Anesthesia: Essays and Researches

ORIGINAL ARTICLE
Year
: 2020  |  Volume : 14  |  Issue : 4  |  Page : 550--554

A comparative study of periarticular infiltration with dexmedetomidine versus ketorolac as an additive to ropivacaine after total knee arthroplasty: A prospective, randomized double-blind study


Sapna Annaji Nikhar1, Monu Yadav1, Shashi Damera1, Lalith Mohan2, V Jyotsna Ch1, Gopinath Ramachandran3,  
1 Department of Anaesthesiology and Intensive Care, Nizam's Institute of Medical Sciences, Hyderabad, Telangana, India
2 Department of Orthopedics, Nizam's Institute of Medical Sciences, Hyderabad, Telangana, India
3 Department of Anesthesiology, ESIC Medical College and Hospital, Sanath Nagar, Hyderabad, Telangana, India

Correspondence Address:
Dr. Sapna Annaji Nikhar
Department of Anaesthesiology and Intensive Care, Nizam's Institute of Medical Sciences, Hyderabad - 500 082, Telangana
India

Abstract

Background: Periarticular infiltration (PAI) analgesia has been found to be an effective analgesia modality after total knee arthroplasty (TKA). Dexmedetomidine has many beneficial effects on postoperative analgesia by different routes, but studies on PAI are lagging. Aims and Objectives: In this study, we compared postoperative analgesia after PAI with dexmedetomidine versus ketorolac as an additive to ropivacaine after TKA. Setting and Design: This is a prospective, randomized, double-blind study conducted on 75 patients belonging to American Society of Anesthesiologists I to III, undergoing total knee arthroplasty, of either gender, belonging to American Society of Anesthesiologists I to III. Materials and Methods: After institutional ethics committee approval and written informed consent, patients were randomly allocated into three groups. Group C (n = 25) received cocktail of 60 mL ropivacaine (0.25%) infiltration with adrenaline 5 mL (0.1 mg.mL−1), Group D (n = 25) received additive dexmedetomidine 1 ug.kg−1 to above cocktail, and Group K (n = 25) received ketorolac 30 mg. Postoperatively pain by Visual Analog Scale, vitals, total duration of analgesia, need for rescue analgesia, sedation, patient satisfaction, mobilization time, and complications were recorded. Statistical Analysis: The Statistical Package for the Social Sciences version 20 was used for statistical analysis. Analysis of variance has been used to find the significance of study parameters between the three groups of patients. P < 0.05 was considered statistically significant. Results: Postoperative pain score was lesser in the ketorolac group (1.52 ± 0.71, P = 0.001) than the other two groups. Duration of analgesia was more with ketorolac (343.00 ± 144.45, P < 0.001) compared with the other two groups, and epidural activation timings (462 ± 235.84) were significantly delayed in Group K compared to Group C and Group D. There was no significant difference in mobilization time, patient satisfaction, and complications between the three groups. Conclusion: Ketorolac was a better additive to ropivacaine than dexmedetomidine for postoperative analgesia after TKA.



How to cite this article:
Nikhar SA, Yadav M, Damera S, Mohan L, Ch V J, Ramachandran G. A comparative study of periarticular infiltration with dexmedetomidine versus ketorolac as an additive to ropivacaine after total knee arthroplasty: A prospective, randomized double-blind study.Anesth Essays Res 2020;14:550-554


How to cite this URL:
Nikhar SA, Yadav M, Damera S, Mohan L, Ch V J, Ramachandran G. A comparative study of periarticular infiltration with dexmedetomidine versus ketorolac as an additive to ropivacaine after total knee arthroplasty: A prospective, randomized double-blind study. Anesth Essays Res [serial online] 2020 [cited 2021 Jun 13 ];14:550-554
Available from: https://www.aeronline.org/text.asp?2020/14/4/550/316970


