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Liposomal Bupivacaine (Exparel)

Liposomal bupivacaine is a multivesicular-liposomal formulation of bupivacaine designed to release drug over up to 72 hours from a single injection, theoretically an ideal ERAS adjunct for wound infiltration and peripheral or fascial-plane blocks. In the 2021 review of liposomal bupivacaine, clinically relevant primary-outcome benefit was uncommon with surgical infiltration, while perineural-block comparisons yielded mixed results.[1] Across 76+ RCTs reviewed in a comprehensive Anesthesiology 2021 analysis, only 11% (4/36) of surgical-infiltration trials comparing liposomal bupivacaine (LB) with unencapsulated bupivacaine or ropivacaine showed a clinically relevant and statistically significant primary-outcome benefit, and manufacturer-related financial conflicts were associated with higher odds of reporting positive pain outcomes (OR 14.31).[1][2] The CLEVELAND trial (online December 2025; print March 2026) found no significant opioid or pain-score differences between its pre-incision four-quadrant TAP regimens.[9]

For the broader local-anesthetic class (lidocaine, ropivacaine, standard bupivacaine across 12 urologic use cases) see Local anesthetics. For ERAS workflow context see ERAS.

Pharmacology​

Formulation​

Multivesicular liposomes: microscopic honeycomb-like lipid-based particles with multiple aqueous chambers separated by lipid bilayers. Upon injection, liposomes gradually erode and release bupivacaine over an extended period. Like all amide-type local anesthetics, released bupivacaine blocks sodium channels and inhibits nerve impulse generation and conduction.[3][4]

Pharmacokinetics​

ParameterDetail
AbsorptionDepends on total dose, route, vascularity. Systemic plasma levels observed for 96 h after local infiltration, 120 h after interscalene block, 168 h after sciatic / adductor-canal block[4]
Protein binding95% (plasma)
DistributionHighly perfused organs; crosses placenta (F/M ratio 0.2–0.4)
MetabolismHepatic metabolism of bupivacaine — caution in hepatic disease
Systemic levelsDo not correlate with local efficacy

FDA-Approved Indications & Dosing​

IndicationDoseVolumeAge
Local infiltration (adults)Up to 266 mg (20 mL of 1.3%)Dilute with NS or LR up to 1:14 (final concentration ≥ 0.89 mg/mL)≥ 18 yr [4]
Local infiltration (pediatric)4 mg/kg (max 266 mg)Same dilution rulesLabel dosing subsection: 6 to <17 yr
Interscalene brachial plexus block133 mg (10 mL)10 mLAdults
Sciatic nerve block (popliteal fossa)133 mg (10 mL)10 mLAdults
Adductor canal block133 mg + 50 mg bupivacaine HCl 0.5% (10 mL each = 20 mL total)20 mLAdults [4]

Source: current US EXPAREL label. Infiltration is indicated from age 6; the pediatric dosing subsection specifies ages 6 to less than 17. TAP blocks are not among the three labeled perineural indications. EXPAREL is not dose-interchangeable with standard bupivacaine.[4]

Preparation and Drug-Interaction Rules — Critical and Unique​

Preparation rules specific to liposomal bupivacaine. These rules are different from standard bupivacaine and are the most common source of drug-waste and lost sustained-release effect.

