The Opioid Crisis and the Orthopedic Surgeon

The Opioid Crisis and the Orthopedic Surgeon

Accepted Manuscript The opioid crisis and the orthopedic surgeon Nicholas A. Trasolini, MD, Braden McKnight, MD, Lawrence D. Dorr, MD PII: S0883-5403...

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Accepted Manuscript The opioid crisis and the orthopedic surgeon Nicholas A. Trasolini, MD, Braden McKnight, MD, Lawrence D. Dorr, MD PII:

S0883-5403(18)30610-7

DOI:

10.1016/j.arth.2018.07.002

Reference:

YARTH 56698

To appear in:

The Journal of Arthroplasty

Received Date: 29 June 2018 Accepted Date: 2 July 2018

Please cite this article as: Trasolini NA, McKnight B, Dorr LD, The opioid crisis and the orthopedic surgeon, The Journal of Arthroplasty (2018), doi: 10.1016/j.arth.2018.07.002. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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Please address all correspondence to:

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Lawrence D. Dorr, MD Keck Medical Center of USC 1520 San Pablo Street, Suite 2000 Department of Orthopedics Los Angeles, CA 90033 Phone 323-442-7974 FAX 323-865-9438 Email: [email protected]

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1. Keck Medical Center of USC 1520 San Pablo Street, Suite 2000 Department of Orthopedics Los Angeles, CA 90033 Phone 323-442-7974 FAX 323-865-9438 Email: [email protected]

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Nicholas A. Trasolini, MD1 Braden McKnight, MD1 Lawrence D. Dorr, MD1

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The opioid crisis and the orthopedic surgeon

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The opioid crisis and the orthopedic surgeon

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Abstract

Opioid use and abuse has become a National crisis in the United States. Many opioid abusers

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become addicted through an initial course of legal, physician-prescribed medications.

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Consequently, there has been increased pressure on medical care providers to be better stewards

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of these medications. In orthopaedic surgery and total joint replacement, pain control after

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surgery is critical for restoring mobility and maintaining patient satisfaction in the early post-

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operative period. Prior to the opioid misuse epidemic, orthopaedic surgeons were frequently

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influenced to “treat pain with pain medications.” Long acting opioids, such as Oxycontin

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(Purdue Pharma, Stamford, CT), were used commonly. In the past decade, there has been a

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paradigm shift in favor of multimodal pain control with limited opioid use. This review will

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discuss four major topics. First, we will describe the pressures on Orthopaedic Surgeons to

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prescribe narcotic pain medications. We will then discuss the major and minor complications and

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side effects associated with these prescriptions. Second, we will review how these factors

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motivated the development of alternative pain management strategies and a multimodal

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approach. Third, we will look at peri-operative interventions that can reduce post-operative

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opioid consumption, including wound injections and peripheral nerve blocks, which have shown

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superb clinical results. Finally, we will recommend an evidence-based program that avoids

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parenteral narcotics and facilitates rapid discharge home without readmissions for pain-related

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complaints.

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Introduction

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The United States is facing a significant opioid misuse epidemic. A percentage of opioid users

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begin their cycle of dependence after receiving legal opioid prescriptions from medical

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providers1. Opioid-naïve patients undergoing surgery are especially at risk for chronic opioid

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dependence2. Orthopaedic surgery specifically accounts for an estimated 8.8% of these cases1.

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This creates both a responsibility and an opportunity for orthopaedic surgeons. Elimination of

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the use of parenteral narcotics in the acute post-operative setting will reduce the rates opioid

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misuse and dependence (particularly, if the take home medications do not include Oxycontin). In

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addition, more limited use has the potential to reduce the incidence of harmful opioid side

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effects. Opioid medications can cause nausea, vomiting, constipation and sedation. More severe

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reactions can include respiratory depression, hypotension, ileus, urinary retention, and

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dehydration. Managing pain without parenteral morphine, meperidine, epidural narcotics and

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patient-controlled analgesia (PCAs) is an attainable goal that every orthopaedic surgeon

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performing total hip and total knee arthroplasties should strive to achieve.

