Acute Postoperative Pain and Catastrophizing in Patients Undergoing Unicompartmental Knee Arthroplasty - A Prospective, Observational, Single-center, Cohort Study
Conditions: Post Operative Pain
Sponsor: Copenhagen University Hospital, Hvidovre

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Protocol 
Acute Postoperative Pain and Catastrophizing in Patients 
Undergoing Unicompartmental Knee Arthroplasty - A 
Prospective, Observational, Single-center, Cohort study 
 
 
Protocol ID: UKAPCS 
 
Brief title: Acute Postoperative Pain and Catastrophizing in Patients Undergoing Unicompartmental 
Knee Arthroplasty 
 
ClinicalTrials.gov ID: NCT05510947 
 
 
The protocol is based on three previous studies involving pain after total knee arthroplasty of which 
one is published and two are being prepared for publication. The studies are approved by the Local 
Ethics comity: De Videnskabsetiske Komiteer for Region Hovedstaden (H-18034756, H-18034778, 
and H-18034782), by the knowledge-Centre for Data Protection (reference numbers VD-2018-528, 
VD-2019-04, and VD-2019-05), and by the Danish Medicine Agency (DKMA) (EudraCT-numbers 2018-
002634-20, 2018-002635-23, and 2018-002636-25).  

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Contact Information 
Main contact: 
Anders Deichmann Springborg, MD, PhD-student 
Department of Anaesthesiology, Copenhagen University Hospital Hvidovre 
Kettegaards Allé 30, 2650 Hvidovre, Denmark 
Mail: anders.deichmann.springborg.01@regionh.dk 
Phone: +45 40499097 
 
Additional team members: 
Nicolai Bang Foss, MD, professor, overlæge, dr.med. 
Department of Anaesthesiology, Copenhagen University Hospital Hvidovre  
Kettegaards Allé 30, 2650 Hvidovre, Denmark 
Mail: nicolai.bang.foss@regionh.dk 
Phone: +45 38622532 
 
Christian Bredgaard Jensen, MD, PhD-student 
Department of Orthopaedic Surgery, Copenhagen University Hospital Hvidovre 
Kettegårds Allé 30, 2650 Hvidovre 
Mail: christian.bredgaard.jensen@regionh.dk 
Phone: +45 20825950 
 
Henrik Kehlet, MD, professor, overlæge, dr.med. 
Section of Surgical Pathophysiology, 7621, Rigshospitalet, University of Copenhagen 
Blegdamsvej, 2100 Copenhagen, Denmark 
Mail: Henrik.Kehlet@regionh.dk 
Phone: +45 35454774 
 
Kirill Gromov, MD, associate professor, overlæge, PhD 
Department of Orthopaedic Surgery, Copenhagen University Hospital Hvidovre 
Kettegårds Allé 30, 2650 Hvidovre 
Mail: kirill.gromov@regionh.dk 
Phone: +45 24971150 
 
Anders Troelsen, MD, professor, overlæge, dr.med. 
Department of Orthopaedic Surgery, Copenhagen University Hospital Hvidovre 
Kettegårds Allé 30, 2650 Hvidovre 
Mail: a_troelsen@hotmail.com 
 
 

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Table of Contents 
Contact Information ................................................................................................................................ 2 
Introduction ............................................................................................................................................ 4 
Background ......................................................................................................................................... 4 
Aim ...................................................................................................................................................... 4 
Study design ............................................................................................................................................ 4 
Sample size ......................................................................................................................................... 4 
Outcomes............................................................................................................................................ 4 
Primary outcome ............................................................................................................................ 4 
Secondary outcomes ....................................................................................................................... 4 
Inclusion criteria ................................................................................................................................. 5 
Exclusion criteria ................................................................................................................................. 5 
Study location ..................................................................................................................................... 5 
The inclusion will take place at the Dept. of Orthopaedic Surgery, Arthroplasty unit at Hvidovre 
Hospital, Capital Region of Denmark. ................................................................................................. 5 
Timespan ............................................................................................................................................ 5 
Study plan ............................................................................................................................................... 5 
Study specific ...................................................................................................................................... 6 
Data collection ........................................................................................................................................ 6 
Data protection ................................................................................................................................... 6 
Collected variables .............................................................................................................................. 6 
Statistics .................................................................................................................................................. 6 
Power calculation ............................................................................................................................... 6 
Data analysis ....................................................................................................................................... 6 
Financial conditions ................................................................................................................................ 7 
Publication .............................................................................................................................................. 7 
References .............................................................................................................................................. 7 
 

