Cannabis Use Does Not Affect Outcomes After Total Knee Arthroplasty

Cannabis Use Does Not Affect Outcomes After Total Knee Arthroplasty

Accepted Manuscript Cannabis use does not affect outcomes after TKA Jason Jennings, MD, DPT, Marc Angerame, MD, Catherine L. Eschen, Alexandra Phocas,...

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Accepted Manuscript Cannabis use does not affect outcomes after TKA Jason Jennings, MD, DPT, Marc Angerame, MD, Catherine L. Eschen, Alexandra Phocas, Douglas A. Dennis, MD PII:

S0883-5403(19)30347-X

DOI:

https://doi.org/10.1016/j.arth.2019.04.015

Reference:

YARTH 57214

To appear in:

The Journal of Arthroplasty

Received Date: 7 February 2019 Revised Date:

18 March 2019

Accepted Date: 8 April 2019

Please cite this article as: Jennings J, Angerame, M, Eschen CL, Phocas A, Dennis DA, Cannabis use does not affect outcomes after TKA, The Journal of Arthroplasty (2019), doi: https://doi.org/10.1016/ j.arth.2019.04.015. 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.

ACCEPTED MANUSCRIPT Cannabis use does not affect outcomes after TKA Alexandra Phocas Colorado Joint Replacement 2535 S. Downing St. Suite 100 Denver, CO 80210 [email protected]

Marc Angerame, MD Illinois Bone and Joint Institute 27401 W State Rte 22 #112 Barrington, IL [email protected]

Douglas A. Dennis, MD Colorado Joint Replacement 2535 S. Downing St. Suite 100 Denver, CO 80210 Assistant Clinical Professor, Dept. of Orthopaedics, University of Colorado School of Medicine, Denver, CO Adjunct Professor, Dept. Of Biomedical Engineering, University of Tennessee, Knoxville, TN Adjunct Professor of Bioengineering, Dept. of Mechanical and Materials Engineering, University of Denver, Denver, CO [email protected]

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Jason Jennings, MD, DPT Colorado Joint Replacement 2535 S. Downing St. Suite 100 Denver, CO 80210 Adjunct Professor of Bioengineering, Dept. of Mechanical and Materials Engineering, University of Denver, Denver, CO [email protected]

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Catherine L. Eschen Colorado Joint Replacement 2535 S. Downing St. Suite 100 Denver, CO 80210 [email protected]

Conflict of Interest Statement: None of the authors has received funding for this research study and there were no individual funds received by any of the authors personally. Each author certifies that he or she has no commercial associations (eg, consultancies, stock ownership, equity interest, patent/licensing arrangements, etc) that might pose a conflict of interest in connection with the submitted article.

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DAD has or may receive payments or benefits from DePuy, Innomed, Joint Vue, Corin U.S.A and Wolters Kluwer Health not related to this work. JMJ has or may receive payments or benefits from DePuy, Total Joint Orthopedics, and Xenex not related to this work.

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Ethical Review Committee Statement: Our study involves human data and we have ethical board approval for our study.

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Statement of the Location: Date collected for the use of this study was done at Colorado Joint Replacement. Corresponding Author: Douglas A. Dennis, MD Email: [email protected]

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Cannabis use does not affect outcomes after TKA

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INTRODUCTION: The self-reported use of cannabis has increased since its recent legalization

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in several states. The primary purpose of this study was to report total knee arthroplasty (TKA)

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outcomes in patients using cannabis.

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METHODS: Seventy-one patients who underwent a primary unilateral TKA with minimum

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one-year follow-up who self-reported cannabis use, were retrospectively reviewed. The study

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period was from January 2014 to February 2018 at a single institution. Patients with a history of

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opioid consumption, alcohol abuse, tobacco or illicit drug use were excluded. A matched control

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was conducted based on age, BMI, gender, smoking status, and insurance type (surrogate of

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socioeconomic status) in patients with a unilateral TKA who did not report cannabis use.