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How did we get here?

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Arthroplasty procedures require deep dissection, soft tissue releases, and bone cuts. These

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invasive maneuvers are inherently painful. Consequently, pain after arthroplasty cannot be

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avoided entirely by surgical technique. In the early era of total joint replacement, surgeons often

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employed large incisions with extensive dissection. Recovery often necessitated long hospital

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stays3. More refined techniques allowed for more limited dissection and shorter hospital stays4,5.

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Nonetheless, patients continued to have pain post-operatively that limited early mobilization. In

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fact, the amount of pain that patients have is the most important determinant of satisfaction after

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surgery6.

52 While there is limited published data on pain management protocols prior to the 2000s, reports of

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non-narcotic treatments such as epidural bupivicaine and continuous cooling pads can be found

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as early as 1989 and 1991, respectively7,8. In addition, investigations into the adverse effects of

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opioids on arthroplasty patients began as early as 19859. In the past 15 years, there has been an

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exponential increase in published reports on alternative pain management strategies in

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arthroplasty patients.

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Prior to the recognition of the opioid epidemic, surgeons were encouraged to treat this pain with

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pain medications. There was pressure to prescribe pain medications whenever pain was reported.

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Much of this pressure was in response the work of Dr. Mitchell Max in 1990, which promoted

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more awareness of patient’s pain levels and more therapeutic use of opioids10,11. Pain became

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marketed as the “fifth vital sign” and an “enemy that needed to be eradicated” 11. By 1999, the

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California legislature had passed an act requiring that facilities record pain levels along with

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routine vital sign measurements12. Over this time period, opioid prescribing grew from 76

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million prescriptions in 1990 to 116 million in 1999 and 219 million by 201111.

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When Oxycontin was FDA-approved in 1995, it rapidly became one of the most highly

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prescribed pain medications because of its efficacy and misleading reassurance that it was not

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addicting13. In many ways, this would drive the opioid crisis. It was easy for doctors to write a

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prescription for an opioid pain medication any time patients called in with complaints of pain.

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This became the habit in the offices of many physicians. The situation was exacerbated by

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aggressive sales and marketing strategies from Purdue Pharmaceuticals13. Unknown to

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physicians initially, Oxycontin in its original form was a rapidly addictive medication. By 2004,

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Oxycontin was already a leading drug of abuse in the US13.

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77 The risks of opioids in the acute post-operative period

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The majority of the arthroplasty population is 65 years and older and patients often suffer from

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multiple medical co-morbidities. Many patients in this population live in a delicate medical

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balance in the post-operative setting. Patients are at increased risk for delirium and lethargy with

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the use of morphine and parenteral narcotics. They are also at risk for falls due to lower

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extremity pain and post-operative weakness. As mentioned above, patient satisfaction is often

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determined by the efficacy of pain control, but it is also determined by the presence of nausea

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and vomiting14,15. Opioid medications, and parenteral opioids in particular, carry risks of nausea,

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constipation, and cognitive impairment16. Parenteral narcotics can also cause respiratory

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depression, hypotension, urinary retention, and dehydration.

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Some patients are at elevated risk for adverse reactions and prolonged opioid dependence.

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Patients with depression, drug or alcohol use, and benzodiazepine use have been shown in a

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large database study to be at increased risk for chronic opioid use after surgery17. A smaller study

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found back pain and diabetes to be contributing factors18. Opioid use pre-operatively is also a

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risk factor for increased surgical complications. A prospective series of 802 patients found that

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pre-operative opioid users required more post-operative intravenous rescue narcotics despite the

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use of a multimodal pain regimen19. This cohort also had increased in-hospital complications, the

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most common of which was the need for intravenous fluid bolus for hypotension or decreased

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urine output. The effects can also be seen on a broader scale. A study of the NIS database found

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that pre-operative opioid abusers were at increased risk for morbidity and mortality after

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orthopaedic surgery20. The pre-operative opioid users are also at risk for long term complications

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and have been shown to have worse outcome scores and higher rates of total knee arthroplasty

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revisions compared to matched controls21.

