Trial Outcomes & Findings for Peripheral Nerve Blocks vs Periarticular Local Anesthetic Injection for Total Knee Arthroplasty (TKA) (NCT NCT02223364)

Results Overview

Pain was measured on a 1-10 numeric pain rating scale (NRS) with 0=no pain, and 10=worst pain imaginable.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

165 participants

Primary outcome timeframe

Post-Operative Day 1, approximately 6 am to 12:00 pm

Results posted on

2017-08-31

Participant Flow

Subjects were recruited at Mayo Clinic in Rochester, Minnesota from October 2014 to December 2015.

Participant milestones

Participant milestones
Measure	Peripheral Nerve Block (PNB) This group received a continuous femoral nerve block and a single injection sciatic nerve block consisting of the following: Peripheral nerve blocks with Bupivacaine.	Ropivacaine (PAI-R) This group received intra articular injection with Ropivacaine, a total volume of 120 milliliters (mL) injected in the periarticular structures by the surgeon. Following the current, standardized practice for periarticular infiltration, approximately 30 - 40 mL of solution was injected into the posterior capsule just prior to cementing the implants in place and 40 - 50 mL of solution injected into the medial and lateral retinaculum while the cement was hardening and prior to deflation of the tourniquet. The remaining volume of approximately 40 mL was injected into the quadriceps tendon and subcutaneous tissue prior to skin closure.	Liposomal Bupivacaine (PAI-L) This group received Intra articular injection with liposomal bupivacaine, a total volume of 120 milliliters (mL) injected in the periarticular structures by the surgeon. Following the current, standardized practice for periarticular infiltration, approximately 30 - 40 mL of solution was injected into the posterior capsule just prior to cementing the implants in place and 40 - 50 mL of solution injected into the medial and lateral retinaculum while the cement was hardening and prior to deflation of the tourniquet. The remaining volume of approximately 40 mL was injected into the quadriceps tendon and subcutaneous tissue prior to skin closure.
Overall Study STARTED	55	55	55
Overall Study COMPLETED	50	55	52
Overall Study NOT COMPLETED	5	0	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Peripheral Nerve Block (PNB) This group received a continuous femoral nerve block and a single injection sciatic nerve block consisting of the following: Peripheral nerve blocks with Bupivacaine.	Liposomal Bupivacaine (PAI-L) This group received Intra articular injection with liposomal bupivacaine, a total volume of 120 milliliters (mL) injected in the periarticular structures by the surgeon. Following the current, standardized practice for periarticular infiltration, approximately 30 - 40 mL of solution was injected into the posterior capsule just prior to cementing the implants in place and 40 - 50 mL of solution injected into the medial and lateral retinaculum while the cement was hardening and prior to deflation of the tourniquet. The remaining volume of approximately 40 mL was injected into the quadriceps tendon and subcutaneous tissue prior to skin closure.
Overall Study Protocol Violation	3	3
Overall Study subject expired before surgery	1	0
Overall Study Physician Decision	1	0

Baseline Characteristics

Peripheral Nerve Blocks vs Periarticular Local Anesthetic Injection for Total Knee Arthroplasty (TKA)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Peripheral Nerve Block (PNB) n=50 Participants This group received a continuous femoral nerve block and a single injection sciatic nerve block consisting of the following: Peripheral nerve blocks with Bupivacaine.	Ropivacaine (PAI-R) n=55 Participants This group received intra articular injection with Ropivacaine, a total volume of 120 milliliters (mL) injected in the periarticular structures by the surgeon. Following the current, standardized practice for periarticular infiltration, approximately 30 - 40 mL of solution was injected into the posterior capsule just prior to cementing the implants in place and 40 - 50 mL of solution injected into the medial and lateral retinaculum while the cement was hardening and prior to deflation of the tourniquet. The remaining volume of approximately 40 mL was injected into the quadriceps tendon and subcutaneous tissue prior to skin closure.	Liposomal Bupivacaine (PAI-L) n=52 Participants This group received Intra articular injection with liposomal bupivacaine, a total volume of 120 milliliters (mL) injected in the periarticular structures by the surgeon. Following the current, standardized practice for periarticular infiltration, approximately 30 - 40 mL of solution was injected into the posterior capsule just prior to cementing the implants in place and 40 - 50 mL of solution injected into the medial and lateral retinaculum while the cement was hardening and prior to deflation of the tourniquet. The remaining volume of approximately 40 mL was injected into the quadriceps tendon and subcutaneous tissue prior to skin closure.	Total n=157 Participants Total of all reporting groups
Age, Continuous	67 years STANDARD_DEVIATION 9 • n=5 Participants	68 years STANDARD_DEVIATION 8 • n=7 Participants	67 years STANDARD_DEVIATION 8 • n=5 Participants	67.7 years STANDARD_DEVIATION 8.8 • n=4 Participants
Sex: Female, Male Female	25 Participants n=5 Participants	34 Participants n=7 Participants	27 Participants n=5 Participants	86 Participants n=4 Participants
Sex: Female, Male Male	25 Participants n=5 Participants	21 Participants n=7 Participants	25 Participants n=5 Participants	71 Participants n=4 Participants
Region of Enrollment United States	50 Participants n=5 Participants	55 Participants n=7 Participants	52 Participants n=5 Participants	157 Participants n=4 Participants

