|Year : 2016 | Volume
| Issue : 1 | Page : 38-42
Comparison of analgesic effect of intra-articular administration of levobupivacaine and clonidine versus ropivacaine and clonidine in day care knee arthroscopic surgery under spinal anesthesia
Sudeshna Senapati1, Anjana Basu1, Dipasri Bhattacharya1, Sunit Hazra2, Debjit Sarkar3, Partha Dandapat1
1 Department of Anaesthesiology, Critical Care Medicine and Pain, R. G. Kar Medical College, Kolkata, West Bengal, India
2 Department of Orthopaedics, Critical Care Medicine and Pain, R. G. Kar Medical College, Kolkata, West Bengal, India
3 Department of Community Medicine, Critical Care Medicine and Pain, R. G. Kar Medical College, Kolkata, West Bengal, India
|Date of Web Publication||7-Jan-2016|
Dr. Anjana Basu
46/2, Bosepukur Road, Canvas Appartment, Kolkata - 700 042, West Bengal
Source of Support: None, Conflict of Interest: None
Introduction: Intra-articular (IA) local anesthetics are often used for the management and prevention of pain after arthroscopic knee surgery. Clonidine prolongs the duration of local anesthetics. In this study, analgesic effect of intra-articular administration of levobupivacaine and clonidine was compared with ropivacaine and clonidine in knee joint arthroscopic surgery under spinal anesthesia. Method: 88 patients, aged between 15 to 55 years, ASA I and II undergoing knee arthroscopy under spinal anesthesia were assigned into two equal groups (n = 44) in a randomized double blind protocol. Patients in Group L received 10 ml of 0.50% levobupivacaine and 1 mcg/kg clonidine and Group R received 10 ml of 0.75% ropivacaine and 1 mcg/kg of clonidine through intra-articular route at the end of the procedure. In the post-operative period, pain intensity was assessed by VAS (Visual Analogue Scale) Score recorded at 1 st , 5 th , 8 th , 12 th , 18 th post-operative hours. Duration of analgesia, total rescue analgesic dose in first 18 hours and any side effects were also recorded. Result: Group L experienced significantly longer duration of effective postoperative analgesia and lesser rescue analgesic compared to group R. Group R had higher mean VAS score at 5 th and 12 th post-operative hours (P < 0.05). No side effects were observed among the groups. Conclusion: Intra-articular administration of levobupivacaine and clonidine give better post-operative pain relief by increasing duration of analgesia, and decreasing need of rescue analgesic compared to intra-articular ropivacaine and clonidine.
Keywords: Clonidine, intra-articular administration, levobupivacaine, rescue analgesic, ropivacaine
|How to cite this article:|
Senapati S, Basu A, Bhattacharya D, Hazra S, Sarkar D, Dandapat P. Comparison of analgesic effect of intra-articular administration of levobupivacaine and clonidine versus ropivacaine and clonidine in day care knee arthroscopic surgery under spinal anesthesia. Indian J Pain 2016;30:38-42
|How to cite this URL:|
Senapati S, Basu A, Bhattacharya D, Hazra S, Sarkar D, Dandapat P. Comparison of analgesic effect of intra-articular administration of levobupivacaine and clonidine versus ropivacaine and clonidine in day care knee arthroscopic surgery under spinal anesthesia. Indian J Pain [serial online] 2016 [cited 2019 Jun 24];30:38-42. Available from: http://www.indianjpain.org/text.asp?2016/30/1/38/173464
| Introduction|| |
Incidence of day care orthopedic surgery is increasing day by day as it helps rapid return of patient to normal daily life with practically no side effects or complications.