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Outcome measures included Knee Society Scores (KSS), range of motion (ROM), VR-12 mental

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(MCS) and physical component scores (PCS). No preoperative differences were noted with

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these measures. Postoperative complications were recorded and reported.

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RESULTS: No difference in length of stay was noted between the users (46.9 hours ± 15.7) and

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nonusers (49.3 hours ± 20.4), p=0.464. In hospital total morphine equivalents did not differ

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between the two groups (user = 137±104 mg, nonuser = 146±117 mg), p=0.634. Postoperative

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ROM did not differ between users (128.4º ± 10.4º) and nonusers (126.9º ± 7.5º), p=0.346. No

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mean differences in follow-up KSS (user =180.1 ± 24.9, nonuser = 172.0 ± 33.9, p=0.106) or

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total change (user = 61.7 ± 32.8, nonuser = 62.7 ± 30.7, p=0.852) in KSS were noted. Likewise,

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no significant mean differences in VR-12 (MCS [user = 54.8 ± 9.3, nonuser = 55.9 ± 8.79,

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p=0.472] and PCS [user = 48.3 ± 9.9, nonuser = 45.8 ± 10.1, p=0.145]) scores were

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demonstrated. There were no differences in readmissions (user = 5, nonuser = 4, p=0.730) or

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reoperations (user = 5, nonuser = 2, p=0.238).

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CONCLUSION: Cannabis use does not appear to influence (adverse or beneficial) short-term

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outcomes in patients undergoing a primary TKA. Further studies are warranted to determine the

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efficacy and safety of cannabis as a constituent of multimodal pain management following TKA

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before endorsements can be made by orthopaedic surgeons.

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KEYWORDS: Marijuana; Pain; Total Knee; Opioid; Cannabinoids

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INTRODUCTION Opioid consumption after total knee arthroplasty (TKA) is often needed to obtain

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adequate pain control despite the use of multimodal pain management. Alternatives to narcotic

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use have gained recent attention secondary to the potential morbidity and mortality that has been

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reported in this patient population[6, 8, 10, 12–14].

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The self-reported use of cannabis has increased in patients undergoing elective total joint

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arthroplasty (TJA) since its recent legalization in several states[9]. The endocannabinoid system

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may function to reduce sensitization of the nociceptive sensory pathways and induce alterations

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in cognitive and autonomic processing[7, 11]. For these reasons, cannabis may have potential to

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be an adjuvant for perioperative pain control. However, a recent study was unable to show

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differences in morphine equivalents in patients using dronabinol vs. those who did not during

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their inpatient hospitalization (post-operative days 1-3) in patients undergoing an elective

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primary total joint arthroplasty[8]. Additionally, drug use has been associated with a higher risk

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of post-operative complications and potentially worse outcomes in patients undergoing elective

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TJA[4, 10]. These results are difficult to interpret since cannabis use in many of these patients

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may have been used in conjunction with other types of substances (i.e. tobacco, narcotics,

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alcohol) that have been shown to increase complications and decrease outcomes after TJA[3, 5,

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10]. Therefore, the purpose of this study was to report outcomes and complications in patients

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self-reporting cannabis use and undergoing primary TKA.

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METHODS

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This study was approved by our institutional review board prior to initiation. The study

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period was from January 2014-February 2018. The commercial sale of cannabis to the general

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public in the authors’ state was initiated January 1, 2014. We utilized our institution’s

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longitudinally maintained total joint arthroplasty database to identify all patients who underwent

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unilateral primary TKA with a minimum one-year follow-up duration. We retrospectively

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evaluated outpatient office charts for self-reported use of cannabis. Patients were excluded if

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they did not have adequate follow-up or had incomplete charts for analysis. Additional

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exclusion criteria included patients with a history of opioid consumption, (within 90 days)

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current tobacco use or illicit drug abuse. Seventy-one patients were included who met the above

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criteria.

