Assessment and Management of Knee Pain

Home , Ballottement, Drawer test, Lachman test, McMurray test, Valgus stress test

Topics in PAIN MANAGEMENT Vol. 34, No. 7 Current Concepts and Treatment Strategies February 2019 CONTINUING EDUCATION ACTIVITY Assessment and Management of Knee Pain

Angela Starkweather, PhD, ACNP-BC, FAAN The purpose of this article is to review evidence about the assessment and management of knee pain. Learning Objectives/Outcomes: After participating in this CME/CNE activity, the provider should be better able to: 1. Describe 3 of the most common causes of knee pain in adult patients. 2. Explain the various physical examination maneuvers that can be performed to detect mechanical knee injuries. 3. Compare treatment approaches for the common causes of knee pain, including active and passive therapies. Key Words: Knee pain, Meniscal injuries, Osteoarthritis, Patellofemoral pain syndrome

nee pain is one of the top 10 most common reasons for adjustments for age and body mass index.2 Athletes with pre- K outpatient visits.1 Data from the National Health and vious knee injuries are at significantly higher risk of suffering Nutrition Examination Survey and Framingham Osteoarthritis from chronic knee pain than the general population.3 Overall, Study found that knee pain and symptomatic knee osteoarthri- people with knee pain report worse physical functioning and tis have risen 10% to 25% over the past several decades, after quality of life, compared with those without knee pain, which emphasizes the need for effective management of pain in affected individuals.4 Because knee pain can be caused by a Inside This Issue wide range of bone or soft tissue injuries, infections, or chronic Assessment and Management of Knee Pain ...... 1 diseases (gout, osteoarthritis), identifying the most efficient Walking the Line: FDA Warns Against Any Off-Label Dr. Starkweather is Professor and Director, Center for Advancement in Managing Pain, University of Connecticut School of Nursing, 231 or Compounded Drugs for Intrathecal Pumps ...... 8 Glenbrook Rd, Storrs, CT 06269; E-mail: angela.starkweather@ ICYMI: In Case You Missed It ...... 9 uconn.edu. The author, faculty, and staff in a position to control the content of this CE Quiz ...... 11 CME activity have disclosed that they and their spouses/life partners (if any) have no financial relationships with, or financial interests in, any commercial organizations relevant to this educational activity.

CME Accreditation Lippincott Continuing Medical Education Institute, Inc., is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. Lippincott Continuing Medical Education Institute, Inc., designates this enduring material for a maximum of 1.5 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity. To earn CME credit, you must read the CME article and complete the quiz and evaluation assessment survey on the enclosed form, answering at least 70% of the quiz questions correctly. This CME activity expires on January 31, 2021. CNE Accreditation Lippincott Professional Development is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center’s Commission on Accreditation. Lippincott Professional Development will award 1.0 contact hours for this continuing nursing education activity. Instructions for earning ANCC contact hours are included on page 11 of the newsletter. This CNE activity expires on December 4, 2020.

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CO-EDITORS process for diagnosis and treatment is a priority for clinicians across different settings. Elizabeth A.M. Frost, MD Professor of Anesthesiology Icahn School of Medicine at Mount Sinai New York, NY Knee pain and symptomatic knee osteoarthritis have risen 10% to 25% Angela Starkweather, PhD, ACNP-BC, CNRN, FAAN Professor of Nursing over the past several decades. University of Connecticut School of Nursing Storrs, CT Initial Assessment of Knee Pain

ASSOCIATE EDITOR With presentation of acute knee pain, initial assessment should focus on history-taking with determination of mecha- Anne Haddad nism of injury, precise location and characteristics of symp- Baltimore, MD toms, and function.5 The clinician should elicit the patient’s description of the pain and its characteristics, such as timing (acute or insidious), EDITORIAL BOARD location, duration, intensity, quality, radiation, and alleviating Jennifer Bolen, JD or aggravating factors. The clinician should also ask about The Legal Side of Pain, Knoxville, TN other symptoms that may not seem to be related, and which either precede or accompany the presence of knee pain. These C. Alan Lyles, ScD, MPH, RPh symptoms might include fever, chills, pharyngitis or sore University of Baltimore, Baltimore, MD throat, or skin rash. Examination of the knee includes observation and palpation for joint tenderness, range of motion, weight-bearing ability, and specific tests to identify joint insta- Stephen Silberstein, MD 6 Jefferson Headache Center, Philadelphia, PA bility (Table 1). During the physical examination, compare findings to the contralateral uninjured knee and assess adja- cent joints for referral pain, including the hip and ankle.7 Steven Silverman, MD Michigan Head Pain and Neurological Institute, Ann Arbor, MI The continuing education activity in Topics in Pain Management is intended for clinical and academic physicians from the specialties of anesthesiology, neurology, psychiatry, physical and rehabilitative medicine, and neurosurgery, as well as residents in those fields Sahar Swidan, PharmD, BCPS and other practitioners interested in pain management. Pharmacy Solutions, Ann Arbor, MI Topics in Pain Management (ISSN 0882-5646) is published monthly by Wolters Kluwer Health, Inc. at 14700 Citicorp Drive, Bldg 3, Hagerstown, MD P. Sebastian Thomas, MD 21742. Customer Service: Phone (800) 638-3030, Fax (301) 223-2400, or Email Syracuse, NY [email protected]. Visit our website at lww.com. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved. Priority postage paid at Hagerstown, MD, and at additional mailing offices. GST registration number: 895524239. POSTMASTER: Send address changes to Topics in Pain Management, Emily Wakefield, PsyD PO Box 1610, Hagerstown, MD 21740. Connecticut Children’s Medical Center, University of Publisher: Randi Davis Connecticut School of Medicine, Hartford, CT Subscription rates: Individual: US $399, international: $506. Institutional: US $990, international $1129. In-training: US $156 with no CME, international $179. Single copies: $95. Send bulk pricing requests to Publisher. COPYING: Contents of Topics in Pain Management are protected by copyright. Reproduction, photocopying, and storage or transmission by magnetic or electronic Marjorie Winters, BS, RN means are strictly prohibited. Violation of copyright will result in legal action, including civil and/ Michigan Head Pain and Neurological Institute, Ann Arbor, MI or criminal penalties. Permission to reproduce copies must be secured in writing; at the newsletter website (www.topicsinpainmanagement.com), select the article, and click “Request Permission” under “Article Tools” or e-mail [email protected]. For commercial reprints and all quantities of 500 or more, e-mail [email protected]. For Steven Yarows, MD quantities of 500 or under, e-mail [email protected], call 1-866-903-6951, or fax 1-410-528- 4434. Chelsea Internal Medicine, Chelsea, MI PAID SUBSCRIBERS: Current issue and archives (from 1999) are now available FREE online at www.topicsinpainmanagement.com. Topics in Pain Management is independent and not affiliated with any organization, vendor Lonnie Zeltzer, MD or company. Opinions expressed do not necessarily reflect the views of the Publisher, Editor, or Editorial Board. A mention of products or services does not constitute endorsement. All com- UCLA School of Medicine, Los Angeles, CA ments are for general guidance only; professional counsel should be sought for specific situa- tions. Editorial matters should be addressed to Anne Haddad, Associate Editor, Topics in Pain Management, 204 E. Lake Avenue, Baltimore, MD, 21212; E-mail: [email protected]. Topics in Pain Management is indexed by SIIC HINARI and Google Scholar.

