Key points

Introduction

Osteoarthritis (OA), also known as degenerative joint disease, affects approximately 27 million people in the United States. For OA of the hip and knee, nonoperative management is directed at reducing pain and functional impairment. Conservative measures include weight loss, activity modification, physical therapy, acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), and intra-articular injections of glucocorticoids and hyaluronic acid. When nonoperative treatment fails, and intolerable pain and disability are present, total joint arthroplasty is a widely accepted treatment.

Total knee replacement (TKA) and total hip replacement (THA) are two of the most common surgeries performed today. The alleviation of pain, usually stemming from OA, is a primary indication for TKA and THA. Both surgeries predictably alleviate pain in most patients postoperatively. However, in the acute postoperative period, TKA and THA can cause significant pain. The fear of acute postoperative pain has been cited as a reason why patients put off arthroplasty surgery. TKA, in particular, has a reputation for being an especially painful procedure from which to recover. It is not uncommon for patients to be thrilled with the results of their TKA surgery months afterward, but often state that they are unsure whether they would undergo the procedure again, now knowing how intense the immediate postoperative pain would be.

In 1995, the American Pain Society declared that pain is “the fifth vital sign.” Shortly afterward, the Joint Commission on Accreditation of Healthcare Organizations said that patients should have a “right” to adequate pain management. These declarations came as evidence continued to mount demonstrating the impact of pain in patients’ lives. Indeed, the orthopedic and pain literature show that if pain is not adequately controlled after TKA or THA, several detrimental pathophysiologic processes are set in motion. These processes increase the risk of complications and morbidity, disrupt sleep, cause cognitive dysfunction, and increase patient anxiety. Specific medical morbidities associated with inadequate pain control include venous thrombosis, coronary ischemia, myocardial infarction, and pneumonia. In addition, uncontrolled pain hinders physical therapy and rehabilitation, thereby increasing the length of hospital stay and escalating the cost of care. Furthermore, the failure to control pain also leads to worse patient satisfaction with their surgery. As such, orthopedic and anesthesia providers must recognize the importance of managing pain after TKA and THA.

Introduction

Osteoarthritis (OA), also known as degenerative joint disease, affects approximately 27 million people in the United States. For OA of the hip and knee, nonoperative management is directed at reducing pain and functional impairment. Conservative measures include weight loss, activity modification, physical therapy, acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), and intra-articular injections of glucocorticoids and hyaluronic acid. When nonoperative treatment fails, and intolerable pain and disability are present, total joint arthroplasty is a widely accepted treatment.

Total knee replacement (TKA) and total hip replacement (THA) are two of the most common surgeries performed today. The alleviation of pain, usually stemming from OA, is a primary indication for TKA and THA. Both surgeries predictably alleviate pain in most patients postoperatively. However, in the acute postoperative period, TKA and THA can cause significant pain. The fear of acute postoperative pain has been cited as a reason why patients put off arthroplasty surgery. TKA, in particular, has a reputation for being an especially painful procedure from which to recover. It is not uncommon for patients to be thrilled with the results of their TKA surgery months afterward, but often state that they are unsure whether they would undergo the procedure again, now knowing how intense the immediate postoperative pain would be.

In 1995, the American Pain Society declared that pain is “the fifth vital sign.” Shortly afterward, the Joint Commission on Accreditation of Healthcare Organizations said that patients should have a “right” to adequate pain management. These declarations came as evidence continued to mount demonstrating the impact of pain in patients’ lives. Indeed, the orthopedic and pain literature show that if pain is not adequately controlled after TKA or THA, several detrimental pathophysiologic processes are set in motion. These processes increase the risk of complications and morbidity, disrupt sleep, cause cognitive dysfunction, and increase patient anxiety. Specific medical morbidities associated with inadequate pain control include venous thrombosis, coronary ischemia, myocardial infarction, and pneumonia. In addition, uncontrolled pain hinders physical therapy and rehabilitation, thereby increasing the length of hospital stay and escalating the cost of care. Furthermore, the failure to control pain also leads to worse patient satisfaction with their surgery. As such, orthopedic and anesthesia providers must recognize the importance of managing pain after TKA and THA.