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All patients in this cohort underwent a pre-operative medical history and physical with our internal medicine physicians. A social history which included a drug screen (intake form and

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questioning by the physician) is standard practice at our institution. No attempt was made to

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determine frequency or duration of use because these questions were not asked by our medical

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team at the time of this study. Route of administration (inhalation, edible, topical, combination

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[i.e. inhalation + edible]) was documented when available. There were no patients in this study

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with incomplete medical records concerning drug, alcohol, opioid or tobacco use. A matched

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control was conducted based on age, BMI, gender, smoking status, and insurance type (surrogate

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of socioeconomic status) in patients with a unilateral TKA who did not report cannabis use.

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Charts were reviewed by one of the authors not involved in patient care.

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Outcome measures included Knee Society Scores (KSS), range of motion (ROM), VR-12

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mental (MCS) and physical component scores (PCS). There were no preoperative differences

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noted in any parameters between the two groups. Postoperative complications were reported

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based on inpatient and outpatient patient chart review.

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Descriptive statistics were provided using means and standard deviations for continuous variables while frequencies and relative percentages are reported for categorical variable. The

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paired Student’s t-tests was used to test the difference between the users and non-users for

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continuous variable outcomes including length of stay, morphine equivalents while in the

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hospital, pain, function, ROM, KSS, VR-12 scores. Statistical analyses were performed using

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Minitab version 17.0 (Statistical Analysis Software, State College, Pennsylvania, USA). P

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values of less than 0.05 were considered indicating statistical significance.

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RESULTS

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The mean age of the cannabis group was 61.0 ± 7.0, BMI was 27.1 ± 4.0 and the gender

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comparison was 48 males (67.6%) to 23 females (32.4%). This group was matched to a control

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group with age +/- 3, BMI +/- 3 and same gender. The mean length of stay was 46.9±15.7

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(users) vs. 49.3±20.4 (nonuser) hours (p=0.464). In hospital total morphine equivalents did not

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differ between the two groups (user = 137±104 mg, nonuser = 146±117 mg), p=0.634.

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Postoperative ROM did not differ between users (128.4º ± 10.4º) and nonusers (126.9º ± 7.5º),

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p=0.346. No mean differences in follow-up KSS (user =180.1 ± 24.9, nonuser = 172.0 ± 33.9,

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p=0.106) or total change (user = 61.7 ± 32.8, nonuser = 62.7 ± 30.7, p=0.852) in KSS were

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noted. Likewise, no significant mean differences in VR-12 (MCS [user = 54.8 ± 9.3, nonuser =

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55.9 ± 8.79, p=0.472] and PCS [user = 48.3 ± 9.9, nonuser = 45.8 ± 10.1, p=0.145]) scores were

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demonstrated. There were no differences in readmissions (user = 5, nonuser = 4, p=0.730) or

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reoperations (user = 5, nonuser = 2, p=0.238). The reoperations for the nonuser group included a

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polyethylene liner exchange for instability and an irrigation and debridement with polyethylene

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liner exchange for infection. The reoperations for the nonuser group included a knee arthroscopy

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for crepitus, a manipulation under anesthesia, polyethylene liner exchange for arthrofibrosis and

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two patients had an explantation and two stage revision in the setting of infection.

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DISCUSSION

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Currently there is little evidence to support the routine use of cannabis for medicinal purposes in patients undergoing elective TJA. Despite this, it appears more patients undergoing total joint arthroplasty may be using, or reporting use for both medicinal and/or recreational

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purposes since its legalization[9]. The primary aim of this study was to determine if cannabis

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use had clinical implications (i.e. complications and outcomes) in patients undergoing primary

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unilateral TKA. Our results suggest there are no beneficial or adverse effects on short-term

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outcomes in patients who use cannabis in the post-operative phase of care after TKA.