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Table 1. Components of the Initial Evaluation of Knee Pain History Physical Examination Specific Mechanical Injuries History of knee pain, injury, or joint disease Observation of color, swelling, alignment, Integrity of the ACL: Lachman test, Medical history, comorbidities, and present medications deformity, gait, weight-bearing, wounds, pivot shift test Travel, exposures (eg, tick bite), and sexual contacts inflammation (calor, rubor, tumor, dolor) Involvement of other organ systems Occupation, sports, and functional abilities or Palpation for temperature and to detect Integrity of the MCL and LCL: varus limitations swelling, tenderness, joint effusion (patellar and valgus stress tests ballottement), masses, or tendon defects Mechanism of injury Range of motion (active and passive) Meniscal injury: combination of joint- Position of knee at time of injury and amount of Hypermobility line tenderness and results of Apley force/direction, and torsion test, McMurray test, Thessaly test, Onset of pain and swelling and Ege’s test Acuity of injury Neurovascular assessment: pallor, Patellar dislocation: patella tilt, patella Characteristics of pain and associated symptoms: paresthesias, paresis, pain, poikilothermia, glide clicking, locking, catching, giving away, and stiffness and pulses of the lower extremity ACL, anterior cruciate ligament; LCL, lateral collateral ligament; MCL, medial collateral ligament.

Differential Diagnosis Other rare conditions, such as adult-onset Still’s disease, can be misdiagnosed as septic arthritis.8 There have been 3 types The differential diagnosis list for knee pain is quite exten- of disease progression for this condition: sive but can be narrowed down based on the presence of localized versus systemic signs and symptoms, the presence 1. Monocyclic type characterized by systemic symptoms of or absence of inflammation, and anterior or posterior fever, rash, organomegaly, and serositis; knee pain. 2. Polycystic type characterized by multiple recurrences that An acute onset of monoarticular pain and swelling is most may or may not affect the joints; and commonly associated with trauma, infection, or crystalline 3. Chronic articular type that primarily targets the joints with disease.5,6 In contrast, chronic pain and swelling are associ- severe joint destruction being an end result in untreated ated with autoimmune disorders, such as rheumatoid arthri- cases. tis, seronegative spondyloarthropathies, sarcoidosis, Criteria of adult onset Still’s disease are developed by chronic infection or foreign-body synovitis, avascular Yamaguchi et al9 and include major, minor, and exclusion crite- necrosis, sickle cell disease, hemophilia, Charcot joint, and ria, of which 5 or more major/minor criteria must be present, joint tumors.6 Arthrocentesis is indicated when infection or including 2 or more major criteria. In 2002, Fautrel10 proposed a crystalline disease, foreign-body synovitis, or neoplasm is new set of classification criteria with 4 or more major criteria or suspected. 3 major criteria and 2 minor criteria (Table 2) displaying a sensi- Knee bursitis (also called housemaid’s knee) is associated tivity of 80.6%, a specificity of 98.5%, and positive and negative with localized inflammation and swelling and caused by predictive values of 96.7% and 90.1%, respectively. First-line repeated kneeling, trauma, or conditions such as gout or rheu- treatment of adult-onset Still’s disease is corticosteroids with matoid arthritis. A high index of suspicion for gout should be methotrexate as a second-line treatment.11 Refractory cases have made for patients with a history of tophi and articular symp- been treated with agents blocking interleukin-1 or interleukin-6.11 toms, particularly the first metatarsophalangeal articulation (MTP).5 Pseudogout is more common in advanced age, particularly in the setting of metabolic stress, such as in patients Table 2. Criteria of Adult-Onset Still’s Disease with pneumonia or recent surgery, and chondrocalcinosis may Major Criteria Minor Criteria be seen on radiography. Spiking fever ≥39°C Maculopapular rash Systemic disease may be evident from bilateral knee involvement, disorders of the skin and/or involvement of other organ Arthralgia Leukocytosis (white blood cell ≥ 3 systems. A reddish-purple raised rash may indicate lupus Transient erythema count 10,0000/mm ) pernio, a cutaneous manifestation of sarcoidosis. Psoriasis Pharyngitis may indicate psoriatic arthropathy. Bruising may indicate Polymorphonuclear count ≥80% bleeding diathesis, and a pustular rash may indicate an infec- ≤ tious process such as disseminated gonorrhea.5 Glycosylated ferritin 20%

