Original Article 把 國考參考書 看 熟

Ibuprofen Use Did Not Affect Outcome Metrics

After Arthroscopic Rotator Cuff Repair,
Nicholas R. Kraus, M.S., B.A., Kirsten D. Garvey, M.S., B.A.,
Laurence D. Higgins, M.D., M.B.A., and Elizabeth Matzkin, M.D.

鬆緊度 1 - 2
指 鞍 是票的
Purpose: To determine whether patients who are prescribed ibuprofen after arthroscopic rotator cuff repair have
significantly different patient-reported outcomes for pain, function, and overall health at baseline and 1 and 2 years after
operation relative to patients only prescribed opioids. Methods: Patients who underwent a rotator cuff repair by a total of
3 surgeons and participated in the outcomes registry from 2012 to 2016 were screened for inclusion in this study. In-
clusion criteria were primary arthroscopic rotator cuff repair, at least 2 years from the date of surgery and over the age of
18. Exclusion criteria were revision and open rotator cuff repair. All patients followed the standard postoperative reha-
bilitation protocol for rotator cuff repair. Patients were divided into 2 cohorts. Group I included patients who received
ibuprofen/nonsteroidal anti-inflammatory agents (NSAID) after surgery (n ¼ 281), and Group II consisted of patients who
did not receive ibuprofen/NSAID after surgery (n ¼ 182). Patient-reported outcome measures for Visual Analogue Scale,
American Shoulder Elbow Surgeons score, Single Assessment Numeric Evaluation score, Simple Shoulder Test and The
Veterans Rand 12-Item Health Survey were collected preoperatively and at 3 and 6 months, 1 year, and 2 years after
surgery. Statistical analysis was performed to compare patient-reported outcome measures between Group I and II.
Results: This study consisted of 463 patients who underwent arthroscopic rotator cuff repair, and patients were divided
into 2 cohorts. There were 281 patients who did not receive ibuprofen/NSAID after operation in Group I and 182 patients
who did receive ibuprofen in Group II. There were no statistically significant differences between the 2 groups in age at
treatment, mean body mass index, gender, ethnicity, diabetes, and number of rotator cuff tendons involved; however,
there was a statistically significant difference in receiving worker’s compensation (P ¼ .005), and this was subsequently
adjusted for in our analysis. There were no significant differences in patient-reported outcomes for all metrics between the
group prescribed ibuprofen and the group that was not prescribed ibuprofen at 1 and 2 years after surgery or in change
from baseline. Conclusion: Patients receiving ibuprofen did as well as patients who did not receive ibuprofen after
arthroscopic rotator cuff repair on patient-reported outcome measures assessing shoulder pain, function, and overall
health. Level of Evidence: Level III, retrospective comparative study.

R otator cuff injury is one of the most widespread

musculoskeletal disorders, accounting for more
than 4.5 million physician visits and 250,000 surgeries
per year in the United States.1-4 Injury to the rotator
cuff often causes shoulder pain, loss of strength, com-
plex sequelae, and partial or total inability to work, thus
reducing a patient’s quality of life.5-8
The treatment algorithm for rotator cuff tears is
From Tufts University School of Medicine (N.R.K., K.D.G.) and Depart-
ment of Orthopaedic Surgery, Brigham and Women’s Hospital (N.R.K., multifactorial.9 The rotator cuff has a limited ability for
K.D.G., L.D.H., E.M.), Boston, Massachusetts. intrinsic repair, in part due to poor vascularization of
The authors report the following potential conflicts of interest or sources of the tendon tissue.2,10,11 Management depends on the
funding: L.D.H reports personal fees from Arthrex, Inc., outside the submitted presence and severity of impingement, extent of tendon
work. Full ICMJE author disclosure forms are available for this article online, tear, degree of retraction, and functional demands.12
as supplementary material.
Received April 6, 2020; accepted November 15, 2020. Nonoperative treatment can lead to tear progression,
Address correspondence to Elizabeth Matzkin, M.D., Harvard Medical tendon retraction, and muscle degeneration.11 Surgical
School, 75 Francis St., Boston, MA 02115. E-mail: [email protected]. rotator cuff repair has demonstrated satisfactory long-
edu term clinical results,13 with more than 90% good or
! 2020 THE AUTHORS. Published by Elsevier Inc. on behalf of the excellent results at 10 years after surgery.14
Arthroscopy Association of North America. This is an open access article under
the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
The ideal rotator cuff repair restores kinematics, im-
2666-061X/20434 proves strength and function while decreasing pain.15,16
https://doi.org/10.1016/j.asmr.2020.11.004 Despite advances in both open and arthroscopic surgical

