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1 [Downloaded free from on Wednesday, July 16, 2014, IP: ] Click here to download free Android application for th ORIGINAL ARTICLE Page 233 Pain relief after Arthroscopic Knee Surgery: A comparison of intra-articular ropivacaine, fentanyl, and dexmedetomidine: A prospective, double-blinded, randomized controlled study Mohammed Babrak Manuar, Saikat Majumdar, Anjan Das 1, Bimal Kumar Hajra, Soumyadip Dutta 2, Dipankar Mukherjee, Tapobrata Mitra 3, Ratul Kundu 3 Departments of Anaesthesiology, NRS Medical College, 1 College of Medicine and Sagore Dutta Hospital, 2 Orthopedics, R.G. Kar Medical College, 3 R.M.O cum CT, B.I.N, Kolkata, West Bengal, India Address for correspondence: Dr. Anjan Das, 174, Gorakshabashi Road, Royal Plaza Apartment (4 th Floor, Flat No-1), Nagerbazar, Kolkata - 28, West Bengal, India. anjan2k8@yahoo.com A B S T R A C T Background: Postoperative pain is very common distressing symptom after any surgical procedure. Different drugs in different routes have been used for controlling post-arthroscopic pain. No one proved to be ideal. We have compared the analgesic effect of ropivacaine, fentanyl, and dexmedetomidine when administered through the intra-articular route in arthroscopic knee surgery. Materials and Methods: From March 2008 to July 2010, 99 patients undergoing arthroscopic knee surgery were randomly assigned into three groups (A,B,C) in a prospective double-blinded fashion. Group A received 10 ml of 0.75% ropivacaine, where Group B received 50 μg fentanyl, and Group C received 100 μg of dexmedetomidine through the intra-articular route at the end of procedure. Pain assessed using visual analog scale and diclofenac sodium given as rescue analgesia when VAS >4. Time of first analgesia request and total rescue analgesic used in 24 hours were calculated. Results: Demographic profiles are quite comparable among the groups. Time for requirement of first postoperative rescue analgesia in Group A was ± min, in Group B was ± min and in Group C was ± minutes. Total rescue analgesia requirement was less in Group A (1.394 ± 0.496) compared to Group B (1.758 ± 0.435) and Group C (2.546 ± 0.546). Group A had higher mean VAS score at 6 th and 24 th postoperative hours. No side effects found among the groups. Conclusion: Therefore, it suggests that intra-articular ropivacaine gives better postoperative pain relief, with increased time of first analgesic request and decreased need of total postoperative analgesia compared to fentanyl and dexmedetomidine. Key words: Dexmedetomidine, fentanyl, intra-articular, rescue analgesia, ropivacaine INTRODUCTION Postoperative arthroscopic knee surgery is the one of the most common minimally invasive surgical procedures in modern orthopedic setup. It is associated with variable amount of postoperative pain, which is caused by irritation Quick Response Code: Access this article online Website: DOI: / X of free nerve endings of synovial tissue, anterior fat pad, and joint capsule during surgical excision and resection. [1] Undoubtedly, postoperative pain has a negative impact on patient s early mobilization, rehabilitation, and psychology. This leads to prolonged hospital stay. Adequate pain relief reduces surgical stress response, so reduces patient s morbidity and improves postoperative recovery. Several analgesic strategies such as systemic medication (narcotic, NSAID), [2] central or peripheral nerve block, and intraarticular drug administration (ketorolac, [3] α 2 -agonists, [4-7] opioids, [8-12] local anesthetics [13-16] ) have been used to interrupt the pain pathway, which is called a multimodal approach. However, none is free from limitations such as needs for special equipments, monitoring, and risks of complications. Utilizing the peripheral receptors for