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Introduction 
Background 
Primary knee arthroplasty is a frequently performed procedure and is expected to increase in 
numbers over the next decade [1, 2]. Advantages of unicompartmental knee arthroplasty (UKA) 
compared to total knee arthroplasty (TKA) include shorter hospital stays, faster recovery [3-6], fewer 
infections and readmissions [6-9], and lower costs [9]. The length of hospital stay after UKA is 
variable, but an increased length of hospitalization has been associated with more complications and 
higher readmission rates [10]. A recent study has shown that the main reasons for continued 
hospitalization beyond 24 hours after surgery are pain and lack of mobilization [11]. Strategies to 
decrease the length of stay after UKA should thus be aimed at improved analgesia and postoperative 
mobilization. 
There is a large interindividual variability in the postoperative pain response. It is well documented 
in TKA-surgery that high pain responders (HPR), evaluated using the Pain Catastrophizing Scale (PCS), 
have higher postoperative pain responses compared to low pain responders (LPR) [12-15]. Recently, 
it has been shown that HPR patients undergoing TKA benefit from a larger preoperative dose of 
glucocorticoid compared to a previously recommended dose [16]. Interestingly, the same difference 
has not been found in LPR patients (Nielsen et al.: IN PREPARATION, clinicaltrials.gov ID 
NCT03758170, EudraCT 2018-002634-20, VEK H-18034756). These HPR patients constitute a 
vulnerable high-risk patient group and potentially benefit from targeted treatment [17]. 
Currently, the distribution of HPR- and LPR patients and their association with acute pain following 
UKA is not well investigated. The generated knowledge from this research project is essential to 
determine how studies with analgesia interventions should be designed. In the future, this will 
contribute to targeting treatment for high-risk patient groups to reduce pain and improve 
postoperative mobilization, and ultimately decrease the length of hospital stay in patients 
undergoing UKA. By targeting treatment, potential overtreatment is also avoided.  
Aim 
To investigate the prevalence of high- and low-pain responders, defined by a PCS score > 20 and ≤ 20 
respectively, as well as the acute postoperative course of pain for these groups after 
unicompartmental knee arthroplasty. 
Study design 
Prospective observational single-center cohort study. 
Sample size 
120 patients 
Outcomes 
Primary outcome 
• 
Ratio between HPR:LPR patients defined as patients with PCS > 20 and PCS ≤ 20 respectively 
Secondary outcomes 
• 
Incidence of moderate to severe pain (VAS > 30 mm) during a 5-meter walk test 24h 
postoperatively in LPR patients 
• 
Incidence of moderate to severe pain (VAS > 30 mm) during a 5-meter walk test 24h 
postoperatively in HPR patients 

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• 
Differences between HPR- and LPR patients for the following variables: 
o Incidence of moderate to severe pain (VAS > 30 mm) during a 5-meter walk test 24h 
postoperatively 
o Incidence of moderate to severe pain (VAS > 30 mm) at rest 24h postoperatively 
o Cumulated pain upon ambulation in a 5-meter walk test day 2-7 
o Cumulative use of rescue-analgesics per day in hospital day 0 to discharge, and at 
home from day of discharge to day 7 
o Quality of sleep, lethargy, dizziness, and nausea pre- and postoperatively from day 0 
to day 7 
o Length of stay (LOS) in hospital 
Inclusion criteria 
• 
Primary unilateral UKA 
• 
Age ≥ 18 years 
• 
Ability to participate in the study (understand written and spoken Danish language, self-
reported pain, and satisfaction) 
• 
Filled out the Pain Catastrophizing Scale preoperatively 
• 
Signed written informed consent form 
Exclusion criteria 
• 
Mental disability that could impair a patient’s decision-making capability of giving informed 
consent and not enabling valid data collection 
• 
Insulin-treated diabetes mellitus 
• 
Patients with known diagnoses of schizophrenia, ongoing psychosis, bipolar disease and/or a 
history of ongoing anti-psychotic treatment 
• 
Patients with modulated pain-reception (experience) based on other diseases or injuries, 
e.g. spinal cord or brain injury, severe polyneuropathies, or neurologic disorder 
• 
Peripheral nerve block per- or postoperatively 
Study location 
The inclusion will take place at the Dept. of Orthopaedic Surgery, Arthroplasty unit at Hvidovre 
Hospital, Capital Region of Denmark. 
Timespan 
Expected start of project: September 1, 2022 
Expected end of data collection: July 1, 2023 
Expected end of data analysis: September 1, 2023 
Study plan 
In the outpatient clinic, the screening procedure will be performed among patients planned to UKA 
by the surgeons. Patients will be asked if they may be contacted with the purpose of participating in 
a research project. Patients will undergo a preliminary examination where, as a standard procedure, 
the patient will receive a PCS questionnaire. Patients will be informed of the research project either 
in the outpatient clinic or by phone from an investigator. 
All patients will receive verbal and written information about the project. All patients must give a 
signed informed consent on paper prior to inclusion to participate in the study. 

