Liposomal Bupivacaine Versus Standard of Care in Total Knee Surgery

Liposomal bupivacaine (Exparel®) is a local anesthetic made up of liposomal encapsulated bupivacaine. It is designed to be injected at the time of surgery into the local soft tissues. Because of its unique liposomal delivery system, Liposomal bupivacaine (Exparel®) has been shown to provide up to 96 hours of pain relief following surgeries. This makes it an attractive option in total knee arthroplasty patients. Combined with the proven efficacy of regional anesthesia, intraoperative liposomal bupivacaine (Exparel®) may provide extended pain relief following total knee arthroplasty. This has the potential to avoid the need for opioid medications. With better pain control, medication side effects can be avoided and patient's length of stay in the hospital can be shortened.

• Liposomal bupivacaine (Drug), also known as Exparel
• Standard of Care (Drug): Pre-operative adductor canal nerve block (20mL of 0.5% ropivacaine). Intra-operative popliteal nerve block from the surgeon: 20mL 0.2% ropivacaine and a peri-articular injection of 10mg morphine, 30mg ketorolac and 40mg methylprednisolone.

Primary outcomes

• Number Physical Therapy Sessions Necessary for Discharge [Participants will be followed for the duration of their hospital stay, an expected average of 2.5 days.]: Number of physical therapy (PT) sessions necessary for discharge. A significant decrease in the number of sessions will be defined as ≥ 2. Typically, there are 2 sessions per day, with each patient completing an average of 4-5 sessions during their admission.

Secondary outcomes

• Mean Visual Analog Scale (VAS) Pain Scores During Hospital Stay [Participants will be followed for the duration of their hospital stay, an expected average of 2.5 days.]: VAS was measured using a scale that ranged from 0 to 10. Higher scores indicate more pain, or a worse outcome. Patients had pain measured a variable number of times following surgery before discharge. Mean VAS score during the hospital stay for each patient was calculated
• Length of Stay (LOS, in Days) [Participants will be followed for the duration of their hospital stay, an expected average of 2.5 days.]
• Opioid Consumption in Oral Morphine Equivalents (OMEs, in Milligrams) [Participants will be followed for the duration of their hospital stay, an expected average of 2.5 days.]
• Number of Participants With Opioid-related Adverse Events (ORAEs) During Hospital Stay [Participants will be followed for the duration of their hospital stay, an expected average of 2.5 days.]: 1. Nausea 2. Vomiting 3. Constipation 4. Ileus 5. Pruritus 6. Respiratory depression 7. Over-sedation
• Total Cost of Care (Dollars) [Participants will be followed for the duration of their hospital stay, an expected average of 2.5 days.]
• Hospital Readmission Not Including Admissions Planned Procedures [Participants will be followed for 30 days after leaving the hospital.]

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* At least 18 years of age
* Scheduled to undergo total knee arthroplasty (TKA) performed by the principal investigator

Exclusion Criteria:

* Age <18 years
* Pregnant or breastfeeding
* Non-English-speaking
* Unable to give informed consent
* Patients admitted from or discharged to a medical facility (due to likelihood of limited mobility and/or required minimum lengths of stay, confounding primary outcome), including other hospitals, skilled nursing facilities, long-term acute care hospitals, etc.
* Patients unable to complete a device-assisted 140 foot walk at baseline
* Patients with contraindication(s) to any bupivacaine or ropivacaine formulation, to nerve blocks or any of the local agents used (IV morphine, ketorolac, or methylprednisolone).
* Patients on a long-acting maintenance opioid prior to admission for surgery (e.g., methadone, oxycontin)
* Patients undergoing simultaneous bilateral TKAs, as this would increase the dose of Exparel per patient (we are limited to one dose per patient)

Participant flow

Outcome results

• Number Physical Therapy Sessions Necessary for Discharge (Primary), Mean, Physical Therapy Sessions: Liposomal Bupivacaine 3.0 +/- 1.2; Standard of Care 3.6 +/- 1.3 (p 0.137)
• Mean Visual Analog Scale (VAS) Pain Scores During Hospital Stay (Secondary), Mean, Units on a scale: Liposomal Bupivacaine 4.4 +/- 1.3; Standard of Care 4.7 +/- 1.5 (p 0.343)
• Length of Stay (LOS, in Days) (Secondary), Mean, Days: Liposomal Bupivacaine 2.5 +/- 0.8; Standard of Care 2.3 +/- 0.5 (p 0.208)
• Opioid Consumption in Oral Morphine Equivalents (OMEs, in Milligrams) (Secondary), Mean, Milligrams: Liposomal Bupivacaine 274.6 +/- 121.0; Standard of Care 304.8 +/- 143.4 (p 0.385)
• Number of Participants With Opioid-related Adverse Events (ORAEs) During Hospital Stay (Secondary), Number, participants: Liposomal Bupivacaine 13; Standard of Care 11 (p 0.843)
• Total Cost of Care (Dollars) (Secondary), Median, Dollars: Liposomal Bupivacaine 64582.90 (55424.50 to 121583.50); Standard of Care 62601.50 (52435.90 to 97367.50) (p 0.438)
• Hospital Readmission Not Including Admissions Planned Procedures (Secondary), Number, participants: Liposomal Bupivacaine 0; Standard of Care 1

Adverse events

Other adverse events by term

• Robert Fada, MD, Principal investigator, OhioHealth
• Sara Jordan, PharmD, BCPS, Study director, OhioHealth