  • Avoid admixture of EXPAREL with drugs other than label-permitted bupivacaine HCl. Bupivacaine HCl may be given in the same syringe or immediately before EXPAREL when the bupivacaine HCl:EXPAREL milligram ratio does not exceed 1:2; this is not restricted to adductor-canal block. Toxicity is additive, and site-specific dose limits still apply. Lidocaine and other non-bupivacaine local anesthetics may cause immediate release of encapsulated bupivacaine if given together locally, potentially affecting safety and efficacy.[4]
  • Lidocaine may be administered ≥ 20 min before liposomal bupivacaine (label wording: EXPAREL may follow lidocaine after a delay of 20 minutes or more). Other non-bupivacaine locals have no data supporting pre-administration.
  • Avoid additional local anesthetics within 96 h after EXPAREL; this warning is not limited to the same site. Reconcile the entire anesthetic plan, including label-permitted immediate-release adjuncts for the indicated nerve blocks, with anesthesia and pharmacy.
  • Do not dilute with water or hypotonic agents. Disrupts liposomal particles. Use 0.9% preservative-free NS or LR only.[4]
  • Use a 25-gauge or larger-bore needle to preserve liposomal particle integrity; inject slowly with frequent aspiration for blood to reduce inadvertent intravascular injection.[4]
  • Invert vial multiple times to re-suspend particles immediately before withdrawal. Let topical povidone-iodine dry before injecting; EXPAREL should not contact antiseptic solution. Do not heat, autoclave or filter the suspension.[4]
  • Storage and prepared product: refrigerate vials at 2–8 °C. Sealed, intact vials may be held at 20–25 °C for up to 30 days; do not re-refrigerate. Do not use a vial suspected to have been frozen or exposed above 40 °C for an extended period. Use diluted EXPAREL within 4 h.[4]
  • Methemoglobinemia risk with concurrent nitrates or nitrites, other local anesthetics, dapsone, sulfonamides, antimalarials, or acetaminophen.[4]

Evidence — Infiltration vs Standard Bupivacaine​

The most-studied comparison and the most consistently negative signal in local-anesthesia literature.

SourceFinding
Ilfeld 2021 Anesthesiology comprehensive review of 76 RCTsOnly 11% (4/36) of surgical-infiltration RCTs showed clinically relevant and statistically significant primary-outcome benefit versus unencapsulated bupivacaine or ropivacaine. 92% (11/12) of trials suggested better analgesia with a peripheral nerve block using unencapsulated bupivacaine than with surgical infiltration of LB; this comparison changes both technique and formulation. Among low-risk-of-bias trials, only 14% (4/28) reported significant differences — vs 84% (16/19) of high-risk-of-bias trials[1]
Ji 2021 J Surg Res SR of 63 RCTs, n = 6,770LB did not demonstrate significant pain relief in 74.6% of RCTs; no opioid reduction in 85.7% overall (83.3% vs standard bupivacaine). Financial COI association: OR 14.31 for pain (p = 0.0001), OR 12.35 for opioid reduction (p = 0.024). Among 265 unpublished ClinicalTrials.gov RCT records, 47.5% were withdrawn, terminated, suspended or completed without available results[2]
Dinges 2021 RAPM meta + trial sequential analysis, 23 RCTs, n = 1,867Pain ↓ 0.37 points on 10-point scale at 24 h (p < 0.05) — statistically significant, below the paper's >1.5-point clinical-relevance threshold. 15% morphine-equivalent ↓ at 24 h. No significant pain difference at 72 h[5]
Hamilton 2017 CochraneLower cumulative 0–72 h pain vs placebo (very-low-certainty); no difference vs standard bupivacaine (very-low-certainty)[6]
Sandhu 2021 JAMA Network Open RCT, n = 280, sternotomy / thoracotomy / laparotomy (cardiovascular department)No improvement in 3-day pain scores, and more adjunctive opioid with LB (median 41.5 vs 33.0 MEU; p = 0.03)[7]
Saad Sayed 2025 meta (8 RCTs, n = 810, abdominal surgery)No significant pain score difference POD 0, 1, 2, 3. No morphine reduction any day. LB not superior to standard bupivacaine in the surgical plane for abdominal procedures[8]

Across administration routes: compared with bupivacaine HCl, a meta-analysis found a 0.37-point lower pain score at 24 h, below its clinical-relevance threshold, with no significant pain-score difference at 72 h.[5][2] In a separate review, manufacturer-related financial conflicts were associated with higher odds of reported pain relief (OR 14.31).[5][2]

Evidence — TAP Blocks​

Particularly relevant for the reconstructive urologist; TAP blocks are a standard ERAS adjunct for major abdominopelvic surgery.