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Recognition of these risks of medication side effects, prolonged dependence, and post-operative

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complications necessitated a new approach to pain management. The advent of alternative

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treatment ideas, with improved understanding of the physiology of pain, lead to a paradigm shift

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in arthroplasty pain management - the multimodal pain management model.

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The multimodal pain control model

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In 2001 and 2002 the opioid epidemic was not entirely recognized, but there was a desire to

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shorten hospital stays, send patients home as opposed to rehab units, and make the experience

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with total joint replacement a more comfortable one. To accomplish this, the pioneer of

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multimodal pain regimens, Richard Berger at Rush Medical Center, began to realize that patients

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undergoing ACL reconstructions could leave same day. As such, he applied the regimens used in

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ACL surgery at their institution to joint replacement patients. Those regimens include: pre-

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medication with selective nonsteroidal anti-inflammatory medications (e.g. celecoxib), consistent

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generous fluid hydration, propofol sedation, anti-emetic medications, and epidurals22.

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Adequate pain control in the perioperative period is associated with reduced hospital length of

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stay, a decreased rate of readmission, fewer post-operative complications, and improved patient

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satisfaction with surgery. Prior to the advent of multimodal pain control, much of post-operative

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analgesia was accomplished with patient controlled parenteral narcotic pain medication. While

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high enough doses could be effective in controlling pain, side effects including nausea and

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lethargy prevented early aggressive physical therapy, extended hospital stays, and often resulted

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in discharging patients to rehab facilities as opposed to home. Avoiding these as well as more

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dreaded side effects of parenteral opioids including respiratory depression, ileus, urinary

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retention and drug induced hypotension drove the development of multimodal pain regimens for

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total joint arthroplasty.

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As the name implies, multimodal pain regimens utilize medications that work on multiple

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locations of the pain pathway via different mechanisms to produce analgesia. This concept23,24

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involves prevention of pain transduction (local tissue), transmission (peripheral nerves and spinal

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cord), and perception (brain). When tissue damage occurs the inflammatory cascade is activated

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in the traumatized tissue which causes the production of inflammatory markers, partly via the

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cyclooxygenase (COX) pathway, that initiate the peripheral pain signal. Nociceptors in

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peripheral nerves are activated and begin sending signals via neurotransmitters to cells in the

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dorsal horn of the spinal cord. This signal is then relayed up the white matter spinothalamic

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tracts and to the thalamus. The thalamus transmits this to the cerebral cortex and the receipt of

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this signal is perceived as acute pain (Figure 1).

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In the early 2000s these principles began to gain popularity in total joint arthroplasty with a

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number of studies outlining strategies to modulate the pain pathway at each of these points with

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the goal of decreasing parenteral opioid use25–31. These studies showed that utilizing a

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multimodal pain control regimen could result in improved pain control with a lower rate of side

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effects compared to historical controls using predominantly parenteral opioids26.

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In the multimodal model, brain perception of pain is first influenced by pre-operative classes to

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teach patients what to expect with surgery and what a successful pain management program will

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provide25,26. This is perhaps the most important arm of the treatment program because it is in the

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pre-op class that the patient can be effectively conditioned into expecting that their pain will be

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controlled and will not be intolerable. It is emphasized to them that they will get pre-emptive

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medications. This reduces the anxiety of worrying that they will face delays from pain onset to

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medication deliverance. This conditioning of the cortex of the brain is critical, because if it is not

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done and pre-emptive medications are not given, the brain is conditioned the opposite way and

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any stimulus will cause pain. Deconditioning is very difficult so patients enter an unpleasant

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cycle of exaggerated pain response and diminished pain medication effects. This is why pre-

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operative education and preparation is perhaps most important. An aggressive pre-medication

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protocol is then utilized which prevents extreme pain at any time point, thereby preventing

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central sensitization which has been shown to augment the perception of pain23,32. Part of this