The biology and psychology of surgical pain

Pain is defined as “an unpleasant sensory and emotional experience associated with actual or potential tissue damage.” From the time the incision is made for either TKA or THA, the nociceptor pain system is activated. This includes the activation of pathways in the peripheral and the central nervous systems. Unavoidably, tissue is damaged during total joint arthroplasty. This direct damage produces a noxious stimulus that is detected by nociceptors in the peripheral nervous system. The signal is transmitted, via action potentials, to the spinal cord and then to the central nervous system. In addition to the noxious stimulus from the direct tissue damage, postoperative inflammation also leads to cell injury, and serves as a second source of pain. Furthermore, Dalury and colleagues have noted that following direct tissue injury and postoperative inflammation, there is a release of inflammatory substances and cytokines including hydrogen and potassium, histamine, serotonin, prostaglandins, leukotrienes, thromboxane, and substance P.

Knowledge of the physiology of acute pain has improved greatly in recent years. Information is gathered from basic science and clinical studies from various disciplines. Although the mechanisms and physical chemistry of pain are well understood, patients have variable responses to pain.

The psychology of pain seems to be just as important as the biology, and effective pain control must take this into consideration. For example, Riddle has explored how patients’ psychological status influences their perception of pain after TKA by focusing on the roles of depression, anxiety, and coping mechanisms. His group found that pain catastrophizing was a consistent predictor of poor outcome after TKA. Given there are physiologic and psychological components of pain, surgeons must consider the many options available to best manage the impact of perioperative pain and improve patient outcomes.

Opioids

Opioid therapy has traditionally provided the foundation of pain control in the postoperative period for orthopedic surgery and other surgical disciplines. Oral, intravenous (IV), intramuscular, subcutaneous, transdermal, and other delivery methods are available, in a myriad of strengths and combination formulas. Some of the most commonly used opioids are morphine, hydromorphone, oxycodone, hydrocodone, and fentanyl. Morphine is one of the earliest, and still most commonly used opioids. Its use is so ubiquitous, that opioid use is often measured in terms of the equivalent morphine dose.

Opioids act by binding to opioid receptors, which are principally found in the central nervous system, the peripheral nervous system, and the gastrointestinal tract. These receptors mediate the somatic and psychoactive effects of opioids. Somatic effects include the desired pain control, and itchiness, nausea, somnolence, respiratory depression, and constipation. Psychoactive effects include euphoria in some patients. Tolerance and dependence develop with continuous use, requiring increasing doses to achieve the same effects. Withdrawal symptoms also develop if long-term use is discontinued abruptly.

The most common strategy for treating postoperative pain is to administer opioids in response to escalating pain. When managed pro re nata (translated as “in the circumstances”), opioid administration is often delayed by the patient waiting too long to request it and the nurse being able to provide the medicine. This process has been shown to reduce the effect of the medicine. Alternatively, IV opioids are administered via a patient controlled analgesia (PCA) device that administers a dose of IV opioid when the patient pushes a button. Although appealing in that it shortens the time from pain sensation to medicine administration, adverse effects are associated with PCA use. These include sedation and somnolence, respiratory depression, nausea and vomiting, and constipation and urinary retention. These side effects, coupled with the lack of evidence showing that PCA is superior to nurse-provided analgesia, has led to PCA losing popularity for pain control after arthroplasty.

