Anesthesia: Essays and Researches  Login  | Users Online: 305 Home Print this page Email this page Small font sizeDefault font sizeIncrease font size
Home | About us | Editorial board | Ahead of print | Search | Current Issue | Archives | Submit article | Instructions | Copyright form | Subscribe | Advertise | Contacts


 
Table of Contents  
ORIGINAL ARTICLE
Year : 2017  |  Volume : 11  |  Issue : 4  |  Page : 864-870  

Effect of clonidine as adjuvant in thoracic paravertebral block for patients undergoing breast cancer surgery: A prospective, randomized, placebo-controlled, double-blind study


1 Department of Anaesthesiology, College of Medicine and Sagore Dutta Hospital, Kolkata, West Bengal, India
2 Department of Anaesthesiology, Murshidabad Medical College, Berhampore, West Bengal, India
3 Department of Anaesthesiology, Midnapore Medical College and Hospital, Medinipur, West Bengal, India

Date of Web Publication28-Nov-2017

Correspondence Address:
Anjan Das
174, Gorakshabashi Road, Royal Plaza Apartment (4th Floor, Flat No-1), Nagerbazar, Kolkata - 700 028, West Bengal
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/aer.AER_162_17

Rights and Permissions
   Abstract 


Background and Aims: Postoperative pain after breast cancer surgery is unavoidable. Thoracic paravertebral block (TPVB), a locoregional anesthetic technique, has been proven successful for postoperative pain management in different thoracic surgical procedures, such as thoracotomy, breast cancer surgeries. Clonidine, an adjuvant, in TPVB may enhance the quality and prolong the duration of analgesia. This prospective study was to evaluate the effectiveness of clonidine; administered with TPVB; in addition to conventional local anesthetic solution. Materials and Methods: Fifty-two patients (25–55 years) scheduled for breast cancer surgery under general anesthesia were randomly divided into Group A (n = 26) receiving preoperative TPVB at T3with clonidine added to local anesthesia solution and Group B (n = 26) receiving identical TPVB with local anesthesia but without any adjuvant. This was followed by balanced general anesthesia. A visual analog scale was used to assess pain postoperatively up to 48 h. Meantime to administration of the first dose of rescue analgesic was noted. Total dose of fentanyl consumption, hemodynamic parameters, and side effects were all recorded for each patient. Results: The dosage of fentanyl required in the intraoperative period was significantly lower in Group A. Mean time to administration of rescue analgesic was found to be significantly longer in clonidine group. Hemodynamics and side effects were quite comparable among two groups. Conclusion: Clonidine as adjuvant in TPVB provided profound analgesia for up to 48 h postoperatively for patients undergoing breast cancer surgery without any appreciable side effects.

Keywords: Anesthesia general, anesthesia local, clonidine, thoracic paravertebral block, visual analog scale


How to cite this article:
Mayur N, Das A, Biswas H, Chhaule S, Chattopadhyay S, Mitra T, Roybasunia S, Mandal SK. Effect of clonidine as adjuvant in thoracic paravertebral block for patients undergoing breast cancer surgery: A prospective, randomized, placebo-controlled, double-blind study. Anesth Essays Res 2017;11:864-70

How to cite this URL:
Mayur N, Das A, Biswas H, Chhaule S, Chattopadhyay S, Mitra T, Roybasunia S, Mandal SK. Effect of clonidine as adjuvant in thoracic paravertebral block for patients undergoing breast cancer surgery: A prospective, randomized, placebo-controlled, double-blind study. Anesth Essays Res [serial online] 2017 [cited 2019 Aug 23];11:864-70. Available from: http://www.aeronline.org/text.asp?2017/11/4/864/216043




   Introduction Top


Postoperative pain after breast cancer surgery is strongly associated with increased morbidity, prolonged hospital stay, and hence, higher economic burden and patient's suffering.[1] This excruciating pain is very often associated with chronic pain syndrome.[2]

The paravertebral block is a popular analgesic modality for intraoperative and postoperative pain management in inguinal herniorrhaphy, lithotripsy, nephrectomy, hepatectomy, ventral hernia repair, gastrectomy,[3] and thoracotomy [4] with no opioid and nonsteroidal anti-inflammatory drugs such as side effects.

