancer patients who were randomly divided into two groups (each group containing 44 patients) using a computerized random number table. Female patients undergoing breast cancer surgery (age 35–60 years) having American Society of Anesthesiologists (ASA) physical status I and II, from May 2014 to January 2015, were enrolled in the study. Patients of both the groups received a 20 ml of mixture of local anesthetic agents (19 ml ropivacaine [0.5%] solution with clonidine or dexmedetomidine 1 mcg/kg to make the additive solution 1 ml with mixing normal saline [NS] to it) as paravertebral block (TPVB). Group D patients were administered the above-mentioned LA mixture along with dexmedetomidine. Group C patients were administered clonidine in place of dexmedetomidine. In Group D, 19 ml ropivacaine (0.5%) (Ropin ® 0.5%, NEON Laboratories Ltd., Mumbai, India) and 1 ml adjuvant (dexmedetomidine + NS) solution (Dextomid ® Neon Laboratories Ltd., India) mixture was prepared. In Group C, 19 ml ropivacaine (0.5%) and 1 ml adjuvant (clonidine + NS) solution (Cloneon ® Neon Laboratories Ltd., Mumbai, India) mixture was prepared. The above mixture was prepared for both the groups in the presence of resident doctor not taking part in the study.
Noncooperative patients, patients known allergic to ropivacaine, dexmedetomidine, and clonidine; or with hepatorenal or cardiopulmonary abnormalities were excluded from the study. Alcoholic or diabetic patients were also excluded from the study. Patients with neuropsychiatric or neuromuscular disorders were also kept out of the study. Thrombocytopenia, coagulation, or seizure disorders were excluded from the study. Anatomical anomalies of thoracic spine were also excluded from this study. In preoperative assessment, every patient was enquired about a history of drug allergy, previous anesthesia. Airway and spine assessment was also done.
In all cases, preoperative fasting of minimum 6 h was ensured before operation. All patients were given tablet lorazepam 1 mg and pantoprazole 40 mg orally at the night before surgery as premedication.
All baseline parameters such as heart rate (HR), systolic blood pressure (BP), diastolic BP, mean arterial BP, and oxygen saturation were noted in the observation room. Then, all patients were transferred to operation theater and continuously monitored using multipara monitor. In sitting position, the same technique was used for paravertebral block in every patient. 2% lignocaine was used for skin infiltration at 2.5 cm lateral to the spinous process of third, fourth, and fifth thoracic vertebra. Through the skin wheal, Tuohy needle (17G) was inserted till it comes in contact with transverse process of the intended thoracic vertebras. Tuohy needle was then walked off the cephalad edge of the transverse process, and it was further advanced till it enters in paravertebral space which was identified by loss of resistance technique using air. Local anesthetic mixture which was already prepared by resident doctor (drawn in identical looking syringes) was injected in the desired position. The anesthesiologist performing the paravertebral block was completely unaware of the group allocation or composition of the local anesthetic mixture. Data collection was done by another resident doctor. The mixture was injected in small aliquots with repeated aspiration. This local anesthetic mixture administration was followed by GA administration in supine position.
NS was started through 18 G intravenous (IV) cannula done before transport of patient to OT. Preoxygenation was done with 100% O2 for 5 min. Premedication was given with injection glycopyrrolate (0.2 mg), injection fentanyl (100 μg), and injection ondansetron (8 mg) 3 min before induction. Propofol (2 mg/kg) was used as inducing agent. Then, laryngoscopy and intubation were done with the help of atracurium (0.5 mg/kg). Less than 20 s was taken for laryngoscopy, intubation, and cuff inflation in all cases. Intraoperative muscle relaxation was maintained with intermittent IV atracurium (0.2 mg/kg) as per requirement. Anesthesia workstation was used for controlled ventilation which was maintained with 66% N2O in O2 and isoflurane up to 1.5 MAC (under guidance of BIS monitoring). On completion of modified radical mastectomy, injection glycopyrrolate 0.01 mg/kg and injection neostigmine 0.05 mg/kg were used for reversal of anesthesia and extubation was done with adequate spontaneous ventilation and BIS ≥70. Ten minutes after extubation, patients were all transferred to postanesthesia care unit (PACU) for observation and postoperative pain management.
Insufficient analgesia was reflected by the presence of hypertension or tachycardia (>20% of baseline) during anesthesia (while BIS was 40–60 [i.e., within desired range]) and fentanyl 1 μg/kg was used to treat the condition.