CLEVELAND — 2025 online / 2026 print[9]​

Triple-blinded 3-arm RCT (261 in the modified intention-to-treat analysis) comparing LB plus plain bupivacaine TAP versus plain bupivacaine TAP versus saline placebo TAP for major abdominal surgery:[9]

  • Opioid consumption 0–24 h: 26 MME (LB) versus 33 MME (plain bupivacaine) versus 31 MME (saline); no significant differences
  • 24–48 h opioid consumption: comparable
  • Pain scores at 24, 48, 72 h: similar across all arms
  • Authors' conclusion: single-shot four-quadrant TAP with LB, plain bupivacaine, or normal saline produced similar postoperative opioid consumption and pain scores

The trial questions routine pre-incision four-quadrant TAP in this mixed surgical population.

EXPLANE 2022[10]​

Multicenter RCT (n = 498 analyzed), LB TAP versus continuous epidural for major abdominal surgery; stopped at a prespecified futility boundary:[10]

  • Pain at rest: TAP non-inferior to epidural (difference 0.09 points; p < 0.05 for non-inferiority)
  • Less hypotension with TAP (31% versus 48%)[10]
  • Pain met noninferiority; the coprimary opioid outcome showed higher use with TAP (+21 mg over 3 days).[10]
  • Important for cystectomy / major-reconstruction patients who are often volume-depleted post-op

Hussain 2024 Anesthesiology meta[11]​

Abdominal fascial-plane blocks, LB versus plain local anesthetics: primary outcome (AUC pain 24–72 h) not different (SMD −0.21; p = 0.058). Unchanged in the COI- and mixing-with-plain-bupivacaine subgroup. The authors found no evidence-based preference for LB.

Evidence — Urologic Surgery Specifically​

Radical cystectomy with diversion​

StudyDesignFinding
Chu 2021 (retrospective cohort)LB infiltration vs epidural at fascial closureLB: shorter LOS (4.9 vs 5.9 d); less opioid; lower cost. Potentially confounded by patient selection and differences in perioperative care[12]
Schmidt 2021 (prospective standard-bupivacaine cohort, n = 28, vs historical LB cohort, n = 34)LB infiltration vs high-volume standard bupivacaine infiltrationNo statistically significant differences in PACU opioid (LB 6.5 vs standard bupivacaine 9.0 mean MED; p = 0.29), later hospital opioid (LB 42.1 vs standard bupivacaine 36.8 mean MED; p = 0.81), POD 1/2/3 pain scores, or LOS (LB 4.9 vs standard bupivacaine 5.0 mean days). Authors: "no significant difference"[13]

Zeng 2026 (RCT, n = 160, open cystectomy) randomized thoracic epidural, rectus sheath block, and surgeon infiltration with LB or standard bupivacaine. Pain scores were similar at 24, 48 and 96 h; at 72 h, epidural and standard-bupivacaine infiltration had lower resting VAS than LB infiltration. Opioid use at individual time points, treatment-related side effects and LOS were similar across groups, but patients assigned to thoracic epidural used less cumulative opioid during the first 72 h than patients assigned to standard-bupivacaine infiltration. Thoracic epidural was not associated with more hypotension, acute kidney injury or delayed ambulation.[19] Unlike the historical cystectomy cohort, this trial randomized patients to both bupivacaine formulations within one study.[19]

The retrospective epidural comparison is vulnerable to changes in care and patient selection. The direct formulation comparison did not detect benefit over standard bupivacaine.