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Particularly in children, infections such as Group A strepto- following to evaluate potentially significant injuries: signifi- cocci (GAS), also known as Streptococcus pyogenes, can cant tenderness, loss of range of motion with crepitus, joint cause bacterial pharyngitis and superficial skin infections, effusion within 24 hours of injury, severe muscle tears or ten- and sudden and severe onset of extremity pain.12 Although don rupture, suspected knee dislocation or osteonecrosis, or GAS complicated by streptococcal toxic shock syndrome in neurovascular compromise.5 The practitioner should exercise children can mimic symptoms of septic knee arthritis, it is clinical judgment to determine the need for radiographs in all more commonly associated with invasive soft tissue infections cases, but the decision-guiding knee rules can help reduce in adults or children with chickenpox.13,14 unnecessary imaging.19,21 If acute traumatic injury is evident on history, a thorough CT is used to evaluate for occult fracture or define the sever- evaluation of the structural integrity of the joint should be ity of the fracture. Ultrasound may be used to detect patella or assessed (Table 3).15 When performing physical examination quadriceps tendon rupture.22 For clinical suspicion of internal maneuvers, keep the patient as comfortable as possible, and derangement or joint effusion on radiograph, an MRI of the test the contralateral noninjured knee first to provide a com- knee can be performed at follow-up. An MRI is also appropri- parison and show the patient how it is performed. Describe the ate for primary traumatic patella dislocation to assess chon- test before you perform it and stop the maneuver if pain is dral and patellofemoral soft-tissue damage.21 In cases of induced. degenerative joint disease, inflammatory arthritis, stress frac- Anterior cruciate ligament (ACL) injury is most often ture, or osteonecrosis found on radiographs, further imaging accompanied by a positive Lachman test and pivot shift and with MRI is not indicated, as it will not alter management.5 these 2 tests are preferred tests over the anterior drawer for detecting ACL injury. Medial collateral ligament (MCL) or Treatment Considerations lateral collateral ligament (LCL) injury should be suspected For the most common causes of knee pain in adults, includ- with a positive varus or valgus stress test. A meniscal injury is ing osteoarthritis, patellofemoral pain syndrome, and menis- supported by a combination of joint-line tenderness, and posi- cal, tendon, and ligament injuries, nonsurgical approaches are tive Apley, McMurray, Thessaly, and Ege tests.15,16 most often the first-line treatment.23-25 As opposed to inflammatory conditions, infections, or acute Active rehabilitation for osteoarthritis is a cornerstone of mechanical injuries, the most common knee conditions, oste- therapy and should include components of stretching and a oarthritis of the knee and patellofemoral pain syndrome (run- combination of aerobic and strength training.23 Pain relief can ner’s knee) often present with a more insidious onset. Both be enhanced with patellar taping, therapeutic ultrasonography, conditions increase with age and are more prevalent in ice massage, and weight loss for those with a body mass women. These 2 conditions are also more prevalent in people index of more than 25 kg/m2.25 with occupations that require frequent repetitive movements Extended-release acetaminophen or selective/nonselective of the knee or who participate in sports that predispose to nonsteroidal anti-inflammatory drugs (NSAIDs) may also be joint injury.5 Pain is reported to be most severe when the knee used for pain relief. However, glucosamine/chondroitin sup- is bearing weight or moving. Crepitus may be present, espe- plements are not recommended by the American Academy of cially when going up- and downstairs.17 Osteoarthritis, in par- Orthopaedic Surgeons due to low level of effectiveness.25 ticular, is associated with early morning stiffness of the knee Corticosteroid injections can be used for short-term improve- that lasts for a short period, and hard bony enlargement of the ment but have been associated with complications, including knees. septic arthritis.26 A recent study evaluating intra-articular injection of hyalu- Diagnostic Testing ronic acid (HA), platelet-rich plasma (PRP), or combination of Septic arthritis or an acute inflammatory arthropathy should HA and PRP was evaluated in 360 patients.27 After an 8-week be considered when patients present with nontraumatic effu- baseline period, participants with knee osteoarthritis were ran- sion or significant pain with slight range of motion. domized into groups undergoing once-weekly double-blind Evaluation for septic arthritis should start with initial labora- treatment with HA (0.1–0.3 mg), PRP (2–14 mL), combina- tory studies including a complete blood cell count, sedimenta- tion therapy of PRP and HA, or placebo (normal saline). tion rate, and C-reactive protein.5 In endemic regions, a Lyme In this study, overall duration of PRP and HA treatment was disease titer should also be tested. Arthrocentesis may be indi- 8 weeks, and 277 (75%) completed the maintenance period of cated to rule out septic arthritis or other conditions, such as the study up to 52 weeks, whereas the other 25% stopped the crystalline disease or neoplasm. study due to side effects. Use the Ottawa Knee Rule or Pittsburgh Knee Rule (Table 4) The combination treatment significantly improved pain, to determine the need for x-rays (anteroposterior, lateral views physical function, stiffness, and total Western Ontario and ± skyline view)18-20 in acute injury. However, radiographs McMaster Universities Osteoarthritis Index (WOMAC) score should be highly considered in the presence of any of the compared with PRP or HA alone (P < 0.05) and PRP

