A phase 3 active-controlled trial of liposomal bupivacaine via sciatic nerve block in the popliteal fossa after bunionectomy.

STUDY OBJECTIVE: To investigate the efficacy, safety, pharmacodynamics, and pharmacokinetics of liposomal bupivacaine (LB) administered via ultrasound-guided sciatic nerve block in the popliteal fossa in participants undergoing bunionectomy. DESIGN: Two-part, randomized, double-blind, active-controlled trial (NCT05157841). SETTING: Operating room, postanesthesia care unit, and health care facility (6 sites). PATIENTS: Adults with American Society of Anesthesiologists physical status classification ≤3 and body mass index ≥18 to <40 kg/m2 undergoing elective distal metaphyseal osteotomy. INTERVENTIONS: Part A participants were randomized 1:1:1 to LB 266 mg, LB 133 mg, or bupivacaine hydrochloride 50 mg (BUPI). Part B participants were randomized 1:1 to LB (at the dose established by part A) or BUPI. MEASUREMENTS: The primary endpoint was area under the curve (AUC) of numerical rating scale (NRS) pain intensity scores 0-96 h after surgery. Secondary endpoints included total postsurgical opioid consumption, opioid-free status 0-96 h after surgery, and pharmacokinetic endpoints. MAIN RESULTS: Part A enrolled 22 participants per group. In part B, additional participants were randomized to LB 133 mg (n = 59) and BUPI (n = 60) (185 total). LB 133 mg had significant reductions versus BUPI in the AUC of NRS pain intensity score (least squares mean [LSM], 207.4 vs 371.4; P < 0.00001) and total opioid consumption 0-96 h after surgery (LSM, 17.7 [95% confidence interval (CI), 13.7, 22.8] morphine milligram equivalents [MMEs] vs 45.3 [95% CI, 35.1, 58.5] MMEs; P < 0.00001) and an increased proportion of opioid-free participants (24.4% vs 6%; odds ratio, 5.04 [95% CI, 2.01, 12.62]; P = 0.0003) in parts A + B. Adverse events were similar across groups. CONCLUSIONS: LB 133 mg administered via sciatic nerve block in the popliteal fossa after bunionectomy demonstrated superior and long-lasting postsurgical pain control versus BUPI. The clinical relevance of these findings is supported by concurrent reductions in pain and opioid consumption over 4 days after surgery and a significantly greater percentage of participants remaining opioid-free.

Relationship between injectate volume and disposition in erector spinae plane block: a cadaveric study.

INTRODUCTION: Erector spinae plane (ESP) blocks can be used to provide analgesia following thoracoabdominal and lumbar spine surgical procedures. However, the influence of injectate volume and injection location on the spread of anesthetic with ESP blocks remain unclear. METHODS: Ultrasound-guided ESP injections were performed on two fresh cadavers using a solution of iopamidol radiographic contrast, indocyanine green or methylene blue dye, and saline. The relationship between injectate volume and cephalocaudal spread was assessed using real-time fluoroscopic recordings after incremental ESP injections to the lumbar and thoracic region. Cadavers were then dissected to expose tissue staining and document the precise disposition of the dye within the ES muscle, paravertebral space, dorsal and ventral rami, and other relevant structures. RESULTS: Larger injection volumes resulted in more extensive cephalocaudal spread in most cases, with fluoroscopic images revealing a small but direct relationship between injectate volume and contrast spread. Dissection reinforced the radiographic findings, with staining ventral to the ES muscle ranging from 4 to 7 paravertebral levels with injections of 30-40 mL vs 12-13 levels following injections of 60-80 mL. No spread of dye to the lamina, transverse processes, paravertebral space, epidural space, or pleura was observed following any injection. CONCLUSIONS: Increased ESP injection volumes resulted in more extensive cephalocaudal spread, resulting in anesthetic spread to the dorsal rami and ventral ES muscle without involvement of the ventral rami or other anterior structures. Injection volumes of 30 mL may be optimal for ESP blocks requiring analgesia across 4-7 levels.