PRIMARY outcome

Timeframe: Post-Operative Day 1, approximately 6 am to 12:00 pm

Population: Intent-to-Treat Analysis

Pain was measured on a 1-10 numeric pain rating scale (NRS) with 0=no pain, and 10=worst pain imaginable.

Outcome measures

Outcome measures
Measure	Peripheral Nerve Block (PNB) n=50 Participants This group received a continuous femoral nerve block and a single injection sciatic nerve block consisting of the following: Peripheral nerve blocks with Bupivacaine.	Ropivacaine (PAI-R) n=55 Participants This group received intra articular injection with Ropivacaine, a total volume of 120 milliliters (mL) injected in the periarticular structures by the surgeon. Following the current, standardized practice for periarticular infiltration, approximately 30 - 40 mL of solution was injected into the posterior capsule just prior to cementing the implants in place and 40 - 50 mL of solution injected into the medial and lateral retinaculum while the cement was hardening and prior to deflation of the tourniquet. The remaining volume of approximately 40 mL was injected into the quadriceps tendon and subcutaneous tissue prior to skin closure.	Liposomal Bupivacaine (PAI-L) n=52 Participants This group received Intra articular injection with liposomal bupivacaine, a total volume of 120 milliliters (mL) injected in the periarticular structures by the surgeon. Following the current, standardized practice for periarticular infiltration, approximately 30 - 40 mL of solution was injected into the posterior capsule just prior to cementing the implants in place and 40 - 50 mL of solution injected into the medial and lateral retinaculum while the cement was hardening and prior to deflation of the tourniquet. The remaining volume of approximately 40 mL was injected into the quadriceps tendon and subcutaneous tissue prior to skin closure.
Maximum Pain Post-Operative Day (POD) 1 (Morning)	3 units on a scale Interval 1.0 to 6.0	4 units on a scale Interval 2.0 to 6.0	4.5 units on a scale Interval 3.0 to 6.0

SECONDARY outcome

Timeframe: Post-operative Day 0, approximately 12 pm to 12 am

Population: Intent-to-Treat analysis

Pain was measured on a 1-10 numeric pain rating scale (NRS) with 0=no pain, and 10=worst pain imaginable.

Outcome measures

Outcome measures
Measure	Peripheral Nerve Block (PNB) n=50 Participants This group received a continuous femoral nerve block and a single injection sciatic nerve block consisting of the following: Peripheral nerve blocks with Bupivacaine.	Ropivacaine (PAI-R) n=55 Participants This group received intra articular injection with Ropivacaine, a total volume of 120 milliliters (mL) injected in the periarticular structures by the surgeon. Following the current, standardized practice for periarticular infiltration, approximately 30 - 40 mL of solution was injected into the posterior capsule just prior to cementing the implants in place and 40 - 50 mL of solution injected into the medial and lateral retinaculum while the cement was hardening and prior to deflation of the tourniquet. The remaining volume of approximately 40 mL was injected into the quadriceps tendon and subcutaneous tissue prior to skin closure.	Liposomal Bupivacaine (PAI-L) n=52 Participants This group received Intra articular injection with liposomal bupivacaine, a total volume of 120 milliliters (mL) injected in the periarticular structures by the surgeon. Following the current, standardized practice for periarticular infiltration, approximately 30 - 40 mL of solution was injected into the posterior capsule just prior to cementing the implants in place and 40 - 50 mL of solution injected into the medial and lateral retinaculum while the cement was hardening and prior to deflation of the tourniquet. The remaining volume of approximately 40 mL was injected into the quadriceps tendon and subcutaneous tissue prior to skin closure.
Average Pain Post-Postanesthesia Care Unit (PACU)	0.6 units on a scale Interval 0.0 to 2.2	1.7 units on a scale Interval 0.9 to 2.5	2.4 units on a scale Interval 1.1 to 3.6

SECONDARY outcome

Timeframe: Post-operative Day 0, approximately 12 pm to 12 am

Population: Intent-to-Treat Analysis

Pain was measured on a 1-10 numeric pain rating scale (NRS) with 0=no pain, and 10=worst pain imaginable.