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Table 3. Physical Examination Maneuvers to Detect Mechanical Injury Physical Examination Maneuvers Performing the Examination Findings Valgus stress test Position the patient supine with the thigh resting on the Inducing a substantial gap in the medial aspect of (evaluates MCL stability) edge of the examination table and support the foot the knee joint implies impairment of the MCL With the knee in 30-degree flexion, press with one hand on Increased laxity of the medial side of the knee the lateral aspect of the knee with the knee in extension indicates additional With the other hand, direct the ankle laterally, attempting damage to posterior structures, such as the to open the knee joint on the medial side posterior joint capsule and the PCL Varus stress test Position the patient supine with the thigh resting on the A difference in the degree of lateral knee tautness (evaluates LCL stability) edge of the examination table and support the foot when comparing the affected knee to the Push medially upon the knee and laterally against the uninjured side indicates disruption of the LCL ankle, trying to open the knee joint on the lateral side Lateral instability with the knee extended sug- gests injury to the LCL and the lateral capsule, and likely damage to the ACL or the PCL Lachman maneuver Place the patient supine and flex the knee 20 to 30 degrees Damage to the ACL manifests as excessive (confirms ACL integrity) in slight external rotation forward motion of the tibia without a firm end Place one hand behind the tibia and the other hand on the point patient’s thigh, with the thumb positioned on the tibial If viewed from the lateral aspect, the natural tuberosity concave silhouette of the knee, extending from Pull the tibia anteriorly to detect translational movement the tibial tubercle to the superior aspect of the In patients with large thighs, the position may need to be patella, obliterates when ACL damage occurs modified Position the large thigh of the patient over the knee of the examiner Push downward on the patient’s femur with one hand, while the other hand grasps the proximal tibia and attempts to move it anteriorly Anterior drawer testing Place the patient in the supine position, flex the hip to The anterior drawer test is less sensitive in (evaluates integrity of the ACL) 45 degrees, and bend the knee to 90 degrees with the detecting ACL damage than the Lachman patient’s foot planted firmly on the examination table maneuver Sitting on the dorsum of the foot, place both hands behind the knee. Once the hamstrings appear relaxed, discreetly try to displace the proximal leg anteriorly Posterior drawer testing Posterior drawer testing is done in a similar manner to Posterior instability arising from PCL injury (evaluates integrity of the PCL) anterior drawer testing, except that the pressure is manifests as an abnormal increase in posterior directed backward on the proximal tibia tibial translation Tibial sag test Flex the patient’s hips and knees to 90 degrees while In this position, the PCL impaired-knee will (used to distinguish disorders of supporting the patient’s heels clearly sag backward from the effects of the ACL from those of the PCL) gravity (Godfrey sign) Pivot-shift test Elicit by lifting the tibia of the affected side. If the ACL is As the knee joint approaches 20 to 40 degrees of (evaluates capsular tears and impaired, the tibia subluxates anteriorly during knee flexion, an abrupt jerking movement occurs in injury to the ACL) extension the ACL-impaired knee McMurray testing With the patient supine and the knee in maximum flexion, If a tear is present in the medial meniscus, an (identifies meniscal disorders) palpate the posteromedial margin of the affected knee joint audible, palpable, and painful clunk occurs as with one hand and support the foot with the opposite hand the femur passes over the damaged portion of Externally rotate the lower leg as far as possible the meniscus Affix varus pressure, and cautiously extend the knee joint Clicks unassociated with pain or joint-line To check the lateral meniscus, repeat the above technique, tenderness, especially during lateral meniscus but place one hand over the posterolateral aspect of the testing, may represent a normal variant and knee joint and internally rotate the lower leg to its should not be interpreted as evidence of a maximum extent meniscal tear Slowly extend the leg again, listening and feeling for a click or pop, and observe the patient for distress (continues)

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Table 3. Physical Examination Maneuvers to Detect Mechanical Injury (Continued) Physical Examination Maneuvers Performing the Examination Findings Apley compression or grind test Place the patient in the prone position and flex the knee to Any pain in the joint should be noted, and any (evaluates the soundness of the 90 degrees resonance or irritation emanating from the menisci, especially the posterior Stabilize the patient’s thigh against the examination table knee horn) with the knee of the examiner, and apply a downward- directed force onto the patient’s foot and leg Rotate the leg, while mildly flexing and extending the knee joint Ege’s test With the patient standing in full extension, the feet can be The test is positive when the pain or a click is felt (weight-bearing McMurray test turned outward to test the medial meniscus or inward to by the patient at the related site of the joint used to evaluate meniscal test the lateral meniscus line injury) The patient performs a squat as far as possible and then returns to full extension Thessaly test With the patient standing, have them place one hand on a With dynamic reproduction of joint loading in the (used to evaluate meniscal fixed surface for support, and then flex the knee at knee, a meniscal tear will result in lateral injury along with other tests) 5 degrees joint-line discomfort, with potential locking or The patient then rotates the knee internally and externally catching 3 times. Repeat at 20 degrees of flexion ACL, anterior cruciate ligament; LCL, lateral collateral ligament; MCL, medial collateral ligament; PCL, posterior cruciate ligament.

treatment was significantly more effective than HA and pla- focused on understanding potential contributing factors and cebo using the WOMAC pain score (P < 0.05). treatment options and appropriate activity modifications and Although additional studies need to be completed, the com- their role in active rehabilitation. bination therapy seems promising. Consideration of open kinetic chain exercises (nonweight As with all patients starting active rehabilitation, adequate bearing; ie, leg extension and leg curl) may be used in the supervision should be provided in the early program to ensure early stages of rehabilitation to target deficits in strength that correct techniques are used for the exercises.25 To and movement. However, preference is given to closed enhance independence and compliance with the home pro- kinetic chain exercises to replicate function (ie, squats and gram, the number of exercises should be minimized to 3 or 4 lunges).28 in the early phase. Assist the patient in independent exercise Tailored patellar taping can help reduce pain or a patel- rehabilitation by using mirrors or videos to monitor quality of lofemoral brace may be used for people with skin irritation. In the exercises and facilitate good technique.17 addition, foot orthoses may help relieve pain as might mas- Treatment for patellofemoral pain syndrome involves educa- sage and/or acupuncture.17,28 tion, active rehabilitation, passive interventions for pain Initial management of ACL/posterior cruciate ligament reduction, and optimization of biomechanics.17 Education is (PCL)/MCL/LCL and meniscal injuries includes analgesia with NSAIDs and acetaminophen, rest, ice, compression, and Table 4. Decision Rules for Ordering Knee elevation during the acute phase of recovery.5,29 Radiographs Immobilization with a functional brace can be used for ACL Ottawa knee rules Age > 55 yr injuries or acute severe PCL and MCL injuries.5 Isolated tenderness of the patella Gentle mobilization, while avoiding aggravating positions, Tenderness at the head of the fibula should be used to restore full range of motion. Practitioners Inability to flex knee to 90 degrees should consider referral to orthopedics for MRI and, if indi- Inability to bear weight immediately after injury cated, operative management of the injury, with expedient and in the emergency department or clinic for follow-up for patients with ACL tear or locked knee to avoid 4 steps development of a stiff joint.30 Referral to physiotherapy Pittsburgh knee Blunt trauma or fall as mechanism of injury and should also be made for exercises and rehabilitation. rules age less than 12 or greater than 50 years For patella dislocation, immobilization is performed by plac- Inability to walk 4 full weight-bearing steps in ing a cast, splint, or locked orthosis in extension for comfort the emergency department or clinic (2–3 weeks) and referral to orthopedics for consideration of