Hospital discharge (eye-opening – discharge from hospital), the time for PACU stay (admission – discharge from PACU), and also the incidence of adverse events were noted. Patients were considered ready for discharge from the PACU when the modified Aldrete postanesthesia score was ≥9. After being discharged from PACU, patients were transferred to ward. Ondansetron 0.1 mg/kg IV was administered for nausea and vomiting. The same surgeon operated all the cases.
During operation, efficacy of the paravertebral block was the primary outcome of the study. Intraoperative absence of significant (>20%) change in HR and mean arterial pressure (MAP) defines the efficacy of paravertebral block. Intraoperative fentanyl requirement was judged by measuring HR and MAP. The time of administration of first dose of rescue analgesic (injection diclofenac sodium 75 mg intramuscular) following the performance of paravertebral block was taken as the duration of block. VAS (0 = “no pain ” and 10 = “worst possible pain ”) was used to assess the magnitude of postoperative pain for 48 h. Perioperative adverse reactions and hemodynamic changes were also observed.
Estimation of sample size was done on the basis of first rescue analgesic requirement among two groups. Each group enjoyed analgesia on an average of 27 h and for detecting a difference of 10% (i.e., 2.7 h), at the P < 0.05 level, with a probability of detecting a difference, if it exists, of 80% (1−beta = 0.80). On reviewing the previous literatures, we calculated within-group standard deviation (SD) of 6 h and we needed to study at least 40 patients per group to reject the null hypothesis, and this number will be increased to 44 to eliminate the possibility of dropouts. Data were entered into a MS Excel spreadsheet and analyzed using standard statistical software SPSS ® statistical package version 18.0 (SPSS Inc., Chicago, IL, USA). All the data were expressed as number (%) or mean ± SD Pearson's Chi-square test was used to analyze categorical variables. Independent sample t-test was used to analyze continuous variables. P < 0.05 was considered to be statistically significant.
| Results and Analysis|| |
Each group in our study consists of 44 patients which was greater than the calculated sample size. As the dropout cases were nil, 44 patients were in the dexmedetomidine Group (D) and 44 patients in the clonidine Group (C) were considered for effectiveness analysis.
From [Table 1], it is evident that body weight, age, ASA physical status, hemoglobin level in preoperative reports, and operative and anesthetic duration were all found to be comparable (P > 0.05). PACU discharge time was comparable among two groups [Table 1]. Baseline HR and MAP were also quite comparable among two groups [Table 1]. [Table 2] shows the types of different breast surgeries and they were comparable too. Peroperative mean fentanyl and propofol requirement were compared among two groups and they were much less in amount and statistically significant (P < 0.05) in Group D than C [Table 3].
|Table 1: Demographic profile and the preoperative hematologic status in both groups|
Click here to view
|Table 2: Types of surgery in breast cancer for randomized patient groups|
Click here to view
As rescue analgesic, dexmedetomidine group (Group D) received much less diclofenac sodium than clonidine group (Group C) [Table 4]. The time of administration of rescue analgesic is much later in Group D than C. Both the above-mentioned results were statistically significant.
For detection of pain, VAS score was used at different time intervals. It was significantly low (P < 0.05) at 1, 2, 4, and 6 h after surgery with a better pain control in Group D patients than in Group C patients [Table 5].
|Table 5: Pain score (visual analog scale) at rest in postoperative period|
Click here to view
Side effects such as sedation, shivering, bradycardia, hypotension, and dry mouth were all comparable among two groups (P > 0.05) [Table 6]. MAP and HR among two groups were found to be quite comparable among two groups (P > 0.05) [Figure 1] and [Figure 2] respectively].
| Discussion|| |
Pain in a breast cancer patient itself has a negative impact on the quality of life. Persistent pain after breast cancer surgery is increasingly recognized as a potential problem facing a sizeable subset of the millions of women who undergo surgery as part of their treatment of breast cancer. Postmastectomy persistent neuropathic pain, possibly triggered by dissection of intercostobrachial or axillary nerve, is a chronic pain condition which significantly lowers the quality of life in survivors. With excellent pain management protocol, breast cancer surgery-related acute postsurgical pain can be alleviated; at the same time, anxiety, morbidity, cost, and length of hospital stay in the postoperative period can be decreased.
Varied combinations of local anesthetics and adjuvants are being tried in paravertebral block for the patients undergoing thoracic or breast cancer surgeries to reduce the perioperative pain.,,,,
Among α2-adrenergic agonists, dexmedetomidine is very selective, and when it is used in systemic route, it has sedative, analgesic, and anesthetic-sparing effects. Dexmedetomidine has also successfully been used in central neuraxial block along with local anesthetic agents., Again while performing peripheral nerve block or nerve plexus block, dexmedetomidine has shown its perfect adjuvant role in all the cases.