Outcome measures

Outcome measures
Measure	Peripheral Nerve Block (PNB) n=50 Participants This group received a continuous femoral nerve block and a single injection sciatic nerve block consisting of the following: Peripheral nerve blocks with Bupivacaine.	Ropivacaine (PAI-R) n=55 Participants This group received intra articular injection with Ropivacaine, a total volume of 120 milliliters (mL) injected in the periarticular structures by the surgeon. Following the current, standardized practice for periarticular infiltration, approximately 30 - 40 mL of solution was injected into the posterior capsule just prior to cementing the implants in place and 40 - 50 mL of solution injected into the medial and lateral retinaculum while the cement was hardening and prior to deflation of the tourniquet. The remaining volume of approximately 40 mL was injected into the quadriceps tendon and subcutaneous tissue prior to skin closure.	Liposomal Bupivacaine (PAI-L) n=52 Participants This group received Intra articular injection with liposomal bupivacaine, a total volume of 120 milliliters (mL) injected in the periarticular structures by the surgeon. Following the current, standardized practice for periarticular infiltration, approximately 30 - 40 mL of solution was injected into the posterior capsule just prior to cementing the implants in place and 40 - 50 mL of solution injected into the medial and lateral retinaculum while the cement was hardening and prior to deflation of the tourniquet. The remaining volume of approximately 40 mL was injected into the quadriceps tendon and subcutaneous tissue prior to skin closure.
Maximum Pain Post-PACU	1 units on a scale Interval 0.0 to 4.0	4 units on a scale Interval 2.0 to 6.0	5 units on a scale Interval 3.0 to 6.0

SECONDARY outcome

Timeframe: POD 1, approximately 12 am to 12 am next day

Population: Intent-to-Treat Analysis

Pain was measured on a 1-10 numeric pain rating scale (NRS) with 0=no pain, and 10=worst pain imaginable.

Outcome measures

Outcome measures
Measure	Peripheral Nerve Block (PNB) n=50 Participants This group received a continuous femoral nerve block and a single injection sciatic nerve block consisting of the following: Peripheral nerve blocks with Bupivacaine.	Ropivacaine (PAI-R) n=55 Participants This group received intra articular injection with Ropivacaine, a total volume of 120 milliliters (mL) injected in the periarticular structures by the surgeon. Following the current, standardized practice for periarticular infiltration, approximately 30 - 40 mL of solution was injected into the posterior capsule just prior to cementing the implants in place and 40 - 50 mL of solution injected into the medial and lateral retinaculum while the cement was hardening and prior to deflation of the tourniquet. The remaining volume of approximately 40 mL was injected into the quadriceps tendon and subcutaneous tissue prior to skin closure.	Liposomal Bupivacaine (PAI-L) n=52 Participants This group received Intra articular injection with liposomal bupivacaine, a total volume of 120 milliliters (mL) injected in the periarticular structures by the surgeon. Following the current, standardized practice for periarticular infiltration, approximately 30 - 40 mL of solution was injected into the posterior capsule just prior to cementing the implants in place and 40 - 50 mL of solution injected into the medial and lateral retinaculum while the cement was hardening and prior to deflation of the tourniquet. The remaining volume of approximately 40 mL was injected into the quadriceps tendon and subcutaneous tissue prior to skin closure.
Average Pain POD 1 (24 Hours)	2.5 units on a scale Interval 1.2 to 4.2	3.5 units on a scale Interval 2.5 to 4.6	3.7 units on a scale Interval 2.9 to 4.6

SECONDARY outcome

Timeframe: POD 1, approximately 12 am to 12 am next day

Population: Intent-to-Treat Analysis

Pain was measured on a 1-10 numeric pain rating scale (NRS) with 0=no pain, and 10=worst pain imaginable.