General anesthesia is currently the standard technique used for surgical treatment of breast cancer. However, general anesthesia alone has not sufficient control over postoperative pain.[5] Thoracic paravertebral block (TPVB) is a successful alternative to general anesthesia for breast cancer surgery.[6] Benefits include a prolonged postoperative pain relief, potential for early discharge, and reduction in postoperative opioid consumption and hence postoperative nausea and vomiting (PONV).[7] It shortens the duration of hospital stay and hence cost constraints.[8] Chronic postsurgical pain is a common complication after breast cancer surgery. Preincisional paravertebral block before breast cancer surgery causes a significant reduction in acute as well as chronic pain.[9] The most commonly used drugs for PVB are bupivacaine, lignocaine, levobupivacaine, ropivacaine, and combination of these drugs.[10] Various adjuvants such as opioids,[10] epinephrine,[10] dexamethasone,[11] magnesium,[12] clonidine,[10] etc., were added to local anesthetics in TPVBs to achieve quick, dense, and prolonged block, but the results are either inconclusive or associated with side effects.

Clonidine is a selective α2 adrenergic agonist with some α1 agonist property. In clinical studies, the addition of clonidine to local anesthetic solutions when used in caudal block,[13] brachial plexus block,[14] axillary plexus block,[15] paravertebral block,[16] a reduced onset time, improved efficacy of the block during surgery, and extended postoperative analgesia is obtained.

Very few published clinical studies have evaluated clonidine in preincisional TPVB to assess its efficacy in prolonging duration of action of local anesthetic agents. The aim and objective of our placebo-controlled study were to compare the analgesic efficacy of clonidine as adjuvant to local anesthetic agent in TPVB for the patients undergoing general anesthesia.


   Materials and Methods Top


On getting approval from the Institutional Ethical committee, written consent was obtained from every patient. Totally 52 adult patients were randomly allocated into two equal groups (n = 26 in each group) using computer-generated random number list. From December 2013 to June 2015, female patients having American Society of Anesthesiologists (ASA) physical status I and II, aged 25–55 years undergoing breast cancer surgery under general anesthesia were enrolled in the study. Patients of both the groups received a 19.5 ml of mixture of local anesthetic agents (lignocaine [2%] 6.5 ml; lignocaine [2%] with adrenaline 6 ml; bupivacaine [0.5%] 7 ml) as paravertebral block (TPVB). Group A received 0.5 ml (75 μg) clonidine with the above-mentioned local anesthetic mixture. Control means, Group B received 0.5 ml of normal saline instead of clonidine. In Group A, 6.5 ml lignocaine (2%), 6 ml (lignocaine [2%] + adrenaline [1:200,000]) solution, 7 ml bupivacaine (0.5%), and 0.5 ml clonidine mixture was prepared in the presence of resident doctor not taking part in the study. A similar process was maintained for Group B patients.

Patient refusal, noncooperative patients, pregnant or lactating mothers, patients with known allergy or contraindication to lignocaine, bupivacaine, clonidine; or with hepatic, renal or cardiopulmonary abnormality, alcoholics, and diabetics were excluded from the study. Patients having a history of significant neuropsychiatric or neuromuscular disorders were also excluded. Patients having infection at the site of injection, coagulopathy, and platelet count <100,000 mm −3, or having seizure disorder were excluded from the study. Patients having gross anatomical abnormality of thoracic spine or vasomotor disturbances were also excluded from this study.

