Chapter 145 A Multimodal Approach to Pain Management in Total Joint Arthroplasty

Asokumar Buvanendran, Bryan S. Williams, Craig J. Della Valle

NSAIDS, COX-2 INHIBITORS, AND ACETAMINOPHEN

Nonselective NSAIDs

INTERVENTIONAL TECHNIQUES

Regional Blockade

Periarticular Infiltration

PROTOCOL

CONCLUSION

Total joint arthroplasty (TJA) is considered one of the most successful operations as demonstrated by a variety of quality of life outcome and superior cost-effectiveness measures in comparison with other medical and surgical interventions such as solid organ transplantation and hemodialysis.³ Total knee arthroplasty (TKA) is one of the most common surgical procedures performed in the United States and represents the greatest single Medicare procedural expenditure.¹⁶ Total knee arthroplasty has also been shown to improve long-term quality of life,⁴⁴ but the immediate postoperative period may be associated with intense postoperative pain that can hamper rehabilitation and eventual restoration of function of the knee. Therefore, effective postoperative analgesia is paramount in the recovery period. In fact, the 10% to 15% of patients who are dissatisfied with TKA relate chronic persistent pain in the operated knee as a key factor.^2,^4,^5,²⁸

Appropriate patient management could potentially reduce associated total direct medical costs for lower extremity joint replacement surgeries by reducing hospital stays and services needed during hospitalization. Over the past 20 years, the mean duration of hospitalization has decreased for patients who undergo TKA in the United States from approximately 9 to 4 days,^27,^33,³⁷ with trends now reaching less than a 24-hour stay in selected centers.¹³ Reports indicate that patients who were discharged from the hospital earlier as part of accelerated clinical pathway programs had similar short-term clinical outcomes to patients who had longer hospitalizations. Factors contributing to shorter lengths of stay include homogeneous entities, regular staff, high continuity, use of more timely and up-to-date information, including expectations on a short stay, functional discharge criteria, early mobilization, and multimodal opioid-sparing analgesia.²⁵ Several anesthetic and postoperative analgesic protocols have been developed to facilitate the recovery of patients undergoing joint replacement surgery; most of them heavily depend on the use of regional anesthesia as part of a multimodal approach to postoperative analgesia.¹³

A multimodal approach has been advocated as a method to treat pain best in the perioperative period for TKA patients. What is multimodal analgesia? Multimodal analgesia is achieved by combining different analgesics that act by different mechanisms, resulting in additive or synergistic analgesia with reduced adverse effects related to the sole administration of individual analgesics.³⁰ Opioids have long been the mainstay of postoperative analgesia, but the addition of adjuvant medications permits the use of lower doses of opioids while addressing pain by alternative mechanisms. Synergistically or additively, these adjuvants enhance analgesia provided by opioids and reduce potential adverse effects. Additionally, acute opioid tolerance has been described, and a correlation between high-dose intraoperative opioid administration necessitated an increase in postoperative opioid requirements,⁴⁹ but this may be avoided by the use of a multimodal perioperative anesthesia and analgesia model.

The efficacy of pain relief influences postoperative recovery after TKA. Consequences of severe postoperative pain include prolonged hospital stays, increased hospital readmissions, and increased opioid use, with a parallel increase in postoperative nausea and vomiting, resulting in overall low patient satisfaction and potentially greater cost and, more important, chronic persistent pain in the operated knee.² In addition, severe acute postoperative pain after TKA may be a predictor for development of chronic pain after TKA at 6 months. The advantages of a multimodal approach are highlighted in Box 145-1.

Operative procedures produce an initial afferent barrage of pain mediators, which lead to local inflammation. Local tissue inflammation triggers the production of prostaglandins (PGs), particularly PGE₂,³⁴ which has been implicated in acute postoperative pain.¹⁰ Several inflammatory mediators are released with surgical trauma, including histamine, bradykinin, and prostaglandins. Increased sensitivity to painful stimuli is mediated by repetitive, excitatory amino acids (glutamate and aspartate) with expression of c-fos, nitric oxide (NO) synthase, and the cyclooxygenase (COX)-2 gene, with ensuing sensitization. Amplification of painful stimuli increases the concentration of prostaglandins and NO, which may be the primary mediators of central sensitization (secondary hyperalgesia).¹⁷ Multimodal analgesic techniques reduce the total dose of any one medication by attending to analgesic requirements through various receptor modulations. Multimodal analgesia is achieved by combining different analgesics that act by different mechanisms, resulting in additive or synergistic analgesia with lowered adverse effects of the sole administration of individual analgesics.⁴⁹

This chapter reviews multimodal analgesia for TJA, including enteral medications (nonsteroidal anti-inflammatory drugs [NSAIDs], acetaminophen, selective COX-2 inhibitors, gabapentinoids) and regional anesthesia techniques.

