Table 5 Articles included in the review analyzing the use of liposomal bupivacaine in periarticular infiltrations

Marino et al. [57]

RCT

65 total knee arthroplasty

1. CFNB + PAI of bupivicaine

2. PAI bupivicaine + liposomal bupivicaine

1. continuous femoral nerve block 20 mL 0.5% bolus bupivacaine with continuous infusion -.2% at 8 ml/h for 48 h, spinal anesthetic with 12.5 mg bupivacaine 0.75%, periarticular injection of 60 cc solution of 30 mL 0.5% bupivacaine HCl, 0.5 ml epi 1:200,000

2. PAI 30 ml 0.5% bupivacaine 10 mL NaCl, 0.5 ml epi 1:200,000, 20 ml 266 mg liposomal bupivacaine

No difference in pain at rest, increased pain with maximum flexion in LB vs CFNB at 24 h. Similar patient satisfaction, similar narcotic use overall except CFNB started use of PCA earlier (205.8 min vs 116.5 min). 9.4% vs 57.6% required use of knee immobilizer for knee buckling postop until POD2. Same active knee ROM at 24 h, CFNB better at 48 h (74.1 degree vs 62.74 degree)

1 patient exceeded the toxicity threshold for bupivacaine in CFNB, none in LB. No participants with symptoms of local anesthetic systemic toxicity

Zlotnicki et al. [64]

RCT

80 total knee arthroplasty patients

1. PAI bupiv

2. PAI liposomal bupivacaine

3. Retrospectively reviewed control with no PAI

1. 20 ml 0.5% plain bupivacaine + 70 mL NS

2. 20 mL 0.5% liposomal bupivacaine + 70 mL NS

Decreased pain with PT with LB compared to bupivacaine at 24 h but not 48 h. No difference in total pain medications, ROM on POD1 or at discharge

Both superior to no PAI

None reported

Dizdarevic et al. [58]

RCT

25 (interim analysis, 90 total) total knee arthroplasty

1. ACB + PAI bupivacaine

2. ACB + PAI bupivicaine/liposomal bupivicaine

1. Adductor canal block + 40 mL 0.25% bupivacaine PAI 2. Adductor canal block + 40 mL 0.65% exparel, 0.25% bupivacaine

No change in 48 h opioid use, no change in function (measured via 6-Clicks score), no difference for numerical pain rating scale at 24 or 48 h

None reported

Dysart et al. [56]

RCT

139 total knee arthroplasty

1. LIA with LB + bupivacaine

2. LIA with bupivicaine

1. LIA with LB 266 mg/20 mL mixed with bupivacaine 0.5% 20 mL 2. bupivacaine alone

LB group less likely to use opioid rescue medications within first 24 h, reduced opioid consumption over first 24 h (3.5 vs 38.5), reduced pain intensity. More likely to be discharge ready within 12 h of surgery (42.9 vs 27.5%), higher satisfaction with pain treatment. Timed up and go test no difference

No serious adverse events, nausea/dizziness/vomiting similar between groups

Hyland et al. [59]

RCT

59

1. ACB + PAI (ropivicaine, morphine, ketoralac, methylprednisolone)

2. ACB + PAI liposomal bupivicaine

1. PAI: 20 ml 0.2% ropivacaine, 10 mg morphine, 30 mg ketorolac, 40 mg methylprednisolone

2. 60 ml liposomal bupivicaine 266 mg

No difference in number of PT sessions necessary for discharge, total opioid consumption, average pain scores. Average total drug charges significantly higher for liposomal bupivacaine

None listed

Smith et al. [60]

RCT

200 total knee arthroplasty

1. intra-articular slow infusion delivery system (ON-Q) of bupivacaine

2. 20 ml 266 mg liposomal bupivicaine with 40 ml .9% saline + intra-articular slow infusion delivery system (ON-Q) of saline

20 ml 266 mg liposomal bupivicaine with 40 ml .9% saline

No difference in morphine equivalents consumed, hospital stay length, satisfaction pain scores, scores for ability to fall asleep. Bupivicaine infusion had less pain with PT