Clonidine, a relatively older α2 agonist, is commonly used as premedication in GA. The drug, by acting on pre- and post-synaptic α2 receptors, produces preoperative sedation, anxiolysis, perioperative analgesia, and good control over hemodynamics by reducing sympathetic tone. The drug was also used along with peripheral nerve block. Again Burlacu et al. used clonidine along with local anesthetics in thoracic paravertebral route for modified radical mastectomy patients.
However, surprisingly, not a single clinical trial compared the effectiveness of two above-mentioned α2-agonists combining separately with ropivacaine in TPVB for the breast cancer surgery patients to be operated under GA.
In this randomized, prospective trial, we have compared the efficacy of dexmedetomidine and clonidine at1 μg/kg used as adjuvant in TPVB given with 19 ml 0.5% ropivacaine for the patients undergoing breast cancer surgery under GA. Here, we had measured the time of administration of the first dose of rescue analgesic as diclofenac sodium. Total dose of intraoperative analgesic fentanyl and hemodynamics and side effects were also assessed.
While comparing demographic profile among two groups, it was found to be statistically insignificant (P > 0.05) which allows us a uniform platform to evenly compare the results obtained. Channabasappa et al. in a comparative study between dexmedetomidine and clonidine as adjuvant in cervical epidural anesthesia found exactly similar results regarding demographic parameters.
In our study, we have observed that intraoperative analgesic requirement as fentanyl was quite less in dexmedetomidine group as compared with clonidine group, and the outcome was statistically significant. This result was in accordance with a study conducted by Kumar et al., who compared premedication with the same dexmedetomidine and clonidine in laparoscopic cholecystectomy and found that VAS score was significantly less in dexmedetomidine group.
In this prospective study, we have found dexmedetomidine-treated group asked for rescue analgesics much later than clonidine group. Channabasappa et al., while performing a comparative study between clonidine and dexmedetomidine as adjuvant in cervical epidural, found similar result showing dexmedetomidine group requiring rescue analgesic (286.76 ± 34.65 min vs. 234.65 ± 23.76 min) in much later period. On the contrary, Kanazi et al. found no significant difference between clonidine and dexmedetomidine (272 ± 38 min vs. 303 ± 75 min) group, while the two adjuvants were added to intrathecal bupivacaine.
In our study, postoperative diclofenac consumption was much less in dexmedetomidine group than clonidine. Similarly, Channabasappa et al. in their study found in cervical epidural anesthesia with ropivacaine for breast cancer surgery when administered with dexmedetomidine, produced lesser requirement of ropivacaine than clonidine (48.67 ± 16.98 mg vs. 66.46 ± 18.42 mg).
While comparing VAS score, it was found significantly higher at 1, 2, 4, and 6 h and clonidine group showed higher values than dexmedetomidine group. Shaikh et al. similarly found that adjuvant dexmedetomidine group showed lower VAS score while comparing epidural analgesic effects of levobupivacaine with clonidine. Sardesai et al. similarly found significantly lower VAS score in dexmedetomidine group while comparing with clonidine in IVRA along with preservative-free lignocaine for upper limb orthopedic surgeries.
In our study, we had found that sedation was quite similar and comparable among two groups. Channabasappa et al. experienced similar results with epidural dexmedetomidine and clonidine. In our study, bradycardia was more in dexmedetomidine group, but on the contrary, Kumar et al. found that more bradycardia was with clonidine group.
In our study, hypotension in both the groups was quite comparable and not at all remarkable. Kanazi et al. also observed similar finding in their study with intrathecal dexmedetomidine and clonidine along with bupivacaine. We had found that dry mouth was slightly (though statistically insignificant) more in dexmedetomidine than clonidine group. However, Bajwa et al. on the contrary found that dry mouth was slightly higher in clonidine group where clonidine and dexmedetomidine were used in epidural route. Again among side effects in our study, nausea and vomiting was quite comparable and dexmedetomidine produced slightly greater nausea. This result is very similar to Bajwa et al. who also found that nausea was insignificantly more in epidural dexmedetomidine group.