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pre-medication involves the use of acetaminophen which works as a centrally acting analgesic

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agent by blocking the COX-3 enzyme in the thalamus, increasing a patient's overall pain

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threshold33. Other commonly utilized medications at this pre-operative time point include COX-2

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inhibitors (most commonly Celebrex), which decrease the local production of prostaglandins to

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dampen the local inflammatory response, are also employed. The main reason to give these is to

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neutralize transmission of the dorsal spinothalamic tract, which is inhibited by COX-2

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inhibitors34. COX-2 blockers work in the spine and at the local tissues while COX-3 blockers

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work at the thalamus. Oral opioids may also be used, which act to inhibit the ߤ-receptor thereby

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decreasing the production of excitatory neurotransmitters. The most frequently used narcotic pre-

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medication is Oxycontin which is used only as a pre-operative medication. Some surgeons

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continue to use it in the post-operative period, but we would recommend against that, except in

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rare cases. In our 10-year experience, we have not found it necessary to use Oxycontin except in

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rare cases. Patients that come into the hospital as Oxycontin abusers are managed by the pain

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management service, with the goal of weaning off of these medications.

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During surgery, much of a multimodal pain management strategy is targeted at producing a

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localized response, rather than a systemic one. Use of epidural anesthesia, regional blocks like

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adductor canal never blocks, and periarticular injections have all proven to decrease post-

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operative pain, improve patient satisfaction, and accelerate the progression with physical

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therapy15,30,35–37.

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Post-operatively, a combination of peripherally and centrally acting agents are used to optimize

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analgesia and prevent opioid use. It is critical that postoperative mediations are given

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preemptively. These include NSAIDS and other COX inhibitors, peripheral nerve blocks, oral

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opioids, icing, and alpha-agonists such as gabapentin. Ketamine, an N-methyl-D-aspartate

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(NMDA) receptor antagonist, has also been shown to be effective in this time period to reduce

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pain scores and total morphine consumption38. Although there are multiple studies that have

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looked at the individual components of the multimodal program trying to determine if one is

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more important than the other, that is not the purpose of the program. To effectively use the

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multimodal program means that you do everything possible to reduce the pain - from pre-

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operatively preparing the patient to intra-operative injections and post-operative medications. We

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do not see a purpose in separating the components, because their true value is in their synergistic

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effect. In our experience, patients that are 80 years of age or older (and most 75 years of age or

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over) can be treated with medications of Tylenol or Tramadol post-operatively, combined with

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ice and pre-operative education. Rarely, do we have to use any opioid medications in these

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patients. Only after all other avenues are exhausted are parenteral opioids used to prevent

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breakthrough pain. In the post-operative period there is also a strong emphasis on nausea control

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with ondansetron and metoclopramide. Nausea and emesis are known to decrease satisfaction in

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a way similar to pain. Controlling these side effects of anesthesia and narcotics is critical.

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With the multimodal model, patients on the floor are given scheduled (pre-emptive) medications

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as opposed to having the ask the nurse for them. This is particularly important in the first 48

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hours to prevent imprinting and sensitization to pain. In our experience, 25% of post-op patients

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require a breakthrough dose of hydromorphone (Dilaudid) in the post-anesthesia care unit, but on

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the inpatient floor only 3% require this. A well-administered multimodal program can nearly

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eliminate the need for parenteral narcotics. Total knee replacement patients require parenteral

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narcotics more often than THA patients. In our experience with THA patients, the use of pre-

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operative classes, medications, and the use of spinal anesthesia and intra-operative wound

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injection of morphine, ketorolac (Toradol), and rupivicaine have eliminated the need for oral

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pain medications stronger than Norco. In patients >80yo, acetaminophen (Tylenol) is all that is

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required. Two other important treatments post-operative include the use of IV cortisol as

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recommended by HSS39, and the other is the use of ice which is used around the clock for 24-

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4840. We encourage patients to use it for the first week at home.

