Evidence-Based Orthopaedic Post-Operative Opioid Prescribing Recommendations Following Hip and Knee Arthroplasty

Total knee arthroplasty (TKA) and total hip arthroplasty (THA) are frequently performed surgeries to relieve joint pain, with TKA known for its high postoperative pain rates. However, the rise in opioid prescriptions for managing pain, including chronic pain, has led to concerns among healthcare professionals and researchers due to the significant number of opioid-related deaths and nonfatal overdoses, emphasizing the need for alternative pain management strategies. The current guidelines established by the American Association of Hip and Knee Surgeons (AAHKS) recommend non-opioid multimodal anesthesia strategies and cautious opioid use for primary total joint arthroplasty. A multimodal anesthesia approach is recommended for all hip and knee arthroplasty procedures, with a preference for surgeon-administered intraoperative intra-articular adductor canal blocks and pericapsular injections for TKAs. For THAs, a local soft tissue injection is administered, and a fascia iliac block is recommended if a block is necessary.


INTRODUCTION
Two of the most frequent and effective surgical procedures to alleviate pain in the affected joint are total knee arthroplasty (TKA) and total hip arthroplasty (THA). 1,2The number of arthroplasty surgeries performed annually is estimated to rise remarkably. 3TKA is widely acknowledged as one of the most painful orthopedic surgeries, with 60% of patients experiencing intense pain following the procedure. 4Post-surgical pain hinders early movement, delays the start of physical therapy, and extends the rehabilitation period. 5n the US, between 1999 and 2020, over 564,000 individuals lost their lives due to an overdose that involved any form of opioid, including both prescription and illegal opioids. 6The number of nonfatal drug overdoses far exceeds the number of overdose-related deaths; each nonfatal overdose carries its own emotional and economic burden. 6pioid drugs are now commonly prescribed as the first or second option for primary care providers to manage pain associated with osteoarthritis. 7From 2003-2009, there was a significant rise in the prescription of opioids for knee osteoarthritis symptoms, with an increase from 31% to 40%. 8ile opioids are the primary approach to pain management after discharge following TKA and THA, there is increasing scrutiny among clinicians and researchers regarding their prolonged use for treating chronic pain. 9pioid medications are frequently prescribed by surgeons specializing in total hip and knee surgeries to manage post-operative pain.However, it has been observed within this field that when more significant amounts of opioids are prescribed, patients tend to consume more of these medications, which increases their risk of dependence and addiction. 10,11Arthroplasty surgeons and other healthcare providers who prescribe pain medications must prioritize the improvement of opioid prescribing practices through opioid stewardship while also ensuring that their patients' pain management needs are met.

PROBLEM STATEMENT
Following primary hip and knee arthroplasty surgeries, there is a risk that postoperative opioid prescribing may lead to unintended consequences such as dependency, abuse, diversion, and even death.However, there is a lack of clear guidelines regarding appropriate opioid dosing and pain management strategies in this context.

PROPOSED SOLUTION
Comprehensive, evidence-based guidelines for postoperative pain management regimens following primary hip and knee arthroplasty are available.These guidelines can be found on the website of the American Association of Hip and Knee Surgeons (AAHKS) (https://www.aahks.org/clinical-practice-guidelines/),which are grounded in evidence published in both the arthroplasty literature and the broader medical and surgical literature.We aim to offer evidence-based recommendations for prescribing pain medication based on our institution's specific practices.

