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A Multimodal Analgesia Protocol for Total Knee ArthroplastyA Randomized, Controlled Study
Pascal-André Vendittoli, MD, FRCS(C); Patrice Makinen, MD; Pierre Drolet, MD, FRCPC; Martin Lavigne, MD, FRCS(C); Michel Fallaha, MD, FRCS(C); Marie-Claude Guertin, PhD; France Varin, BPharm, PhD
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Orthopaedic Surgery Unit, Department of Surgery (P.-A.V.,P.M., M.L., and M.F.), and Department of Anaesthesia (P.D.),Maisonneuve-Rosemont Hospital, 5345 boul l'Assomption, Suite 55, Montreal, H1T4B3 QC, Canada. E-mail address for P.-A. Vendittoli:pa.vendittoli@sympatico.ca
Montreal Heart Institute, 5000 Belanger Street, Montreal, H1T 1C8 QC,Canada
University of Montreal, C.P. 6128 Succursale Centre-ville, Montreal, H3C 3J7QC, Canada
Investigation performed at Maisonneuve-Rosemont Hospital, Montreal, Quebec, Canada

Copyright © 2006 by The Journal of Bone and Joint Surgery, Inc.
J Bone Joint Surg Am, 2006 Feb 01;88(2):282-289. doi: 10.2106/JBJS.E.00173
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This article was updated on February 1, 2012, because of a previous error. The academic degree for Pierre Drolet was listed as MD, MSc. It should have been listed as MD, FRCPC.


Although numerous methods of postoperative analgesia have been investigated in an attempt to improve pain control after total knee arthroplasty, parenteral narcotics still play a major role in postoperative pain management. Local anesthetics have the advantage of blocking pain conduction at its origin and minimizing the systemic side effects associated with postoperative narcotic use. This study was performed to evaluate the benefits and safety of a multimodal analgesia protocol that included periarticular injection of large doses of local anesthetics in patients undergoing total knee arthroplasty.


We compared morphine consumption during the first twenty-four hours after unilateral total knee arthroplasty in forty-two patients who had been randomized to receive either (1) a perioperative infiltration mixture, consisting principally of local anesthetic, and self-administered morphine or (2) self-administered morphine only. Narcotics consumption, pain control, medication-related side effects, plasma levels of the local anesthetic (ropivacaine), and postoperative rehabilitation were monitored.


Although there was high satisfaction and good pain control in both groups, morphine consumption was significantly lower in the local analgesia group than it was in the control group (28.8 ± 17.4 mg compared with 50.3 ± 25.4 mg twenty-four hours after surgery, and 46.7 ± 19.4 mg compared with 68.6 ± 38.6 mg forty hours after surgery). Both groups achieved a similar amount of knee flexion on the fifth postoperative day. Over the five-day period after the procedure, the patients in the local analgesia group reported a total of 2.6 ± 3.9 hours of nausea compared with 7.1 ± 12.2 hours in the control group. No complications related to the infiltration of the local anesthetic were observed, and all plasma concentrations of the local anesthetic were below the toxic range.


This multimodal perioperative analgesia protocol that included infiltration of a local anesthetic offered improved pain control and minimal side effects to patients undergoing total knee arthroplasty. Our study also confirmed the safety of the protocol.

Level of Evidence: 

Therapeutic Level I. See Instructions to Authors for a complete description of levels of evidence.

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    These activities have been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint sponsorship of the American Academy of Orthopaedic Surgeons and The Journal of Bone and Joint Surgery, Inc. The American Academy of Orthopaedic Surgeons is accredited by the ACCME to provide continuing medical education for physicians.
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    Pascal A. Vendittoli, M.D., FRCS(C)
    Posted on June 03, 2006
    Dr Vendittoli et al respond to Drs. Baumgarten and Boezaart
    Hopital Maisonneuve-Rosemont, Montreal, Quebec, CANADA

    We thank Drs.Baumgarten and Boezaart for having raised some very interesting questions.