Outcome measures

Outcome measures
Measure	Peripheral Nerve Block (PNB) n=50 Participants This group received a continuous femoral nerve block and a single injection sciatic nerve block consisting of the following: Peripheral nerve blocks with Bupivacaine.	Ropivacaine (PAI-R) n=55 Participants This group received intra articular injection with Ropivacaine, a total volume of 120 milliliters (mL) injected in the periarticular structures by the surgeon. Following the current, standardized practice for periarticular infiltration, approximately 30 - 40 mL of solution was injected into the posterior capsule just prior to cementing the implants in place and 40 - 50 mL of solution injected into the medial and lateral retinaculum while the cement was hardening and prior to deflation of the tourniquet. The remaining volume of approximately 40 mL was injected into the quadriceps tendon and subcutaneous tissue prior to skin closure.	Liposomal Bupivacaine (PAI-L) n=52 Participants This group received Intra articular injection with liposomal bupivacaine, a total volume of 120 milliliters (mL) injected in the periarticular structures by the surgeon. Following the current, standardized practice for periarticular infiltration, approximately 30 - 40 mL of solution was injected into the posterior capsule just prior to cementing the implants in place and 40 - 50 mL of solution injected into the medial and lateral retinaculum while the cement was hardening and prior to deflation of the tourniquet. The remaining volume of approximately 40 mL was injected into the quadriceps tendon and subcutaneous tissue prior to skin closure.
Maximum Pain POD 1 (24 Hours)	5.5 units on a scale Interval 3.0 to 7.0	6 units on a scale Interval 5.0 to 7.0	6 units on a scale Interval 5.0 to 8.0

SECONDARY outcome

Timeframe: POD 2, approximately 12 am to 12 am next day

Population: Intent-to-Treat Analysis. For POD 2, data are missing for 5 subjects (1 on Peripheral Nerve Block (PNB) arm, 1 on Ropivacaine (PAI-R) arm, and 3 on Liposomal Bupivacaine (PAI-L) arm).

Pain was measured on a 1-10 numeric pain rating scale (NRS) with 0=no pain, and 10=worst pain imaginable.

Outcome measures

Outcome measures
Measure	Peripheral Nerve Block (PNB) n=49 Participants This group received a continuous femoral nerve block and a single injection sciatic nerve block consisting of the following: Peripheral nerve blocks with Bupivacaine.	Ropivacaine (PAI-R) n=54 Participants This group received intra articular injection with Ropivacaine, a total volume of 120 milliliters (mL) injected in the periarticular structures by the surgeon. Following the current, standardized practice for periarticular infiltration, approximately 30 - 40 mL of solution was injected into the posterior capsule just prior to cementing the implants in place and 40 - 50 mL of solution injected into the medial and lateral retinaculum while the cement was hardening and prior to deflation of the tourniquet. The remaining volume of approximately 40 mL was injected into the quadriceps tendon and subcutaneous tissue prior to skin closure.	Liposomal Bupivacaine (PAI-L) n=49 Participants This group received Intra articular injection with liposomal bupivacaine, a total volume of 120 milliliters (mL) injected in the periarticular structures by the surgeon. Following the current, standardized practice for periarticular infiltration, approximately 30 - 40 mL of solution was injected into the posterior capsule just prior to cementing the implants in place and 40 - 50 mL of solution injected into the medial and lateral retinaculum while the cement was hardening and prior to deflation of the tourniquet. The remaining volume of approximately 40 mL was injected into the quadriceps tendon and subcutaneous tissue prior to skin closure.
Average Pain POD 2 (24 Hours)	3.3 units on a scale Interval 2.0 to 4.2	3.2 units on a scale Interval 2.4 to 4.0	3.5 units on a scale Interval 2.8 to 4.3

SECONDARY outcome

Timeframe: POD 2, approximately 12 am to 12 am next day

Population: Intent-to-Treat Analysis. For POD 2, data are missing for 5 subjects (1 on PNB arm, 1 on PAI-R arm, and 3 on PAI-L arm).

Pain was measured on a 1-10 numeric pain rating scale (NRS) with 0=no pain, and 10=worst pain imaginable.

Outcome measures

Outcome measures
Measure	Peripheral Nerve Block (PNB) n=49 Participants This group received a continuous femoral nerve block and a single injection sciatic nerve block consisting of the following: Peripheral nerve blocks with Bupivacaine.	Ropivacaine (PAI-R) n=54 Participants This group received intra articular injection with Ropivacaine, a total volume of 120 milliliters (mL) injected in the periarticular structures by the surgeon. Following the current, standardized practice for periarticular infiltration, approximately 30 - 40 mL of solution was injected into the posterior capsule just prior to cementing the implants in place and 40 - 50 mL of solution injected into the medial and lateral retinaculum while the cement was hardening and prior to deflation of the tourniquet. The remaining volume of approximately 40 mL was injected into the quadriceps tendon and subcutaneous tissue prior to skin closure.	Liposomal Bupivacaine (PAI-L) n=49 Participants This group received Intra articular injection with liposomal bupivacaine, a total volume of 120 milliliters (mL) injected in the periarticular structures by the surgeon. Following the current, standardized practice for periarticular infiltration, approximately 30 - 40 mL of solution was injected into the posterior capsule just prior to cementing the implants in place and 40 - 50 mL of solution injected into the medial and lateral retinaculum while the cement was hardening and prior to deflation of the tourniquet. The remaining volume of approximately 40 mL was injected into the quadriceps tendon and subcutaneous tissue prior to skin closure.
Maximum Pain POD 2 (24 Hours)	5 units on a scale Interval 3.0 to 7.0	6 units on a scale Interval 4.0 to 7.0	6 units on a scale Interval 5.0 to 7.0

SECONDARY outcome

Timeframe: baseline

Population: Intent-to-Treat Analysis

Opioid consumption will be documented in the patient electronic medical record by the nursing staff caring for the patient.