In preoperative assessment, patients were enquired about history of previous anesthesia, drug allergy. General and systemic examinations and assessment of the airway and spine were done. Preoperative fasting of minimum 6 h was ensured before operation in all cases. All patients received premedication of tablet alprazolam 0.5 mg and ranitidine 150 mg orally at the night before surgery.

Patients were brought to the observation room; baseline parameters such as heart rate (HR), systolic blood pressure, diastolic blood pressure, mean arterial blood pressure (MBP), and oxygen saturation (SpO2) were measured. After that, patient were shifted to operation theater and continuously monitored using Philips IntelliVue (MP20) monitor. A standard technique of paravertebral block was followed in every patient in the sitting position. The skin was infiltrated with 2.5 ml of 2% lignocaine, 2.5 cm lateral to the spinous process of third thoracic vertebra. A 17-guage Tuohy needle was inserted through the skin wheal till it contacted the transverse process of the thoracic vertebra. Needle was then redirected and walked off the cephalad edge of the transverse process and advanced till it reached paravertebral space which was identified by loss of resistance technique using air. This technique was applied in three consecutive levels (T3, T4, and T5). Previously, prepared local anesthetic mixture; drawn in identical looking syringes; was injected in the desired positions in divided doses. The anesthesiologist who performed the ipsilateral TPVB was not aware of the group allocation or the exact composition of the local anesthetic mixture that was being injected. He was also not involved in data collection. The study drug mixture was injected in small aliquots with repeated aspiration. The patient was then turned supine, and a standard technique of general anesthesia was performed in all patients.

Intravenous (i.v.) Ringer lactate started with the help of 18-guage cannula done previously. After 5 min, preoxygenation with 100% O2, premedication was given with injection glycopyrrolate (0.02 mg), injection fentanyl (100 μg) 3 min before induction. Induction was done with i.v. injection propofol (2 mg/kg). After that, atracurium (0.5 mg/kg) was given to facilitate laryngoscopy and intubation. Laryngoscopy, intubation, and cuff inflation were completed within 20 s in all cases. Muscle relaxation was maintained with intermittent i.v. atracurium (0.2 mg/kg) as and when required and controlled ventilation was maintained with 70% N2O in O2 and isoflurane up to 1–2 minimum alveolar concentration (under the guidance of bispectral index (BIS) monitoring) using anesthesia workstation. After completion of surgery, neuromuscular block was reversed with injection glycopyrrolate 0.01 mg/kg and injection neostigmine 0.05 mg/kg and extubated when adequate spontaneous ventilation was established and BIS ≥70. After extubation, all patients were transferred to postanesthesia care unit (PACU) for observation.

The presence of hypertension or tachycardia (>20% of baseline) during anesthesia, while BIS was 40–60 (i.e., within desired range), was attributed to insufficient analgesia and a bolus dose of fentanyl 1 μg/kg was given.

The time for PACU stay (admission-discharge from PACU) and hospital discharge (eye opening-discharge from hospital) and the incidence of adverse events were also recorded. Patients were considered ready for discharge from the PACU when the modified Aldrete post anesthesia score was ≥9. Patients were transferred to ward after being discharged from PACU. For nausea and vomiting, ondansetron 0.15 mg/kg i.v was administered. All the patients were operated by the same surgeon.

The primary outcome of the study was the clinical efficacy of the paravertebral block during operation. Paravertebral block efficacy is defined as the intraoperative absence of significant (>20%) change in HR and MBP. This is measured with help of intraoperative fentanyl requirement. The time of administration of the first dose of rescue analgesic (injection diclofenac sodium 75 mg i.m.) following the performance of paravertebral block was taken as the duration of block. The magnitude of postoperative pain is assessed using a visual analog scale (VAS: 0 = “no pain” and 10 = “worst possible pain”) for postoperative 48 h. Postoperative pain was assessed using a VAS (VAS: 0 = “no pain” and 10 = “worst pain imaginable”). Hemodynamic changes and perioperative adverse reactions were also observed.