3 patients with LB required MUA for stiffness, 5 patients for bupivicaine infusion required MUA. 1 LB had wound dehiscence and suspected infection,

Perets et al. [61]

RCT

107 total hip arthroplasty patients

1. PAI with LB + bupivicaine HCl

2. Control of bupivicaine HCl and epinephrine

1. 60 ml 0.25% bupivicaine with epinephrine 2. 20 ml liposomal bupivicaine, 40 ml 0.25% bupivicaine with epinephrine

No statistical significant difference in morphine equivalent use (total or at any time point), no falls for either, no difference in mean time to ambulation, no difference in VAS pain scores

Similar rates of constipation, nausea, vomiting

Johnson et al. [65]

RCT

159 total hip arthroplasty

1. Peripheral nerve block

2. PAI with ropivacaine, ketorolac, epinephrine

3. PAI with liposomal bupivacaine,ketorolac, epinephrine

1. Peripheral nerve block (0.5% bupivicaine with epi 30 mL with bupivicaine infusion 0.2% in PACU

2. PAI with ropivacaine, ketorolac, epinephrine, weight based Ropivacaine of 200–400 mg, 100–300 µg epinephrine, 30 mg ketorolac diluted to 120 ml solution

3. PAI with liposomal bupvicaine, ketorolac, epinephrine, 266 mg liposomal bupivicaine, 30 mg ketorolac, 125 mg bupivicaine, 125 µg epinephrine. diluted to 120 ml

No difference in postoperative pain scores on POD1 morning, LB had lower pain scores than no LB but not lower than PNB. No difference in postoperative opioid use or need for IV analgesic. No difference in hospital length of stay, adverse events during hospitalization. No difference in change of physical/mental composites scores for SF36 over 3 months or pain at rest/with movement

2 falls after discharge in bupivicaine group, 1 fall in liposomal bupivicaine group

Talmo et al. [66]

RCT

373 knee arthroplasty patients

1. Femoral nerve block

2. PAI with liposomal bupivicaine + placebo saline FNB

1. 30 ml 0.25% bupivicaine + 30 ml 0.25% bupivacaine

2. 30 mL 0.25% bupivacaine + 20 ml (266 mg liposomal bupivicaine) + 40 ml saline

Control group had lower pain scores, higher range of motion at 12 h. Liposomal bupivacaine group was more likely to be able to perform straight leg raise at 12 h postoperatively and scored higher in physical function short form 12 score at 3 months post op. No significant difference in median walking distance at 12, 24, 36, 48 h postoperatively. All variables had similar variables at 1 year postoperatively. No difference in pain medication use between the two groups

2 patients in the nerve block group required additional rescue FNB for severe postoperative pain. No difference in complication rates

Alijanipour et al. [62]

RCT

162 total knee arthroplasty patients

1. Liposomal bupivacaine

2. Free bupivicaine

1. 20 ml (266 mg) liposomal bupivicaine with 40 ml NS and 0.5 ml epinephrine 1 mg/ml

2. 20 ml (50 mg) free bupivicaine 0.25% with epinephrine 1:200,000 with 40 ml NS

No difference in postoperative pain scores, narcotic side effects, surgical/medical complications, length of stay, patient satisfaction, or Knee Society Score

Similar complication rates between liposomal bupivicaine and bupivicaine

Ali et al. [63]

Dual center RCT

108 shoulder arthroplasty patients

1. Local liposomal bupivacaine

2. Interscalene nerve block

1. 20 ml suspension of 266 mg LLB with 20 mL saline solution, injected into skin/subcut, deltoid, pectoralis muscle, pericapsular, periarticular + 30 mL 0.5% bupivicaine—epinephrine (given slower onset of action

3. 0.5% ropivacaine for INB, dosed by weight

VAS pain score in INB were better than LLB at 6 h, no difference after 6 h

Similar intra-op opioid requirements, INB had fewer morphine milligram equivalents 18 + -12 compared to LLB 36 +—48 over first 24 h, similar results over days 2–4,

PACU stay shorter for INB 102 +—53 versus LLB 139 +—77 min

No difference i duration of hospital stay or satisfaction with pan control in hospital or at home

No adverse events experienced