Anesthesia for Total Knee Replacement

Christopher S. Wahal, MD

Eric S. Schwenk, MD

INTRODUCTION

Total knee arthroplasty (TKA) is one of the most common operations performed in the United States with over 700,000 being performed annually.¹ With an aging population, the number of TKAs performed annually per capita is expected to increase by 150% by the year 2050.² Additionally, there is a greater push to decrease length of stay in the setting of rising healthcare costs. Complicating the matter is the intense and complex postoperative pain experienced after TKA, often considered one of the most painful orthopedic procedures.³ For these reasons, the importance of a multifaceted approach to pain as well as an anesthetic allowing for a rapid recovery is paramount to any TKA operative pathway.

PREOPERATIVE PHASE

One of the most important aspects of any operative pathway is the setting of realistic expectations for patients who are undergoing TKA. Educating patients and realistic goal setting typically begin with information provided on a pamphlet or website. Education then continues at the preoperative visit in the surgeon’s office, followed by preadmission testing when available, and lastly completed by the anesthesia team prior to surgery. At some institutions, the process has been streamlined by combining these visits.

Ideally, preadmission testing visits occur 3 to 4 weeks prior to the actual date of surgery. This allows the preoperative team to optimize the patient and intervene on any risk factors which could lead to increased perioperative morbidity. Modifiable risk factors include but are not limited to smoking, anemia, diabetic control, BMI, and significant opioid tolerance. Anemia has been shown to independently increase risk of infection, increase length of stay, and lead to a greater than twofold increase in mortality for noncardiac surgery.⁴

Preoperative testing not only allows for medical optimization, but it also allows for a detailed explanation of the anesthetic plan to be delivered to the patient as well as what to expect after surgery, reducing anxiety. High levels of stress and anxiety have shown to both inhibit wound healing and extend hospital length of stay.⁵ Alternatively, patients who have been mentally prepared for surgery with realistic expectations experience improved outcomes. Preemptive cognitive and behavioral interventions have shown to both increase the response to and decrease the consumption of analgesics and reduce postoperative pain.⁶ Even with the use of a multimodal analgesic regimen in combination with a regional anesthetic, patients should still expect to have discomfort in the immediate postoperative period. Telling patients that “you won’t have any pain” does them a disservice and is unrealistic. Patient expectations can even have an impact on a patient’s discharge destination (e.g., home versus a rehab facility or skilled nursing facility), where they have shown to be both an independent and strong predictor.⁷

Preoperative anesthetic evaluation begins with a complete history and physical to identify any specific medical conditions which could result in a challenging intraoperative and postoperative course. Patients are encouraged to stay well hydrated prior to surgery and may continue clear liquids until 2 hours prior to surgery. The opioid-tolerant patient deserves special attention. When compared to opioid-naïve patients, opioid-tolerant patients undergoing total hip arthroplasty had a longer length of stay, used more opioids, and were more likely to still be on opioids 6 weeks postoperatively.⁸ There is a dearth of evidence with respect to weaning opioids prior to total joint arthroplasty (TJA). One study showed improved functional outcomes in TJA patients who successfully weaned opioid use by at least 50% compared to patients who did not wean.⁹ However, there is no evidence comparing different opioid weaning strategies prior to TKR. It would be prudent to allow at least several weeks for patients to reduce opioid doses, especially if they are doing it on their own schedules. If weaning is not possible or desired, patients who are taking chronic opioids should be given their normal dose, whether it be immediate acting or sustained release, in addition to “as-needed” doses for breakthrough pain on the day of surgery. However, we recommend that multimodal nonopioid analgesics form the foundation of perioperative analgesia with opioids being reserved for severe pain not effectively treated with other agents. It is essential that a multidisciplinary discussion between the anesthesiologist and orthopedic surgeon take place to develop a postoperative plan. Adjustments to standard orders and pathways are often necessary. Opioid tolerance has been shown to be an independent predictor of increased length of stay and greater 30-day
readmission rates.¹⁰ Additionally, high pain trajectories postoperatively have also been shown to increase emergency room visits and readmission rates.¹¹ The consultation of an inpatient pain service, if available, may speed up discharge in these patients and help to prevent readmission for pain-related reasons.

The administration of analgesics prior to surgical incision is known as preemptive analgesia. The goal of preemptive analgesia is twofold: help limit opioid use and prevent peripheral and central sensitization that occurs with tissue trauma associated with surgery. In theory, through the administration of analgesics prior to surgical incision, the production of inflammatory mediators can be attenuated. Typically, inflammatory mediators generated from tissue trauma sensitize nerve fibers which can lead to nonpainful stimuli being perceived as painful (allodynia) and eventually be the genesis of chronic postsurgical pain.¹² Targets of specific analgesics use for TKA patients are shown in Fig. 3-1. The idea that preemptive analgesia can prevent sensitization remains controversial. The following sections will review some commonly used analgesics and available clinical evidence for their use.