Pain is one of the most important complaints in day care surgery so its relief is to be done very effectively. Spinal anesthesia is the most convenient anesthetic technique that offers many advantages over general anesthesia, including reduced stress response, and improved postoperative pain relief but its action persists only for few hours. Spinal anesthesia with adjuvant prolongs duration of analgesia but may produce several side effects such as hypotension, bradycardia, and drowsiness which may not be ideal for day care procedures. ,
Arthroscopic knee surgery is the one of the most common minimally invasive surgical procedure in modern orthopedic setup. It is commonly performed as an outpatient procedure and is associated with variable amount of postoperative pain, which is caused by irritation of free nerve endings in synovial tissue, anterior fat pad, and joint capsule during surgical excision and resection, so intra-articular administration of local anesthetic provides good pain relief. 
In an effort to provide an effective, safe, and long lasting postarthroscopy analgesia, several studies using different drugs and regimes have been published during the last two decades including intra-articular administration of local anesthetics. ,
Levobupivacaine and ropivacaine are most commonly used newer local anesthetics.
Intra-articular clonidine with local anesthetics have been used in lower doses (1-2 mcg/kg) to reduce post-operative pain and supplemental analgesic consumption for arthroscopic knee surgery. 
Therefore, the purpose of this clinical investigation was to compare the analgesic efficacy of levobupivacaine (0.75%) with clonidine 1 mcg/kg and ropivacaine (0.5%) with clonidine 1 mcg/kg by intra-articular route following day care arthroscopic knee surgery under spinal anesthesia.
| Materials and Methods|| |
After obtaining approval from Institutional Ethics Committee and informed written consent from the patients, the study was done.
To calculate a sample size for the proposed study, 80% power and 95% confidence interval (CI) using standard deviation of the two groups the formula for two equal sized parallel groups was
Where, Zα at 95% CI = 1.96
Zβ at 80% power = 0.84
σ1 = 18.96, σ2 = 14.28
δ = expected clinically difference of 10%
Now putting the values we get
So number of people required in each group was 44.
A total of 88 adult patients were randomly allocated into the two equal groups (n = 44 in each group) using computer-generated random number list. Patients in both groups, American Society of Anesthesiologists (ASA) status I and II, aged between 15 and 55 years of both sexes with body weight of 50-70 kg undergoing elective arthroscopic knee surgery (such as meniscectomy, chondral debridement, loose body removal, diagnostic arthroscopy, lavage, and synovectomy) under spinal anesthesia were included in this study.
Patients with ASA, three or more or those having any spinal deformity with comorbidities such as hypertension, diabetes, ischemic heart disease, any contraindication to regional anesthesia, allergy to local anesthetic, preexisting neurological deficit, pregnancy, lactation, and psychiatric illness were excluded from the study.
Patients in Group L received 10 ml of 0.50% levobupivacaine and 1 mcg/kg clonidine, and Group R received 10 ml of 0.75% ropivacaine and 1 mcg/kg of clonidine.
This study was conducted in the orthopedic operation theater of R. G. Kar Medical College and Hospital, Kolkata, for 6 months.
All patients were clinically examined in the preoperative period, when whole procedure was explained. Ten centimeters visual analogue scale (VAS) (0, no pain and 10, worst pain imaginable) were also explained during the preoperative visit.
The laboratory investigations such as blood for hemoglobin, total count, differential count, erythrocyte sedimentation rate, urea, creatinine, and fasting blood sugar/postprandial blood sugar were done during preanesthetic check-up. A 12-lead electrocardiogram (ECG) and chest X-ray were also taken. Routine monitoring in the form of noninvasive blood pressure NIBP, ECG, and pulse oximetry were used perioperatively.
The anesthetic technique was standardized for all patients. Lumbar puncture was done in a sitting position at L3 and L4 intervertebral space in midline approach with 26-gauge spinal needles. 2.5 ml of 0.5% (12.5 mg) hyperbaric bupivacaine was given in the subarachnoid space and then the patient were placed in supine position immediately. After 5 min of subarachnoid injection confirming the sensory blockade (T10) arthroscopic procedure was allowed to start. During the procedure, if any patient needed further dose of analgesia that patient was excluded from the study. At the end of the surgery before the skin closure, study drug was administered through the port site in the intra-articular space by the surgeon.