The sample size was estimated using first rescue analgesic requirement among two groups as the main primary variable. The average duration in each group was 29 h and to detect a difference of 10% (i.e., 2.9 h), at the P < 0.05 level, with a probability of detecting a difference, if it exists, of 80% (1−β = 0.80). On the basis of the previous study assuming within-group SD of 7.5 h and we needed to study at least 24 patients per group to be able to reject the null hypothesis which will be increased to 26 patients for possible dropouts. Raw data were entered into a Microsoft Excel spreadsheet and analyzed using standard statistical software SPSS ® statistical package version 18.0 (SPSS Inc., Chicago, IL, USA). Values were expressed as number (%) or mean ± standard deviation and/or standard error. Categorical variables were analyzed using the Pearson's Chi-square test. Normally distributed continuous variables were analyzed using the independent sample t-test. One-way anova test was used to determine the difference between the means of different independent groups. Nonparametric alternative Mann–Whitney U-test was used to compare other variables in the study and control groups in different points of time. P < 0.05 was considered statistically significant.


   Results and Analysis Top


We recruited 26 subjects per group, slightly more than the calculated sample size. There were no dropouts. Twenty-six patients in the clonidine group (A) and 26 in the placebo group (B) were eligible for effectiveness analysis.

The age, body weight, ASA physical status, preoperative hemoglobin, duration of surgery and anesthesia all were found to be (P > 0.05) comparable [Table 1]. PACU and hospital discharge time were also more prolonged but statistically insignificant in Group A than Group B [Table 1]. Basic hemodynamic parameters were quite comparable among two groups [Table 1]. Types of different surgeries were described in [Table 2]. Intraoperative mean fentanyl requirement was compared among two groups and found to be much less in clonidine Group (A) than placebo Group (B), and the difference was statistically significant (P < 0.05) [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
Table 3: Intraoperative fentanyl requirement

Click here to view


Clonidine group (Group A) received diclofenac as rescue analgesic much later than placebo group (Group B) [Table 4]. VAS score was used to detect pain at rest and on shoulder movement. VAS score was significantly low (P = 0.0001) at 12, 24, and 48 h after surgery with a better pain control in group A patients than in Group B patients. By applying Mann–Whitney U-test, P value was found to be <0.0001 at 12, 24, and 48 h after surgery [Table 5].
Table 4: Comparison of time of rescue analgesia among two groups

Click here to view
Table 5: Pain score at rest and on shoulder movement

Click here to view


Side effects 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]. [Figure 3] shows the patient enrollment, allocation, follow-up, and analysis of all the patients in the study.
Table 6: Side effects

Click here to view
Figure 1: Comparison of mean arterial pressure between two groups

Click here to view
Figure 2: Comparison of mean heart rate between two groups

Click here to view
Figure 3: CONSORT 2010 flow diagram

Click here to view



   Discussion Top


Inadequate pain management in the perioperative period specifically in cancer patients leads to both short and long-term consequences.[13],[17] Among these complications, basal atelectasis, pneumonia, deep vein thrombosis, pulmonary embolism, psychological trauma which even may lead to posttraumatic stress disorder.[18] With the help of excellent pain management protocol, the anxiety, morbidity, cost and length of hospital stay in the postoperative period can be decreased. Acute postoperative pain occurs after breast cancer surgery in approximately most of the patients and is a key risk factor for the development of chronic pain.[2],[19] TPVB provides superior analgesia for breast cancer surgery when used in conjunction with general anesthesia and reduces the severity of chronic pain after mastectomy.[20]

For a long time, a number of local anesthetic agents and adjuvants have been tried in TPVB for the patients undergoing breast cancer surgery to reduce the intraoperative as well as postoperative pain.[10],[11]