Arthroscopy, Sports Medicine, and Rehabilitation, Vol 3, No 2 (April), 2021: pp e491-e497 e491
e492 N. R. KRAUS ET AL.

techniques, shoulder surgery is frequently associated with were screened on the basis of inclusion and exclusion
severe postoperative pain.17,18 Traditional pain manage- criteria reviewed. Inclusion criteria were primary
ment for shoulder injuries has included local injection of arthroscopic rotator cuff repair during the study period,
analgesics, nerve blocks, intravenous patient-controlled at least 2 years from the date of surgery, and age over
analgesia, opioid drugs, and nonsteroidal anti- 18 years. Exclusion criteria were revision rotator cuff
inflammatory agents (NSAIDs), with the latter two be- repair and open rotator cuff repair. All patients followed
ing the most frequently used.19,20 Despite the widespread the standard postoperative rehabilitation protocol for
use of opioids and NSAIDs in the postoperative setting, rotator cuff repair.
both have risks, limitations, and side effects. Patients included in the study were divided into two
Opioids are associated with adverse effects including cohorts based on post-operative analgesic therapy:
nausea and vomiting, pruritus, sleep disturbance, con- Group I (no ibuprofen/NSAID use) and Group II
stipation, and dependency.21 Conversely, NSAIDs (ibuprofen use). Group I patients were instructed to
function by inhibiting cyclooxygenase (COX) enzymes, avoid ibuprofen/NSAIDs after surgery for 12 weeks and
reducing the synthesis of inflammatory prostaglan- were provided opioids for pain management. Group II
dins22 but diminishing platelet counts, leading to patients were sent home with a prescription for 800 mg
bleeding and gastric ulceration.23 Although NSAIDs of Ibuprofen and instructed to take regularly and use
have been shown to minimize pain and decrease opioid opioid pain medication when needed. The groups were
requirements after surgery,24 they have traditionally predetermined by surgeon preference; all patients un-
been avoided by orthopedic surgeons. This avoidance dergoing surgery with a particular surgeon either were
could be based on past studies that have shown that prescribed ibuprofen or were instructed to avoid
selective NSAIDs (COX-2 inhibitors) impede fracture ibuprofen/NSAIDs for 3 months after surgery.
and tendon healing.25-28 Additionally, in vitro NSAID All participants were administered a preoperative sur-
treatment has been shown to impede proliferation and vey consisting of the following outcome-measuring tools:
migration of tendon cells that are necessary for tendon (i) Visual Analog Scale (VAS) used to measure overall
repair after injury.29 Despite literature indicating pain level, (ii) the Veterans Rand 12-Item Health Survey
NSAID use leads to adverse in vitro and clinical out- (VR-12), a standard self-reported global health measure
comes, other studies have shown neutral or positive tool that is used to assess a patient’s overall perspective of
effects of selective and nonselective NSAID use.30-33 their health, (iii) the American Shoulder and Elbow
Given the widespread use of NSAIDs for post- Surgeons Shoulder Score (ASES) used to measure func-
operative pain relief, it is important to identify what tional limitations and pain of the shoulder, (iv) standard
effects NSAID use has on patient-reported outcomes for preoperative form consisting of 4 questions regarding
pain, function, and overall health after arthroscopic their expectations of recovery, (v) Single Assessment
rotator cuff repair. There is limited information Numeric Evaluation (SANE) shoulder score used to
regarding the direct effect of NSAIDs on clinical and determine a patient self-assessment of their shoulder
patient-reported outcomes in rotator cuff repair.34 The function, and (vi) Simple Shoulder Test used to assess
purpose of this study is to determine whether patients functional disability of the shoulder based on a 12-item
that are prescribed ibuprofen after arthroscopic rotator score card. The same outcome measures were reas-
cuff repair have significantly different patient-reported sessed at 3 and 6 months and 1 and 2 years after surgery.
outcomes for pain, function, and overall health at At each data collection point, participants were e-mailed
baseline and 1 and 2 years after surgery relative to an electronic survey with one e-mail reminder and one
patients only prescribed opioids. We hypothesized that phone call reminder by a research assistant if outcome
patients who were prescribed ibuprofen after arthro- measures were not completed in a timely manner. Paper-
scopic rotator cuff repair would not have significantly based questionnaires were not used in this study.
different patient-reported outcome measures as those
that were instructed not to take ibuprofen after surgery. Statistical Analysis
The scores for all functional assessment metrics were
Methods tallied for each cohort at each of the time points of data
Approval by the institutional review board was ob- collection pre- and post-operatively. Baseline differences
tained before the initiation of the present study. Data in covariates were assessed using the t-test (continuous)
were collected prospectively on consecutive surgeries and c2 test (categorical variables). A linear mixed effects
performed by 3 surgeons at an academic medical center model to compare outcomes between the groups at each
and retrospectively reviewed for the present study. All timepoint accounted for all available data and did not
patients signed an informed consent. An electronic require that subjects have complete data at all time-
surgical outcomes registry was used for data collection. points. Multivariable models adjusted for covariates that
Patients who underwent a rotator cuff repair and were imbalanced at baseline (worker’s compensation
participated in the outcomes registry from 2012 to 2016 status). Statistical analysis was performed to determine
 IBUPROFEN DID NOT AFFECT OUTCOMES AFTER RCR e493

