Why Use a Multimodal Approach to Analgesia?

    When an orthopaedic surgeon makes an incision in a patient’s skin, a few things happen:

    • A host of humeral mediators are released.
    • Neuronal impulses are generated.
    • The result is pain.

    Nerve blocks are typically used to block impulse conduction from the periphery to the spinal cord. But what about the humeral mediators? What can be done to blunt their pain-producing effects?

    That is where the concept of multimodal analgesia comes in, according to Asokumar Buvanendran, MD, the Director of Orthopaedic Analgesia at Rush University Medical Center, Chicago, Illinois.

    Speaking at the ICJR South/RLO Course, Dr. Buvanendran explained that multimodal analgesia combines different analgesics that act by different mechanisms, resulting in additive or synergistic effects of the drugs. The drugs target different pain pathways, which is a better approach to perioperative pain management than administration of an individual drug.

    The goal of this approach, Dr. Buvanendran said, is to decrease postoperative use of opioids, thus reducing their potentially dangerous side effects, including respiratory depression.

    What the Literature Says

    The literature, Dr. Buvendran noted, supports the benefits of a multimodal approach:

    A 2009 meta-analysis of 52 randomized, controlled trials with non-steroidal anti-inflammatory drugs (NSAIDs), COX-2 inhibitors, and acetaminophen show decreased opioid consumption, decreased pain scores, and decreased opioid-related side effects. [1]

    In a 2011 study, 48 patients undergoing total knee arthroplasty (TKA) received 125 mg of methprednisolone. They had decreased 48-hour pain scores and 48-hour opioid use, as well as reduced postoperative nausea and vomiting. The authors of the study cautioned that safety of steroid use in surgery patients remains to be determined. [2] The same authors repeated the study in total hip arthroplasty (THA) patients, with similar results. [3]

    A meta-analysis published in 2011 looked at 14 clinical trials in patients undergoing TKA and 6 clinical trials in patients THA who had an intra-articular injection of various anesthetics and analgesics. There was too much variability in the THA studies to make a conclusion, but the TKA studies showed decreased pain scores in the immediate postoperative period. There were no long-term effects in pain relief, however. [4]

    In a 2013 study of 160 patients who received a spinal infusion of either 0.5% bupivacaine on saline via elastomeric pump, patients in the bupivacaine group had decreased pain scores and decreased opioid consumption. [5]

    Reducing the Risk of Chronic Pain

    Dr. Buvanendran also addressed the issue of chronic pain developing after total joint arthroplasty. Patients will experience pain after arthroplasty – that’s a given. But some of them go on to develop chronic pain.

    In a 2011 study of 632 TKA patients in the United Kingdom, 44% reported persistent pain, as measured by their WOMAC scores, 34 to 39 months after surgery. Of these patients, 17% had moderate pain, 15% had severe pain, and 6% developed chronic neuropathic pain after surgery. [6]

    The severity of acute postoperative pain is a strong predictor for the development of persistent postoperative pain (PPP), Dr. Buvanendran said. The duration of that pain (1 to 7 days) is also a strong predictor of PPP.

    What can orthopaedic surgeons do to reduce the risk of patients developing PPP? Many are adding gabapentin and pregabalin to their perioperative pain management protocol.

    Dr. Buvanendran was involved in a study published in 2010 in which arthroplasty patients were randomized to receive either pregabalin or a placebo. At 1, 3, and 6 months after surgery, the pregabalin patients had decreased allodynia and hyperalgesia, as well as decreased incidence of chronic neuropathic pain. [7]

    In a 2007 meta-analysis of 18 randomized controlled trials that included 1,181 patients, the researchers found a decreased in 24-hour opioid use, as well as decreased pain scores at 24 hours. The only issue they found was an increased in sedation among patients who received gabapentin. [8]

    A 2012 meta-analysis of 11 randomized controlled trials of patients who received either gabapentin or pregabalin reported a decreased in chronic pain if the drugs were administered in the perioperative period. [9]

    Practical Clinical Protocol for TKA Patients

    Orthopaedic surgeons at Dr. Buvanendran’s facility do an average of 15 joint replacements a day. Guided by the evidence – as well as evaluation of their outcomes every 3 to 6 months – the orthopaedic surgeons and anesthesiologists follow this protocol with patients undergoing TKA:


    • Discontinue NSAIDs 3 to 7 days preoperatively
    • Administer
    • Celoxocib, 400 mg
    • Intravenous (IV) acetaminophen, 1 gram
    • Pregabalin, 75 to 110 mg
    • Use a scopolamine patch as an antiemetic to prevent postoperative nausea and vomiting
    • Keep the patient hydrated with IV fluids


    • Provide regional anesthesia with clonidine; avoid opioids
    • Administer IV ketamine and propofol
    • Dexamethasone and Zofran to prevent postoperative nausea and vomiting
    • Keep the patient warm (normothermia, Bier huger, fluid warmer)

    Postoperative Day 1

    • Continue regional anesthesia
    • Administer celacoxib, 200 mg every 12 hours; pregabalin, 50 to 75 mg every 12 hours; acetaminophen, 1 gram 3 times a day
    • Provide cryotherapy

    Postoperative Day 2

    • Stop regional anesthesia
    • Administer oral oxycodone or hydrocodone; continue acetaminophen if oxycodone is given; celacoxib, 200 mg every 12 hours; pregabalin, 50 mg every 12 hours
    • Provide cryotherapy

    As the patient undergoes physical therapy, the doses are titrated down but continued for 10 to 14 days after surgery. This timing, Dr. Buvanendran said, coincides with resolution of the humeral responses to the incision.


    With 10 years of experience using a multimodal pain management pathway for total joint patients, Dr. Buvanendran concludes that:

    • Multimodal and regional anesthesia should be administered in the perioperative period to reduce the severity of acute postoperative pain
    • Severe acute postoperative pain can lead to PPP

    With the advent of recent healthcare regulations, patient satisfaction – often measured by their satisfaction with pain management – will be essential.


    1. Elia N. Lysakowski C, Tramèr MR. Does multimodal analgesia with acetaminophen, nonsteroida antiinflammatory drugs, or selective cyclooxygenase-2 inhibitors and patient-controlled analgesia morphine offer advantages over morphine alone? Meta-analyses of randomized trials. Anesthesiology 2009;103:1296-1304
    2. Lunn TH, Kristensen BB, Andersen LØ,et al. Effect of high-dose preoperative methylprednisolone on pain and recovery after total knee arthroplasty: a randomized, placebo-controlled trial.Br J Anaesth.2011;106(2):230-8
    3. Lunn TH,Andersen LØ,Kristensen BB et al. Effect of high-dose preoperative methylprednisolone on recovery after total hip arthroplasty: a randomized, double-blind, placebo-controlled trial.Br J Anaesth 2013;110(1):66-73
    4. Kehlet H, Anderson LO. Local infiltration analgesia in joint replacement: the evidence and recommendations for clinical practice. Acta Anaesthesiol Scand 2011; 55(7):778-84
    5. Goyal N, McKenzie J, Sharkey PF, Parvizi J, Hozack WJ, Austin MS. The 2012 Chitranjan Ranawat award: intraarticular analgesia after TKA reduces pain: a randomized, double-blinded, placebo-controlled, prospective study. ClinOrthopRelat Res 2013;471(1):64-75.
    6. Wylde V, Hewlett S, Learmonth ID, Dieppe P. Persistent pain after joint replacement: prevalence, sensory qualities, and postoperative determinants. Pain 2011;152(3):566-572
    7. Buvanendran A, Kroin JS, Della Valle CJ, Kari M, Moric M, Tuman KJ. Perioperative oral pregabalin reduces chronic pain after total knee arthroplasty: a prospective, randomized, controlled trial. Anesth Analg. 2010 Jan 1;110(1):199-207
    8. Peng PW, Wijeysundera DN, Li CC. Use of gabapentin for perioperative pain control — a meta-analysis. Pain Res Manag.2007;12(2):85-92.
    9. Clarke H, Bonin RP, Orser BA, Englesakis M, Wijeysundera DN, Katz J. The prevention of chronic postsurgical pain using gabapentin and pregabalin: a combined systematic review and meta-analysis. Anesth Analg 2012;115(2):428-42