FIGURE 3-1 Key elements of the pain pathway highlighting the pharmacological rationale of the multimodal approach. Note the different but complementary sites of action, producing the desired synergistic analgesic effects. DRG, dorsal root ganglion; NSAIDs, nonsteroidal anti-inflammatory drugs. (Halawi M, Grant S, Bolognesi M. Multimodal analgesia for total joint arthroplasty. Orthopedics. 2015;38:e616-e625. Reprinted with permission from SLACK Incorporated.)

MULTIMODAL AGENTS

Acetaminophen

Acetaminophen is one of the most common oral medications used to treat postoperative pain. While it has been available as an analgesic since the 1950s, its mechanism of action has still not been fully elucidated. Studies have shown it inhibits prostaglandins at a central level via the cyclooxygenase (COX) pathway, acts as a nitric oxide pathway inhibitor, acts on cannabinoid receptors, as well as modulates descending serotonergic pathways in the spinal cord.¹³ Despite being available over the counter, it is an effective analgesic and has been shown to have similar efficacy to intramuscular morphine 10 mg in treating moderate to severe pain.¹⁴ Additionally, it is generally well tolerated and has been extensively used both as an analgesic as well as an antipyretic for decades resulting in a well-known safety profile. When total daily dose is kept at or below 4 g, the risk for acute hepatotoxicity is rare, and its safety has also been confirmed in those with chronic liver disease.¹⁵ Acetaminophen has shown to decrease morphine use by up to 33% as well as provide
more effective pain control when compared to placebo.¹⁶ An additional benefit of decreased postoperative nausea and vomiting (PONV) has also been shown.¹⁷

FIGURE 3-2 Commonly used nonsteroidal anti-inflammatory drugs ordered in increasing ratio of COX-2 to COX-1 inhibition. Number represents the 80% inhibitory concentration ratios of COX-2 relative to COX-1 in human whole blood assays.⁸²

The Food and Drug Administration (FDA) recommends keeping the total daily dose of acetaminophen under 4 g.¹⁸ We recommend a scheduled dose of 650 to 1000 mg every 6 hours. While combination formulas (i.e., oxycodone/acetaminophen) are available, it is our experience that separating combination analgesics into their individual components will lead to more consistent administration of the nonopioid agents.

An IV formulation of acetaminophen has been available in the United States since being approved by the FDA in 2010. Proposed benefits of an IV formulation are pharmacokinetic data showing the IV formulation leads to higher concentration in the cerebral spinal fluid in the first 6 hours of therapy.¹⁹ However, the daily cost difference between 4 g of IV acetaminophen and 4 g of the PO formulation is substantial ($43 vs. $0.10), which has slowed its adoption.²⁰ Additionally, none of the limited number of randomized controlled trials evaluating the IV formulation versus the oral formulation in total joint arthroplasty has showed any significant differences in opioid consumption, pain scores, or length of stay.²¹,²²,²³

Nonsteroidal Anti-inflammatory Drugs

Nonsteroidal anti-inflammatory drugs (NSAIDs) are another class of highly effective nonopioid analgesics which have been extensively used to treat pain for centuries. Their mechanism of action, inhibition of the synthesis of prostaglandins, was first described in 1971.²⁴ They work by inhibiting the enzymes COX-1 and COX-2, which are responsible for the conversion of arachidonic acid to both prostaglandins and thromboxane A2.²⁴ When formed, prostaglandins, specifically prostaglandin E2 (PGE2), play a role in central sensitization, which can lower pain thresholds. The COX-1 isoform is expressed in most tissues, while the COX-2 isoform is normally found only in the brain and kidneys. However, production of COX-2 is induced when tissues are damaged and cytokines and growth factors are released. The prostaglandins that are produced sensitize tissues leading to increased levels of pain.²⁵

NSAIDs are used not only for their analgesic properties but also their anti-inflammatory and antipyretic effects. Despite their prevalent use, all prescription NSAIDs do carry a warning from the FDA due to their risk of gastrointestinal bleeding, cardiovascular side effects (increased risk of stroke and myocardial infarction), and risk of acute kidney injury.²⁶ NSAIDs are categorized into either nonselective or COX-2-selective agents, the latter of which were designed to reduce the risks associated with nonselective NSAIDs, such as gastrointestinal bleeding and platelet dysfunction.²⁷

Despite being categorized as “nonselective NSAIDs,” each drug varies in its selectivity for the COX-1 and COX-2 isoforms. Some commonly used NSAIDs and their degree of COX-2/COX-1 inhibition are displayed in Fig. 3-2. While no specific NSAID has been shown to provide superior analgesia, COX-2-selective drugs may be more desirable due to their more limited side effect profile. Celecoxib is the only FDA-approved COX-2-selective medication currently available in the United States. COX-2 inhibitors have been shown to reduce opioid consumption, pain, vomiting, and sleep disturbances as well as improve knee range of motion after TKA when used in addition to epidural anesthesia.²⁸

Gabapentinoids

Gabapentinoids, which consist of gabapentin and pregabalin, work by binding to the alpha-2-delta subunit of voltage-gated calcium channels and prevent the release of neurotransmitters. They work at both the level of the brain and dorsal horn of the spinal cord, where they decrease excitatory signaling. Both medications are renally cleared and doses need to be adjusted in patients with chronic kidney disease. Absorption between the two medications differs. With escalating doses of gabapentin, its absorption decreases. Pregabalin, on the other hand, is absorbed both more rapidly and in a linear fashion with escalating doses, leading to maximum plasma concentrations being achieved more quickly than with gabapentin.²⁹ Gabapentin has been available for over a decade longer than pregabalin, leading to a much larger wealth of studies evaluating gabapentin.