Among the limitations, though we had measured bispectral index for anesthesia depth assessment, we had not compared the same among two groups. We had not measured the plasma catecholamine concentration which ideally should have been decreased by both the drugs, being α2 agonists. Both the drugs had been used as per optimal and safe dose used by our previous researchers. In future, a larger study with larger sample size needs to be conducted to establish author's point of view with solidarity.
| Conclusion|| |
It can be concluded that if before breast cancer surgery; dexmedetomidine or clonidine (at 1 mcg/kg) is administered along with TPVB before induction of GA, it will prolong the duration of anesthesia. Dexmedetomidine provides intra- and postoperative analgesia (indicated by lesser fentanyl and diclofenac requirement, respectively). Dexmedetomidine maintains a relatively lower VAS score both in resting and in shoulder movement state. It also renders a delayed and lesser analgesic requirement without major hemodynamic alteration and side effects.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Costa WA, Eleutério J Jr., Giraldo PC, Gonçalves AK. Quality of life in breast cancer survivors. Rev Assoc Med Bras (1992) 2017;63:583-9.
Karmakar MK, Samy W, Lee A, Li JW, Chan WC, Chen PP, et al.
Survival analysis of patients with breast cancer undergoing a modified radical mastectomy with or without a thoracic paravertebral block: A 5-year follow-up of a randomized controlled trial. Anticancer Res 2017;37:5813-20.
Wu J, Buggy D, Fleischmann E, Parra-Sanchez I, Treschan T, Kurz A, et al.
Thoracic paravertebral regional anesthesia improves analgesia after breast cancer surgery: A randomized controlled multicentre clinical trial. Can J Anaesth 2015;62:241-51.
Gessling EA, Miller M. Efficacy of thoracic paravertebral block versus systemic analgesia for postoperative thoracotomy pain: A systematic review protocol. JBI Database System Rev Implement Rep 2017;15:30-8.
Al-Shather H, El-Boghdadly K, Pawa A. Awake laparoscopic sleeve gastrectomy under paravertebral and superficial cervical plexus blockade. Anaesthesia 2015;70:1210-1.
Paleczny J, Zipser P, Pysz M. Paravertebral block for open cholecystectomy. Anestezjol Intens Ter 2009;41:89-93.
Baik JS, Oh AY, Cho CW, Shin HJ, Han SH, Ryu JH, et al.
Thoracic paravertebral block for nephrectomy: A randomized, controlled, observer-blinded study. Pain Med 2014;15:850-6.
Fahy AS, Jakub JW, Dy BM, Eldin NS, Harmsen S, Sviggum H, et al.
Paravertebral blocks in patients undergoing mastectomy with or without immediate reconstruction provides improved pain control and decreased postoperative nausea and vomiting. Ann Surg Oncol 2014;21:3284-9.
Terkawi AS, Tsang S, Sessler DI, Terkawi RS, Nunemaker MS, Durieux ME, et al.
Improving analgesic efficacy and safety of thoracic paravertebral block for breast surgery: A mixed-effects meta-analysis. Pain Physician 2015;18:E757-80.
Garutti I, Olmedilla L, Cruz P, Piñeiro P, De la Gala F, Cirujano A, et al.
Comparison of the hemodynamic effects of a single 5 mg/kg dose of lidocaine with or without epinephrine for thoracic paravertebral block. Reg Anesth Pain Med 2008;33:57-63.
Tomar GS, Ganguly S, Cherian G. Effect of perineural dexamethasone with bupivacaine in single space paravertebral block for postoperative analgesia in elective nephrectomy cases: A double-blind placebo-controlled trial. Am J Ther 2017;24:e713-7.
Bhuvaneswari V, Wig J, Mathew PJ, Singh G. Post-operative pain and analgesic requirements after paravertebral block for mastectomy: A randomized controlled trial of different concentrations of bupivacaine and fentanyl. Indian J Anaesth 2012;56:34-9.
] [Full text]
Ammar AS, Mahmoud KM. Does the addition of magnesium to bupivacaine improve postoperative analgesia of ultrasound-guided thoracic paravertebral block in patients undergoing thoracic surgery? J Anesth 2014;28:58-63.
Shukla U, Prabhakar T, Malhotra K. Postoperative analgesia in children when using clonidine or fentanyl with ropivacaine given caudally. J Anaesthesiol Clin Pharmacol 2011;27:205-10.
] [Full text]
Chatrath V, Sharan R, Kheterpal R, Kaur G, Ahuja J, Attri JP, et al.
Comparative evaluation of 0.75% ropivacaine with clonidine and 0.5% bupivacaine with clonidine in infraclavicular brachial plexus block. Anesth Essays Res 2015;9:189-94.