Clonidine is an α2-agonist that has been used for premedication in adult and pediatric patients. Clonidine is effective by the stimulation of pre- and post-synaptic α2 agonists in many areas of the central nervous system leading to sedation, analgesia, and reduction of sympathetic tone.[21] Oral clonidine (5 μg/kg) premedication can reduce postoperative patient-controlled analgesia administered morphine requirement by 37%.[22] Mohamed and Abdel-Ghaffar found that locally administered clonidine along with bupivacaine reduces VAS score, significantly delays first dose of rescue analgesic, and reduces its consumption in modified radical mastectomy patients.[23]

Unfortunately, no sufficient clinical trials studied the effectiveness of combining α2-agonist (clonidine) with bupivacaine in TPVB for the patients undergoing breast cancer surgery under general anesthesia.

In this prospective, randomized, placebo-controlled trial, we had compared the efficacy of (75 μg) clonidine in TPVB to assess its efficacy in prolonging the duration of action of local anesthetic agents for the patients undergoing breast cancer surgery under general anesthesia. This study measured mean time for administration of the first dose of rescue (diclofenac sodium) analgesic, total dose of intraoperative fentanyl consumption, hemodynamic parameters, and side effects if any.

The demographic profile, between two groups, which was statistically insignificant (P > 0.05) of our patients was quite similar with other research investigations and provided us the uniform platform to evenly compare the results obtained.[24] Mohamed and Abdel-Ghaffar.[23] in their study found operative duration in all the four groups were quite comparable. Burlacu et al.[25] in their study found that types of operations among four groups and basic hemodynamic parameters among them were quite comparable.

We had found that intraoperative fentanyl requirement was significantly less in the clonidine treated group than placebo group. On the contrary, Turan et al.[26] in a perioperative ischemia evaluation trial found that oral clonidine did not reduce intraoperative and postoperative opioid consumption.

In our study, postoperative rescue analgesic administration was significantly delayed in clonidine group. Similar findings were evidenced by Faria-Silva et al., who conducted shoulder arthroscopic surgeries under brachial plexus block and found clonidine mixed local anesthetic group asked for morphine as rescue analgesic much later and in lesser amount.[27] Gupta et al. also demonstrated similar findings while clonidine was used in epidural route for knee replacement surgeries.[24]

In our study, we had found a higher VAS score at 12, 24, and 48 h interval at resting and shoulder elevated state. These differences were statistically significant. Ali et al. in their study on various orthopedic surgeries of the upper extremities under supraclavicular block found that from 8th h onward pain score in clonidine-ropivacaine-treated group was much lesser than ropivacaine-normal saline group.[28] Again, in another study by Singh and Aggarwal based on the upper limb surgeries under brachial plexus block found that after 240 min of block VAS score sharply raised in nonclonidine-treated group.[29]

Various previous studies indicate that clonidine is well tolerated if administered on a short-term single-use basis. Commonly observed side effects with this adjuvant were hypotension, dryness of mouth, and sedation when clonidine was administered epidurally.[24] Burlacu et al. observed hypotension and bradycardia when the drug was used in paravertebral route.[25] Similar sedation, dryness of mouth, hypotension, and bradycardia were found in our study. Faria-Silva et al. and Ali et al. in two different studies found clonidine reduced PONV in an appreciable manner by an opioid-sparing effect.[27],[28] In our study, we had similarly found less nausea, vomiting, shivering in clonidine-treated group.

There were some limitations of our study that need discussion. One of the limitations we had used BIS for assessing the depth of anesthesia but did not compare it among two groups. We had not measured plasma catecholamine or stress hormone concentrations which may reveal relations with sympatholytic properties of α2-agonists and earlier discharge after their use. Another limitation is that we had used clonidine based on their known optimal as well as safe adjuvant dose for regional block without the knowledge of its exact optimal dose. However, a larger study with large sample size needs to be conducted in the future to establish the author's point of view with solidarity.