Outcome measures

Outcome measures
Measure	Peripheral Nerve Block (PNB) n=50 Participants This group received a continuous femoral nerve block and a single injection sciatic nerve block consisting of the following: Peripheral nerve blocks with Bupivacaine.	Ropivacaine (PAI-R) n=55 Participants This group received intra articular injection with Ropivacaine, a total volume of 120 milliliters (mL) injected in the periarticular structures by the surgeon. Following the current, standardized practice for periarticular infiltration, approximately 30 - 40 mL of solution was injected into the posterior capsule just prior to cementing the implants in place and 40 - 50 mL of solution injected into the medial and lateral retinaculum while the cement was hardening and prior to deflation of the tourniquet. The remaining volume of approximately 40 mL was injected into the quadriceps tendon and subcutaneous tissue prior to skin closure.	Liposomal Bupivacaine (PAI-L) n=52 Participants This group received Intra articular injection with liposomal bupivacaine, a total volume of 120 milliliters (mL) injected in the periarticular structures by the surgeon. Following the current, standardized practice for periarticular infiltration, approximately 30 - 40 mL of solution was injected into the posterior capsule just prior to cementing the implants in place and 40 - 50 mL of solution injected into the medial and lateral retinaculum while the cement was hardening and prior to deflation of the tourniquet. The remaining volume of approximately 40 mL was injected into the quadriceps tendon and subcutaneous tissue prior to skin closure.
Preoperative Daily Opioid Use	15 mg oral morphine equivalents (OME) Interval 0.0 to 15.0	15 mg oral morphine equivalents (OME) Interval 0.0 to 15.0	15 mg oral morphine equivalents (OME) Interval 1.0 to 15.0

SECONDARY outcome

Timeframe: During the procedure, approximately 2 hours after start of the procedure

Population: Intent-to-treat analysis

Opioid consumption was documented in the patient electronic medical record by the nursing staff caring for the patient.

Outcome measures

Outcome measures
Measure	Peripheral Nerve Block (PNB) n=50 Participants This group received a continuous femoral nerve block and a single injection sciatic nerve block consisting of the following: Peripheral nerve blocks with Bupivacaine.	Ropivacaine (PAI-R) n=55 Participants This group received intra articular injection with Ropivacaine, a total volume of 120 milliliters (mL) injected in the periarticular structures by the surgeon. Following the current, standardized practice for periarticular infiltration, approximately 30 - 40 mL of solution was injected into the posterior capsule just prior to cementing the implants in place and 40 - 50 mL of solution injected into the medial and lateral retinaculum while the cement was hardening and prior to deflation of the tourniquet. The remaining volume of approximately 40 mL was injected into the quadriceps tendon and subcutaneous tissue prior to skin closure.	Liposomal Bupivacaine (PAI-L) n=52 Participants This group received Intra articular injection with liposomal bupivacaine, a total volume of 120 milliliters (mL) injected in the periarticular structures by the surgeon. Following the current, standardized practice for periarticular infiltration, approximately 30 - 40 mL of solution was injected into the posterior capsule just prior to cementing the implants in place and 40 - 50 mL of solution injected into the medial and lateral retinaculum while the cement was hardening and prior to deflation of the tourniquet. The remaining volume of approximately 40 mL was injected into the quadriceps tendon and subcutaneous tissue prior to skin closure.
Intraoperative Opioid Use	10 mg OME Interval 5.0 to 15.0	10 mg OME Interval 5.0 to 15.0	10 mg OME Interval 7.0 to 20.0

SECONDARY outcome

Timeframe: Approximately 2 hours after entry in PACU

Population: Intent-to-treat analysis

Opioid consumption was documented in the patient electronic medical record by the nursing staff caring for the patient.