212 In total knee replacement patients, an adductor canal nerve block is used in all patients which

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gives these patients excellent pain relief. The use of nerve blocks in both the hip and the knee

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have been documented most completely by the Mayo Clinic37. We send these patients home with

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the nerve block in place and teach them how to remove it. They can keep it for 1-3 days. This is

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the main difference between knee and hip patients at our institutions. Ice may also be more

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effective in this patient population owing to the superficial nature of the knee joint. In both hip

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and knee patients the home pain medication is whatever they required in the hospital (e.g. Norco,

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acetaminophen, tramadol) and each patient is asked to take celecoxib 200mg 2x per day for 3

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weeks. We do not send patients home on Oxycontin or Percocet. Each patient is also called at

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home at least once in the first week which significantly reduces emergency room visits. If there

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are issues identified, they are dealt with on an outpatient basis. With this multimodal program we

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have no readmissions for pain control. Our rate of patients going to rehabilitations units with this

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program is 1%. We make it clear to patients that the expectation is to go home and arrangements

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are made with patients and their families to go home post-operatively.

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Summary/Conclusion

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The opioid epidemic was stimulated by the government and industry and not by doctors. After

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being instructed to provide more access to narcotic medications, doctors became the villain when

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the ill effects of these medications became apparent. It was doctors who recognized this problem,

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and initiated the multimodal protocols that are effective and have eliminated the need for

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parenteral narcotics and strong oral narcotics (e.g. Oxycontin). The orthopaedic community has

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been very responsive in converting to multimodal programs. This article summarizes the history

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of the problem for the orthopaedic surgeon and outlines a successful multimodal program for

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those that still have not initiated one. Our experience with using a multimodal program without

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parenteral narcotics is now beyond 10 years. We reduced our inpatient rehab load from 40% to

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1%. We reduced our hospital stays from 5.2 days to just over 1 day. We have been sending many

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patients home the same day since 2005. We are not the only group with this success. There is

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plenty of clinical experience to support the use of multimodal programs without parenteral

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narcotics, Oxycontin, or Percocet. It is our hope that this trend will continue as we strive to

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provide our patients with compassionate pain relief without addiction and narcotic side effects.

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Dalury DF, Lieberman JR, Macdonald SJ. Current and innovative pain management techniques in total knee arthroplasty. Instr Course Lect. 2012;61:383-388. http://www.ncbi.nlm.nih.gov/pubmed/22301246. Reuben SS, Sklar J. Pain management in patients who undergo outpatient arthroscopic surgery of the knee. J Bone Joint Surg Am. 2000;82-A(12):1754-1766. http://www.ncbi.nlm.nih.gov/pubmed/11130650. Zhou TJ, Tang J, White PF. Propacetamol versus ketorolac for treatment of acute postoperative pain after total hip or knee replacement. Anesth Analg. 2001;92(6):15691575. http://www.ncbi.nlm.nih.gov/pubmed/11375848. Yamamoto T, Sakashita Y. COX-2 inhibitor prevents the development of hyperalgesia induced by intrathecal NMDA or AMPA. Neuroreport. 1998;9(17):3869-3873. http://www.ncbi.nlm.nih.gov/pubmed/9875720. Pagnano MW, Hebl J, Horlocker T. Assuring a Painless Total Hip Arthroplasty: A Multimodal Approach Emphasizing Peripheral Nerve Blocks. J Arthroplasty. 2006;21(4):80-84. doi:10.1016/j.arth.2006.03.001. Johnson RL, Amundson AW, Abdel MP, et al. Continuous Posterior Lumbar Plexus Nerve Block Versus Periarticular Injection with Ropivacaine or Liposomal Bupivacaine for Total Hip Arthroplasty: A Three-Arm Randomized Clinical Trial. J Bone Joint Surg Am. 2017;99(21):1836-1845. doi:10.2106/JBJS.16.01305. Sculco PK, Pagnano MW. Perioperative Solutions for Rapid Recovery Joint Arthroplasty : Get Ahead and Stay Ahead. J Arthroplasty. 2015;30(4):518-520. doi:10.1016/j.arth.2015.01.036. Remérand F, Le Tendre C, Baud A, et al. The early and delayed analgesic effects of ketamine after total hip arthroplasty: a prospective, randomized, controlled, double-blind study. Anesth Analg. 2009;109(6):1963-1971. doi:10.1213/ANE.0b013e3181bdc8a0. Jules- Elysee KM, Wilfred SE, Memtsoudis SG, et al. Steroid modulation of cytokine release and desmosine levels in bilateral total knee replacement: a prospective, doubleblind, randomized controlled trial. J Bone Joint Surg Am. 2012;94(23):2120-2127. doi:10.2106/JBJS.K.00995. Su EP, Perna M, Boettner F, et al. A prospective, multi-center, randomised trial to evaluate the efficacy of a cryopneumatic device on total knee arthroplasty recovery. J Bone Joint Surg Br. 2012;94(11 Suppl A):153-156. doi:10.1302/0301620X.94B11.30832.