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advanced imaging and operative management.5 Education 13. Chiang MC, Jaing TH, Wu CT, et al. Streptococcal toxic shock regarding the injury, plan of care, and risks for future instabil- syndrome in children without skin and soft tissue infection: report of four cases. Acta Paediatr. 2005;94(6):763-765. ity should be provided to the patient and family, emphasizing 14. Laupland KB, Davies HD, Low DE, et al. Invasive group A strep- the need for follow-up with orthopedics and physiotherapy to tococcal disease in children and association with varicella-zoster progress range of motion and weight-bearing status. infection. Pediatrics. 2000;105(5):e60. 15. Meserve BB, Cleland JA, Boucher TR. A meta-analysis examining Conclusion clinical test utilities for assessing meniscal injury. Clin Rehabil. Knee pain is prevalent in the US adult population and dis- 2008;22:143-161. proportionately affects women and athletes. The presentation 16. Hegedus E, Cook C, Hasselblad V, et al. Physical examination tests for assessing a torn meniscus in the knee: a systematic review of knee pain, associated signs and symptoms, and characteris- with meta-analysis. J Orthop Sports Phys Ther. 2007;37(4): tics of the patient can help guide the differential diagnosis and 541-550. appropriate diagnostic testing. For the most common causes 17. Lack S, Neal B, De Oliveira Silva D, et al. How to manage patel- of knee pain, including osteoarthritis, patellofemoral pain syn- lofemoral pain—understanding the multifactorial nature and treat- drome, and meniscal injuries, active and passive rehabilitation ment options. Phys Ther Sport. 2018;32(1):155-166. and pharmacologic management can help provide the best 18. Cheung TC, Tank Y, Breederveld RS, et al. Diagnostic accuracy and reproducibility of the Ottawa Knee Rule vs the Pittsburgh route for pain management, and for functional recovery. ■ Decision Rule. Am J Emerg Med. 2013;31:641-645. References 19. Konan S, Zang TT, Tamimi N, et al. Can the Ottowa and Pittsburgh rules reduce requests for radiography in patients referred to acute 1. Centers for Disease Control and Prevention. National Ambulatory knee clinics? Ann R Coll Surg Engl. 95(3):188-191. Medical Care Survey: 2015 State and National Summary Tables. Washington, DC: Centers for Disease Control and Prevention; 20. Tuite MJ, Kransdorf MJ, Beaman FD, et al. ACR appropriateness 2015. https://www.cdc.gov/nchs/data/ahcd/namcs_summary/2015_ criteria acute trauma to the knee. J Am Coll Radiol. 2015;12:1164- 1172. namcs_web_tables.pdf. Accessed November 23, 2018. 21. Frobell RB, Lohmander LS, Roos HP. Acute rotational trauma to 2. Nguyen US, Zhang Y, Zhu Y, et al. Increasing prevalence of knee the knee: poor agreement between clinical assessment and mag- pain and symptomatic knee osteoarthritis: survey and cohort data. netic resonance imaging findings. Scand J Med Sci Sports. Ann Intern Med. 2011;155(11):725-732. 2007;17(1):109-114. 3. Fernandes GS, Parekh SM, Moses J, et al. Prevalence of knee pain, 22. Kilic TY, Yesilaras M, Atilla OD, et al. The accuracy of point-of- radiographic osteoarthritis and arthroplasty in retired professional care ultrasound as a diagnostic tool for patella fractures. Am J footballers compared with men in the general population: a cross- Emerg Med. 2016;34(10):1576-1578. sectional study. Br J Sports Med. 2018;52(10):678-683. 23. Jones BQ, Covey CJ, Sineath MH Jr. Nonsurgical management of 4. Kim IJ, Kim HA, Seo Y, et al. Prevalence of knee pain and its knee pain in adults. Amer Family Phys. 2015;92(10):875-883. influence on quality of life and physical function in the Korean 24. Buchbinder R, Richards B, Harris I. Knee osteoarthritis and role elderly population: a community based cross-sectional study. J for surgical intervention: lessons learned from randomized clinical Korean Med Sci. 2011;26(9):1140-1146. trials and population-based cohorts. Curr Opin Rheumatol. 5. Strudwick K, Mcphee M, Bell A. Review article: best practice 2014;26(2):138-144. management of common knee injuries in the emergency depart- 25. American Academy of Orthopaedic Surgeons. Treatment of ment (part 3 of the musculoskeletal injuries rapid review series). Osteoarthritis of the Knee: Evidence-Based Guideline. 2nd ed. Emerg Med Australasia. 2018;30(1):327-352. Rosemont, IL: American Academy of Orthopaedic Surgeons; 6. Yen YM. Assessment and treatment of knee pain in the child and 2013. adolescent athlete. Ped Clin North Am. 2014;61(6):1155-1173. 26. Ross K, Mehr J, Carothers B, et al. Outbreak of septic arthritis 7. Décary S, Ouellet P, Vendittoli P-A, et al. Diagnostic validity of associated with intra-articular injections at an outpatient practice— physical examination tests for common knee disorders: an over- New Jersey, 2017. MMWR Morb Mortal Wkly Rep. 2017;66(29): view of systematic reviews and meta-analysis. Phys Ther Sport. 777-779. 2017;23(1):143-155. 27. Yu W, Xu P, Huang G, et al. Clinical therapy of hyaluronic acid 8. Song SJ, Bae DK, Noh JH, et al. A case of adult onset Still’s dis- combined with platelet-rich plasma for the treatment of knee oste- ease misdiagnosed as septic arthritis. Knee Surg Relat Res. oarthritis. Exp Therapeut Med. 2018;16:2119-2125. 2011;23(3):171-176. 28. Barton CJ, Lack S, Hemmings S, et al. The “best practice guide to 9. Yamaguchi M, Ohta A, Tsunematsu T, et al. Preliminary criteria for conservative management of patellofemoral pain”: Incorporating level 1 evidence with expert clinical reasoning. Br J Sports Med. classification of adult Still’s disease. J Rheumatol. 1992;19(3):424-430. 2015;49:923-934. 10. Fautrel B. Proposal for a new set of classification criteria of adult- 29. Mordecai SC, Al-Hadithy N, Ware HE, et al. Treatment of menis- onset still disease. Medicine. 2002;81(3):194-200. cal tears: an evidence based approach. World J Orthop. 2014;5(3): 11. Fautrel B. Adult-onset Still disease. Best Pract Res Clin 233-241. Rheumatol. 2008;22(5):73-792. 30. American Academy of Orthopaedic Surgeons. Management of 12. Alwattar BJ, Strongwater A, Sala DA. Streptococcal toxic shock Anterior Cruciate Ligament Injuries. Evidence-Based Clinical syndrome presenting as septic knee arthritis in a 5-year-old child. J Practice Guideline. 1st ed. Rosemont, IL: American Academy of Ped Orthopaed. 2008;28(1):124-127. Orthopaedic Surgeons; 2014.