Table 1. Patient Demographics

Demographic characteristics No ibuprofen/NSAIDS Use (281 patients) Ibuprofen use (182 patients) P value
Age at treatment (mean " SD) 57.01 " 9.13 55.93 " 9.72 .229
BMI, median (IQR) 28 (22.14-33.86) 27.90 (20.8-35.0) .805
Gender .157
Males (% of total) 162 (58%) 94 (51%)
Females (% of total) 117 (42%) 89 (49%)
Missing 2 0
Ethnicity .525
Hispanic (% of total) 7 (3%) 6 (3%)
Non-Hispanic White (% of total) 221 (81%) 143 (79%)
Non-Hispanic Black (% of total) 8 (3%) 2 (1%)
Other (% of total) 38 (14%) 29 (16%)
Missing 7 3
Diabetic .465
No (% of total) 269 (96%) 172 (95%)
Yes (% of total) 10 (4%) 9 (5%)
Missing 2 2
Workers compensation .005
No 263 (94%) 156 (87%)
Yes 16 (6%) 24 (13%)
Missing 2 3
Number of tendons involved .897
1 82 (42.3%) 81 (44.5%)
2 77 (39.7%) 72 (39.6%)
3 31 (16.0) 27 (14.8%)
4 4 (2.1%) 2 (1.1%)
Missing 89 6
BMI, body mass index; IQR, interquartile range, NSAID, nonsteroidal anti-inflammatory agent; SD, standard deviation.

whether there was any correlation between ibuprofen Differences in baseline characteristics between the
use and functional outcome measures collected. Statis- included subjects are presented in Table 1. There were
tical significance was set at P < .05. no statistically significant differences between the 2
groups in terms of age at treatment, mean body mass
index, gender, ethnicity, and diabetes; however, there
Results
was a statistically significant difference between both
Patient Characteristics groups with regard to worker’s compensation status
In total, 591 patients undergoing primary rotator cuff (P ¼ .005).
repair were initially identified. Of these patients, 471 There was a total of 281 patients in Group I (no
were included (80%), and 120 did not have complete NSAIDs use) and 182 patients in Group II (ibuprofen/
preoperative and 1- and 2-year postoperative PROMs NSAID use) who underwent rotator cuff repair during
data (20%) and were therefore excluded. For patients the data collection period. These patients were admin-
who underwent multiple surgeries, only the first sur- istered the preoperative and postoperative surveys at
gery was included, leaving an analytic dataset of 463. each of the study time points. Clinical characteristics of