STRATEGIES
Individual pain management needs can vary depending on a variety of factors.Pain management principles are generally categorized according to the type of pain, including acute, post-operative, chronic, and palliative pain management.This review will focus on acute and post-operative pain management principles and present the most up-todate evidence-based recommendations for defining these principles. 12In this section, you will find the principles that define postoperative analgesia regimens, whereas specific recommendations for evidence-based regimens will be provided later.
It is advisable to integrate non-pharmacological approaches into the treatment plan whenever feasible.Such policies may involve but are not restricted to, rest, ice, elevating the affected area, and utilizing surgical dressings that are securely fastened but not excessively tight. 13on-opioid analgesics should be considered a first-line pharmacologic treatment for pain and the foundational agent in a multi-modal pain management strategy of pain.Moreover, non-opioid analgesics are best utilized on standing rather than on an as-needed (PRN) basis.5][16] Regimens are further detailed below.However, opioid-acetaminophen combination medica-tions (i.e., Percocet, Roxicet, Vicodin, etc.) should be avoided to prevent accidental overdosing on acetaminophen.
To assist with decreasing post-operative pain and opioid consumption, regional blocks and/or periarticular injections are recommended. 17The advantage of a periarticular injection over a regional block is that it produces no motor blockade, in turn allowing for faster and safer patient mobilization post-operatively. 18While no consensus periarticular injection combination exists, our preferred injection combination and surgeon-administered adductor canal block are included in Table 1.
Risk factors for opioid abuse and dependence should be considered prior to providing opioid prescriptions.These include preoperative opioid use, psychiatric conditions, chronic pain syndrome, and longstanding back pain. 19,20roviders should utilize their state's Prescription Drug Monitoring Program (PDMP) to review the patient's prescription drug history before prescribing opioids and periodically throughout their course of therapy beyond the acute period.
Before prescribing an opioid, counseling on safe opioid use should be performed with the patient.2][23][24] Counseling should establish the duration of therapy and goals of opioid use (patients are recommended to start weaning medications by three weeks postoperative with a maximum time of opioid use set at eight weeks) and may include the use of a physician-patient opioid agreement.Lastly, patients should be advised on safely storing prescribed opioids to avoid diversion and abuse. 25f an opioid is prescribed, the lowest dose and shortest duration possible should be prescribed. 26The CDC recommends a maximum of 50 morphine milligram equivalents (approximately six doses of 5mg of Oxycodone) for no more than 3-7 days in most acute musculoskeletal injuries.There is no clear recommendation from the CDC for postoperative prescribing.However, surgeons should work to keep the use of opioid pain medications as short as possible while still providing adequate pain control.Tramadol may be considered an alternative first-line opioid agent as it is equally effective as other more potent opioids but with a lower risk of dependency. 27Medication interactions with tramadol must be considered on an individual basis.
Surgeon prescribers should engage other providers in the patient's healthcare delivery team during the perioperative period (i.e., primary care provider or pain management specialist).This communication can avoid doubleprescribing and discrepancies in prescribing assumptions. 28If patients with prior opioid use history proceed to surgery, baseline opioid prescription doses should be continued, and postoperative analgesia is best managed by their pain management provider, if applicable.

Whenever feasible, non-pharmacological treatment
approaches should be utilized.2. Non-opioid analgesics, combined with periarticular injections and regional blocks, should be regarded as the initial option for pain management prescription and are preferably prescribed as a standing regimen rather than on an as-needed basis.3. Opioids should only be administered as needed for breakthrough pain and at the lowest feasible dose, duration, and quantity.4. Before prescribing an opioid, risk factors for opioid abuse should be considered.5.When prescribing opioids, education on their use should be provided.
Evidence-Based Orthopaedic Post-Operative Opioid Prescribing Recommendations Following Hip and Knee Arthroplasty SurgiColl MEDICATIONS

