Influence of Patient Sex on Pain Control and Multimodal Analgesia in Total Knee Arthroplasty
Influence of Patient Sex on Pain Control and Multimodal Analgesia in Total Knee Arthroplasty
The purpose of this study is to examine the influence of sex on postoperative pain, following
 total knee arthroplasty (TKA). Patients will first be stratified by sex and then be
 randomized into one of two multimodal analgesic regimen (MAR), which differ in presence of
 pregabalin. We hypothesize that that acute postoperative pain scores are different over time
 between males and females and between multimodal analgesic regimens following TKA.
 Investigators will be blinded to which multimodal group patients are in. Patients will
 complete surveys in the office, during their hospital stay, and at followup intervals for up
 to six months.
The overall goal of this study is to better understand the influence of patient-sex on
 postoperative pain perception in men versus women following total knee arthroplasty (TKA)
 utilizing two different multimodal analgesia regimens.

 Pregabalin is a neuromuscular antagonist of voltage gated calcium channels at the
 post-synaptic dorsal horns in the spinal cord and brain. It binds to the alpha-2-delta
 subunit and interrupts pain signal transmission. The use of pregabalin as part of multimodal
 pain control has been associated with a decrease in postoperative opioid use.

 This will be a randomized, single-blinded control trial in which patients either will or will
 not receive pregabalin as part of their multimodal analgesia regimen following TKA. It will
 be performed at a single institution, with multiple tertiary academic centers.

 Patients will first be grouped according to their sex, then randomized into one of two arms:

 1. Multimodal analgesia regimen including pregabalin;

 2. Multimodal analgesia regimen not including pregabalin.

 For the intervention group, patient will be provided with an oral preoperative pregabalin
 dose of 150mg on the day of surgery. Patient will continue pregabalin 75mg two times a day,
 for two weeks postoperatively. For both both groups, the operative technique and additional
 perioperative analgesic modalities will follow a standard protocol.

 Primary Endpoint: Acute postoperative pain difference (up to 72 hours), measured by 100mm
 visual analogue scale (VAS) while at rest and mobilization, between males and females and
 between multimodal analgesic regimens in patients undergoing TKA.

 Secondary Endpoints:

 -  Pain control measured by 100mm visual analogue scale (VAS) while at rest and
 mobilization.

 -  Pain control additionally measured by morphine equivalent units (MEq).

 -  Number of postoperative days to opioid cessation.

 -  Pain measured by Knee Injury and Osteoarthritis Outcome Score (KOOS).

 -  Physical function measured by KOOS, physical component summary (PCS-12) of VR-12.

 -  Mental health measured by mental component summary (MCS-12) of VR-12.

 -  Safety will be tracked by adverse reactions reported or observed by investigators. These
 will be collected via patient communication and review of the medical record.

 -  Additionally, severity of common short-term postoperative complications like nausea,
 vomiting, dizziness, and sedation will be assessed by 100mm VAS.

 The study recruitment phase is estimated to last for 6 months. Subject followup is 6 months.
Inclusion Criteria:

 1. Provision of signed and dated informed consent form

 2. Stated willingness to comply with all study procedures and availability for the
 duration of the study

 3. Male or female, age 18-80

 4. Undergoing primary unilateral TKA for primary osteoarthritis

 5. English speaking

 6. Patients whose primary residence is in a home and not a facility or rehabilitation
 center.

 Exclusion Criteria:

 1. Chronic (>6 months) use of neuromodulators pregabalin or gabapentin.

 2. Pregnancy or lactation

 3. Prior history of adverse reactions to pregabalin

 4. Coexisting chronic pain condition rated ≥50mm on 100-mm VAS requiring narcotics.

 5. Coexisting condition leading to sedation or dizziness

 6. Kidney disease

 7. History of angioedema

 8. History of depression with suicidal ideation.

 9. Extensive history of opioid/ substance use and/or abuse.

 10. Receiving active or maintenance treatment for cancer or solid organ and/or marrow
 transplant.

 11. Patient staying less than one night in the hospital.

 12. Patients with a history of chronic obstructive pulmonary disease (COPD) with
 supplementary oxygen requirements.