Intraoperative assessment of NIBP, SPO2, Pulse, and Heart Rate were recorded immediately after anesthesia and thereafter at every 3 min interval. The intensity of pain was assessed by VAS score in immediate postoperative period and thereafter at 1 h and 5 th , 7 th , 12 th , and 18 th intraoperative postoperative period which was explained to the patients preoperatively.
Rescue analgesic was given when VAS score ≥3 or on patient demand. Our study ended at the time of discharge of the patient. Injection diclofenac sodium (75 mg intramuscular) was used as rescue analgesic. First postoperative analgesia request time, total diclofenac used in first 18 h were recorded.
All data were collected by an observer who was unaware of patients' group assignment.
Statistical analysis was done and P < 0.05 was considered to be significant.
| Results|| |
Raw data were entered into a MS Excel™ spreadsheet and analyzed using standard statistical software SPSS® statistical package version16 (SPSS Inc., Chicago, IL, USA).
There were no significant differences between the two groups with regard to demographic data such as age, sex, weight, and height [Table 1].
Time for the request of first postoperative rescue analgesia (duration of analgesia) in Group R (10.81 ± 2.02) h was shorter compared to Group L (12.42 ± 1.65) h (P < 0.05) [Table 2].
|Table 2: Mean, SD, and significance level of duration of postoperative analgesia in hours|
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Total amount of rescue analgesia requirement in first 18 h in the postoperative period was also significantly less in Group L (127.84 ± 34.61) mg compared to Group R (155.11 ± 33.92)mg (P < 0.05) [Table 3].
|Table 3: Mean, SD, and significance level of rescue analgesia required in 24 h in mg|
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The VAS score was 0 in all the groups at a 1 st postoperative hour. Compared with Group L, Group R had higher mean VAS score at 5 th , and 12 th postoperative hours [Table 4].
|Table 4: The comparison of visual analog scale score at 1 st , 5 th , 8 th , 12 th , and 18 th postoperative hours|
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Mean blood pressure variation was not significant in between the two groups in the postoperative period [Figure 1].
|Figure 1: Mean blood pressure over time in Group L and Group R, postoperatively|
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No incidence of adverse effects such as nausea, vomiting, urinary retention, itching, or sedation was observed in anyone in the study population.
| Discussion|| |
Pain control in day care arthroscopy is essential for patient comfort and early hospital discharge. Intra-articular administration of single-dose local anesthetics solutions is used to provide better analgesia after knee arthroscopy and reduce consumption and possible side effects of oral and intravenous anesthetics. 
Utilizing the peripheral receptors for postoperative pain management is an important mode of such approach. Intra-articular route of drug administration is an example for management of pain after joint surgery utilizing the peripheral receptors. It provides analgesia locally with minimal systemic side effects. ,
A variety of analgesic techniques have been used to manage postoperative pain after arthroscopic knee surgery. Lidocaine,  prilocaine,  and bupivacaine  single-dose have all been administered intra-articularly (IA) to provide intraoperative local anesthesia and postoperative analgesia. Levobupivacaine is often chosen because of its longer duration of action. Clonidine has been shown to prolong the duration of action of local anesthetics in the laboratory setting.  IA clonidine alone has recently been shown to provide effective postoperative analgesia. 
Prolonged postoperative analgesia and decreased requirement of rescue analgesia in the intra-articular drug administration may be due to a slower rate of absorption through poorly vascular intra-articular surface. 
Most of the orthopedic day care procedures are done under spinal anesthesia. Intra-articular administration of drugs at the end of surgery not only prolongs analgesia but is devoid of side effects.  So in our study we have used local anesthetics with clonidine by intra-articular route at the end of surgery.
The newer local anesthetics such as levobupivacaine and ropivacaine are devoid of systemic side effects if they are used judiciously.