    First, they suggested that the analgesic effect observed in our study is partly due to the local analgesic plasma level, and this is possibly the case as some trials have suggested(1). However, its contribution is probably negligible. Many trials have demonstrated the efficacy of local anesthetic administration directly at the surgical site (2-4) or as nerve blocks. None of these studies included a control group in which the local anesthetics were administered uniquely by the systemic route. An interesting clinical observation which reinforces our viewpoint was that most subjects who receive our local anesthetic infiltration protocol complain mainly of pains at the tourniquet site (thighs) and not at the surgical (infiltration) site in the first eight hours after surgery. This is what compelled us to reduce the use of tourniquets. We think, in effect, that the great majority of clinicians have almost no doubt that local anesthesia is likely to be more effective in inhibiting the nociception emanating from the site than systemic administration.

    As for the safety of the dose levels used, other well designed trials have reported the administration of comparable doses without incident(5, 6). And similar doses have been given in other institutions in hundreds of patients without problems related to the potential toxicity of local anesthetics (Geelong, Australia, data presented but unpublished).

    While the risk of infection appears not to be elevated in our study, we agree that it was not sufficiently powerful to draw a definitive conclusion on the subject. It must, however, be known that local anesthetics, alone or in combination, are generally not favorable to bacterial growth (7, 8, 9), but it is impossible, without further investigations, to conclude decisively on the subject.

    Many factors affect hospital length of stay: patient selection, hospital management, surgical technique, blood / haemoglobin management, and discharge site (home/rehab centre). Comparing hospital length of stay outside a randomized study is of little value.

    Finally, the goal of our study was not to discourage anyone from having recourse to nerve blocks, as they are performed regularly in our institution. What we are proposing here is a relatively simple alternative, which may be interesting to many patients. A study is under way in our institution to compare peripheral nerve blocks with the presented local infiltration protocol. We hope to better define the indications, advantages and inconveniences of each of these techniques to propose the most appropriate analgesic modality for specific condition.


    (1) Koppert W, Weigand M, Neumann F, Sittl R, Schuettler J, Schmelz M, Hering W. Perioperative intravenous lidocaine has preventive effects on postoperative pain and morphine consumption after major abdominal surgery. Anesth Analg 2004;98(4):1050-5.

    (2) White PF, Rawal S, Latham P, Markowitz S, Issioui T, Chi L, Dellaria S, Shi C, Morse L, Ing C. Use of a continuous local anesthetic infusion for pain management after median sternotomy Anesthesiology 2003;99(4):918-23.

    (3) Blumenthal S, Dullenkopf A, Rentsch K, Borgeat A. Continuous infusion of ropivacaine for pain relief after iliac crest bone grafting for shoulder surgery. Anesthesiology 2005;103(4):900-1.

    (4) Kulkarni M, Elliot D. Local anaesthetic infusion for postoperative pain. J Hand Surg [Br] 2003;28(4):300-6.

    (5) Busch CA, Shore BJ, Bhandari R, Ganapathy S, MacDonald SJ, Bourne RB, Rorabeck CH, McCalden RW. Efficacy of periarticular multimodal drug injection in total knee arthroplasty. A randomized trial. J Bone Joint Surg Am. 2006 May;88(5):959-63.

    (6) Salonen MH, Haasio J, Bachmann M, Xu M, Rosenberg PH. Evaluation of efficacy and plasma concentrations of ropivacaine in continuous axillary brachial plexus block: high dose for surgical anesthesia and low dose for postoperative analgesia. Reg Anesth Pain Med 2000;25(6):664-5.

    (7) Tamanai-Shacoori Z, Shacoori V, Vo Van JM, Robert JC, Bonnaure- Mallet M. Sufentanil modifies the antibacterial activity of bupivacaine and ropivacaine. Can J Anaesth 2004;51(9):911-4.

    (8) Kampe S, Poetter C, Buzello S, Wenchel HM, Paul M, Kiencke P, Kasper SM. Ropivacaine 0.1% with sufentanil 1 microg/mL inhibits in vitro growth of Pseudomonas aeruginosa and does not promote multiplication of Staphylococcus aureus. Anesth Analg. 2003 Aug;97(2):409-11.

    (9) Aydin ON, Eyigor M, Aydin N. Antimicrobial activity of ropivacaine and other local anaesthetics. Eur J Anaesthesiol. 2001 Oct;18(10):687-94.