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Walking the Line: FDA Warns Against Any Off-Label or Compounded Drugs for Intrathecal Pumps he FDA on November 14 issued a “safety communica- pain, fever, vomiting, muscle spasms, cognitive changes, Ttion” to prescribers and patients reminding them that only weakness, and cardiac or respiratory distress. 2 drugs are approved for use in implanted intrathecal pumps, “The treatment of pain has become increasingly complex,” said and that any other drugs, including any compounded drugs, Scott Gottlieb, MD, commissioner of the FDA, in a press release.2 could lead to serious complications and even damage the tub- “While medical devices, such as implanted pumps that ing and other components of the pump system.1 deliver medication directly into the spinal fluid, have the The FDA issued this safety communication after reviewing potential to play an important role in treating pain, their use medical device reports, premarket device applications, man- must be judicious and their instructions for use must be care- dated FDA postapproval studies, publicly available scientific fully followed,” Gottlieb said. literature, current device labeling, and information from “This is especially true when it comes to implantable pumps health care providers and device manufacturers.2 that deliver analgesic medicine directly into the nervous sys- Patients and providers, who experience an adverse event due tem,” he continued. “We urge health care providers, patients to an implanted pump or suspect an infusion pump is having and caregivers to be aware of the information the FDA is pro- problems, are encouraged to file a voluntary report through viding today so they can make informed treatment decisions. MedWatch, the FDA Safety Information and Adverse Event The FDA will continue to monitor the safety of these and Reporting program. other medical devices involved in the treatment of pain, and take action where needed to protect patients.” Implanted pumps require a health care provider to periodi- The FDA has approved only 2 drugs cally refill the pump with medication. Currently, the for use in intrathecal pumps. FDA-approved implanted pump labeling (Instructions for Use) identifies pain medicines that have been evaluated by the FDA for compatibility with the pump, including Infumorph and Prialt (not all pumps are currently approved for use with Prialt). That Leaves Only Two Choices—or The FDA has found that patients are sometimes being Sometimes Just One treated with medications that are not approved (including The FDA has approved only 2 drugs for use in intrathecal compounded medicines, hydromorphone, bupivacaine, fenta- pumps. The safety communication contained Table 1, show- nyl, and clonidine) for use with an intrathecal implanted ing those 2 drugs, and examples of drugs that have been used pump. The reasons sometimes cited for the use of drugs not off-label in the pumps for patients who did not find enough approved for use with implanted pumps have included that relief or suffered side effects from the 2 approved drugs. approved medications listed in the pump labeling may have For patients who have not had pain relief from other less undesirable side effects or may fail to deliver adequate pain invasive approaches, implanted pumps are surgically inserted relief for some patients.2 under the skin and connected to an implanted catheter to “The FDA has determined that implantable intrathecal pump deliver medicines into the spinal fluid to manage pain. failure is more frequent with the use of medicines not Complications may include dosing errors, pump failure, opi- approved for use with the pump. For example, some medicines oid withdrawal, infection and other complications, such as or fluids may contain preservatives or other characteristics that

Table 1. Drugs Approved/Not Approved by the FDA for Use in Intrathecal Pumps1 Approved Medications* Off-Label Medications† Infumorph (morphine sulfate), preservative-free, injectable solution Medicines not FDA-approved for intrathecal administration or intrathecal implanted pump use (eg, hydromorphone, bupivacaine, fentanyl, and clonidine) Prialt (preservative-free ziconotide sterile solution), but only in certain Any mixture of 2 or more different kinds of medicines pumps for which the FDA has approved it Any compounded medicine (eg, to achieve higher concentration or different formulation of an FDA-approved medicine) *Only medications identified in implanted pump labeling for intrathecal infusion to treat or manage pain. †Examples of medications not identified in the implanted pump labeling for intrathecal infusion to treat or manage pain.

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unintended dosing errors, The reasons sometimes cited for the use of drugs not approved according to the FDA. The accuracy of the software calcu- for use with implanted pumps have included that approved lations depends on using the medications listed in the pump labeling may have undesirable approved medicine. For example, if there is more than one side effects or may fail to deliver adequate pain relief for some medicine in the pump reservoir, the pump software can only patients. calculate the dose based on the infusion rate of a single medi- can damage the pump tubing or lead to corrosion of the pump- cine, according to the FDA. ing mechanism,” according to the FDA press release. “This may cause the implanted pump to perform in unex- References pected ways, including motor stalls, which ultimately stop the 1. US Food and Drug Administration. FDA Safety Communication: medication delivery, leading to potential opioid withdrawal,” “Use Caution with Implanted Pumps for Intrathecal Administration of Medicines for Pain Management: FDA Safety Communication.” according to the press release. November 14, 2018. https://www.fda.gov/MedicalDevices/Safety/ When a pump fails, patients must undergo surgery to AlertsandNotices/ucm625789.htm. remove or replace the pump. 2. US Food and Drug Administration. FDA News Release: “FDA Dosage errors may also occur, because programmable implanted alerts doctors, patients about risk of complications when certain implanted pumps are used to deliver pain medications not pumps have dose calculation software that provides options for approved for use with the devices.” November 14, 2018. https:// users to select preprogrammed medicines and concentrations www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ identified in the approved pump labeling to help prevent ucm625840.htm.