Levobupivacaine is a long acting local anesthetic agent. The S-enantiomer of bupivacaine is comparatively newer local anesthetic introduced into clinical practice with less cardiac and neural toxicity but similar potency to bupivacaine. Levobupivacaine is generally as effective as bupivacaine for management of postoperative pain especially when combined with clonidine, morphine of fentanyl. The tolerability profiles of levobupivacaine and bupivacaine is very similar in clinical trials. No clinically significant ECG abnormalities or serious central nervous system events occur with the dose used.  Intra-articular administration of levobupivacaine is safe for postoperative pain relief as stated by different studies. 
Ropivacaine is a new aminoamide local anesthetic. It is prepared as the pure S-enantiomer and it blocks the peripheral afferents acting on voltage dependent Na channels. It blocks nerve fibers involved in pain transmission (A δ and C fibers) to a greater degree than those controlling motor functions ( A β fibers).  It is less cardiac and neurotoxic than other long acting local anesthetics like bupivacaine. Intra-articular administration of ropivacaine is safe. Samoladas et al. found that intra-articular ropivacaine is effective to reduce postoperative pain minimizing the use of systemic analgesia. 
Clonidine, is an imidazoline derivative with predominantly alpha two adrenergic agonist activities, is being extensively evaluated as an adjuvant to intrathecal local anesthetics and has proven to be a potent analgesic free of opioid related side effects. It is known to increase both sensory and motor blockade of local anesthetics without any clinical significant side effects. The overall effect is to decrease sympathetic activity, enhance parasympathetic tone, and reduce circulating catecholamines. Intra-articular clonidine has been used in lower doses (1-2 mcg/kg) to reduce postoperative pain and supplemental analgesic consumption for arthroscopic knee surgery  and has been utilized extensively in several ambulatory centers. Clonidine has also been added to local anesthetic drugs IA to reduce postoperative pain following arthroscopic knee surgery. 
Clonidine prolongs the duration of local anesthetics. The IA administration of clonidine (1-2 mcg/kg) has been shown to decrease postoperative pain because clonidine can enhance peripheral nerve block when added to local anesthetics. Reuben SS showed that clonidine, when administered along with bupivacaine via the IA route, results in a significant improvement in analgesia. There was an increased time to first analgesic request and a decreased need for postoperative analgesics. 
Hence, we used local anesthetics with clonidine in 1 mcg/kg for intra-articular administration in our study to observe the effectiveness of the drug in lowest possible dose to avoid any side effects if any.
In our study, time for the request of first postoperative rescue analgesia in Group R was shorter (10.81 ± 2.02) h compared to Group L (12.42 ± 1.65) h and the results were clinically, as well as statistically significant (P < 0.05). Rosen et al. found that intra-articular ropivacaine had not produced any significant change in VAS score and narcotic usage when compared with placebo.  Here, we found that levobupivacaine produced prolonged analgesia than ropivacaine when used by intra-articular route.
Total amount of mean rescue analgesia requirement in first 18 h in the postoperative period was significantly less in Group L (127.84 ± 34.61) mg compared to Group R (155.11 ± 33.92) mg, P< 0.05. It is supported by the study by Das et al.  who found that intra-articular levobupivacaine increases the duration of analgesia and decreases the need for rescue analgesic in first postoperative 24 h. 
Compared with Group L, Group R had higher mean VAS score at 5 th , 12 th postoperative hours which were also supported by the study of Kazak Bengisun et al. who found that use of levobupivacaine and bupivacaine IA produced lesser rescue analgesic consumption, lower VAS score, shorter hospital stay, and higher patient satisfaction score while compared with placebo  which conforms to our study.
| Conclusion|| |
Intra-articular levobupivacaine and clonidine increase the duration of analgesia decrease the need for rescue analgesic for the patients undergoing arthroscopic knee surgery under spinal anesthesia. So analgesic efficacy of intra-articular levobupivacaine and clonidine is superior to that of intra-articular ropivacaine and clonidine in reducing pain in day care arthroscopic procedure.