    Richard K. Baumgarten, M.D.
    Posted on April 27, 2006
    Peripheral Neural Blockade Should Be Incorporated Into Multimodal Rehabilitation Pathways for TKA
    Farms Anesthesia and Pain Management, P.C.

    To The Editor:

    Vendittoli, et al,(1) recently reported the effect of periarticular injection of large doses of ropivacaine for successful pain control after total knee arthroplasty (TKA). The authors suggest that local anesthetics “block pain conduction at its origin”; however, other properties of local anesthetics better explain the modest analgesic improvement observed in this study. The excellent, overall pain relief in both treatment groups (around <25/100 throughout), was probably due to the large doses of systemic and parenteral analgesics utilized in the multimodal pathway.

    Infiltrating mega-doses of ropivacaine into the joint and surrounding tissues creates a depot that releases local anesthetic into the bloodstream over time. As expected, the Montreal group measured prolonged, pharmacologic blood levels of ropivacaine in their patients. Steady-state blood levels of local anesthetics have significant analgesic effects in themselves. Groudine, et al,(2) administered a steady state lidocaine infusion during surgery and found decreased VAS scores throughout the entire hospitalization! Local anesthetics have local and systemic anti-inflammatory effects(3) which could also contribute to analgesia. To properly control this study, the authors should, more appropriately, have administered a steady-state intravenous infusion of local anesthetic in a third control group.

    As anesthesiologists, we are concerned that the extremely large doses of local anesthetic used in this study (550 mg ropivacaine over a 16-24 hr. period) could cause toxicity in patients who are often elderly with concomitant medical problems. Determining the safe limits of plasma ropivacaine is not as straightforward as the authors suggest(4). Furthermore, their study is underpowered to determine the true risk of local anesthetic toxicity in this population.

    The extensive intra- and peri-articular injection used in this study may jeopardize local blood flow and increase the risk of infection. If the primary effect is due to sustained blood levels of local anesthetic, this can be produced by simple intravenous administration, without taking the chance of causing an infection in the fresh prosthesis.

    Peripheral nerve blocks do not prolong hospitalization when incorporated in a clinical pathway. Recently, Salinas, et al,(5) reported a prospective randomized clinical trial (PRCT) measuring hospital length of stay(LOS) as a primary outcome. LOS for TKA with femoral block(either continuous or single-shot) was 3.75 days. This LOS is a full day less that the LOS reported by the Montreal group(4.8 days), and is comparable with the LOS at other U.S. hospitals not utilizing peripheral neural blockade.

    Mega-dose infiltration probably does not block pain pathways, and could add to the infection risk. The anti-inflammatory and central analgesic effects of local anesthetics can readily explain Vendittoli, et al,’s results. This inadequately controlled study should not dissuade orthopaedic surgeons from incorporating peripheral neural blockade into multimodal pathways for total joint rehabilitation.


    1. Vendittoli PA, Makinen P, Drolet P, Lavigne M, Fallaha M, Guertin MC, Varin F. A multimodal analgesia protocol for total knee arthroplasty. A randomized,controlled study. J Bone Joint Surg Am. 2006;88:282-9.

    2. Groudine SB, Fisher HA, Kaufman RP Jr, Patel MK, Wilkins LJ, Mehta SA,Lumb PD. Intravenous lidocaine speeds the return of bowel function, decreases postoperative pain, and shortens hospital stay in patients undergoing radical retropubic prostatectomy. Anesth Analg. 1998;86:235-9.

    3. Arlander E, Ost A, Stahlberg D, Lofberg R. Ropivacaine gel in active distal ulcerative colitis and proctitis – a pharmacokinetic and exploratory clinical study. Aliment Pharmacol Ther. 1996;10:73-81.

    4. Hoeft MA, Rathmell JP. Continuous infusion of 0.5% bupivacaine for local analgesia: What are “toxic” blood levels? Reg Anes Pain Med 2006;31:184-5.

    5. Salinas FV, Liu SS, Mulroy MF. The effect of single-injection femoral nerve block versus continuous femoral nerve block after total knee arthroplasty on hospital length of stay and long-term functional recovery within an established clinical pathway. Anesth Analg. 2006;102:1234-9.

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