Outcome measures

Outcome measures
Measure	Peripheral Nerve Block (PNB) n=50 Participants This group received a continuous femoral nerve block and a single injection sciatic nerve block consisting of the following: Peripheral nerve blocks with Bupivacaine.	Ropivacaine (PAI-R) n=55 Participants This group received intra articular injection with Ropivacaine, a total volume of 120 milliliters (mL) injected in the periarticular structures by the surgeon. Following the current, standardized practice for periarticular infiltration, approximately 30 - 40 mL of solution was injected into the posterior capsule just prior to cementing the implants in place and 40 - 50 mL of solution injected into the medial and lateral retinaculum while the cement was hardening and prior to deflation of the tourniquet. The remaining volume of approximately 40 mL was injected into the quadriceps tendon and subcutaneous tissue prior to skin closure.	Liposomal Bupivacaine (PAI-L) n=52 Participants This group received Intra articular injection with liposomal bupivacaine, a total volume of 120 milliliters (mL) injected in the periarticular structures by the surgeon. Following the current, standardized practice for periarticular infiltration, approximately 30 - 40 mL of solution was injected into the posterior capsule just prior to cementing the implants in place and 40 - 50 mL of solution injected into the medial and lateral retinaculum while the cement was hardening and prior to deflation of the tourniquet. The remaining volume of approximately 40 mL was injected into the quadriceps tendon and subcutaneous tissue prior to skin closure.
PACU Opioid Use	0 mg OME Interval 0.0 to 0.0	0 mg OME Interval 0.0 to 0.0	0 mg OME Interval 0.0 to 0.0

SECONDARY outcome

Timeframe: POD 0, approximately 12 pm to 12 am

Population: Intent-to-treat

Additional opioid medications that were taken by subjects (recorded at the same time as the time points for measuring pain). Opioid consumption was documented in the patient electronic medical record by the nursing staff caring for the patient.

Outcome measures

Outcome measures
Measure	Peripheral Nerve Block (PNB) n=50 Participants This group received a continuous femoral nerve block and a single injection sciatic nerve block consisting of the following: Peripheral nerve blocks with Bupivacaine.	Ropivacaine (PAI-R) n=55 Participants This group received intra articular injection with Ropivacaine, a total volume of 120 milliliters (mL) injected in the periarticular structures by the surgeon. Following the current, standardized practice for periarticular infiltration, approximately 30 - 40 mL of solution was injected into the posterior capsule just prior to cementing the implants in place and 40 - 50 mL of solution injected into the medial and lateral retinaculum while the cement was hardening and prior to deflation of the tourniquet. The remaining volume of approximately 40 mL was injected into the quadriceps tendon and subcutaneous tissue prior to skin closure.	Liposomal Bupivacaine (PAI-L) n=52 Participants This group received Intra articular injection with liposomal bupivacaine, a total volume of 120 milliliters (mL) injected in the periarticular structures by the surgeon. Following the current, standardized practice for periarticular infiltration, approximately 30 - 40 mL of solution was injected into the posterior capsule just prior to cementing the implants in place and 40 - 50 mL of solution injected into the medial and lateral retinaculum while the cement was hardening and prior to deflation of the tourniquet. The remaining volume of approximately 40 mL was injected into the quadriceps tendon and subcutaneous tissue prior to skin closure.
POD 0 Post-PACU Opioid Use	0 mg OME Interval 0.0 to 15.0	8 mg OME Interval 0.0 to 30.0	15 mg OME Interval 0.0 to 30.0

SECONDARY outcome

Timeframe: POD 1, approximately 12 am to 12 am next day

Population: Intent-to-treat analysis

Additional opioid medications that were taken by subjects (recorded at the same time as the time points for measuring pain). Opioid consumption was documented in the patient electronic medical record by the nursing staff caring for the patient.

Outcome measures

Outcome measures
Measure	Peripheral Nerve Block (PNB) n=50 Participants This group received a continuous femoral nerve block and a single injection sciatic nerve block consisting of the following: Peripheral nerve blocks with Bupivacaine.	Ropivacaine (PAI-R) n=55 Participants This group received intra articular injection with Ropivacaine, a total volume of 120 milliliters (mL) injected in the periarticular structures by the surgeon. Following the current, standardized practice for periarticular infiltration, approximately 30 - 40 mL of solution was injected into the posterior capsule just prior to cementing the implants in place and 40 - 50 mL of solution injected into the medial and lateral retinaculum while the cement was hardening and prior to deflation of the tourniquet. The remaining volume of approximately 40 mL was injected into the quadriceps tendon and subcutaneous tissue prior to skin closure.	Liposomal Bupivacaine (PAI-L) n=52 Participants This group received Intra articular injection with liposomal bupivacaine, a total volume of 120 milliliters (mL) injected in the periarticular structures by the surgeon. Following the current, standardized practice for periarticular infiltration, approximately 30 - 40 mL of solution was injected into the posterior capsule just prior to cementing the implants in place and 40 - 50 mL of solution injected into the medial and lateral retinaculum while the cement was hardening and prior to deflation of the tourniquet. The remaining volume of approximately 40 mL was injected into the quadriceps tendon and subcutaneous tissue prior to skin closure.
POD 1 Opioid Use	26 mg OME Interval 0.0 to 53.0	38 mg OME Interval 15.0 to 53.0	45 mg OME Interval 15.0 to 82.0

SECONDARY outcome

Timeframe: POD 2, approximately 12 am to 12 am next day

Population: Intent-to-treat analysis. For POD 2, data are missing for 5 subjects (1 on PNB arm, 1 on PAI-R arm, and 3 on PAI-L arm).