A recent meta-analysis of six studies with 859 TKA patients evaluated gabapentin versus placebo and found gabapentin resulted in statistically significant decreased opioid use at 12, 24, and 48 hours as well as decreased incidence of pruritis.³⁰ Another meta-analysis evaluating all types of surgery found gabapentin decreased opioid use and improved pain scores for the first 24 hours after surgery while also leading to decreased incidence of postoperative nausea, vomiting, pruritis, and preoperative anxiety while increasing patient satisfaction.³¹ In addition to the benefits seen in the immediate postoperative period, long-term benefits have also been observed. A 2-week course of pregabalin initiated on the day of surgery led to a decreased incidence in chronic neuropathic pain when compared to placebo (0% vs. 8.7% and 0% vs. 5.2% at 3 and 6 months, respectively) in TKA patients.³²

While numerous positive studies have been performed, there are some studies showing conflicting results. In a study comparing pregabalin to placebo in TKA patients who also received a femoral nerve block, epidural, oxycodone-paracetamol, and meloxicam, there was no difference in pain at rest or with ambulation, but the addition of pregabalin did result in a higher rate of sedation and decreased satisfaction.³³ Additionally, the incidence of sedation and dizziness with these medications is not insignificant and special attention should be paid to the elderly population.³¹ Despite these concerns, gabapentinoids provide several benefits in the TKA patient and we recommend their perioperative use. Dosing suggestions for common oral multimodal analgesics are provided in Table 3-1.

INTRAOPERATIVE PHASE

Anesthesia Techniques

The goal when choosing an anesthetic technique is to optimize operating conditions while also improving outcomes such as pain, PONV, and patient satisfaction. The decision is often based on the anesthesiologist’s, surgeon’s, and patient’s preferences; patient comorbidities and contraindications; and institutional protocols. The two most common options for TKA are neuraxial and general anesthesia.

TABLE 3-1 Recommended Dosing for Commonly Used Multimodal Oral Analgesics

Medication	Preoperative Dose (mg)	Route of Administration	Postoperative Dose
Acetaminophen	1000	PO/IV	650-1000 mg every 6 hours
Celecoxib	400	PO	200-400 mg every 12 hours
Gabapentin	300	PO	300-1200 mg every 8-12 hours
Ketorolac	15-30	PO/IV	15-30 mg every 6 hours, max of seven doses
Meloxicam	7.5-15	PO	7.5-15 mg every 24 hours
Pregabalin	75	PO	75-150 mg every 12 hours

Neuraxial anesthesia includes both spinal anesthesia as well as epidural anesthesia. Spinal anesthesia involves the injection of a local anesthetic directly into the intrathecal space, while epidural anesthesia often involves the placement of a catheter into the epidural space, which is subsequently dosed with a local anesthetic. Recent database studies have shown numerous benefits of spinal anesthesia compared to general anesthesia. One such study from 2013 of over 14,000 patients showed spinal anesthesia was associated with lower rates of wound infections (0.68% vs. 0.92%), blood transfusions, and complications in addition to decreased operating time and hospital length of stay.³⁴ These differences were again noted, with the exception of operating time, in another large database study of 1236 patients from 2017.³⁵

There are numerous choices for local anesthetic as well as opioid additives used during spinal anesthesia. The most commonly used local anesthetics are 0.5% isobaric bupivacaine, 0.5% hyperbaric bupivacaine, and 0.75% hyperbaric bupivacaine. Typical doses range from 7.5 to 15 mg of bupivacaine for a primary TKA, with larger doses being used for longer surgical times. Lower doses have been shown to be effective; for example, one study evaluating the optimal intrathecal dose of 0.5% isobaric bupivacaine for fast-track TKA found an ED95 of 5 mg.³⁶ In addition to local anesthetics, opioids can also be administered intrathecally with the spinal anesthesic. Intrathecal morphine has been used effectively to treat pain associated with major orthopedic surgery for a number of years.³⁷,³⁸ It has been shown to provide similar postoperative analgesia to a single injection femoral nerve block in TKA patients.³⁹ The use of intrathecal opioids, especially morphine, comes with the drawback of increased side effects such as sedation, pruritis, nausea, vomiting, urinary retention, and delayed respiratory depression which can last for up to 24 hours. In healthy volunteers, doses as low as 200 mg have shown to produce respiratory depression.⁴⁰ Due to the increased incidence of side effects with intrathecal morphine, we utilize a local anesthetic only spinal for our TKA patients.

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