Full Text

 Introduction



Pain relief after total knee replacement is always a main concern of the anesthesiologist. Insufficient pain control after total knee arthroplasty (TKA) may result in less patient satisfaction, insomnia, delayed mobilization, and difficulty with rehabilitation. Multimodal analgesia is considered as the choice for pain relief after surgery including periarticular infiltration (PAI) and peripheral nerve blocks.[1] Peripheral nerve block consists of femoral nerve block and adductor canal block. Femoral nerve block is associated with quadriceps weakness leading to delayed mobility while adductor canal block has a better motor function.[2] The combination adductor canal block with PAI had better pain scores and decreased opioid consumption.[3] PAI analgesia has been found to be effective for postoperative analgesia with better patient satisfaction compared to other analgesic techniques.[4] The previous studies proved that local infiltration with ketorolac results in reduced morphine consumption, reduced pain intensity, and earlier readiness for hospital discharge.[5] Dexmedetomidine has been proved as a good analgesic for arthroscopic surgeries.[6] The effectiveness of dexmedetomidine for TKA is lacking. With the same concept, an experimental prospective randomized double-blind study was conducted to evaluate the analgesic efficacy of PAI of cocktail of dexmedetomidine versus ketorolac as an additive to ropivacaine in patients undergoing TKA.

 Materials and Methods



After institutional ethics committee approval, written and informed consent was obtained from all patients and their relatives. A power analysis was performed using a power of 90% and a level of significance at 5%. We assumed that the minimum difference of pain scores at rest (primary outcome of the study) was 20% and standard deviation (SD) 20%. The sample size was calculated to be 22 patients, so we decided to include 25 patients in each group in the study (sample size – 75). All patients with age between 18 and 65 years, of either gender, or belonging to American Society of Anesthesiologists (ASA) physical status I, II, and III were included in the study. They were all explained about the nature of the study, procedure, mode of anesthesia, postoperative pain relief that will be provided, and the patient's participation in evaluating the duration of postoperative analgesia. All the patients were familiarized with the Visual Analog Scale (VAS) in their native language. Patients with history of infection and malignant disease, cardiac disease (receiving beta-blockers, calcium channel blockers, or α-methyldopa), coagulopathy, hepatic or kidney dysfunction, using any analgesics within 24-h period preceding the study, or with previous history of allergic reactions any of the relevant drugs were excluded from the study.

All patients received oral tablet alprazolam 0.25 mg at night before operation. The patients were reassessed and reassured in the preoperative room. Preoperative monitoring included baseline heart rate, blood pressure, and oxygen saturation. After securing intravenous (i.v.) line, ringer lactate was used as a fluid of choice. Under all aseptic and antiseptic precautions, combined spinal-epidural anesthesia was given. Subarachnoid block was achieved with injection bupivacaine 0.5% (heavy) 2.5 mL in the sitting position using a 27G Quincke spinal needle positioned at the L2–L3 or L3–L4 interspace using a needle through needle technique. An epidural catheter was fixed at 11–12 cm. Patients were immediately turned to the supine position. The onset and level of sensory and motor block were recorded. Sensory level was checked after 2–3 min with pinprick method and achieved between T8 and T10 segment. The pneumatic thigh tourniquet was applied on the lower limb to be operated with inflation pressure 250–350 mmHg during surgery. Intraoperative monitoring included blood pressure, heart rate and oxygen saturation, end-tidal CO2, electrocardiography, and respiratory rate till completion of surgery. Cases with failed spinal or epidural that was activated in view of pain were not included in the study.

