Methadone in the Management of Post-Operative Pain in Total Knee Replacement

Inclusion Criteria:

1. Provision of signed and dated informed consent from
2. Stated willingness to comply with all study procedures and availability to attend all required visits for the duration of the study.
3. Age 21- 75
4. Unilateral total knee arthroplasty at Colorado Joint Replacement
5. All individuals will be screened for drug use (opioid use, illicit drug use) at their preoperative appointment
6. For females of reproductive potential: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation.

Exclusion Criteria:

1. Narcotic use in the past 6 weeks
2. Current or previous history of drug and alcohol abuse
3. Tobacco use in the previous 90 days
4. Treatment with another investigational drug
5. Patients that cannot receive spinal anesthesia
6. Patients that cannot receive the standardized multimodal pain medications (i.e. Tylenol, gabapentin and meloxicam)'
7. Patients that are not able to go home after leaving the hospital and require a short-term rehabilitation facility
8. Obstructive sleep apnea
9. Morbid obesity (BMI \>40)
10. Patients with liver disease.
11. Significant kidney disease - stage 3 CKD or greater
12. Pregnant or nursing females
13. Baseline QTc \>480
14. severe COPD (GOLD 3 or 4)
15. home oxygen requirement