Brazilian Journal of Anesthesiology
Brazilian Journal of Anesthesiology
Clinical Research

Inkk Trial – Intraoperative ketamine for perioperative pain management following total knee endoprosthetic replacement in oncology: a double-blinded randomized trial

V. Susan Paulin; Sumitra Bakshi; Prateek C. Hegde; Akansha Rathod; Ashish Gulia; Ajeeta M. Kulkarni; Vincent S. Paramanandam

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There has been a growing interest in the use of ketamine following orthopedic surgeries. We hypothesized that low dose intravenous ketamine during surgery would help in mobilization following total knee replacement (TKR) in oncology patients as assessed by the timed to up and go (TUG) test at 72 hours post-surgery. Our secondary objectives were to compare the opioid requirement at end of 72 hours, pain scores, satisfaction with pain management, adverse effects, range of joint movement achieved in the post-operative period and the functional recovery at the end of 1 month.

After ethics approval, registration of the trial with CTRI, and informed consent, this double-blinded trial was conducted. Using computer generated randomization charts, an independent team randomized the patients into ketamine group which received at induction, a ketamine bolus dose of 0.5 before the incision followed by 10 µ min-1 infusion which was maintained intraoperatively till skin closure and the saline group received an equivalent volume of saline. Postoperatively, patient controlled morphine pumps were given and the pain score with morphine usage were recorded for 72 hours. The TUG tests and range of motion were asessed by the physiotherapists until 72 hours.

Fifty-two patients were enrolled in the trial. Demographics were comparable. No significant intraoperative hemodynamic changes and post-operative adverse were noted between the groups. A decrease in the TUG test, along with decreased opioid usage with a better range of movements, was noted in the ketamine group, but this was not statistically significant. Day of discharge, patient satisfaction score, and functional recovery assessed by Oxford Knee Score (OKS) were comparable between the groups.

In conclusion, low dose intraoperative ketamine infusion does not provide clinical benefit in perioperative pain management and postoperative rehabilitation following total knee endoprosthetic replacement in oncology.


Ketamine;  Post-operative pain;  Orthopedic rehabilitation surgery;  Total knee replacement


1 H. Husted, T.H. Lunn, A. Troelsen, et al. Why still in hospital after fast-track hip and knee arthroplasty? Acta Orthop, 82 (2011), pp. 679-684

2 Korean Knee Society Guidelines for the management of post-operative pain after total knee arthroplasty Knee Surg Relat Res, 24 (2012), pp. 201-207

3 N. Patel, O. Solovyova, G. Matthews, et al. Safety and efficacy of continuous femoral nerve catheter with single shot sciatic nerve block vs epidural catheter anesthesia for same-day bilateral total knee arthroplasty J Arthroplasty, 30 (2015), pp. 330-334

4 A. Ahmed, T. Baig Incidence of lower limb motor weakness in patients receiving postoperative epidural analgesia and factors associated with it: An observational study Saudi J Anaesth, 10 (2016), p. 149

5 M. Ricardo Buenaventura, M. Rajive Adlaka, M. Nalini Sehgal Opioid complications and side effects Pain Physician, 11 (2008), pp. S105-S120

6 S. Sharma, R. Iorio, L.M. Specht, et al. Complications of femoral nerve block for total knee arthroplasty Clin Orthop Relat Res, 468 (2010), p. 135

7 J. Jouguelet-Lacoste, L. La Colla, D. Schilling, et al. The use of intravenous infusion or single dose of low-dose ketamine for postoperative analgesia: a review of the current literature Pain Med, 16 (2015), pp. 383-403

8 B. Xu, Y. Wang, C. Zeng, et al. Analgesic efficacy and safety of ketamine after total knee or hip arthroplasty: a meta-analysis of randomised placebo-controlled studies BMJ Open, 9 (2019), Article e028337

9 K. Anagnostakos, D. Kohn Megaprostheses of the knee joint Der Orthopade, 39 (2010), pp. 949-959

10 D.L. Givens, S. Eskildsen, K.E. Taylor, et al. Timed up and go test is predictive of patient-reported outcomes measurement information system physical function in patients awaiting total knee arthroplasty Arthroplasty Today, 4 (2018), pp. 505-509

11 M.J. Bade, J.M. Kittelson, W.M. Kohrt, et al. Predicting functional performance and range of motion outcomes after total knee arthroplasty Am J Phys Med Rehabil, 93 (2014), p. 579 Association of Academic Physiatrists