This study adhered to CONSORT guidelines (http://www.consort-statement.org). At the completion of the surgery, these patients were randomly allocated into three groups: Group C (n = 25) received cocktail of 60 mL ropivacaine (0.25%) infiltration with adrenaline 5 mL (0.1 mg.mL − 1), Group D (n = 25) received cocktail of dexmedetomidine 1 ug.kg−1 in 60 mL (0.25%) ropivacaine with adrenaline 5 mL (0.1 mg.mL−1), and Group K (n = 25) received ketorolac 30 mg (1 amp) in 60 mL (0.25%) ropivacaine with adrenaline 5 mL (0.1 mg.mL−1) periarticularly in an aseptic manner by the operating surgeon through the trocar. Randomization was done using computer-generated random numbers. Tourniquet was deflated after 10 min of PAI of drug of all the groups, and compression bandage was applied. Neither the surgeon and the anesthesiologist nor the anesthesiologist looking after the patient postoperatively was aware of the randomization sequence or the content of the injected drugs. Patients were monitored in the postoperative care unit for pulse, respiratory rate, temperature, and blood pressure. Postoperative pain which was assessed by VAS was taken as primary outcome and recordings done 2 hourly for 24 h. When VAS was ≥4, the time was noted and rescue analgesia in the form of injection paracetamol 1 g iintravenously was given then the epidural was activated if VAS persisted to be ≥4. Few patients were given epidural top-ups of ropivacaine 0.125% 5 mL over 10 min if VAS score more than 4 persisted after activation and considered as a part of rescue analgesia. Record of need of rescue drugs was done. Total duration of analgesia was calculated from the time of deposition of the study drug to the first requirement of rescue analgesic. The efficacy of the drug was determined by improvement in VAS score, duration of analgesia, and total number of rescue analgesics during 24 h in postoperative period. Sedation, patient satisfaction, and time of mobilization were also noted. Sedation was assessed using modified Wilson sedation scale: 1 = fully awake and oriented, 2 = drowsy, 3 = eyes closed but arousable to command, 4 = eyes closed but arousable to mild physical stimulation (earlobe tug), and 5 = eyes closed and unarousable to mild physical stimulation.[7] The patients were also monitored for complications related to drug or the procedure such as hypotension, bradycardia, respiratory depression, convulsions, nausea, vomiting, and paresthesia, treated appropriately.

Statistical analysis

Statistical analysis was done using the Statistical Package for the Social Sciences version 20. Descriptive statistics were expressed as mean ± SD unless otherwise stated. Analysis of variance (ANOVA) has been used to find the significance of study parameters between the three groups of patients. If ANOVA test is significant, further pairwise comparison between the groups was carried by Tukey's test. Chi-square/Fisher's exact test has been used to find the significance of study parameters on categorical scale between two or more groups, nonparametric setting for qualitative data analysis. P < 0.05 was considered statistically significant.

 Results



Seventy-five patients of age between 18 and 65 years were included in the study. [Figure 1] shows a flowchart of participants in the study. Out of 75 patients analyzed with 25 in each group, there was no difference in age (P = 0.200), gender (P = 0.946), body mass index (BMI) (P = 0.969), and ASA distribution (P = 0.145) in the three groups. The mean values of age, weight, height, and BMI are given in [Table 1]. Totally 27 (36%) patients were of ASA 1 class and 42 (56%) were belonging to ASA II class while 6 patients (8.0%) were of ASA III. ASA distribution in different groups is given in [Table 1]. Out of 25 patients in Group K, 7 (28%) had hypertension, 3 (12%) were diabetic, and 5 (20%) were both hypertensive and diabetic. In Group D, 11 (44%) were hypertensive, 7 (28%) were both hypertensive and diabetic, and 1 (4%) had only diabetes. In Group C, 6 (24%) had hypertension, 2 (8%) were diabetic, and 6 (24%) were both diabetic and hypertensive (P = 0.704). Duration of surgery was not significant in the three groups (P = 0.09){Table 1}.{Figure 1}

Postoperative pain scores (VAS scores) were significantly less in Group K as compared to Group D and Group C almost for 12 h. VAS scores were significantly different at 24 h [Figure 2]. Duration of analgesia was significantly prolonged in Group K (343 ± 144.4) compared to Group C (230 ± 87.7) and was less in Group D (150 ± 54.22) with P < 0.001. The epidural activation timings (462 ± 235.84) were significantly delayed in Group K compared to Group C (273 ± 108) and earlier in Group D (248 ± 124) with P value of 0.001 [Table 2]. Pairwise comparison for duration of analgesia and timing of epidural activation is given in [Table 3]. Although the difference in need of the rescue analgesia was not significant (0.363) in the three groups, epidural top-ups were needed in 3 patients (12%) in Group K, 6 patients (24%) in Group C, while 18 patients (72%) in Group D after activation of epidural catheter (P < 0.001). Mobilization of patients after 24 h was not statistically significant in the three groups (P = 0.370), and patient satisfaction was also not statistically significant (P = 0.500).{Figure 2}{Table 2}{Table 3}

There was no significantly significant difference with respect to heart rate in the three groups. However, the mean arterial pressure readings were showing a statistically significant difference in Group D from Groups K and C. Although readings in Group D were statistically lower than the rest two groups at maximum hours of measurement, the mean arterial pressure (MAP) was above 70 mmHg requiring no treatment.