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Study specific 
Study-specific tests include an evaluation of pain at hospital, and at home using the electronic pain 
diary. 
Data collection 
Data protection 
All patient-related information will be treated confidentially, and data will be pseudoanonymized. 
Signed informed consent from participating patients will be stored at the Anesthesiologic Dept. 542, 
Hvidovre Hospital, in a locked cabinet. All electronic data will be stored in REDCap.  
Collected variables 
During the hospital stay, data will be collected by contacting the patient at the Orthopaedic Dept. 
and by accessing the electronic patient journal. After discharge patients will be asked to fill out an 
electronic pain diary until 7 days after the operation. The following variables will be collected: 
• 
Number of participating patients (CONSORT) 
• 
Pain during rest (VAS 0-100 mm), measured preoperatively, 24 h postoperatively, and 
twice a day from day 2 to 7 
• 
Pain upon ambulation in a 5-meter walk test (VAS 0-100 mm), measured preoperatively, 
24 h postoperatively, and twice a day from day 2 to 7 
• 
Quality of sleep, lethargy, dizziness, and nausea pre- and postoperatively from day 0 to 
day 7. 
• 
PCS score 
• 
Preoperative analgesia 
• 
Use of rescue-analgesia from day 0 to day 7 
• 
Type and dose of analgesia from day 0 to day 7 
• 
Length of stay (LOS) in hospital, and reasons for prolonged stay (>2 postoperative days) 
• 
Demographical data (gender, age, height, weight, co-morbidity, American Society of 
Anesthesiologist (ASA) score). 
• 
Surgical data (date of surgery, indication, surgical time, procedure information, 
intraoperative bleeding, transfusion data, perioperative analgesics) 
• 
Deviations from standard treatment 
Statistics 
Power calculation 
There is no relevant acute pain data from UKA patients, thus, sample size estimates are based on 
data from TKA patients. The pain response is expected to be higher in a TKA population, although 
this is not known. However, the relative difference in pain between HPR- and LPR patients is not 
necessarily different in UKA patients. We are not familiar with the ratio between HPR- and LPR-
patients based on PCS score in UKA, and thus a power calculation will be associated with substantial 
uncertainty. For this reason and because of the descriptive hypothesis-generating nature of the 
study, we will include 120 patients. 
Data analysis 
Dichotomic data will be tested using chi-square test or Pearson’s exact test and presented as odds 
ratio or proportion with two-sided 95% confidence intervals. Continuous data will be tested for 

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normal distribution using visual inspection of Q-Q plots and histograms and using the Kolmogorov–
Smirnov test. Differences in data will be tested with unpaired t-test or Mann-Whitney U-test 
depending on normal distribution. Uni- and/or multivariate analyses will be performed to test 
independent variables. A P-value < 0.05 is considered significant. Statistical calculations will be made 
using either R statistical software (Open source) or SPSS statistics (IBM, New York, USA).  
Financial conditions 
Expenses are borne by Henrik Kehlet who has received funding from the Candys Foundation. 
Publication 
Based on the data, one or more manuscripts will be made for the purpose of publication in an 
international Peer-Reviewed journal. Results will be published independent of the findings. 
Authorship and co-authorship will be distributed according to the Vancouver Recommendations 
(International Committee of Medical Journal Editors). The order of authors will be as follows: 
Anders Deichmann Springborg, Christian Bredgaard Jensen, Kirill Gromov, Anders Troelsen, Henrik 
Kehlet, Nicolai Bang Foss. 
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