12 T.R. Kannan, A. Saxena, S. Bhatnagar, et al. Oral ketamine as an adjuvant to oral morphine for neuropathic pain in cancer patients J Pain Symptom Manage, 23 (2002), pp. 60-65

13 S McGrane, PP Pandharipande Sedation in the intensive care unit Miner Anestesiol, 78 (2012), pp. 369-380

14 CA Allen, JR Ivester Jr Ketamine for pain management—side effects & potential adverse events Pain Manage Nurs, 18 (2017), pp. 372-377

15 J. Dawson, R. Fitzpatrick, D. Murray, et al. Questionnaire on the perceptions of patients about total knee replacement J Bone Jt Surg Br Vol, 80 (1998), pp. 63-69

16 A. Puri Limb salvage in musculoskeletal oncology: Recent advances Indian J Plast Surg, 47 (2014), p. 175

17 WM Mihalko Arthroplasty of the knee FM Azar, JH Beaty, ST Canale (Eds.), Campbell’s operative orthopaedics (13th ed.), Elsevier, Philadelphia (2017), pp. 396-468

18 R. Oren, A. Zagury, O. Katzir, et al. Principles of rehabilitation after limb-sparing surgery for cancer Musculoskeletal cancer surgery, Springer, Dordrecht (2004), pp. 583-593

19 F. Adam, M. Chauvin, B. Du Manoir, et al. Small dose ketamine improves postoperative analgesia and rehabilitation after total knee arthroplasty Anesth Analg, 100 (2005), p. 475

20 C. Menigaux, D. Fletcher, X. Dupont, et al. The benefits of intraoperative small-dose ketamine on postoperative pain after anterior cruciate ligament repair Anesth Analg, 90 (2000), pp. 129-135

21 C. Menigaux, B. Guignard, D. Fletcher, et al. Intraoperative small-dose ketamine enhances analgesia after outpatient knee arthroscopy Anesth Analg, 93 (2001), pp. 606-612

22 A.B. Petrenko, T. Yamakura, H. Baba, et al. The role of N-methyl-D-aspartate (NMDA) receptors in pain: a review Anesth Analg, 97 (2003), pp. 1108-1116

23 R.L. Schmid, A.N. Sandler, J. Katz Use and efficacy of low-dose ketamine in the management of acute postoperative pain: a review of current techniques and outcomes Pain, 82 (1999), pp. 111-125

24 C. Aveline, J.F. Gautier, P. Vautier, et al. Postoperative analgesia and early rehabilitation after total knee replacement: a comparison of continuous low-dose intravenous ketamine versus nefopam Eur J Pain, 13 (2009), pp. 613-619

25 S.H. Kim, S. Im Kim, S.Y. Ok, et al. Opioid sparing effect of low dose ketamine in patients with intravenous patient-controlled analgesia using fentanyl after lumbar spinal fusion surgery Korean J Anesthesiol, 64 (2013), p. 524

26 P. Cengiz, D. Gokcinar, I. Karabeyoglu, et al. Intraoperative low-dose ketamine infusion reduces acute postoperative pain following total knee replacement surgery: a prospective, randomized double-blind placebo-controlled trial J Coll Physicians Surg Pak, 24 (2014), pp. 299-303

27 F. Remérand, C. Le Tendre, A. Baud, et al. The early and delayed analgesic effects of ketamine after total hip arthroplasty: a prospective, randomized, controlled, double-blind study Anesth Analg, 109 (2009), pp. 1963-1971

28 RK Parker, B Holtmann, PF White Effects of a nighttime opioid infusion with PCA therapy on patient comfort and analgesic requirements after abdominal hysterectomy Anesthesiology, 76 (1992), pp. 362-367

29 C. McAuley, M.D. Westby, A. Hoens, et al. A survey of physiotherapists’ experience using outcome measures in total hip and knee arthroplasty Physiother Can, 66 (2014), pp. 274-285

30 S. Poitras, K.S. Wood, J. Savard, et al. Predicting early clinical function after hip or knee arthroplasty Bone Jt Res, 4 (2015), pp. 145-151

31 PW Stratford, DM Kennedy Performance measures were necessary to obtain a complete picture of osteoarthritic patients J Clin Epidemiol, 59 (2006), pp. 160-167

32 G. Bacci, P. Picci, P. Ruggieri, et al. Primary chemotherapy and delayed surgery (neoadjuvant chemotherapy) for osteosarcoma of the extremities the istituto rizzoli experience in 127 patients treated preoperatively with intravenous methotrexate (high versus moderate doses) and intraarterial cisplatin Cancer, 65 (1990), pp. 2539-2553

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