Additional opioid medications that were taken by subjects (recorded at the same time as the time points for measuring pain). Opioid consumption was documented in the patient electronic medical record by the nursing staff caring for the patient.

Outcome measures

Outcome measures
Measure	Peripheral Nerve Block (PNB) n=49 Participants This group received a continuous femoral nerve block and a single injection sciatic nerve block consisting of the following: Peripheral nerve blocks with Bupivacaine.	Ropivacaine (PAI-R) n=54 Participants This group received intra articular injection with Ropivacaine, a total volume of 120 milliliters (mL) injected in the periarticular structures by the surgeon. Following the current, standardized practice for periarticular infiltration, approximately 30 - 40 mL of solution was injected into the posterior capsule just prior to cementing the implants in place and 40 - 50 mL of solution injected into the medial and lateral retinaculum while the cement was hardening and prior to deflation of the tourniquet. The remaining volume of approximately 40 mL was injected into the quadriceps tendon and subcutaneous tissue prior to skin closure.	Liposomal Bupivacaine (PAI-L) n=49 Participants This group received Intra articular injection with liposomal bupivacaine, a total volume of 120 milliliters (mL) injected in the periarticular structures by the surgeon. Following the current, standardized practice for periarticular infiltration, approximately 30 - 40 mL of solution was injected into the posterior capsule just prior to cementing the implants in place and 40 - 50 mL of solution injected into the medial and lateral retinaculum while the cement was hardening and prior to deflation of the tourniquet. The remaining volume of approximately 40 mL was injected into the quadriceps tendon and subcutaneous tissue prior to skin closure.
POD 2 Opioid Use	23 mg OME Interval 0.0 to 38.0	15 mg OME Interval 0.0 to 38.0	23 mg OME Interval 15.0 to 45.0

SECONDARY outcome

Timeframe: Approximately 3 days

Population: Intent-to-treat analysis

The hospital length of stay was measured from the date of admittance until the date of discharge.

Outcome measures

Outcome measures
Measure	Peripheral Nerve Block (PNB) n=50 Participants This group received a continuous femoral nerve block and a single injection sciatic nerve block consisting of the following: Peripheral nerve blocks with Bupivacaine.	Ropivacaine (PAI-R) n=55 Participants This group received intra articular injection with Ropivacaine, a total volume of 120 milliliters (mL) injected in the periarticular structures by the surgeon. Following the current, standardized practice for periarticular infiltration, approximately 30 - 40 mL of solution was injected into the posterior capsule just prior to cementing the implants in place and 40 - 50 mL of solution injected into the medial and lateral retinaculum while the cement was hardening and prior to deflation of the tourniquet. The remaining volume of approximately 40 mL was injected into the quadriceps tendon and subcutaneous tissue prior to skin closure.	Liposomal Bupivacaine (PAI-L) n=52 Participants This group received Intra articular injection with liposomal bupivacaine, a total volume of 120 milliliters (mL) injected in the periarticular structures by the surgeon. Following the current, standardized practice for periarticular infiltration, approximately 30 - 40 mL of solution was injected into the posterior capsule just prior to cementing the implants in place and 40 - 50 mL of solution injected into the medial and lateral retinaculum while the cement was hardening and prior to deflation of the tourniquet. The remaining volume of approximately 40 mL was injected into the quadriceps tendon and subcutaneous tissue prior to skin closure.
Hospital Length of Stay	2 days Interval 2.0 to 3.0	2 days Interval 2.0 to 3.0	2 days Interval 2.0 to 3.0

SECONDARY outcome

Timeframe: baseline, approximately 12 weeks

Population: Intent-to-treat analysis

In order to measure clinical balance, unipedal stance time (UST) was collected as an indicator of balance and fall risk. Timing (in seconds) began upon withdrawal of support and continued until the uplifted foot returned to the floor, the subject required support, or if the subject reached a time limit of 30 seconds. The best performance of three repetitions was recorded for analysis. Normative values for the UST are available. A UST threshold of 30 seconds yields a sensitivity of 95% and a specificity of 58% in identifying those with a history of falls. The first five seconds of unipedal stance is indicative of dynamic balance; inability to maintain unipedal stance for five seconds is a significant predictor of injurious falls.