ICYMI: IN CASE YOU MISSED IT

Notes from recent studies related to pain management, compiled by Elizabeth A.M. Frost, MD , co-editor of Topics in Pain Management

The authors introduce the concept of “stickiness” as a moniker Comprehensive Review: Why in an attempt to identify the many influences on chronic pain Does an Insult Result in Chronic and pain behavior and the degree of responsiveness to therapy. Focus is also placed on neurobiology, as it relates to reward Pain Only in Certain Patients? and the general resistance to understand that changes in syn- It has long been recognized that despite similar pain charac- aptic complexity, neural networks, and systems such as opioi- teristics, some patients with chronic pain recover, whereas dergic and dopaminergic may add to pain stickiness. others do not. In this comprehensive article, the authors The authors propose an integration of the neurobiological, examine the factors that determine why, after a similar insult, environmental, and social demands on pain behavior, along some people experience pain that resolves, whereas others with treatment approaches based on the vulnerability of the experience persistent pain. patient to the allostatic load, defined as the cost of chronic The authors consider the contributions and interactions of exposure to elevated or fluctuating endocrine or neural chal- biological, social, and psychological perturbations that under- lenges that patients experience as stressful. lie the evolution of treatment-resistant chronic pain. In this The overview aims a research agenda at extending the overview, they explore the potential mechanisms that produce knowledge summarized within the article, and at potential or exacerbate persistent pain, with regard to stress, age, genet- therapeutic opportunities such as the development of more ics, environment, and immune responsivity, even if these neurobiologically informed pain therapies—both pharmaco- mechanisms are not well understood. All of these factors may logic and psychological—that might reverse pain stickiness combine to produce different risk profiles for disease devel- and fixed pain behaviors and facilitate resilience, with a opment, pain severity, and hence chronicity. return to homeostasis.

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In a commentary on the article, Nicholas notes that Borsook Over a 33-month period, the patients participated in their et al consider the broad scope of contributions and interactions respective treatment groups. At 6 weeks, 91% (212 patients) of biological, social, and psychological factors toward the evo- completed the BCTQ. lution of treatment-resistant chronic pain. They have focused The score was significantly better at 6 weeks in the corticos- more on the biological factors rather than social and psycho- teroid injection group (mean, 2.02; standard deviation, 0.81) logical ones. Work still has to be done to clarify all the poten- than was found in the night-splint group (mean, 2.29; stand- tial mechanisms that produce or exacerbate persistent pain. ard deviation, 0.75; adjusted mean difference −0.32; 95% But, differences in the relative contribution of factors such as confidence interval, −0.48 to −0.16; P = 0.0001). There were stress, age, genetics (and epigenetics), environmental charac- no adverse events reported. teristics, and immune responsivity produce different risk pro- The authors concluded that a single corticosteroid injection files for disease development, pain severity, and chronicity. allowed superior clinical effectiveness at 6 weeks compared with night-resting splints and should be the treatment of The authors consider the contributions and interactions of choice for rapid symptom response in mild or moderate biological, social, and psychological perturbations that underlie carpal tunnel syndrome. the evolution of treatment-resistant chronic pain. Funding: Arthritis Research UK. The trial is registered with the European Clinical Trials Methods from other fields, such as network biology, may be Database, number 2013-001435-48, and ClinicalTrial.gov, number used to simulate a complex multifactorial entity like pain, also NCT02038452. (See Chesterton LS, Blagojevic-Bucknall M, incorporating such factors as homeostasis, resilience, allosta- Burton C, et al. The clinical and cost-effectiveness of corticosteroid sis, drug-induced hyperalgesia, synaptic plasticity, endoge- injection versus night splints for carpal tunnel syndrome nous regulation, centralization, and sensitization. (INSTINCTS trial): an open-label, parallel group, randomized con- Nicholas concludes that the article cogently describes where trolled trial. Lancet. 2018;392(10156):1423-1433. doi:10.1016/ each of these constructs and processes may fit into the picture S0140-6736(18)31572-1.) of pain chronification and treatment resistance, adding that the authors have made a major contribution to the field. Intraoperative Nitrous Oxide The authors report that the research in their article has been supported by a grant from the NIH, Award K24NS064050 to D. and Postoperative Pain Borsook NICHD R01HD083133. (See Borsook D, Youssef AM, Both animal and clinical studies have suggested that Simons L, et al. When pain gets stuck: the evolution of pain chron- nitrous oxide may produce long-term analgesia. In this ification and treatment resistance. Pain. 2018;159 (12):2421-2426. study, the authors attempted to evaluate the effect of nitrous Nicholas MK. Why do some people develop chronic, treatment- oxide in preventing chronic postsurgical pain. They also resistant pain and not others? Pain. 2018:159(12):2419-2420. looked at the ability of methylenetetrahydrofolate reductase doi:10.1097/j.pain.0000000000001404.) gene polymorphisms (1298A>C, 667C>T) to enhance nitrous oxide analgesia. Steroid Injection Shown Telephone interviews were conducted at 12 months after Superior to Night-Time Splints surgery on 2924 (41.1%) patients enrolled in the Evaluation of Nitrous Oxide in the Gas Mixture for Anaesthesia-II trial for Carpal Tunnel Syndrome (ENIGMA II trial). Pain at the wound site was recorded using the modified brief pain inventory and the neuropathic pain A randomized, open-label, pragmatic trial in adults (18 years questionnaire. General health status was measured using the and older), with mild or moderate carpal tunnel syndrome of EuroQol-5D (EQ-5D) questionnaire. Genotyping was per- at least 6 weeks’ duration, compared 2 treatments given to the formed in a subset of 674 Asian patients in Hong Kong. randomly assigned 234 patients participating: More than 12% of patients (n = 356) reported chronic 1. A single injection of 20-mg methylprednisolone acetate postsurgical pain at the wound site, and 3.8% of patients (from 40 mg/mL) to 116 of the patients; and (n = 112) had severe pain, requiring regular analgesic inter- 2. A night-resting splint to be worn for 6 weeks by 118 of the ventions. Nitrous oxide did not affect the rate of chronic patients. postsurgical pain (11.8% nitrous oxide group; 12.5% no nitrous oxide group). The primary outcome was the overall score of the Boston Carpal Tunnel Questionnaire (BCTQ) at 6 weeks. Intention-to-treat analysis, with multiple imputation for missing data, was used. Continued on page 12

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Topics in Pain Management CE Quiz