No major complications were noted in any group such as hypotension, bradycardia, respiratory depression, seizures, nausea, vomiting, and paresthesias (P = 0.544). There was no significant difference in sedation scores in three groups at studied time intervals. Maximum sedation score noted was 3 and no over sedation identified in any of the groups. Maximum sedation score was in Group D though it was in 2 and 3 grades.

 Discussion



The present study demonstrated that the PAI of ketorolac with adrenaline and ropivacaine is safe and effective in reducing postoperative pain scores and overall need of rescue analgesia in the form epidural top-ups was less. Postknee arthroplasty pain management has become a challenge to the anesthesiologist, and various techniques are used to have pain-free postoperative period. Femoral nerve blocks are commonly used to decrease postoperative pain from TKA but not effective completely and have many complications.[8],[9] Hence, multimodal analgesia still remains the modality of choice for postoperative pain management including epidural, PAI, peripheral nerve blocks, and systemic opioids.[1],[10],[11] Systemic opioid use is associated with pruritus, nausea, and vomiting while epidural analgesia can cause hypotension and urinary retention.[3] Among the entire techniques, available PAI and adductor canal block are effective modalities.[3] For PAI, local anesthetics (LAs) along with opioids, ketorolac, or many others are infiltrated in tissues and muscles around joint.[12] The precautionary four steps are followed to have a maximal effect and least side effects.[13]

Previous studies have proved that dexmedetomidine is an effective adjuvant to epidural bupivacaine for postoperative analgesia after TKA through reducing the amount of local anesthetic.[14] Dexmedetomidine as an adjuvant in cocktail for PAI has never been studied. Various “cocktails” have been suggested for the local injections. Most include a long-acting local anesthetic along with epinephrine and other additives such as opioids or ketorolac, corticosteroids, and various antibiotics.[15],[16] Local infiltration analgesia (LIA) was associated with better pain relief with a comparable complication rate for patients undergoing TKA than femoral nerve block.[14] Hence, LIA is recommended for pain relief after TKA. The efficacy of several ingredients in a periarticular “cocktail” ropivacaine, epinephrine, ketorolac, and clonidine had shown that, overall, patient pain control was highest and functional outcome was enhanced when all four of the ingredients were combined.[17] When a periarticular injection of liposomal bupivacaine is used in conjunction with a multimodal pain pathway, rapid recovery is possible, and selected patients are able to undergo outpatient TKA.[18] A recent prospective study of 1000 total joint arthroplasties utilizing the long-acting liposomal bupivacaine, as part of a multimodal analgesic protocol, compared to a 1000 patient control group demonstrated improved patient-reported pain scores, increased “pain-free” patients, decreased length of stay, decreased falls, and decreased overall costs with the long-acting analgesic.[19] In a double-blind study, liposomal bupivacaine showed a favorable dose response and statistically significantly greater analgesia with lower NRS scores compared to a bupivacaine. Liposomal bupivacaine is designed to provide prolonged postsurgical analgesia through diffusion.[20] But even PAI of LA agents leads to reduction in pain scores. Similar results were found in our study, with less pain scores even in the ropivacaine group though addition of adjuvants had added advantage. One more study found that patients who received a periarticular injection containing ropivacaine, ketorolac, epimorphine, and epinephrine used less patient-controlled analgesia at 6, 12, and 24 h after surgery and had lower pain scores in the postanesthetic care unit and at 4 h after the operation.[21] Our study also gave us similar results that PAI of cocktail leads to decrease in pain scores and caused reduction in requirement of rescue analgesics in the form of epidural top-ups. Specifically, ketorolac with ropivacaine and adrenaline had a better VAS score and hemodynamic was also maintained.