Laparoscopic / robotic urologic surgery​

Knight 2015 RCT (n = 206): LB versus 0.25% bupivacaine, with no difference in total opioid (15 versus 17.3 mg MME; p = 0.39), pain scores, LOS, or time to first opioid. "No significant difference between liposomal bupivacaine and 0.25% bupivacaine."[14]

Gong 2025 RCT (106 analyzed; 53 per arm) compared lateral supra-arcuate quadratus lumborum block with 133 mg LB versus 75 mg bupivacaine HCl for laparoscopic partial or radical nephrectomy.[28] The trial reported lower 48-hour morphine-equivalent use with LB (20.7 versus 31.8 mg) and a higher 24-hour QoR-15 score (118.6 versus 108.4).[28] The single-center, unequal-dose comparison used a block outside EXPAREL's three labeled nerve-block indications; superiority across urologic surgery was not assessed.[28][4]

Pediatric urologic surgery​

Baby ORIOLES (RCT, 104 randomized and 102 with complete 48-h follow-up, ages 6–18, penile block or inguinal / scrotal infiltration) stopped at its futility boundary: adding LB to bupivacaine HCl showed no statistically significant difference in the 48-h opioid-free rate (60% versus 62%), pain scores or adverse events.[20]

Perineal reconstruction (urethroplasty, AUS, sling)​

In a single-surgeon prospective series of 67 men using a pathway with intraoperative LB mixed with 0.25% bupivacaine and no routine discharge opioid prescription, 26/67 received opioids in recovery and 6/67 (9%) received postoperative opioid prescriptions (four for surgical pain, two for chronic pain); 15/67 (22%) contacted the clinic about pain within 30 days, most often for bladder spasm.[21] There was no comparison group.[21] In a separate 43-patient BMG urethroplasty RCT, LB at the oral harvest site versus no added anesthetic beyond harvest hydrodissection lowered POD1 intravenous morphine equivalents by a mean 8.58 mg (95% CI 1.59–15.56 mg), without a detected POD2 opioid, oral-pain, or oral-morbidity benefit; the trial did not compare LB with plain bupivacaine.[27] Randomized urogynecology evidence is mixed and comparator-dependent. For retropubic slings, LB versus saline lowered 4-hour post-discharge pain (3.5 versus 13.0 mm; absolute scores were low in both arms) and the number using opioids on day 2 in 109 analyzed women; LB versus bupivacaine HCl with lidocaine in 57 women did not yield a clinically important day-1 pain benefit and had lower day-1 QoR-15 scores (124 versus 144).[22][23] For prolapse repair, LB versus saline did not improve pain or opioid use after robotic sacrocolpopexy with posterior repair (64 analyzed).[24] In a separate randomized trial across posterior vaginal-wall operations (100 participants), LB infiltration versus saline did not significantly reduce cumulative vaginal pain on postoperative days 1–7 (P = .14) or morphine-equivalent use (P = .81).[30] In a 120-patient posterior-colporrhaphy RCT using a pudendal block outside EXPAREL's recommended nerve-block routes, LB plus plain bupivacaine reduced POD1–3 vaginal pain versus plain bupivacaine alone, without reducing opioid use.[25][4] In a sacrospinous-suspension RCT (83 randomized), LB pudendal block versus no block did not improve overall pain to a clinically important degree, opioid use, or quality of recovery.[26]

Surgeon-administered TAP in cystectomy​

Roebuck 2022, a retrospective cohort (n = 178) comparing surgeon-administered TAP with no TAP, associated TAP with lower POD 0–3 opioid use (106.4 versus 192.2 MME) and shorter LOS (5.6 versus 7.7 d); formulations were not compared.[15]

Quality of Recovery — The Most Favorable Signal​

Zhang 2025 meta included 11 RCTs (n = 1,357) across operations and non-LB comparators, rather than bupivacaine HCl alone. The 72-hour QoR pool included 8 RCTs (n = 1,124) and was heterogeneous (I² = 82.95%). In scale subgroups, the QoR-15 mean difference of 3.32 was below the cited 6-point MCID; the QoR-40 point estimate of 8.66 exceeded its 6.3-point MCID, but that two-trial subgroup was not statistically significant.[18]

