GENIFEM Trial: Postoperative Pain After Total Knee Arthroplasty (TKA)

The main study outcome is the proportion of patients that have a numeral rating scale (NRS) <4 during mobilization without morphine at 4-6 hours after TKA. Mobilisation will be defined as walking 10 meters with walking aids or an assistant. NRS is a unidimensional, subjective measurement of pain intensity, expressed by the patient as a number between 0 and 10. It is a 11 point scale in which 0 equals no pain and 10 maximal pain. NRS at rest will also be determined

NRS is determined at rest and movement at 24 hours, 48 hours, 72 hours and 1 month after TKA. NRS is a unidimensional, subjective measurement of pain intensity, expressed by the patient as a number between 0 and 10. It is a 11 point scale in which 0 equals no pain and 10 maximal pain.

The amount of morphine that the patient demanded and that was given will be determined at 4-6 hours, 24 hours, 48 hours and 72 hours after TKA

quadriceps strength measured in maximum voluntary isometric contraction (MVIC) at baseline (pre-operative), 4-6 hours, 24 hours, 48 hours after TKA

The distance covered over a time of 6 minutes is used as the outcome by which to compare changes in performance capacity. The 6 minute walking test will be performed at baseline (pre-operative), 24 hours, 48 hours and 72 hours after TKA

In the timed up and go test, subjects are asked to rise from a standard armchair, walk to a marker 3 m away, turn, walk back, and sit down again. The results are expressed in minutes or seconds. The timed up and go test will be performed at baseline (pre-operative), 24 hours, 48 hours and 72 hours after TKA

The Western Ontario and McMaster Universities Arthritis Index (WOMAC) is a widely used self-administered health status measure used in assessing pain, stiffness, and function in patients with osteoarthritis of the knee.

The test questions are scored on a scale of 0-4. Higher scores on the WOMAC indicate worse pain, stiffness, and functional limitations. The questionnaire will be performed at baseline (pre-operative) and 1 month after TKA

The EQ-5D-5L is a patient-reported generic measure of HRQoL comprising five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Responses to the 5 items (one for each dimension) result in a patient's health state that can be transformed into a utility score ranging between 0 (death) and 1 (full health), representing the quality of life of the health state.

HADS is developed to detect anxiety and depression in patients with physical health problems. The questionnaire consists of 14 items: 7 items to measure anxiety and 7 items to measure depression

The patient satisfaction scale is measured in a 5-point Likert scale with response categories consisting of very satisfied, somewhat satisfied, neutral, somewhat dissatisfied, and very dissatisfied

The PCS is often used in clinical settings to measure catastrophic thinking related to pain. The 13 item questionnaire consists of 3 subscales (magnification, rumination and helplessness) and asks patients to reflect on past painful experiences and to indicate the degree on which they experiences each of 13 thoughts of feelings on a 5- point scale (0 not at all and 4 all the time).

(time from first needle insertion to final needle exit)

Complications of TKA (e.g., transfusions, prevalence of venous thrombo-embolic event, infection…) will be assessed per - and post-operative

The discharge readiness will be compared between the three groups.

Discharge readiness is assessed by means of the following:

• Pain is under control (<4) with oral painkillers
• Wound is dry (not purulent)
• Knee flexion is possible over 70 degrees
• Patients are self-sustainable with crutches

The discharge readiness is described as yes or no.

The length of stay will be compared between the three groups by counting the number of days in the hospital

The readmission status of patients will be compared between groups after 1 month of TKA.

Throughout the study, adverse events related to the intervention will be collected.

The frequency of opioid related adverse event will be assessed from the start of surgery until 72 hours after TKA

Mortality which is attributable to study interventions, surgical procedure, underlying condition or other relevant reasons will be investigated during the trial (perioperative, until discharge)

The risk of inpatient fall will be assessed during hospital stay.

Patients will be asked to guess their treatment allocation at 72 hours after TKA