NON-STEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDS)
The AAHKS Clinical Practice Guideline (CPG) for NSAIDs recommends oral NSAID use in the immediate preoperative and/or early postoperative period.There is strong evidence for administering oral NSAIDs at this time to reduce pain and opioid consumption following primary TJA. 29Based on one high-quality study, moderate evidence supports preoperative administration of an oral selective cyclooxygenase inhibitor (COX-2) NSAID.A perioperative oral selective COX-2 NSAID dose led to better pain control.It reduced opioid consumption following primary TJA compared to giving the first NSAID dose in the early postoperative period. 29,30][33] Intravenous (IV) ketorolac given preoperatively, intraoperatively, or within 24 hours postoperatively was strongly recommended for reduction in pain and opioid consumption postoperatively following primary TJA.Regarding lowdose (15 mg) versus high-dose (30 mg) administration of IV ketorolac immediately postoperatively, there was a moderate recommendation that they are equivalent to reducing pain and opioid consumption within the first six-hour postoperative period. 29ollowing discharge, the CPG has a moderate recommendation for administering oral selective COX-2 NSAID to reduce pain and opioid consumption during the six weeks following a primary TKA. 29There is also a consensus recommendation for using COX-2 NSAIDs after discharge as part of a multimodal pain regimen to reduce postoperative pain and opioid consumption in patients undergoing primary THA. 29It is important to note that this recommendation only exists for an oral COX-2 NSAID because no studies on non-selective NSAIDs could likely be used similarly.
Regarding the risk of postoperative medical complications from NSAIDs given preoperatively, intraoperatively, or postoperatively, there is a limited recommendation that oral and IV NSAIDs administered in this period do not appear to increase the risk of medical complications following primary TJA.Still, patient factors and length of administration must be taken into consideration. 29tandard precautions and contraindications of NSAIDs should be considered, and pharmacy or medical specialists should be consulted for assistance in unclear cases.NSAIDs should be used cautiously in patients with renal insufficiency, cardiovascular disease, GI bleeding, and anticoagulation/antiplatelet therapy.A concomitant proton pump inhibitor, such as omeprazole 20 mg BID or pantoprazole 40 mg daily, can be used in patients over 50 years old and/or with gastric ulcer risk factors while taking NSAIDs, particularly since many patients will also be taking aspirin concurrently for venous thromboembolism prophylaxis.Daily ibuprofen dose should not exceed 2400 mg, and daily naproxen dose should not exceed 1100 mg (initial day can be up to 1375 mg). 25

ACETAMINOPHEN
The AAHKS CPG for Tylenol use in primary TJA gives a moderate recommendation for perioperative administration of IV or oral acetaminophen to reduce pain and opioid consumption during the perioperative period of primary TJA. 34This moderate recommendation may change soon as the reason for IV acetaminophen being given a moderate recommendation instead of a strong recommendation was related to its high cost compared to oral acetaminophen.In December 2020, the US Food and Drug Administration (FDA) approved generic versions of IV acetaminophen, which may lower the current cost.The moderate recommendation for oral acetaminophen over a strong recommendation is secondary to inconsistencies in the data comparing it to a placebo. 34Following discharge, a consensus is that oral acetaminophen may be part of a multimodal pain regimen.This recommendation is based on the low cost and low risk of acetaminophen in treating pain following primary TJA. 34he FDA recommendation remains a maximum of 4000 mg daily for less than ten days in healthy adults with normal liver function, no other acetaminophen sources, and less than two alcoholic drinks daily.Recently, recommendations have been made to limit acetaminophen dosing to 3000-3250 mg daily due to reports of overdose in patients taking standard doses up to 4000 mg daily. 25However, these reports have been due to patients unintentionally ingesting acetaminophen through additional sources (sleep medications, cough medications, etc.).Patients with abnormal liver function tests, active hepatitis, cirrhosis, or another active hepatic disease should consider a maximum of 2000 mg daily or less.Standard precautions and contraindications to acetaminophen use should be regarded, and pharmacy or medical specialists should be consulted for assistance in unclear cases.

GABAPENTINOIDS
The AAHKS CPG strongly recommends the perioperative use of pregabalin but not gabapentinoids to reduce opioid consumption after primary TJA. 35A moderate strength recommendation was given that there is no difference in postoperative pain, opioid consumption, or complications between low-dose and high-dose gabapentinoids.This recommendation included a strong warning that gabapentinoids may lead to an increased risk of confusion among elderly patients and respiratory depression when used with opioids. 35Following discharge, pregabalin is strongly recommended to reduce postoperative pain, neuropathic pain, and opioid consumption after TJA, but gabapentin does not appreciably reduce pain or opioid consumption. 35