Table 2. Improvement in VAS Pain Ratings Across All Groups After Rotator Cuff Repair (Adjusted for Worker’s Compensation
Status) and in ASES Pain Ratings Across All Groups After Rotator Cuff Repair (Adjusted for Worker’s Compensation Status)

PRO Time No ibuprofen/NSAIDs use Ibuprofen use P value

VAS Baseline 5.0 (4.6, 5.4) 5.4 (5.0, 5.8) .112
VAS Year 1 1.4 (1.1, 1.7) 1.6 (1.3, 1.9) .279
VAS Year 2 1.2 (0.9, 1.5) 1.3 (1.0, 1.6) .629
VAS Year 1 change from BL #3.6 (#4.0, #3.2) #3.8 (#4.2, #3.4) .437
VAS Year 2 change from BL #3.8 (#4.2, #3.4) #4.1 (#4.5, #3.7) .274
ASESI Baseline 47.1 (44.0, 50.2) 44.0 (41.0, 47.1) .110
ASESI Year 1 83.3 (80.6, 85.9) 82.4 (79.9, 84.9) .559
ASESI Year 2 85.6 (82.8, 88.4) 85.9 (82.9, 88.9) .846
ASESI Year 1 change from BL 36.2 (33.4, 39.1) 38.4 (35.4, 41.4) .297
ASESI Year 2 change from BL 38.5 (35.5, 41.5) 41.9 (38.5, 45.3) .142
BL, baseline; ASES, American Shoulder and Elbow Surgeons Shoulder; NSAID, nonsteroidal anti-inflammatory agent; VAS, Visual Analog Scale.
e494 N. R. KRAUS ET AL.

Table 3. Improvement in SANE Ratings Across All Groups After Rotator Cuff Repair (Adjusted For Worker’s Compensation
Status) And In SST Ratings Across All Groups After Rotator Cuff Repair (Adjusted For Worker’s Compensation Status)

PRO Time No ibuprofen/NSAIDs use Ibuprofen use P value

SANE Baseline 35.1 (31.6, 38.5) 34.8 (31.4, 38.2) .890
SANE Year 1 77.6 (73.8, 81.4) 77.1 (73.4, 80.8) .833
SANE Year 2 79.6 (75.4, 83.8) 79.7 (74.8, 84.5) .987
SANE Year 1 change from BL 42.6 (38.3, 46.8) 42.4 (38.0, 46.7) .947
SANE Year 2 change from BL 44.6 (40.0, 49.1) 44.9 (39.6, 50.2) .924
SST Baseline 37.1 (32.5, 41.7) 31.7 (27.3, 36.2) .053
SST Year 1 77.4 (73.2, 81.5) 76.0 (72.1, 80.0) .577
SST Year 2 79.7 (75.2, 84.3) 78.2 (73.5, 83.0) .588
SST Year 1 change from BL 40.3 (36.0, 44.6) 44.3 (40.0, 48.6) .198
SST Year 2 change from BL 42.7 (38.0, 47.3) 46.5 (41.4, 51.5) .275
BL, baseline; NSAID, nonsteroidal anti-inflammatory agent; SANE, Single Assessment Numeric Evaluation; SST, Simple Shoulder Test.