Naaz S, Ozair E. Dexmedetomidine in current anaesthesia practice – A review. J Clin Diagn Res 2014;8:GE01-4.
Khan ZP, Ferguson CN, Jones RM. Alpha-2 and imidazoline receptor agonists. Their pharmacology and therapeutic role. Anaesthesia 1999;54:146-65.
Kettner SC. Dexmedetomidine as adjuvant for peripheral nerve blocks. Br J Anaesth 2013;111:123.
Obayah GM, Refaie A, Aboushanab O, Ibraheem N, Abdelazees M. Addition of dexmedetomidine to bupivacaine for greater palatine nerve block prolongs postoperative analgesia after cleft palate repair. Eur J Anaesthesiol 2010;27:280-4.
Torres E, Dixon C, Richman AR. Understanding the breast cancer experience of survivors: A qualitative study of African American women in rural Eastern North Carolina. J Cancer Educ 2016;31:198-206.
Schreiber KL, Kehlet H, Belfer I, Edwards RR. Predicting, preventing and managing persistent pain after breast cancer surgery: The importance of psychosocial factors. Pain Manag 2014;4:445-59.
Macdonald L, Bruce J, Scott NW, Smith WC, Chambers WA. Long-term follow-up of breast cancer survivors with post-mastectomy pain syndrome. Br J Cancer 2005;92:225-30.
Amaya F, Hosokawa T, Okamoto A, Matsuda M, Yamaguchi Y, Yamakita S, et al.
Can acute pain treatment reduce postsurgical comorbidity after breast cancer surgery? A literature review. Biomed Res Int 2015;2015:641508.
Huang R, Hertz L. Receptor subtype and dose dependence of dexmedetomidine-induced accumulation of [14C] glutamine in astrocytes suggests glial involvement in its hypnotic-sedative and anesthetic-sparing effects. Brain Res 2000;873:297-301.
Zhang C, Li C, Pirrone M, Sun L, Mi W. Comparison of dexmedetomidine and clonidine as adjuvants to local anesthetics for intrathecal anesthesia: A meta-analysis of randomized controlled trials. J Clin Pharmacol 2016;56:827-34.
Zhang X, Wang D, Shi M, Luo Y. Efficacy and safety of dexmedetomidine as an adjuvant in epidural analgesia and anesthesia: A systematic review and meta-analysis of randomized controlled trials. Clin Drug Investig 2017;37:343-54.
Esmaoglu A, Yegenoglu F, Akin A, Turk CY. Dexmedetomidine added to levobupivacaine prolongs axillary brachial plexus block. Anesth Analg 2010;111:1548-51.
Dahmani S, Brasher C, Stany I, Golmard J, Skhiri A, Bruneau B, et al.
Premedication with clonidine is superior to benzodiazepines. A meta analysis of published studies. Acta Anaesthesiol Scand 2010;54:397-402.
Maze M, Tranquilli W. Alpha-2 adrenoceptor agonists: Defining the role in clinical anesthesia. Anesthesiology 1991;74:581-605.
Burlacu CL, Frizelle HP, Moriarty DC, Buggy DJ. Pharmacokinetics of levobupivacaine, fentanyl, and clonidine after administration in thoracic paravertebral analgesia. Reg Anesth Pain Med 2007;32:136-45.
Channabasappa SM, Venkatarao GH, Girish S, Lahoti NK. Comparative evaluation of dexmedetomidine and clonidine with low dose ropivacaine in cervical epidural anesthesia for modified radical mastectomy: A prospective randomized, double-blind study. Anesth Essays Res 2016;10:77-81.
] [Full text]
Kumar S, Kushwaha BB, Prakash R, Jafa S, Malik A, Wahal R, et al.
Comparative study of effects of dexmedetomidine and clonidine premedication in perioperative hemodynamic stability and postoperative analgesia in laparoscopic cholecystectomy. Internet J Anesthesiol 2014;33:1.
Kanazi GE, Aouad 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.
Shaikh SI, Revur LR, Mallappa M. Comparison of epidural clonidine and dexmedetomidine for perioperative analgesia in combined spinal epidural anesthesia with intrathecal levobupivacaine: A randomized controlled double-blind study. Anesth Essays Res 2017;11:503-7.
] [Full text]
Sardesai SP, Patil KN, Sarkar A. Comparison of clonidine and dexmedetomidine as adjuncts to intravenous regional anaesthesia. Indian J Anaesth 2015;59:733-8.
] [Full text]
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.
] [Full text]
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]