  • Quality of Recovery (QoR) at 72 h: SMD 0.52 (95% CI 0.20–0.85)[18]
  • ↓ pain scores at 24, 48, 72 h
  • The five-study pooled analysis found no significant difference in cumulative 3-day morphine use (MD −3.84 mg; 95% CI −11.74 to 4.06; p = 0.34); a four-study sensitivity analysis excluding one trial favored LB.[18]
  • ↓ PONV
  • ↑ patient satisfaction

Interpretation: the analgesic advantage on traditional pain scales is small-to-none, but the overall recovery experience may be improved. Weigh against cost and the industry-bias concerns in the broader literature.

Cost​

EXPAREL acquisition cost is generally higher than generic bupivacaine.

  • Hamilton 2022 JAMA Surgery. In 533 knee-replacement patients, adding LB to bupivacaine HCl did not improve 72-hour quality of recovery or pain versus bupivacaine HCl alone. The LB arm was economically dominated on point estimates, although 1-year QALY and total-cost differences were not statistically significant; its probability of cost-effectiveness was 37% at £20,000/QALY.[17]
  • Babazade 2019 cost-effectiveness analysis. IVPCA was most cost-effective; TAP with LB narrowly dominated; epidural clearly dominated.[16]

Cost-effectiveness is procedure- and comparator-specific. Limited evidence of routine clinical superiority should be considered alongside local cost.

Safety Profile​

EXPAREL retains serious bupivacaine toxicity risks and has formulation-specific compatibility restrictions.[4][6]

  • Common adverse reactions (≥ 10%) vary by route and age: adult infiltration: nausea, constipation, vomiting; adult nerve block: nausea, pyrexia, headache, constipation; pediatric infiltration (ages 6 to <17 years): nausea, vomiting, constipation, hypotension, anemia, muscle twitching, blurred vision, pruritus and tachycardia.[4]
  • Cardiovascular toxicity: toxic bupivacaine concentrations can cause AV block, ventricular arrhythmias, cardiac arrest, decreased cardiac output and hypotension. Monitor cardiovascular and neurologic status during and after injection.[4]
  • CNS toxicity: restlessness, anxiety, tinnitus, dizziness, blurred vision, tremors, convulsions, unconsciousness, respiratory depression
  • Methemoglobinemia: all patients are at risk with local anesthetics; G6PD deficiency, pre-existing methemoglobinemia, cardiopulmonary compromise and concurrent oxidizing agents increase susceptibility. Cyanosis can begin immediately or hours later and requires prompt evaluation and treatment.[4]
  • Hepatic or renal impairment. Bupivacaine is hepatically metabolized: consider increased LAST monitoring in moderate to severe hepatic disease. Renal impairment may increase the risk of EXPAREL-associated adverse reactions; increase monitoring.[4]
  • Chondrolysis risk. Not approved for intra-articular use
  • Obstetrical paracervical block is contraindicated. EXPAREL has not been studied in pregnant women; the label does not recommend administering it to pregnant patients and advises counseling about potential fetal risks based on animal data.[4]
  • Sensory or motor block: temporary sensory or motor loss may last up to 5 days, depending on injection site and dose; inform patients in advance.[4]
  • Not recommended routes and blocks: epidural, intrathecal, intravascular and intra-articular administration, and regional nerve blocks other than interscalene brachial plexus, popliteal sciatic or adductor canal block.[4]

For the LAST (Local Anesthetic Systemic Toxicity) framework and 20%-lipid-emulsion rescue protocol, see Local anesthetics.[29]