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The use of opioids, tobacco, illicit drugs and alcohol have been shown to increase postoperative complications after TJA[2–4, 6, 10, 12, 14]. Many of these studies are limited by large

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database methodology which is unable to isolate much of the social history with regards to

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substance abuse. Additionally, some have reported only on inpatient data which does not

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account for the complications that arise after discharge and during follow-up[8]. We were able

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to report on the isolated use of cannabis eliminating other variables that may confound results.

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While the current study does not address the efficacy, it is an important initial step in defining

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the safety of cannabis use in arthroplasty patients. We are currently studying the efficacy in a

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prospective study in patients undergoing primary TKA.

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A recent report of a large database (PearlDiver Supercomputer, Warsaw, IN) study stated that cannabis use may increase the risk of revision surgery after TKA[10]. The findings in this

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study imply a significant increase in both the 30- and 90-day incidence of revision TKA. The

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conclusions suggest there may be an increased risk of infection in this patient population as well.

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Our results do not support these conclusions. The aforementioned study did not account for

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other factors that may adversely affect outcomes (i.e. opioid use, tobacco use) after TKA, which

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we eliminated with our matched control. Additionally, patient comorbidities were not stratified

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which may account for the differences as well. Lastly, this study included patients prior to the

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legalization which may have created an inherent selection bias since patients have been more

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likely to report cannabis use since its legalization[9]. Differences in morphine equivalents in the in-patient setting has previously been shown

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to be equivocal in patients using cannabinoids vs. those who do not [8]. Our results, while

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different in design, support this previous finding. To our knowledge, no study has investigated

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this in a prospective randomized fashion. This type of study design would be difficult since

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cannabinoids remain a Class I restricted substance. Additionally, the synthetic form

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(Dronabinol) remains off-label for the use of pain after TJA.

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This study is not without limitations. We utilized the time period after the legalization of

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the commercial sale of cannabis for medicinal and recreational purposes since it appears patients

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have been more willing to report its use[9]. Despite this, there may be a subset of this population

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in our matched control group that used cannabis, opioids, alcohol or tobacco and did not report

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use. We did not record the type (i.e. inhalation, edible), frequency, or duration of use. All

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patient in this study had current cannabis use at the time of their TKA. However, we did not

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quantify the frequency of use in this study which certainly could have led to the lack of statistical

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significance. The type of use (i.e. inhalation, edible) was not readily available based on our

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clinical questioning of the patient prior to this study. The amount of delta-9-tertrahydro-

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cannabinol (THC) and cannabidiol (CBD) is variable in all solutions making these differences

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hard to account for with regards to the pre- and postoperative comparisons. The quality and

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reliability between different types of cannabis is well known to be variable amongst

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manufactures and at this point is not well controlled. We still believe that this is a valid way to

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explore cannabis use in this patient population since there currently is no stringent regulation in

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the United States. The reason for use (medicinal vs. recreational) was not explored in this

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study However, several studies have demonstrated a significant overlap between medicinal and

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recreational users with previous recreational cannabis use reported by many current medicinal

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users, which blurs the distinction between the reason for use in many patients[1, 15]. Further

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research in this area is warranted to determine if these variables will have clinical significance.

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The length of follow-up is one year but we feel these results warrant reporting of the short-term

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follow-up to help guide orthopaedic providers evidence-based guidelines for education of this

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population which has previously not been reported. Longer follow-up is necessary and may

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prove to differ from the current short-term results we report in this cohort. Ideally this cohort

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would be larger and the data would be collected in a prospective manner. We did not assess

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differences in opioid consumption between the two cohorts in this retrospective design. This

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certainly may have future implications for pain management in the early post-operative phase of

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care. We are currently assessing this with a prospective matched control study at our institution.

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Lastly, we concede that the inherent nature of the retrospective chart review may have

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overlooked complications that may have happened and been documented at an outside facility.

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The use of cannabis does not appear to influence (adverse or beneficial) short-term

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outcomes in patients undergoing a primary TKA. Further studies are warranted to determine the

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efficacy and safety as a constituent of multimodal pain management following TKA before

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endorsements can be made by orthopaedic surgeons.

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