   Conclusion Top


In breast cancer surgery, 75 μg clonidine when administered along with TPVB before the induction of general anesthesia was effective for providing analgesia in intraoperative (indicated by lesser requirement of intraoperative fentanyl) and postoperative period. Clonidine maintains a lower VAS score both in resting as well as in shoulder movement state. It also renders a delayed and lesser analgesic requirement without major hemodynamic alteration and side effects.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Tahiri Y, Tran DQ, Bouteaud J, Xu L, Lalonde D, Luc M, et al. General anaesthesia versus thoracic paravertebral block for breast surgery: A meta-analysis. J Plast Reconstr Aesthet Surg 2011;64:1261-9.  Back to cited text no. 1
[PUBMED]    
2.
Poleshuck EL, Katz J, Andrus CH, Hogan LA, Jung BF, Kulick DI, et al. Risk factors for chronic pain following breast cancer surgery: A prospective study. J Pain 2006;7:626-34.  Back to cited text no. 2
[PUBMED]    
3.
El-Boghdadly K, Madjdpour C, Chin KJ. Thoracic paravertebral blocks in abdominal surgery - A systematic review of randomized controlled trials. Br J Anaesth 2016;117:297-308.  Back to cited text no. 3
[PUBMED]    
4.
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.  Back to cited text no. 4
    
5.
Cohen AM, Schaeffer N, Chen ZY, Wood WC. Early discharge after modified radical mastectomy. Am J Surg 1986;151:465-6.  Back to cited text no. 5
[PUBMED]    
6.
Sato M, Shirakami G, Fukuda K. Comparison of general anesthesia and monitored anesthesia care in patients undergoing breast cancer surgery using a combination of ultrasound-guided thoracic paravertebral block and local infiltration anesthesia: A retrospective study. J Anesth 2016;30:244-51.  Back to cited text no. 6
[PUBMED]    
7.
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.  Back to cited text no. 7
    
8.
Buckenmaier CC 3rd, Kwon KH, Howard RS, McKnight GM, Shriver CD, Fritz WT, et al. Double-blinded, placebo-controlled, prospective randomized trial evaluating the efficacy of paravertebral block with and without continuous paravertebral block analgesia in outpatient breast cancer surgery. Pain Med 2010;11:790-9.  Back to cited text no. 8
    
9.
Kairaluoma PM, Bachmann MS, Rosenberg PH, Pere PJ. Preincisional paravertebral block reduces the prevalence of chronic pain after breast surgery. Anesth Analg 2006;103:703-8.  Back to cited text no. 9
    
10.
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.  Back to cited text no. 10
    
11.
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.  Back to cited text no. 11
    
12.
Goravanchi F, Kee SS, Kowalski AM, Berger JS, French KE. A case series of thoracic paravertebral blocks using a combination of ropivacaine, clonidine, epinephrine, and dexamethasone. J Clin Anesth 2012;24:664-7.  Back to cited text no. 12
    
13.
El-Tamer MB, Ward BM, Schifftner T, Neumayer L, Khuri S, Henderson W, et al. Morbidity and mortality following breast cancer surgery in women: National benchmarks for standards of care. Ann Surg 2007;245:665-71.  Back to cited text no. 13
    
14.
Bernard JM, Macaire P. Dose-range effects of clonidine added to lidocaine for brachial plexus block. Anesthesiology 1997;87:277-84.  Back to cited text no. 14
    
15.
Singelyn FJ, Gouverneur JM, Robert A. A minimum dose of clonidine added to mepivacaine prolongs the duration of anesthesia and analgesia after axillary brachial plexus block. Anesth Analg 1996;83:1046-50.  Back to cited text no. 15
    
16.
Bhatnagar S, Mishra S, Madhurima S, Gurjar M, Mondal AS. Clonidine as an analgesic adjuvant to continuous paravertebral bupivacaine for post-thoracotomy pain. Anaesth Intensive Care 2006;34:586-91.  Back to cited text no. 16
    