To earn CME credit using the enclosed form, you must read the To earn nursing CNE credit, you must take the quiz online. Go to CME article and complete the quiz and evaluation assessment survey on www.nursingcenter.com, click on CE Connection on the toolbar at the the enclosed form, answering at least 70% of the quiz questions correctly. top, select Browse Newsletters, and select Topics in Pain Management. Select the best answer and use a blue or black pen to completely fill Log-in (upper right hand corner) to enter your username and in the corresponding box on the enclosed answer form. Please indi- password. First-time users must register. As a subscriber benefit, nurses cate any name and address changes directly on the answer form. If your can earn contact hours when taking CE activities from Topics in Pain name and address do not appear on the answer form, please print that Management for free. You must enter your subscription number information in the blank space at the top left of the page. Make a photo- preceeded by LWW, in your registration profile where there is a field copy of the completed answer form for your own files and mail the orig- for Link to my subscription. The 100% discount is applied when inal answer form in the enclosed postage-paid business reply envelope. payment is requested. Non-subscribers pay a $49.00 fee to earn ANCC Your answer form must be received by Lippincott CME Institute by contact hours for this activity. January 31, 2021. Only two entries will be considered for credit. After log-in, locate and click on the CE activity in which you are Online CME quiz instructions: Go to http://cme.lww.com and click interested. There is only one correct answer for each question. A passing on “Newsletters,” then select Topics in Pain Management. Enter your score for this test is 7 correct answers. If you fail, you have the option of username and password. First-time users must register. After log-in, fol- taking the test again. When you pass, you can print your certificate of low the instructions on the quiz site. You may print your official certificate earned contact hours and access the answer key. For questions, contact immediately. Please note: Lippincott CME Institute, Inc., will not mail Lippincott Professional Development: 1-800-787-8985. The registration certificates to online participants. Online quizzes expire on the due date. deadline for CNE credit is December 4, 2020.

1. Which one of the following is a common cause of knee B. Try to restrict the testing to only the injured side so that pain in adults? you can expedite the examination. A. Rheumatoid arthritis C. Do not tell the patient what you will be doing so that B. Still’s disease you can obtain an accurate result. C. Patellofemoral pain syndrome D. When the pain is replicated, keep performing the D. Foreign-body synovitis maneuver to determine the severity of injury. 2. Which one of the following conditions is most likely in a 7. Positive Lachman and pivot shift test results most likely patient presenting with knee pain and a history of tophi indicate an injury to the and articular symptoms, particularly the first MTP? A. medial collateral ligament A. Sarcoidosis B. lateral collateral ligament B. Charcot joint C. anterior cruciate ligament C. Neoplasm D. posterior cruciate ligament D. Gout 8. Early morning stiffness of the knee lasting for a short period 3. Acute onset of monoarticular pain and swelling is most and hard, bony enlargement of the knee is most likely commonly associated with A. patellofemoral pain syndrome A. avascular necrosis B. meniscal injury B. crystalline disease C. bursitis C. sickle cell disease D. osteoarthritis D. rheumatoid arthritis 9. A positive valgus stress test with the knee in 30-degree 4. Which one of the following patients is at highest risk for flexion, but not full extension, likely indicates injury to pseudogout? the A. A 20 year-old woman who just ran a marathon A. medial collateral ligament B. A 50-year-old man with no previous surgical history B. lateral collateral ligament C. A 75-year-old man who has pneumonia C. anterior cruciate ligament D. A 5-year-old girl with an ankle sprain D. posterior cruciate ligament 5. Which one of the following findings should increase the 10. A recent study evaluating intra-articular injection of provider’s suspicion of a systemic cause of knee pain? HA, PRP, or combination of HA and PRP for patients A. Knee-joint effusion with osteoarthritis of the knee demonstrated that B. Disorders of the skin A. HA was superior to PRP for decreasing pain intensity C. Misalignment of the knee structures B. PRP was significantly better for pain reduction than D. Patellar tenderness with motion combination treatment 6. Which one of the following is a general principle of C. combination treatment was superior to HA or PRP physical examination to detect a mechanical knee injury? alone for pain and function A. Let the patient know what you will be doing by dem- D. HA and PRP alone were not superior to placebo in this onstrating on the noninjured side. trial

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Continued from page 10 2. Infiltration between the popliteal artery and the capsule of the However, in the subgroup analysis, nitrous oxide reduced posterior knee (IPACK) with an adductor canal block (ACB) = the risk of chronic postsurgical pain in Asian patients (rela- and modified periarticular block (intervention group, n 43). tive risk, 0.70; 95% confidence intervals, 0.50–0.98; P = The primary outcome was pain on ambulation on postoper- 0.031). Patients who were homozygous for either gene poly- ative day 1 (POD 1) with numeric rating scale (NRS) pain morphism and who received nitrous oxide during surgery scores. Patient satisfaction and opioid consumption were sec- were less likely to report chronic postsurgical pain. ondary outcomes. The authors concluded that nitrous oxide administration had no Significantly lower NRS pain scores on ambulation were impact on chronic postsurgical pain, but in Asian patients and reported in the intervention group on PODs 0 and 1 (P < patients with variants in methylenetetrahydrofolate reductase .001). Patients in this group were more satisfied and required gene, there was a beneficial effect. (See Chan MTV et al, less opioid medication. The need for IV patient-controlled Australian and New Zealand College of Anaesthetists Clinical analgesia was also reduced (P ≤ 0.037). Trials Network for the ENIGMA-II investigators. Chronic postsurgical pain in The authors concluded that the addition of IPACK and ACB to PAI the Evaluation of Nitrous Oxide in the Gas Mixture for significantly improves analgesia and reduces opioid Anaesthesia (ENIGMA)-II consumption after total knee arthroplasty. trial. Br J Anaesth. 2017;119 (4):851. doi:10.1093/bja/ aex047.) The authors concluded that the addition of IPACK and ACB to PAI significantly improves analgesia and reduces opioid consumption after total knee arthroplasty, strongly support- Periarticular Infiltration ing the addition of these 2 techniques within a multimodal Decreases Pain After Knee analgesic pathway. (See Kim DH, Beathe JC, Lin Y, et al. Addition of infiltration between the popliteal artery and the Arthroplasty capsule of the posterior knee and adductor canal block to periarticular injection enhances postoperative pain control in In a triple-blinded randomized controlled trial, 86 patients total knee arthroplasty: a randomized controlled trial [pub- undergoing unilateral total knee arthroplasty received either: lished online ahead of print September 12, 2018]. Anesth 1. A periarticular injection (PAI) (control group, n = 43); or Analg. doi:10.1213/ANE.0000000000003794.)

Coming Soon: • Cervical Pain Management

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