Dexmedetomidine is a highly selective alpha (α)-2 adrenergic agonist. It binds an alpha-2 receptor up to eight times more than clonidine.[22] Peripheral analgesic effects of dexmedetomidine which enhances the LA effect are mediated by α 2A-AR binding. Systemically, it has sedative, anxiolytic, analgesic, anesthetic-sparing, and sympatholytic effects.[23],[24] Direct intra-articular administration of dexmedetomidine 1 ug.kg−1 as an adjuvant to LA enhances the postoperative analgesia and decreases the need of analgesics after arthroscopic knee surgery.[6],[22],[25] Careful attention to the infiltration method is necessary to prevent leaching from the soft tissues, and care should be taken to avoid intravascular injection. The proper concentration of the PAI in the areas of the knee with increased innervation, dosage of the drug, and compression bandage post-surgery are necessary to maximize benefits from periarticular injection, and can aid in improving postoperative pain control in TKA.[13],[26] There needs to be enough concentration in the areas of the knee with increased innervation to maximize benefits from periarticular injection and can aid in improving postoperative pain control in TKA.[26] The explanation for less efficiency of dexmedetomidine for PAI analgesia could be not placing intra-articular catheter as the surgeon does not prefer to place intra-articular catheter and other explanation could be an insufficient dose. Although 1 ug.kg−1 is effective along with LA for arthroscopic surgeries, the same may not be true as the joint has been replaced by an artificial one and receptors or areas for drug to act are less.[22] Hence, along with proper infiltration or technique, dose also matters.[13]

Still, PAI if combined with epidural infusion can be an efficient modality for the management of postknee arthroplasty pain. This leads to a reduction in the use of systemic analgesic and consecutively decreases side effects and also effective analgesia adds to early mobilization and early recovery.