2 Page 234 postoperative pain management is an important mode of such an approach. The 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. Different authors in their previous studies with intraarticular ropivacaine, [17] fentanyl, [18] and dexmedetomidine [19] had proved their efficacy in providing postoperative analgesia in arthroscopic knee surgery. Ropivacaine is an amino-amide local anesthetic that blocks the peripheral afferents acting on voltage-dependent Na + channels. It is less toxic than other long-acting local anesthetics like bupivacaine. Fentanyl is a synthetic opioid most commonly used for analgesia in clinical anesthesia practice. Opioids can also elicit an analgesic effect by acting on peripheral opioid receptors. [20,21] Dexmedetomidine is highly selective (eight time more selective than clonidine), [22] specific, and potent; α 2 -adrenergic agonist has analgesic, sedative, antihypertensive, and anesthetic sparing effects when used in a systemic route. [23] Our study was carried out to compare the analgesic efficacy of ropivacaine, fentanyl, and dexmedetomidine in the intra-articular route following arthroscopic knee surgery. MATERIALS AND METHODS The study was approved by the Institutional Ethical Committee. ASA physical status I and II, aged between 18 and 60 years of both sexes undergoing elective arthroscopic knee surgery (like synovectomy, ligament reconstruction, and articular cartilage procedures) under spinal anesthesia are included in this study. Selected patients (N = 99) are randomly allocated in three groups (33 patients in each groups). Patients in Group A received 10 ml of 0.75% ropivacaine. Group B received 50 mcg of fentanyl diluted in 10 ml normal saline. Group C received 100 mcg of dexmedetomidine diluted in 10 ml of normal saline. Total volume of drug was 10 ml in each group. Exclusion criteria: Patient refusal, any known allergy or contraindication to ropivacaine, fentanyl or dexmedetomidine, pregnancy, lactating mothers and children, hepatic, renal or cardiopulmonary abnormality, alcoholism, diabetes, long-term analgesic therapy, spinal cord deformities, bleeding diathesis, local skin site infections are excluded from the study. In the preoperative assessment, the patients were enquired about any history of drug allergy, previous operations, or prolonged drug treatment. General examination, systemic examinations, and assessment of the airway were done. Preoperative fasting of minimum 6 hours was ensured before operation in all day care cases. All patients received premedication of tablet diazepam 10 mg orally the night before surgery as per preanesthetic check up direction to allay anxiety, apprehension, and for sound sleep. The patients also received tablet ranitidine 150 mg with sips of water in the previous night and in the morning of operation. All patients were clinically examined in the preoperative period, when whole procedure was explained and written consent obtained. A 10 cm visual analog scale (VAS) (0, no pain and 10, worst pain imaginable) was also explained during preoperative visit. All patients were investigated for Hb%, TLC, DLC, ESR, platelet count, blood sugar, blood urea, serum creatinine, and liver function tests. A 12-lead ECG and chest X-ray were also taken. On entering the patient in the operative room, standard intraoperative monitors like ECG, pulse oxymeter, non-invasive blood pressure were attached and baseline parameters were recorded. Philips IntelliVue MP20 monitor was used for this purpose. The anesthetic technique was standardized for all patients. Lumber puncture was done in sitting position at L3 and L4 inter-vertebral space in median approach with 25-Gauge spinal needle. Then maintaining sitting position, 3 ml of 0.5% hyperbaric Bupivacaine was given in subarachnoid space and the patient was placed in the supine position immediately. After 5 minutes of subarachnoid injection, arthroscopic procedure is allowed to start confirming of block. During the procedure if any patient needed further dose of analgesia, that patient was excluded from the study. At the end of surgery before skin closure, the study drug was administered by the surgeon through the port site in the intra-articular space. Tourniquet was kept inflated for another 20 minutes. Drain put by the surgeon was clamped before administering the study drug and remained clamped for another 20 minutes. HR, NIBP, RR, SPO 2, ECG, and pain VAS will be recorded at 1 st, 2 nd, 4 th, 6 th, 12 th, and 24 th postoperative hours. Injection diclofenac sodium (75 mg IM) was given as rescue analgesia if the pain VAS >4. First postoperative analgesia request time, total diclofenac used in first 24 hours were recorded. All data will be collected by an observer who is unaware of patients group assignment. Statistical analysis: Sample size was estimated using time of first analgesic request as the main primary variable. On the basis of previous study, assuming within group SD of 40 minutes and the true difference in mean time to requirement of first dose rescue analgesic to be 30 minutes, we needed to study 33 experimental subjects per group to be able to reject the null hypothesis that the population means of the groups are equal with probability (power) Raw Vol. 8, Issue 2, April-June 2014 Saudi Journal of Anesthesia