17.
Smetana GW. Postoperative pulmonary complications: An update on risk assessment and reduction. Cleve Clin J Med 2009;76 Suppl 4:S60-5.  Back to cited text no. 17
    
18.
Jagsi R, Jiang J, Momoh AO, Alderman A, Giordano SH, Buchholz TA, et al. Complications after mastectomy and immediate breast reconstruction for breast cancer: A Claims-based analysis. Ann Surg 2016;263:219-27.  Back to cited text no. 18
    
19.
Gärtner R, Jensen MB, Nielsen J, Ewertz M, Kroman N, Kehlet H, et al. Prevalence of and factors associated with persistent pain following breast cancer surgery. JAMA 2009;302:1985-92.  Back to cited text no. 19
    
20.
Karmakar MK, Samy W, Li JW, Lee A, Chan WC, Chen PP, et al. Thoracic paravertebral block and its effects on chronic pain and health-related quality of life after modified radical mastectomy. Reg Anesth Pain Med 2014;39:289-98.  Back to cited text no. 20
    
21.
Maze M, Tranquilli W. Alpha-2 adrenoceptor agonists: Defining the role in clinical anesthesia. Anesthesiology 1991;74:581-605.  Back to cited text no. 21
    
22.
Park J, Forrest J, Kolesar R, Bhola D, Beattie S, Chu C, et al. Oral clonidine reduces postoperative PCA morphine requirements. Can J Anaesth 1996;43:900-6.  Back to cited text no. 22
    
23.
Mohamed SA, Abdel-Ghaffar HS. Effect of the addition of clonidine to locally administered bupivacaine on acute and chronic postmastectomy pain. J Clin Anesth 2013;25:20-7.  Back to cited text no. 23
    
24.
Gupta S, Raval D, Patel M, Patel N, Shah N. Addition of epidural clonidine enhances postoperative analgesia: A double-blind study in total knee-replacement surgeries. Anesth Essays Res 2010;4:70-4.  Back to cited text no. 24
  [Full text]  
25.
Burlacu CL, Frizelle HP, Moriarty DC, Buggy DJ. Fentanyl and clonidine as adjunctive analgesics with levobupivacaine in paravertebral analgesia for breast surgery. Anaesthesia 2006;61:932-7.  Back to cited text no. 25
    
26.
Turan A, Babazade R, Kurz A, Devereaux PJ, Zimmerman NM, Hutcherson MT, et al. Clonidine does not reduce pain or opioid consumption after noncardiac surgery. Anesth Analg 2016;123:749-57.  Back to cited text no. 26
    
27.
Faria-Silva R, de Rezende DC, Ribeiro JM, Gomes TH, Oliveira BA, Pereira FM, et al. Association of clonidine and ropivacaine in brachial plexus block for shoulder arthroscopy. Braz J Anesthesiol 2016;66:335-40.  Back to cited text no. 27
    
28.
Ali QE, Manjunatha L, Amir SH, Jamil S, Quadir A. Efficacy of clonidine as an adjuvant to ropivacaine in supraclavicular brachial plexus block: A prospective study. Indian J Anaesth 2014;58:709-13.  Back to cited text no. 28
[PUBMED]  [Full text]  
29.
Singh S, Aggarwal A. A randomized controlled double-blinded prospective study of the efficacy of clonidine added to bupivacaine as compared with bupivacaine alone used in supraclavicular brachial plexus block for upper limb surgeries. Indian J Anaesth 2010;54:552-7.  Back to cited text no. 29
[PUBMED]  [Full text]  


    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]



 

Top
 
  Search
 
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

 
  In this article
    Abstract
   Introduction
    Materials and Me...
   Results and Analysis
   Discussion
   Conclusion
    References
    Article Figures
    Article Tables

 Article Access Statistics
    Viewed1064    
    Printed11    
    Emailed0    
    PDF Downloaded70    
    Comments [Add]    

Recommend this journal