 Conclusion



PAI is an effective method of analgesia after TKA. PAI of ketorolac with ropivacaine and adrenaline provides effective postoperative analgesia and decreases postoperative analgesic requirements as compared to dexmedetomidine and only ropivacaine infiltration. The limitation of this study is that serum concentration of dexmedetomidine has not been measured to show its less efficiency.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1Milani P, Castelli P, Sola M, Invernizzi M, Massazza G, Cisari C. Multimodal analgesia in total knee arthroplasty: A randomized, double-blind, controlled trial on additional efficacy of periarticular anesthesia. J Arthroplasty 2015;30:2038-42.
2Elkassabany NM, Antosh S, Ahmed M, Nelson C, Israelite C, Badiola I, et al. The risk of falls after total knee arthroplasty with the use of a femoral nerve block versus an adductor canal block: A double-blinded randomized controlled study. Anesth Analg 2016;122:1696-703.
3Ren Y, Liao J, Qin X, Yang J. Adductor canal block with periarticular infiltration versus periarticular infiltration alone after total knee arthroplasty: A randomized controlled trial protocol. Medicine (Baltimore) 2020;99:20.
4Sadigursky D, Simões DP, Albuquerque RA, Silva MZ, Fernandes RJ, Colavolpe PO. Local periarticular analgesia in total knee arthroplasty. Acta Ortop Bras 2017;25:81-4.
5Andersen KV, Nikolajsen L, Haraldsted V, Odgaard A, Søballe K. Local infiltration analgesia for total knee arthroplasty: Should ketorolac be added? Br J Anaesth 2013;20:1-7.
6Tarlika P, Dalwadi D, Thakkar K, Singh P. Effectiveness of intra-articular dexmedetomidine as postoperative analgesia in arthroscopic knee surgery (A comparative study). IOSR J Pharm 2015;7:18-27.
7Mária N, Leonardo P, Pamela G, Thomas JJ. Assessing sedation with regional anesthesia: Inter-rater agreement on a modified Wilson sedation scale. Anesth Analg 2002;94:723-8.
8Zhang Z, Wang Y, Liu Y. Effectiveness of continuous adductor canal block versus continuous femoral nerve block in patients with total knee arthroplasty: A PRISMA guided systematic review and meta-analysis. Medicine (Baltimore) 2019;98:e18056.
9Tan Z, Kang P, Pei F, Shen B, Zhou Z, Yang J. A comparison of adductor canal block and femoral nerve block after total-knee arthroplasty regarding analgesic effect, effectiveness of early rehabilitation, and lateral knee pain relief in the early stage. Medicine (Baltimore) 2018;97:e13391.
10Nakai T, Tamaki M, Nakamura T, Nakai T, Onishi A, Hashimoto K. Controlling pain after total knee arthroplasty using a multimodal protocol with local periarticular injections. J Orthop 2013;10:92-4.
11Teng WN, Su YP, Kuo IT, Lin SM, Tsou MY, Chan KH, et al. Patient controlled epidural analgesia for bilateral versus unilateral total knee arthroplasty: A retrospective study of pain control. J Chin Med Assoc 2012;75:114-20.
12Sawhney M, Mehdian H, Kashin B, Ip G, Bent M, Choy J, et al. Pain after unilateral total knee arthroplasty: A prospective randomized controlled trial examining the analgesic effectiveness of a combined adductor canal peripheral nerve block with periarticular infiltration versus adductor canal nerve block alone versus periarticular infiltration alone. Anesth Analg 2016;122:2040-6.
13Ramamoorthy KG. Local infiltration analgesia following total knee arthroplasty. Indian J Anaesth 2012;56:208-9.
14Eskandr AM, Ebeid AM. A dose reduction study of local anesthetic with addition of dexmedetomidine on postoperative epidural analgesia after total knee arthroplasty. Egypt J Anaesth 2016;32:365-9.
15Kurosaka K, Tsukada S, Seino D, Morooka T, Nakayama H, Yoshiya S. Local infiltration analgesia versus continuous femoral nerve block in pain relief after total knee arthroplasty: A randomized controlled trial. J Arthroplasty 2016;2:23-5.
16Tsukada S, Wakui M, Hoshino A. Postoperative epidural analgesia compared with intraoperative periarticular injection for pain control following total knee arthroplasty under spinal anesthesia: A randomized controlled trial. J Bone Joint Surg Am 2014;96:1433-8.
17Kelley TC, Adams MJ, Mulliken BD, Dalury DF. Efficacy of multimodal perioperative analgesia protocol with periarticular medication injection in total knee arthroplasty: A randomized, double-blinded study. J Arthroplasty 2013;28:1274-7.
18Berger RA, Kusuma SK, Sanders SA, Thill ES, Sporer SM. The feasibility and perioperative complications of outpatient knee arthroplasty. Clin Orthop Relat Res 2009;467:1443-9.
19Barrington JW, Emerson RH. Liposomal Bupivacaine: A case control study of the first, 000 cases in a new total knee arthroplasty era. Orthop Clin North Am 2015;46:469-77.
20Bramlett K, Onel E, Viscusi ER, Jones K. A randomized, double-blind, dose-ranging study comparing wound infiltration of DepoFoam bupivacaine, an extended-release liposomal bupivacaine, to bupivacaine HCl for postsurgical analgesia in total knee arthroplasty. Knee 2012;19:530-6.
21Busch CA, Shore BJ, Bhandari R, Ganapathy S, MacDonald SJ, Bourne RB, et al. Efficacy of periarticular multimodal drug injectionin total knee arthroplasty. A randomized trial. J Bone Joint Surg Am 2006;88:959-63.
22Nasr HM, Metwalli OS, Amer GF, Abotaleb UI. Intraarticular Magnesium versus Dexmedetomidine for postoperative analgesia after knee arthroscopic menisectomy. JSEMP 2012;30:1-6.
23Grewal A. Dexmedetomidine: New avenues. J Anaesthesiol Clin Pharmacol 2011;27:297-302.
24Paul S, Bhattacharjee DP, Ghosh S, Dawn S, Chatterjee N. Efficacy of intra-articular dexmedetomidine for postoperative analgesia in arthroscopic knee surgery. Ceylon Med J 2010;55:111-5.
25Al-Metwalli RR, Mowafi HA, Ismail SA, Siddiqui AK, Al-Ghamdi AM, Shafi MA, et al. Effect of intraarticular Dexmedetomidine on postoperative analgesia after arthrosopic knee surgery. Br J Anaesth 2008;101:395-9.
26Guild GN 3rd, Galindo RP, Marino J, Cushner FD, Scuderi GR. Peri-Articular regional analgesia in total knee arthroplasty. A review of the neuroanatomy and injection technique. Ann Orthop Rheumatol 2014;2:1025.