Outcome measures

Outcome measures
Measure	Peripheral Nerve Block (PNB) n=50 Participants This group received a continuous femoral nerve block and a single injection sciatic nerve block consisting of the following: Peripheral nerve blocks with Bupivacaine.	Ropivacaine (PAI-R) n=55 Participants This group received intra articular injection with Ropivacaine, a total volume of 120 milliliters (mL) injected in the periarticular structures by the surgeon. Following the current, standardized practice for periarticular infiltration, approximately 30 - 40 mL of solution was injected into the posterior capsule just prior to cementing the implants in place and 40 - 50 mL of solution injected into the medial and lateral retinaculum while the cement was hardening and prior to deflation of the tourniquet. The remaining volume of approximately 40 mL was injected into the quadriceps tendon and subcutaneous tissue prior to skin closure.	Liposomal Bupivacaine (PAI-L) n=52 Participants This group received Intra articular injection with liposomal bupivacaine, a total volume of 120 milliliters (mL) injected in the periarticular structures by the surgeon. Following the current, standardized practice for periarticular infiltration, approximately 30 - 40 mL of solution was injected into the posterior capsule just prior to cementing the implants in place and 40 - 50 mL of solution injected into the medial and lateral retinaculum while the cement was hardening and prior to deflation of the tourniquet. The remaining volume of approximately 40 mL was injected into the quadriceps tendon and subcutaneous tissue prior to skin closure.
Balance Testing on Operative Leg Using Unipedal Stance Time baseline	24 seconds Interval 7.0 to 30.0	16 seconds Interval 5.0 to 30.0	17 seconds Interval 3.0 to 30.0
Balance Testing on Operative Leg Using Unipedal Stance Time 12 weeks	20 seconds Interval 8.0 to 30.0	30 seconds Interval 11.0 to 30.0	23 seconds Interval 8.0 to 30.0

Adverse Events

Peripheral Nerve Block (PNB)

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Ropivacaine (PAI-R)

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Liposomal Bupivacaine (PAI-L)

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Peripheral Nerve Block (PNB) n=50 participants at risk This group received a continuous femoral nerve block and a single injection sciatic nerve block consisting of the following: Peripheral nerve blocks with Bupivacaine.	Ropivacaine (PAI-R) n=55 participants at risk This group received intra articular injection with Ropivacaine, a total volume of 120 milliliters (mL) injected in the periarticular structures by the surgeon. Following the current, standardized practice for periarticular infiltration, approximately 30 - 40 mL of solution was injected into the posterior capsule just prior to cementing the implants in place and 40 - 50 mL of solution injected into the medial and lateral retinaculum while the cement was hardening and prior to deflation of the tourniquet. The remaining volume of approximately 40 mL was injected into the quadriceps tendon and subcutaneous tissue prior to skin closure.	Liposomal Bupivacaine (PAI-L) n=52 participants at risk This group received Intra articular injection with liposomal bupivacaine, a total volume of 120 milliliters (mL) injected in the periarticular structures by the surgeon. Following the current, standardized practice for periarticular infiltration, approximately 30 - 40 mL of solution was injected into the posterior capsule just prior to cementing the implants in place and 40 - 50 mL of solution injected into the medial and lateral retinaculum while the cement was hardening and prior to deflation of the tourniquet. The remaining volume of approximately 40 mL was injected into the quadriceps tendon and subcutaneous tissue prior to skin closure.
General disorders Fall	4.0% 2/50 • Number of events 2 • 3 months	1.8% 1/55 • Number of events 1 • 3 months	1.9% 1/52 • Number of events 1 • 3 months
Infections and infestations Superficial wound infection	4.0% 2/50 • Number of events 2 • 3 months	3.6% 2/55 • Number of events 2 • 3 months	3.8% 2/52 • Number of events 2 • 3 months
General disorders Rapid Response Team	0.00% 0/50 • 3 months	1.8% 1/55 • Number of events 1 • 3 months	1.9% 1/52 • Number of events 1 • 3 months
Nervous system disorders Nerve Injury	4.0% 2/50 • Number of events 2 • 3 months	0.00% 0/55 • 3 months	0.00% 0/52 • 3 months
General disorders Additional surgery	2.0% 1/50 • Number of events 1 • 3 months	0.00% 0/55 • 3 months	0.00% 0/52 • 3 months

Additional Information

Dr. Sandra L. Kopp

Mayo Clinic

Phone: 507-284-6637

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place