each group were assessed to evaluate major differences Pain improvement was also measured with the ASES
in rotator cuff tear size by comparing number of ten- assessment tool. After adjusting for worker’s compensa-
dons torn. There were no statistical differences between tion status, there were no statistically significant inter-
the 2 NSAID use groups in terms of the number of group differences in pain improvement at baseline,
tendons involved. 1-year, and 2-years following rotator cuff repair (P ¼
.110, .559,.846, respectively). Patients in Group I
Postoperative Pain improved their ASES shoulder function score by 38.5
Table 2 presents the VAS pain scores after adjusting points at 2 years after surgery and Group II improved by
for worker’s compensation status. Patients experienced 41.9 points at the same time interval (Table 2).
significant improvement in VAS pain scores at 1- and 2-
years after rotator cuff repair in both Group I (no Postoperative Function
NSAID use) and Group II (ibuprofen/NSAID use). Pa- All patients demonstrated improvement in shoulder
tients in Group I had an average baseline VAS pain function after rotator cuff repair as reported by the
score of 5.0 (confidence interval [CI] 4.6-5.4), a 1-year SANE and Simple Shoulder Test (SST) outcome mea-
pain score of 1.4 (CI 1.1-1.7), and a 2-year pain score of sures before and after adjusting for worker’s compen-
1.2 (CI 0.9-1.5). Patients in Group II had an average sation status. SANE and SST outcome measures were
baseline VAS pain score of 5.4 (CI 5.4-5.8), a 1-year used to assess functional disability experienced by pa-
pain score of 1.6 (CI 1.3-1.9) and a 2-year pain score tients because of rotator cuff tear. Both groups experi-
of 1.3 (CI 1.0-1.6). Both Group I and Group II post- enced a significant increase in SANE score: Group I
operative VAS pain scores meet the Minimal Clinically improved by 44.6 points at 2 years after surgery, and
Important Differences measure. There is no significant Group II improved by 44.9 points at 2 years. There were
difference in VAS pain score between patients in group no statistically significant intergroup differences in
I and group II at 1 year (P ¼ .279) and 2 years after SANE score improvement over the course of the study.
operation (P ¼ .629). Patients across both groups There were no significant intergroup differences in SST
demonstrated a similar magnitude of pain improve- score improvement or at baseline and 1 and 2 years
ment at 1 and 2 years after rotator cuff repair. after operation (Table 3).

Table 4. Improvement in the VR-12M and VR-12P Ratings Across All Groups After Rotator Cuff Repair (Adjusted For Worker’s
Compensation Status)

PRO Time No ibuprofen/NSAIDs use Ibuprofen use P value

VR12M Baseline 53.4 (51.6, 55.2) 52.8 (51.1, 54.5) .541
VR12M Year 1 54.9 (53.2, 56.5) 54.9 (53.4, 56.5) .962
VR12M Year 2 54.9 (53.2, 56.7) 54.3 (52.5, 56.2) .569
VR12M Year 1 change from BL 1.5 (0.0, 2.9) 2.1 (0.6, 3.6) .531
VR12M Year 2 change from BL 1.5 (0.0, 3.1) 1.6 (-0.2, 3.3) .987
VR12P Baseline 34.7 (33.2, 36.2) 34.1 (32.7, 35.6) .501
VR12P Year 1 46.3 (44.9, 47.8) 46.2 (44.8, 47.6) .846
VR12P Year 2 47.6 (46.0, 49.1) 47.0 (45.4, 48.6) .550
VR12P Year 1 change from BL 11.6 (10.4, 12.9) 12.0 (10.8, 13.3) .654
VR12P Year 2 change from BL 12.9 (11.5, 14.2) 12.9 (11.3, 14.4) .998
BL, baseline; NSAID, nonsteroidal anti-inflammatory agent; VR-12M, Veterans Rand 12-Item Health Survey for Mental Health; VR-12P,
Veterans Rand 12-Item Health Survey for Physical Health.
 IBUPROFEN DID NOT AFFECT OUTCOMES AFTER RCR e495