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| References|| |
Dye SF, Vaupel GL, Dye CC. Conscious neurosensory mapping of the internal structures of the human knee without intraarticular anesthesia. Am J Sports Med 1998;26:773-7.
Fortier J, Chung F, Su J. Predictive factors of unanticipated admission in ambulatory surgery: A prospective study. Anesthesiology 1996;85:A27.
Aasbø V, Raeder JC, Grøgaard B, Røise O. No additional analgesic effect of intra-articular morphine or bupivacaine compared with placebo after elective knee arthroscopy. Acta Anaesthesiol Scand 1996;40:585-8.
Marquardt HM, Razis PA. Prepacked take-home analgesia for day case surgery. Br J Nurs 1996;5:1114-8.
Das A, Majumdar S, Kundu R, Mitra T, Mukherjee A, Hajra BK, et al.
Pain relief in day care arthroscopic knee surgery: A comparison between intra-articular ropivacaine and levobupivacaine: A prospective, double-blinded, randomized controlled study. Saudi J Anaesth 2014;8:368-73.
Dahl MR, Dasta JF, Zuelzer W, McSweeney TD. Lidocaine local anesthesia for arthroscopic knee surgery. Anesth Analg 1990;71:670-4.
Eriksson E, Häggmark T, Saartok T, Sebik A, Ortengren B. Knee arthroscopy with local anesthesia in ambulatory patients. Methods, results and patient compliance. Orthopedics 1986;9:186-8.
Chirwa SS, MacLeod BA, Day B. Intraarticular bupivacaine (Marcaine) after arthroscopic meniscectomy: A randomized double-blind controlled study. Arthroscopy 1989;5:33-5.
Gaumann DM, Brunet PC, Jirounek P. Clonidine enhances the effects of lidocaine on C-fiber action potential. Anesth Analg 1992;74:719-25.
Gentili M, Juhel A, Bonnet F. Peripheral analgesic effect of intra-articular clonidine. Pain 1996;64:593-6.
Alagol A, Calpur OU, Usar PS. Intra-articular analgesia after arthroscopic knee surgery. Comparison of neostigmine, clonidine, tenoxicam, morphine and bupivacaine. Knee Surgery, Sports Traumatology. Arthroscopy 2005;13:658-63.
Foster RH, Markham A. Levobupivacaine: A review of its pharmacology and use as a local anaesthetic. Drugs 2000;59: 551-79.
Kuthiala G, Chaudhary G. Ropivacaine: A review of its pharmacology and clinical use. Indian J Anaesth 2011;55: 104-10.
Samoladas EP, Chalidis B, Fotiadis H, Terzidis I, Ntobas T, Koimtzis M. The intra-articular use of ropivacaine for the control of post knee arthroscopy pain. J Orthop Surg Res 2006;1:17.
Buerkle H, Huge V, Wolfgart M, Steinbeck J, Mertes N, Van Aken H, et al.
Intra-articular clonidine analgesia after knee arthroscopy. Eur J Anaesthesiol 2000;17:295-9.
Reuben SS, Connelly NR. Postoperative analgesia for outpatient arthroscopic knee surgery with intraarticular clonidine. Anesth Analg 1999;88:729-33.
Rosen AS, Colwell CW Jr, Pulido PA, Chaffee TL, Copp SN. A randomized controlled trial of intraarticular ropivacaine for pain management immediately following total knee arthroplasty. HSS J 2010;6:155-9.
Kazak Bengisun Z, Aysu Salviz E, Darcin K, Suer H, Ates Y. Intraarticular levobupivacaine or bupivacaine administration decreases pain scores and provides a better recovery after total knee arthroplasty. J Anesth 2010;24:694-9.
[Table 1], [Table 2], [Table 3], [Table 4]