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Appendix: Multimodal Pain Management Protocol (modified from Dorr et al. CORR 200626)

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Preoperative (morning of surgery) 1. OxyContin, 10 mg PO 2. Celebrex, 400 mg PO 3. Tylenol, 500 mg PO 4. Prevacid, 30 mg, PO 5. Zofran 4 mg IV

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Operating Room 1. Short acting spinal anesthesia 2. IV corticosteroid (e.g. 10mg dexamethasone, unless patient is diabetic) 3. No parenteral narcotics 4. Zofran or Reglan anti-emetic (if greater than 6 hours after pre-operative dose)

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Recovery room 1. For bilateral hips, keep epidural catheter capped until transferred to floor 2. For primary hips, pull epidural catheter in operating room 3. ASA, 600 mg per rectum 4. Toradol, 30 mg IV × 1 dose as needed for mild to moderate pain (15 mg IV if older than 65 years) 5. OxyIR, 5 mg PO as needed for severe pain 6. Ice applied to operated joint 7. Zofran 4mg IV every 6 hours

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Floor program *all pain medications are given pre-emptively, rather than PRN, except for breakthrough situations 1. If younger than 65 years, Norco, 10 mg/325 mg, 1 tab PO, alternating with Tylenol ES, 500 mg PO every 4 hours from 6 pm to 6 am × 2 days 2. If older than 65 years, Tramadol, 65 mg, 1 tab PO, alternating with Tylenol ES, 500 mg PO every 4 hours from 6 pm to 6 am × 2 days 3. Celebrex, 200 mg PO twice daily, starting post-operative day 1 4. Norco, 10 mg/325 mg, 1–2 tab PO every 3–4 hours as needed for pain 5. Ultram, 50 mg, 1 tab PO every 4–6 hrs as needed for pain 6. Ancef (cefazolin), 1 gm IVPB every 8 hours × 24 hours 7. Zofran, 4 mg IV every 6 hours × 24 8. Reglan, 10 mg IV, IVP every 8 hours × 48 hours 9. Enteric coated acetylsalicylic acid (ECASA), 325 mg, 1 tab PO twice daily (Note: some surgeons use 81 mg, but we use 325 because it also gives the effect of a pain medication) 10. Milk of magnesia 30 mL every 8 hours

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11. Colace, 100 mg PO twice daily 12. Dulcolax suppository per rectum daily as needed for constipation 13. Prevacid, 30 mg PO twice daily 14. Dietary for food preferences 15. Regular diet 16. Cream of wheat for breakfast daily to avoid need for iron tablets

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Discharge 1. Celebrex, 200 mg PO twice daily × 21 days (total of 3 weeks) 2. ECASA, 325 mg 1 tab PO twice daily (for 30 days after surgery) 3. Prevacid, 30 mg twice daily (while on ECASA) 4. Pain medications (whatever patient was best managed with while in the hospital)

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Legend to Figure:

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Figure 1: Multimodal pain control is founded on the idea that the pain cascade can be targeted at multiple levels including transduction at the site of trauma, transmission through the spinal cord, and perception in the brain.

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