Acute Pain Medicine Service

Establishment of an acute pain medicine service (APS) that has the responsibility of managing postoperative pain provides an organizational framework for monitoring an appropriate level of care and adjusting care according to the clinical condition of the patient. Health care providers should use standardized, validated instruments to facilitate regular evaluation and documentation of pain intensity, the effects of pain therapy, and side effects caused by the therapy. Analgesic techniques involve risk for adverse effects that may require prompt medical evaluation. Anesthesiologists responsible for perioperative analgesia should be available at all times to consult with floor nurses, surgeons, or other physicians, and should assist in evaluating patients who are experiencing problems with any aspect of perioperative pain relief. An integrated approach to perioperative pain management that minimizes analgesic gaps includes ordering, administering, and transitioning therapies, and transferring responsibility for perioperative pain therapy, as well as outcomes assessment and continuous quality improvement.⁴² The APS is a multidisciplinary service that provides collaborative efforts by anesthesiologist, surgeons, physical therapists, and nurses. Participation by these parties allows appropriate development of protocols for perioperative pain management. This strategy should enhance restoration of function by allowing patients to participate in rehabilitation programs more easily, thereby improving overall postoperative outcomes. The following section discusses many of the medications and interventional techniques involved in a multimodal approach and protocol.

NSAIDs, COX-2 Inhibitors, and Acetaminophen

Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most widely used analgesic medications in the world because of their ability to reduce pain and inflammation. Cell injury induces the production of phospholipids with conversion to arachidonic acid, and the COX enzyme converts arachidonic acid to prostaglandins. Peripherally, prostaglandins (PGE₁ and PGE₂) are not important mediators of pain transmission, but they contribute to hyperalgesia by sensitizing nociceptive sensory nerve endings to other mediators (histamine and bradykinin) and by sensitizing nociceptors to respond to non-nociceptive stimuli, such as touch.^29,⁴⁹ In the periphery, NSAIDs prevent the sensitization of peripheral nociceptors, diminishing PG formation and central hyperalgesia evoked by the spinal action of substance P and the N-methyl-D-aspartate receptor antagonists (NMDAs).^29,⁴⁹ The mechanism of action of NSAIDs is inhibition of prostaglandin production by reversible or irreversible acetylation of COX. It is the COX-2 isoform that is induced by proinflammatory stimuli and cytokines, causing fever, inflammation, and pain, and thus serving as the target for anti-inflammation by NSAIDs.

Nonselective NSAIDs

Acetylsalicylic acid (aspirin [ASA]) covalently modifies COX-1 and COX-2, irreversibly inhibiting cyclooxygenase activity. This is an important distinction among the NSAIDs because the duration of action of aspirin is related to the turnover rate of cyclooxygenases in different target tissues. Apprehension in prescribing ASA still remains because of its ability to irreversibly inhibit COX activity and possibly increase adverse effects such as gastric irritation and impaired coagulation. Regarding aspirin, irreversible inhibition of COX-1 has limited its use in the postoperative period as compared with nonselective NSAIDs that reversibly inhibit COX-1. Inhibition of platelet COX-1–dependent thromboxane formation is associated with increased bleeding time or decreased platelet aggregation ³⁹ and may limit the use of aspirin in the perioperative period.

Ketorolac

Ketorolac tromethamine is an NSAID with activity at COX-1 and COX-2 enzymes, thus blocking prostaglandin production. Ketorolac is available for enteral, ophthalmic, and parenteral delivery and is the only parenteral NSAID. Ketorolac has an onset of action of approximately 10 minutes, a peak analgesic effect of 2 to 3 hours, and analgesic duration of 6 to 8 hours, making it attractive for postoperative analgesia.⁷ Ketorolac has been used to treat mild to severe pain following major surgical procedures, including general abdominal, gynecologic, and orthopedic surgery. Multiple studies have investigated the analgesic potency of ketorolac, and in animal models, analgesic potency has been estimated to be between 180 and 800 times that of aspirin.^4,²¹ When compared with morphine, ketorolac 30 mg intramuscular (IM) has been shown to be equivalent to 12 mg morphine IM and 100 mg meperidine IM.³⁸ Ketorolac has been used as an adjuvant in arthroplasties of the knee as a means to provide multimodal pain management by reducing the amount of opioid delivered.^15,⁴³ However, caution needs to be exercised in patients with renal insufficiency and elderly patients, in whom creatinine clearances are elevated. Another route of administering ketorolac that is in development because of its high potency of analgesia is the nasal route, with possible higher blood–brain penetration.

Acetaminophen

Acetaminophen (paracetamol) produces its analgesic effect by inhibiting central prostaglandin synthesis with minimal inhibition of peripheral prostaglandin synthesis.^7,²² Often labeled as an NSAID, acetaminophen has important differences from NSAIDs, such as its weak anti-inflammatory effects and its generally poor ability to inhibit COX in the presence of high concentrations of peroxides, as are found at sites of inflammation,^7,²² nor does it have an adverse effect on platelet function⁴⁰ or on the gastric mucosa.²² The comparative efficacy of different analgesics has been shown to vary with the type and extent of surgical procedure.⁴¹ This variation in efficacy has led to the coined term “procedure-specific postoperative pain management.”³¹ A qualitative systematic review comparing acetaminophen versus NSAIDs in postoperative pain management found NSAIDs to be superior after dental surgery; however, acetaminophen showed no significant differences after orthopedic procedures were performed.²⁶ Although currently not available in the United States, the intravenous route of administering acetaminophen is extremely popular in Europe for TKA. Acetaminophen may have a greater central role of action than the commonly used NSAIDs; therefore acetaminophen can be combined with COX-2 inhibitors or NSAIDs as part of the multimodal regimen for TKA.