Overall Health Assessment The effects of NSAIDs on bone, tendon, and muscle
The VR-12 assessment tool was used to assess patient’s healing have been studied in animal models and to a lesser
overall health. The VR-12 form consisted of a series of extent in human models. Conflicting evidence exists in
questions about mental, emotional, and physical health, support of and against the use of NSAIDs in bony and
as well as social functioning. The VR-12 is separated into tendinous healing processes. A study by Carlstedt et al.32
a physician component score and a mental component demonstrated the positive effect of NSAIDs on tendon
score. The higher the score, the better the patient’s healing. Carlstedt et al.32 conducted an in vitro study that
perception of their overall health. Patients in both examined the effects of the nonspecific NSAID indo-
groups demonstrated improvement in the VR-12 methacin on the biomechanical properties of plantaris
physician component score and mental component longus tendon healing in rabbits. The study found that
score after rotator cuff repair. There were no statistically indomethacin therapy significantly increased tendon
significant intergroup differences at baseline and 1 and 2 tensile strength.32 Leadbetter38 demonstrated the
years after surgery. Similarly, there were no statistically importance of cell proliferation, migration, and collagen
significant intergroup differences in improvement at 1 synthesis for tendon repair. In animal models, Tsai et al.39
and 2 years after surgery (Table 4). showed that NSAIDs impeded the proliferation and
migration of tendon cells, delaying the healing process.
Discussion Almekinders et al.30 investigated the in vitro effects of
In this study, we found no significant difference in NSAIDs on human tendon fibroblasts and found that
patient-reported outcome measures between patients these drugs may inhibit the proliferative phase of tendon
who were instructed to use ibuprofen after surgery and healing by impeding DNA synthesis. However, the study
patients who were instructed not to use NSAIDs also found that NSAIDs stimulated protein synthesis in
following surgery for rotator cuff repair. This supports these same cells, demonstrating that NSAIDs may be
the hypothesis that patients would have similar re- beneficial in the remodeling phase of the healing pro-
ported outcomes at 1- and 2-years following arthro- cess.30 Ferry et al.40 found that NSAIDs, with the excep-
scopic rotator cuff repair. tion of ibuprofen, had a detrimental effect on healing
Postoperative pain control is a critical component of strength at the bone-tendon junction in animal models. A
patient care and leads to faster rehabilitation and meta-analysis by Wheatley et al.41 found that NSAID
increased function after surgical repair. There is a broad exposure delayed bone union in the adult population.
range of analgesic therapies for pain control. The These studies indicate that NSAID use plays a hindering
traditional management of postoperative pain after ro- role in tendinous and bony healing processes, but there
tator cuff repair is with opioid drugs, and many consider are fewer studies that identify the direct impact of NSAID
it the gold standard for analgesia after orthopedic sur- use on rotator cuff repair healing.
gery.17 Opioids also have a high potential for abuse, and Despite the theoretical concerns on healing processes,
thus there have been significant efforts to reduce the there is not any strong evidence to avoid the use of
rate of opioids prescribed.35 NSAIDs after rotator cuff surgery. This article supports
Historically NSAID use has been avoided in rotator cuff the use of ibuprofen after arthroscopic rotator cuff
repair surgery because of the potential to inhibit tendon repair and demonstrates no difference in clinical out-
healing.36 NSAIDs have been shown to decrease opioid comes 2 years after surgery. This should encourage
requirements after surgical procedures24,37 but concern surgeons to prescribe ibuprofen after surgery to
for lack of healing and inferior postoperative outcomes potentially minimize the use of opioids.
has prevented many surgeons from using them.
In a Level I RCT, Oh et al.34 determined there were no Limitations
significant differences in pain intensity or incidence of There are several limitations to this study. Although our
adverse effects at 2 weeks after rotator cuff repair in patient response rate was sufficient at 80%, nonresponse
individuals randomized to a selective NSAID group bias is a limitation of any retrospective review of pro-
(celecoxib), a nonselective NSAID group (ibuprofen), or spectively collected data. Surgical technique was not
an opioid group (tramadol). However, the study deter- taken into consideration, but even with variability in
mined that the selective NSAID celecoxib was correlated technique, we demonstrate that outcomes are not
with a significantly higher re-tear rate compared with affected with postoperative ibuprofen use. VAS scores
those taking the nonselective NSAID ibuprofen or the were collected to assess pain, but number of opioids used
opioid tramadol.34 with or without ibuprofen was not the aim of this study,
Despite the efficacy of NSAIDs in postoperative pain rather only patient-reported outcome measures, so we
control, these agents are not without risk. NSAIDs reduce are unable to comment on whether ibuprofen use
pain and inflammation by inhibiting cyclooxygenase ac- decreased opioid use after surgery. We did not assess the
tivity in the arachidonic pathway, decreasing the syn- total consumption of ibuprofen after operation, so we
thesis of proinflammatory prostaglandin molecules. cannot comment on what the patients actually consumed
e496 N. R. KRAUS ET AL.

but only what was prescribed. This study looked at patient 15. Greenspoon JA, Petri M, Warth RJ, Millet P. Massive rotator
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Fayad LM. Complications of rotator cuff surgerydthe role
the potential for a type II or beta error.
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Patients receiving ibuprofen did as well as patients Peelen LM, Kalkman CJ, Meissner W. Pain intensity on the
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