Evidence Summary​

Clinical questionEvidenceStrength
LB surgical infiltration vs unencapsulated bupivacaine or ropivacaineClinically relevant primary-outcome benefit in 4/36 comparisons; a separate bupivacaine-HCl meta-analysis found 0.37/10-point lower pain at 24 h, described by the authors as not clinically relevantMultiple RCTs and reviews across surgical populations[1][2][5][6]
LB TAP block vs standard bupivacaine TAP vs salineCLEVELAND — no significant differences in the tested regimensSingle RCT in a mixed abdominal-surgery population[9]
LB TAP vs epiduralNoninferior resting pain over 3 postoperative days; opioid coprimary endpoint failed noninferiority (geometric-mean ratio 1.37, 95% CI 1.05–1.79; +21 mg morphine equivalents over 3 days); less hypotension, defined as MAP <65 mmHg (31% vs 48%)Single mixed-abdominal-surgery RCT[10]
LB in radical cystectomyRetrospective benefit versus epidural; no benefit versus standard bupivacaine in a small cohort and in the 2026 RCT (LB had higher 72-h resting pain than standard infiltration)Low–moderate[12][13][19]
LB in laparoscopic / robotic and pediatric urologyKnight and Baby ORIOLES found no benefit in their tested regimens; a 2025 nephrectomy QL-block RCT found lower 48-hour opioid use with LB than with a lower milligram dose of plain bupivacaineMixed, procedure-specific RCTs[14][20][28]
Cost-effectivenessDominated in knee replacement; narrowly dominated by IVPCA for abdominal surgeryModerate[16][17]
Financial COIManufacturer-related conflicts were associated with positive pain outcomes across trials (OR 14.31, 95% CI 2.8–73.10)Systematic review of 63 RCTs[2]
Quality of recoveryIn eight RCTs across mixed operations and comparators, pooled 72-h QoR scores favored LB (SMD 0.52, 95% CI 0.20–0.85); the six-trial nerve-block subgroup favored LB, while the two-trial infiltration subgroup showed no significant difference (SMD 0.04, 95% CI −0.12 to 0.20)2025 meta-analysis[18]

Practical Pearls​

  • The preponderance of evidence does not support routine use of liposomal bupivacaine over standard bupivacaine in wound infiltration or TAP for reconstructive / urologic surgery.[1][5] Among the 36 surgical-infiltration comparisons in the 76-RCT review, 4 (11%) demonstrated a clinically relevant benefit.[1][5]
  • Financial COI is a major interpretive concern. Industry-affiliated studies are associated with higher odds of positive pain outcomes (OR 14.31).[2]
  • CLEVELAND found similar outcomes among the three tested regimens; avoid extending this null result to all surgery-specific TAP protocols.[9]
  • In radical cystectomy with diversion, a retrospective cohort associated LB infiltration with shorter stay and less opioid use than epidural. In the 160-patient RCT, LB infiltration had higher resting pain at 72 h than standard-bupivacaine infiltration and epidural; overall side effects and stay were similar, and epidural was not associated with more hypotension or delayed ambulation.[12][13][19]
  • LB TAP may be considered when hypotension risk is a concern, with anesthesia input. EXPLANE compared LB TAP with epidural in major abdominal surgery: resting pain met noninferiority and hypotension was less frequent with LB TAP (MAP <65 mmHg: 31% versus 48%), while the opioid coprimary outcome failed noninferiority (+21 mg morphine equivalents over 3 days).[10] In a cystectomy-specific RCT, thoracic epidural was not associated with more hypotension than the other studied techniques.[19]
  • Preparation rules matter. Local coadministration or admixture with lidocaine may immediately release encapsulated bupivacaine; administer EXPAREL at least 20 minutes after local lidocaine. Hypotonic dilution disrupts liposomal particles. Use a 25-gauge or larger-bore needle and dilute only with preservative-free 0.9% NS or LR.[4]
  • 96-hour warning applies to additional local-anesthetic exposure, not just the injection site.[4]
  • Check local cost and procedure-specific benefit. Historical knee and abdominal surgery cost-effectiveness estimates depend on the local price and procedure.[16][17]
  • Quality-of-recovery data (2025) are the most favorable signal for LB; worth knowing about, but should be weighed against the broader evidence base and industry-bias concerns.[18]

