How Variations in Pharmacogenomic Profiles Affect Pain and Narcotic Needs Following Total Knee Arthroplasty (TKA)

The variation in genetics will be investigated using a standard 20 gene clinical pharmacogenomics panel. Three of these genes (CYP2D6, OPRM1, and COMT) have effects on opioid metabolism, opioid transport, pain perception, and opioid receptors. The results of the pharmacogenomics panel in relation to pain as assessed by the VAS (Visual Analog Scale) numeric pain scale completed by each subject for maximum pain experienced with activity, average pain, and lowest level of pain over the previous 24 hours. The VAS is a self-reported score which measures pain on a 0-10 scale with 10 being the most amount of pain possible and 0 being no pain.

The results of the pharmacogenomics panel in relation to the amount of opioids needed to control post-operative pain for the first month following surgery will be assessed via a daily medication log completed by patients where they record the specific medication and dose taken in the previous 24 hour period each day of the month following surgery. This will be converted to morphine milligram equivalents (MME) and expressed as the total MME used in the first post-operative month.

Study subjects will complete the KOOS Jr questionnaire at pre-op, 4 months and 1 year after surgery. KOOS, Jr is scored by summing the raw response (range 0-28) and then converting it to an interval score using the table provided below. The interval score ranges from 0 to 100 where 0 represents total knee disability and 100 represents perfect knee health.

The knee exam/ROM will be completed by the patient's surgeon at standard-of-care clinic visits pre-op, 1 month, 4 months, and 1 year after surgery.

Subjects will complete the PROMIS-43 questionnaire at pre-op, 4 months and 1 year after surgery. The score comprises questions from seven domains: Depression, Anxiety, Physical Function, Pain Interference, Fatigue, Sleep Disturbance, and Ability to Participate in Social Roles and Activities as well as a numeric rating scale for pain from 0-10 with 10 being the worst. They may be reported as T-scores (difference compared to the population average, measure in standard deviations). A score of 50 is the average for the United States general population. For undesirable concepts such as Depression, a T-score of 60 is one standard deviation worse than average. Alternatively, a Depression T-score of 30 is two standard deviations better than average. For favorable concepts like Ability to Participate in Social Roles and Activities, a T-score of 60 is one standard deviation better than average while a T-score of 30 is two standard deviations worse than average.

Study subjects will complete the VR-12 at pre-op, 4 months and 1 year after surgery. The results of the VR-12 are summarized as two scores - a Mental Component Score (MCS) and a Physical Component Score (PCS). The score encompasses questions from seven domains: general health perceptions, physical functioning, role limitations due to physical and emotional problems, bodily pain, energy/fatigue levels, social functioning and mental health. The scores may be reported as Z-scores (difference compared to the population average, measured in standard deviations). The interval score ranges from 0 to 100 where 0 represents mental or physical disability and 100 represents perfect mental or physical health.