The efficacy of opioids in treating pain from OA has been demonstrated in studies that showed effective reduction in pain and improvements in sleep and mood. As such, opioids were increasingly used as treatment of OA-related pain in the late 1990s and early 2000s. Guidelines from the American College of Rheumatology, the American Geriatrics Society, and the American Pain Society support the use of opioids for chronic OA pain. Although they are effective in alleviating pain, the previously mentioned negative side effects mean that opioids should not be the only means of treating pain after THA and TKA. Indeed, several papers have shown that opioid use actually increases complication rates after total joint arthroplasty. That combined with the opioid epidemic should encourage surgeons to exercise caution when using opioid medications.

In addition to being aware of the side effects of opioids and cognizant of the current epidemic, the surgeon must consider each patient individually when determining a plan for perioperative pain management. This includes the patient’s preoperative use of opioids. In 2016, Sing and colleagues studied preoperative opioid use in patients who underwent THA or TKA for OA. The patients’ home medicines before surgery were reviewed and patients were stratified according to whether they used long-acting opioids, short-acting opioids, or no opioids. The three groups were matched by age, sex, and procedure. The paper showed that the mean milligram of morphine equivalents administered in hospital was significantly higher for the opioid users (46 mg by nonusers vs 102 mg by short-acting users vs 366 mg by long-acting users). Additionally, the opioid users also reported higher visual analog pain scores throughout their hospitalization. Regarding patient outcomes, opioid users walked shorter distances on postoperative Day 1, had longer hospital stays, were more likely to be discharged to a facility instead of home, and had more complications within 90 days of surgery. They conclude that preoperative opioid use is a risk factor for slower recovery, increased cost, and increased complications after THA and TKA.

Aware of the increased risks associated with preoperative opioid use, Nguyen and colleagues assessed whether weaning opioid use preoperatively would improve outcomes following THA and TKA. Their recent study retrospectively defined three cohorts of patients: (1) intervention (patients who successfully weaned their equivalent morphine dose by 50% preoperatively), (2) opioid-dependent control (patients taking opioids regularly preoperatively), and (3) an opioid naive control. The intervention group reduced their opioid use either on their own, or through guidance from their primary care doctor or a pain specialist. The three groups were matched by demographic and disease-specific variables. Compared with the opioid-dependent group, the intervention group had significantly higher increases from baseline in their postoperative physical functional scores (eg, the University of California at Los Angeles [UCLA] activity score, the Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC], and the 12-Item Short Form Survey [SF-12]). The intervention group also had higher scores at final follow-up. Overall, the weaned group performed more similarly to the naive group than to their dependent matches. This study indicates that weaning preoperative opioid use can return a patient’s postoperative recovery to more closely resemble an opioid-naive patient.

In summary, opioids, although effective, are associated with some adverse effects and poor outcomes. As such, multimodal options to reduce the amount of opioid medications required seem to be an effective philosophy.

Multimodal pain management

The term multimodal pain management was first introduced by Wall in 1988. Wall described multimodal pain management as a strategy that incorporates various medicinal and nonmedicinal techniques of providing pain relief. The strategy targets different steps of the aforementioned pain pathways, thereby decreasing the need for opioid pain medicines postoperatively. Multimodal pain management was popularized later in a paper by Kehlet and Dahl, in which they referred to it as “balanced analgesia,” although this term never stuck.

When discussing multimodal pain control, Dahl and Kehlet also stressed the importance of preemptive analgesia. They were pioneers in the belief that by administering medicines before surgery, one could prevent pain nociceptors from entering a state of hyperalgesia. This term refers to the sensitization of peripheral nociceptors following mechanical or thermal injury. The resultant allodynia manifests as amplified and prolonged postoperative pain, and possibly persistent, chronic pain. If the pathway toward hyperalgesia could be disrupted, this would make acute postoperative pain easier to control, with a decreased need for opioids.