See Also​

References​

1. Ilfeld BM, Eisenach JC, Gabriel RA. "Clinical effectiveness of liposomal bupivacaine administered by infiltration or peripheral nerve block to treat postoperative pain." Anesthesiology. 2021;134(2):283–344. doi:10.1097/ALN.0000000000003630

2. Ji YD, Harris JA, Gibson LE, McKinley SK, Phitayakorn R. "The efficacy of liposomal bupivacaine for opioid and pain reduction: a systematic review of randomized clinical trials." J Surg Res. 2021;264:510–533. doi:10.1016/j.jss.2021.02.024

3. Prabhakar A, Ward CT, Watson M, et al. "Liposomal bupivacaine and novel local anesthetic formulations." Best Pract Res Clin Anaesthesiol. 2019;33(4):425–432. doi:10.1016/j.bpa.2019.07.012

4. EXPAREL. US prescribing information, label effective December 2025. Current label.

5. Dinges HC, Wiesmann T, Otremba B, et al. "The analgesic efficacy of liposomal bupivacaine compared with bupivacaine hydrochloride for the prevention of postoperative pain: a systematic review and meta-analysis with trial sequential analysis." Reg Anesth Pain Med. 2021;46(6):490–498. doi:10.1136/rapm-2020-102427

6. Hamilton TW, Athanassoglou V, Mellon S, et al. "Liposomal bupivacaine infiltration at the surgical site for the management of postoperative pain." Cochrane Database Syst Rev. 2017;2:CD011419. doi:10.1002/14651858.CD011419.pub2

7. Sandhu HK, Miller CC, Tanaka A, Estrera AL, Charlton-Ouw KM. "Effectiveness of standard local anesthetic bupivacaine and liposomal bupivacaine for postoperative pain control in patients undergoing truncal incisions: a randomized clinical trial." JAMA Netw Open. 2021;4(3):e210753. doi:10.1001/jamanetworkopen.2021.0753

8. Saad Sayed M, Rath S, Rasool W, et al. "Efficacy of liposomal bupivacaine versus standard bupivacaine following abdominal surgeries: a systematic review and meta-analysis of randomized controlled trials." Pain Pract. 2025;25(5):e70048. doi:10.1111/papr.70048

9. Turan A, Esa WAS, Brooker J, et al. "Liposomal bupivacaine, plain bupivacaine, and saline for transversus abdominis plane blocks: the CLEVELAND randomized trial." Anesthesiology. 2026;144(3):546–558. Published online December 2025. doi:10.1097/ALN.0000000000005869

10. Turan A, Cohen B, Elsharkawy H, et al. "Transversus abdominis plane block with liposomal bupivacaine versus continuous epidural analgesia for major abdominal surgery: the EXPLANE randomized trial." J Clin Anesth. 2022;77:110640. doi:10.1016/j.jclinane.2021.110640

11. Hussain N, Speer J, Abdallah FW. "Analgesic effectiveness of liposomal bupivacaine versus plain local anesthetics for abdominal fascial plane blocks: a systematic review and meta-analysis of randomized trials." Anesthesiology. 2024;140(5):906–919. doi:10.1097/ALN.0000000000004932

12. Chu CE, Law L, Zuniga K, et al. "Liposomal bupivacaine decreases postoperative length of stay and opioid use in patients undergoing radical cystectomy." Urology. 2021;149:168–173. doi:10.1016/j.urology.2020.11.036

13. Schmidt B, Bhambhvani HP, Greenberg DR, et al. "Bupivacaine local anesthetic to decrease opioid requirements after radical cystectomy: does formulation matter?" Urol Oncol. 2021;39(6):369.e1–369.e8. doi:10.1016/j.urolonc.2020.11.008

14. Knight RB, Walker PW, Keegan KA, et al. "A randomized controlled trial for pain control in laparoscopic urologic surgery: 0.25% bupivacaine versus long-acting liposomal bupivacaine." J Endourol. 2015;29(9):1019–1024. doi:10.1089/end.2014.0769