REQUIREMENTS
AAHKS, AAOS, Hip Society, Knee Society, and The American Society of Regional Anesthesia and Pain Medicine have Evidence-Based Orthopaedic Post-Operative Opioid Prescribing Recommendations Following Hip and Knee Arthroplasty SurgiColl collaborated to develop evidence-based guidelines on the use of opioids in TJA as outlined in the CPG.
7][38][39][40] Additionally, there is a correlation between a higher dose of opioids preoperatively and the associated risk of infection and revision surgery. 413][44] Due to heterogeneity in endpoints while examining this evidence, the AAHKS CPG provides a moderate strength recommendation on the association of increased risks and complications, as well as more significant opioid use, in these patients compared to those that are opioid naïve.Therefore, efforts should be made to wean patients off opioids, in coordination with pain management specialists, before TJA if feasible.Although of lower quality, one retrospective study by Ngyuen et al. demonstrated that a reduction in 50% of opioids before surgery resulted in significantly better patient-reported outcomes. 45erioperative administration of opioids is vital in pain management following TJA.Pre-emptive administration of opioids has been shown to lower VAS pain scores and lower morphine consumption post-operatively. 46While additional pre-operative opioids may pose an added risk, the AAHKS CPG strongly endorsed its preoperative administration.Furthermore, intraoperative opioid administration received a moderate strength recommendation due to its ability to decrease opioid consumption within the immediate postoperative period. 47,48hile scheduled opioid administration during the immediate 72-hour post-operative period decreases pain and the need for breakthrough medication, the AAHKS CPG provides a moderate-strength recommendation discouraging this practice due to the associated risks. 491][52] The work group acknowledges risks related to opioid consumption, such as respiratory depression and constipation.Given these risks, it is also essential to be cautious with the use of extendedrelease formulations. 53,54ost-operatively, patients often require opioids upon discharge.Regarding the number of pills a patient should receive, Hannon et al. performed a randomized control trial which demonstrated that when patients were sent home with 30 pills of immediate-release oxycodone as opposed to 90, they had identical pain scores and patient-reported outcomes with no difference in morphine equivalents consumed. 55ramadol is a partial agonist with a milder side-effect profile often utilized in multi-modal regimens.[58]

RECOMMENDATIONS
The existing guidelines, as established by AAHKS on nonopioid multimodal anesthesia strategies and opioid use for primary TJA, have been presented thus far.We recommend a multimodal anesthesia strategy for all hip and knee arthroplasty procedures.For TKAs, we prefer a surgeonadministered intraoperative intra-articular adductor canal block, as previously described by Pepper et al., in addition to a pericapsular injection. 59,60If regional blocks are used for TKAs, adductor canal blocks are recommended over femoral blocks to decrease the risk of delayed return of motor function post-operatively. 61,62For THAs, a local soft tissue injection is given.A fascia iliaca block is recommended if a block is needed. 63Our preferred combination for the local infiltration injection is included in Table 1.As published by Karam et al., Table 2 displays a suggested immediate postoperative analgesia regimen.Variations on this protocol are effective.Table 3 shows a recommended discharge analgesia regimen that should be continued for two weeks. 16

CONCLUSIONS
Opioid stewardship by arthroplasty surgeons is more imperative than ever and can substantively help combat the opioid epidemic.Non-opioid analgesics should be the firstline treatment for pain and the foundation of a multi-modal pain management strategy.
Risk factors for opioid abuse and dependence should be considered prior to prescribing opioids.And counseling on safe opioid use should be performed with the patient before prescribing an opioid.The lowest dose and shortest duration possible should be prescribed for opioids, and other medications should be considered as alternatives.

TABLE 2 . RECOMMENDED POSTOPERATIVE ANALGESIA, AS ADOPTED FROM KARAM ET AL. 16
*if ≥ 65, 15 mg instead of 30 mg ketorolac is used.Ketorolac is not given to patients with chronic kidney disease THA: Total hip arthroplasty; TKA: Total knee arthroplasty; PO: Per os; BID: Bis in die (twice daily); PRN: Pro re nata (Per needed)

TABLE 3 . RECOMMENDED DISCHARGE ANALGESIA, AS ADOPTED FROM KARAM ET AL. 16 Surgery Type Medication Dosing Pills Prescribed
: Total hip arthroplasty; TKA: Total knee arthroplasty; PO: Per os; BID: Bis in die (twice daily); PRN: Pro re nata (Per needed) THA