3 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). Categorical variables were analyzed using the Pearson s chi square test. Normally distributed continuous variables were analyzed using the one-way ANOVA followed by the Boneferroni test and P < 0.05 was considered statistically significant. RESULTS There were no significant differences between the three groups with regard to demographic data such as age, sex, weight, height, and duration of surgery [Tables 1 and 2]. A majority of the patient had undergone repair of the anterior cruciate ligament. Time for the request of first postoperative rescue analgesia in Group A [ ± minutes] was longer compared to Group B [ ± minutes] and Group C [ ± minutes] (P < 0.05) [Table 3 and Figure 1]. The total number of rescue analgesia requirement in first 24 hours in postoperative period was also less in Group A [1.394 ± 0.496] compared to Group B [1.758 ± 0.435] and Group C [2.546 ± 0.506)] (P > 0.05) [Table 4 and Figure 2]. The VAS score was 0 in all the groups at first postoperative hour. Compared with Group B and Group C, Group A had higher mean VAS score at 6 th and 24 th postoperative hours [Figure 3]. No incidence of adverse effects like nausea, vomiting, urinary retention, itching, or sedation was observed in any one in the study population. DISCUSSION Arthroscopic surgery is associated with variable amount of postoperative pain. The intra-articular route of drug administration has an important role to provide postoperative analgesia after the arthroscopic procedure. Different authors in their study have proved the analgesic efficacy of intra-articular ropivacaine, fentanyl, and dexmedetomidine after an arthroscopic procedure. Better time of postoperative analgesia and decreased requirement of rescue analgesia in intra-articular drug administration may be due to slower rate of absorption through poorly vascular intra-articular surface. In our prospective doubleblinded randomized comparative study, we have compared the analgesic efficacy of intra-articular ropivacaine, fentanyl, and dexmedetomidine following arthroscopic knee surgery. Ropivacaine is a commonly used local anesthetic and it is related structurally to bupivacaine. It is less lipid soluble than bupivacaine, but its pharmacokinetic deposition is similar. Ropivacaine seemed to provide similar and effective post-arthroscopy analgesia compared to bupivacaine, Table 1: Comparison of demographic data among the study groups Age A (Ropivacaine) B (Fentanyl) C (Dexmedetomidine) Body A (Ropivacaine) weight B (Fentanyl) C (Dexmedetomidine) Height A (Ropivacaine) B (Fentanyl) C (Dexmedetomidine) Duration A (Ropivacaine) of surgery B (Fentanyl) C (Dexmedetomidine) Table 2: Comparison of demographic sex distribution among the study groups Groups Percentage of either sex A (Ropivacaine) 90.1% (M) [30] % (F) [3] Sex B (Fentanyl) 84.8% (M) [28] 15.2% (F) [5] C (Dexmedetomidine) 93.9% (M) [31] 6.1% (F) [2] Table 3: Showing mean, standard, and significance of duration of postoperative analgesia in minutes Request of 1 st analgesia at A B C showing less CNS and cardiac toxicity. [24] Samoladas et al. (2006) found that intra-articular ropivacaine is effective to reduce postoperative pain minimizing the use of systemic analgesia. [17] This study also stated that intraarticular injection of local anesthetic seems to provide an alternative and effective solution in pain control after knee arthroscopy. Fentanyl is a synthetic opioid commonly used now a days by anesthetics through systemic for analgesia. The understanding that opioids can elicit analgesic effects by acting on peripheral opioid receptors has led to their experimentation in controlled clinical trials. [20,21] The most favorable results have emerged from studies of Page 235