15. Roebuck E, Beano H, Robinson M, et al. "Surgeon-administered transversus abdominis plane (TAP) block is associated with decreased opioid usage and length of stay following radical cystectomy." Urology. 2022;161:135–141. doi:10.1016/j.urology.2021.11.023

16. Babazade R, Saasouh W, Naylor AJ, et al. "The cost-effectiveness of epidural, patient-controlled intravenous opioid analgesia, or transversus abdominis plane infiltration with liposomal bupivacaine for postoperative pain management." J Clin Anesth. 2019;53:56–63. doi:10.1016/j.jclinane.2018.10.003

17. Hamilton TW, Knight R, Stokes JR, et al. "Efficacy of liposomal bupivacaine and bupivacaine hydrochloride vs bupivacaine hydrochloride alone as a periarticular anesthetic for patients undergoing knee replacement: a randomized clinical trial." JAMA Surg. 2022;157(6):481–489. doi:10.1001/jamasurg.2022.0713

18. Zhang L, Yang S, Liu X, et al. "Impact of liposomal bupivacaine on subjective recovery quality after surgery: a meta-analysis of randomized controlled trials." Front Med. 2025;12:1655756. doi:10.3389/fmed.2025.1655756

19. Zeng J, Tachibana I, Sadowski J, et al. "Comparison of 4 local anesthetic techniques for open radical cystectomy: a prospective, randomized controlled trial." Urol Oncol. 2026;44(1):64.e7–64.e14. doi:10.1016/j.urolonc.2025.09.019

20. Gabrielson AT, Galansky L, Sholklapper T, et al. "Effectiveness of liposomal bupivacaine with bupivacaine hydrochloride vs bupivacaine hydrochloride alone as a local anesthetic for children undergoing ambulatory urologic surgery: the Baby ORIOLES randomized clinical trial." J Urol. 2024;211(1):37–47. doi:10.1097/JU.0000000000003764

21. Pence ST, Findlay BL, Bearrick EN, et al. "Evaluation of an opioid-free pathway for perineal reconstructive surgery: a 1-year pilot study." Urology. 2024;190:110–114. doi:10.1016/j.urology.2024.04.032

22. Mazloomdoost D, Pauls RN, Hennen EN, et al. "Liposomal bupivacaine decreases pain following retropubic sling placement: a randomized placebo-controlled trial." Am J Obstet Gynecol. 2017;217(5):598.e1–598.e11. doi:10.1016/j.ajog.2017.07.001

23. Iwanoff C, Salamon C. "Liposomal Bupivacaine Versus Bupivacaine Hydrochloride with Lidocaine during Midurethral Sling Placement: A Randomized Controlled Trial." J Minim Invasive Gynecol. 2019;26(6):1133–1138. doi:10.1016/j.jmig.2018.11.005

24. Yeung J, Crisp CC, Mazloomdoost D, Kleeman SD, Pauls RN. "Liposomal Bupivacaine During Robotic Colpopexy and Posterior Repair: A Randomized Controlled Trial." Obstet Gynecol. 2018;131(1):39–46. doi:10.1097/AOG.0000000000002375

25. Dengler KL, Craig ER, DiCarlo-Meacham AM, et al. "Preoperative pudendal block with liposomal and plain bupivacaine reduces pain associated with posterior colporrhaphy: a double-blinded, randomized controlled trial." Am J Obstet Gynecol. 2021;225(5):556.e1–556.e10. doi:10.1016/j.ajog.2021.08.034

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27. Chua ME, Zuckerman JM, Strehlow R 6th, et al. "Liposomal Bupivacaine Local Infiltration for Buccal Mucosal Graft Harvest Site Pain Control: A Single-blinded Randomized Controlled Trial." Urology. 2020;145:269–274. doi:10.1016/j.urology.2020.06.067

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