Multimodal pain management includes preoperative, intraoperative, and postoperative techniques. In its broadest interpretation, multimodal management even includes preoperative patient education and discussion about pain control and expectations. Patients should have realistic expectations, goals, and education set in the preoperative period to help prepare them for their postoperative care. Preoperative education can influence a patient’s perception of postoperative pain, ambulation and rehabilitation goals, and expectations for length of stay and discharge. Many institutions have created formalized preoperative patient education programs for patients undergoing joint replacement. At our institution, this program, called Joint Academy, is led by our nurses, physician assistants, physical therapists, and nurse coordinators. Furthermore, in addition to these staff members, other members of the care team provide counseling and follow several key guidelines that we believe are important for a successful preoperative education program:

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  Include patients and family members in the program.

  
  
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  Have representation or input from the surgical and anesthesia teams, nursing, and physical and occupational therapy.

  
  
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  Describe the postoperative rehabilitation program, including goals and expectations for specific days and weeks after surgery.

  
  
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  List the methods used for perioperative pain control and set reasonable expectations for postoperative pain levels.

Although the preoperative education is often provided weeks or even months before surgery, the day of surgery is another window of opportunity for intervening the patients postoperative pain experience. In preoperative holding, preemptive analgesia is often administered. Preemptive analgesia limits the sensitization of the nervous system to the painful surgical stimuli by blocking the transmission of noxious efferent information from the peripheral nervous system to the spinal cord and brain. Thus, to be effective, the medicines must be given before incision. Common agents used for preemptive analgesia include long- and short-acting opioids, acetaminophen, centrally acting synthetic analgesics, and NSAIDs. Additionally, the use of clonidine and ketamine has been reported, although they are used less frequently.

In addition to administering pharmacologic agents, anesthesiologists can perform regional anesthetic procedures during the preoperative period to make postoperative pain easier to control and limit the actual perception of painful stimuli during and after the surgical procedure. Such procedures are integral to the practice of multimodal pain management and are discussed later.

In conjunction with the preoperative regional anesthetics described previously, intraoperative injections or periarticular infiltration (PAI) of anesthetics or medications may also be provided by the surgeon. The surgeon has multiple agents available for periarticular injection during the surgery, discussed in more detail later, which may include traditional opioids, anti-inflammatories, and local anesthetics including liposomal bupivacaine (LB).

Postoperatively, multimodal regimens include cryotherapy, pharmacologic agents, and the continued use of preoperatively placed regional anesthetics. Pharmacologic agents discussed are acetaminophen/paracetamol; NSAIDs including cyclooxygenase (COX)-2 inhibitors; centrally acting synthetic analgesics; and anticonvulsants, which have been used for treating neuropathic pain. Also, if a regional block was not used preoperatively, it is performed postoperatively if pain is uncontrolled.

Cryotherapy

Cryotherapy involves the application of a bag of ice or cooled water to the skin surrounding the surgical site. Cryotherapy has long been a mainstay of postoperative pain control, and although often overlooked because of its simplicity, should be considered a component of multimodal analgesia. By lowering the temperature of the surrounding, damaged tissue, cryotherapy decreases postoperative pain in several ways, making it an intrinsically multimodal agent itself : it decreases tissue metabolism and enzymatic activity (including the activity of the COX enzymes); it reduces nerve signal transduction, providing a direct analgesic effect and reducing the development of subsequent hyperalgesia; and it induces vasoconstriction and reduces extravasation of blood into surrounding tissues. This reduces blood loss and secondary inflammation.

Although most orthopedic surgeons, and the medical community overall, agree that cryotherapy is effective for pain control, the literature is equivocal. Some studies show a benefit, whereas others show little to no difference. These studies contain small numbers of patients, are nonrandomized, and unblinded. As such, more research is needed on the benefits of cryotherapy for THA and TKA.

Paracetamol

Paracetamol (Tylenol) is an analgesic and antipyretic. The exact mechanism of action is not known, with early theories focusing on inhibition of COX enzymes, and contemporary research favoring a role in cannabinoid pathways. Tylenol is considered the most basic adjunct to a multimodal regimen. Caution must be used in patients with hepatic disease, because paracetamol is metabolized by the liver, and high doses can lead to hepatotoxicity and death. To decrease the incidence of hepatotoxicity, the Food and Drug Administration in 2011 asked manufacturers to discontinue any pill containing more than 325 mg of acetaminophen. Also in 2011, acetaminophen manufacturers lowered the maximum recommended daily dose from 4 g to 3 g.