4 Page 236 Figure 1: Showing time of 1 st postoperative analgesia request in Group A (Ropivacaine), Group B (Fentanyl) and Group C (Dexmedetomidine). Figure 2: Showing total number of rescue analgesia in 1 st post operative 24 hours in Group A (Ropivacaine), Group B (Fentanyl) and Group C (Dexmedetomidine). Figure 3: Showing the comparison of VAS score at 1 st, 2 nd, 4 th, 6 th, 12 th and 24 th post operative hours in Group A (Ropivacaine), Group B (Fentanyl) and Group C (Dexmedetomidine). Table 4: Showing mean, standard, and significance of total no of rescue analgesia in first post operative 24 hours Total rescue analgesia A B C intra-articular administration of small systemically inactive doses of narcotic during arthroscopic knee surgery. Mondal et al. (2002) reported that intra-articular fentanyl provides prolonged postoperative analgesia following arthroscopic knee surgery. [18] They found that 50 μ fentanyl provides mean of hours postoperative analgesia. But in that study, a majority of procedure was diagnostic arthroscopy. The analgesic effects of α 2 -adenergic agonist could be mediated through supraspinal, spinal, and peripheral action. [25] In our study, the analgesic effect of intra-articular dexmedetomidine appears mainly due to a direct local action. However, a central analgesic effect resulting from systemic absorption cannot be excluded. The mechanism by which dexmedetomidine mediates intra-articular analgesia is not clearly defined. However, the mechanism of analgesic effects for intra-articular dexmedetomidine might be similar to those suggested for intra-articular clonidine. Clonidine may act on presynaptic α 2 -adrenergic receptors and inhibit the release of norepinephrine at peripheral afferent nociceptors. [26] Clonidine has also been shown to provide a local anesthetic effect which inhibits the conduction of nerve signals through C and Aδ fibers [27] and may stimulate the release of enkephalin-like substances at peripheral sites. [28] Al-Metwalli et al. (2008) found that intra-articular dexmedetomidine enhanced postoperative analgesia after arthroscopic knee surgery, with an increased time to first analgesic request and a decrease need for postoperative analgesia. [19] Here intra-articular dexmedetomidine provides mean postoperative analgesia for 6 hours in arthroscopic partial meniscectomy. Demographic profile parameters mainly age, sex, weight, height and duration of surgery are comparable among the groups. Time for requirement of first postoperative rescue analgesia in Group A was ± min, in Group B was ± min, and in Group C was ± min [Table 3 and Figure 1]. Total rescue analgesia requirement was less in Group A [1.394 ± 0.496] compared to Group B [1.758 ± 0.435] and Group C [2.546 ± 0.546] [Table 4 and Figure 2]. Group A had higher mean VAS score at 6 th and 24 th postoperative hours [Figure 3]. No side effects were found among the groups. It was clearly found that analgesic efficacy of intra-articular ropivacaine is superior to fentanyl and dexmedetomidine. Vol. 8, Issue 2, April-June 2014 Saudi Journal of Anesthesia

5 Intra-articular fentanyl showed moderate efficacy and intra-articular dexmedetomidine showed least efficacy in comparison to other. Further clinical studies can be performed to develop a more reliable and clinically efficient regime. This is so that this regime may be used as a component of a multimodal approach of postoperative analgesia. Further studies are also required to define the optimal analgesic dose of intra-articular ropivacaine after an arthroscopic procedure. A limitation of our study is that we did not follow up the patients whether any local tissue damage occurred or not in intra-articular space due to study drugs. CONCLUSSION Intra-articular ropivacaine increases the duration of analgesia and decreases need of rescue analgesic in first postoperative 24 hours. So intra-articular ropivacaine shows superior analgesic efficacy when compared with intra-articular fentanyl and dexmedetomidine following arthroscopic knee surgery. REFERENCES 1. Dye SF, Vaupel GL, Dye CC. 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Eur J Pharmacol 1988;146: How to cite this article: Manuar MB, Majumdar S, Das A, Hajra BK, Dutta S, Mukherjee D, et al. Pain relief after Arthroscopic Knee Surgery: A comparison of intra-articular ropivacaine, fentanyl, and dexmedetomidine: A prospective, double-blinded, randomized controlled study. Saudi J Anaesth 2014;8: Source of Support: Nil, Conflict of Interest: None declared. Page 237