In a 2008 Cochrane Review, Toms and colleagues reported on the efficacy of a single dose of paracetamol (from 600 mg to 1000 mg) for treating acute postoperative pain in adults. The review evaluated 51 randomized, double-blind, placebo-controlled trials. The trials included various types of surgeries: abdominal, orthopedic, thoracic, vascular, gynecologic, and dental surgeries. In summary, they found that a single dose of acetaminophen provided effective pain relief for about half of participants experiencing moderate to severe pain after an operation. Aside from oral paracetamol, an IV option has recently been introduced. However, IV paracetamol is costly and has not been shown to provide greater pain relief in the acute postoperative setting compared with its oral counterpart in total joint arthroplasty cases. Additionally, Kelly and colleagues report no benefit in decreasing perioperative opioid consumption in patients who underwent TKA and received IV paracetamol versus TKA patients who did not receive IV paracetamol. Finally, a recent systematic review demonstrated no clear benefit of using IV versus oral paracetamol and recommended the use of an oral dosage for patients who are able to take oral medications in cardiology, maxillofacial, and orthopedic populations.

Nonsteroidal anti-inflammatory drugs and cyclooxygenase-2 inhibitors

Inflammation is the body’s response to injury and infection, and plays an important role in postoperative pain. Although inflammation is beneficial in that it leads to the removal of offending factors and the restoration of homeostasis, the associated pain is detrimental to recovery from arthroplasty. Prostaglandins are lipid derivatives that play a key role in the inflammatory response. Derived from arachidonic acid, prostaglandins are produced by the COX enzymes, COX-1 and COX-2. Patients with higher prostaglandin E ₂ levels are slower to progress with physical therapy (eg, time to walk milestone distances, get out of bed, and climb stairs).

By inhibiting the COX enzymes, NSAIDs and COX-2 inhibitors are effective for perioperative analgesia. These agents are available in various onset times, durations, routes of administration, efficacy, and side effect profiles. As such, they are a cornerstone of multimodal treatment regimens. Despite their efficacy, NSAIDs must be used with caution, because they have a significant side effect profile: gastrointestinal mucosal damage and renal dysfunction. Thus, they are contraindicated in patients with pre-existing gastrointestinal ulcers or renal impairment. Because platelet activation depends on downstream components of the prostaglandin pathway, NSAIDs also lead to increased perioperative blood loss. Many authors recommend discontinuation of NSAIDs 7 to 10 days before elective arthroplasty because studies have shown a two-fold increase in blood loss after THA. Fortunately, selective COX-2 blockers have minimal gastrointestinal and hemostatic effects. Because of the lowered bleeding risk of COX-2 inhibitors, they are often coadministered with antithrombotic agents, if there is concern for thrombosis in the postoperative period.

Multiple studies have demonstrated the efficacy of NSAIDs and COX-2 inhibitors in arthroplasty. Buvanendran and colleagues performed a randomized, placebo-controlled, double-blind trial using the selective COX-2 inhibitor rofecoxib. The study randomized TKA patients to receive either oral rofecoxib or a placebo. The patients received their medicine before and for 2 weeks after surgery. Patients in the treatment arm had less pain, nausea, and sleep disturbance. They also consumed fewer morphine equivalents of opioids. Moreover, patients with higher plasma levels of the COX-2 inhibitor preoperatively consumed less opioids afterward. Importantly, the treatment group also demonstrated improved active and passive knee range of motion at the time of hospital discharge and 1 month after surgery. Finally, the rofecoxib group showed higher patient satisfaction at discharge and at the 2 week and 1 month follow-up visits. Of note, none of the patients had any bleeding complications.