Awake Spinal Fusion Is Associated with Reduced Length of Stay, Opioid Use, and Time to Ambulation Compared to General Anesthesia: A Matched Cohort Study.

OBJECTIVE: There is increasing interest in performing awake spinal fusion under spinal anesthesia (SA). Evidence supporting SA has been positive, albeit limited. The authors set out to investigate the effects of SA versus general anesthesia (GA) for spinal fusion procedures on length of stay (LOS), opioid use, time to ambulation (TTA), and procedure duration. METHODS: The authors performed a retrospective review of a single surgeon's patients who underwent lumbar fusions under SA versus GA from June of 2020 to June of 2022. SA patients were compared to demographically matched GA counterparts undergoing comparable procedures. Analyzed outcomes include operative time, opioid usage in morphine milligram equivalents, TTA, and LOS. RESULTS: Ten SA patients were matched to 10 GA counterparts. The cohort had a mean age of 66.77, a mean body mass index of 27.73 kg/m2, and a median American Society of Anesthesiologists Physical Status Score of 3.00. LOS was lower in SA versus GA patients (12.87 vs. 50.79 hours, P = 0.001). Opioid utilization was reduced in SA versus GA patients (10.76 vs. 31.43 morphine milligram equivalents, P = 0.006). TTA was reduced in SA versus GA patients (7.22 vs. 29.87 hours, P = 0.022). Procedure duration was not significantly reduced in SA patients compared to GA patients (139.3 vs. 188.2 minutes, P = 0.089). CONCLUSIONS: These preliminary retrospective results suggest the use of SA rather than GA for lumbar fusions is associated with reduced hospital LOS, reduced opioid utilization, and reduced TTA. Future randomized prospective studies are warranted to determine if SA usage truly leads to these beneficial outcomes.

Awake spinal anesthesia facilitates spine surgery in poor surgical candidates: A case series.

BACKGROUND: Annually, hundreds of thousands of patients undergo surgery for degenerative spine disease (DSD). This represents only a fraction of patients that present for surgical consideration. Procedures are often avoided due to comorbidities that make patients poor candidates for general anesthesia (GA) and its associated risks. With increasing interest in awake surgery under spinal anesthesia (SA), the authors have observed that SA may facilitate spine surgery in patients with relative contraindications to GA. With this in mind, the authors set out to summarize the outcomes of a series of highly comorbid patients who received surgery under SA. METHODS: Case logs of a single surgeon were reviewed, and patients undergoing spine surgery under SA were identified. Within this group, patients were identified with relative contraindications to GA, such as advanced age and medical comorbidities. For these patients, for whom surgery was facilitated by SA, the medical records were consulted to report demographic information and patient outcomes. RESULTS: Ten highly comorbid patients were identified who received lumbar spine surgery for DSD under SA. Comorbidities included octogenarian status, obesity, and chronic health conditions such as heart disease. The cohort had a mean age of 75.5 and a mean American Society of Anesthesiologists Physical Status (ASA-PS) score of 3.1. The patients were predicted to have a 2.74-fold increase of serious complications compared to the average patient. There were no adverse events. CONCLUSION: For patients with symptomatic, refractory DSD and relative contraindications to GA, SA may facilitate safe surgical intervention with excellent outcomes.

Regional Anesthesia Associated With Decreased Inpatient and Outpatient Opioid Demand in Tibial Plateau Fracture Surgery.

BACKGROUND: Regional anesthesia (RA) has been used to reduce pain and opioid usage in elective orthopedic surgery. The hypothesis of this study was that RA would be associated with decreased opioid demand in tibial plateau fracture surgery. METHODS: Inpatient opioid consumption and 90-day outpatient opioid prescribing in all patients ≥18 years of age undergoing tibial plateau fracture surgery from July 2013 to July 2018 (n = 264) at a single, level I trauma center were recorded. The presence or absence of perioperative RA was noted. Of 60 patients receiving RA, 52 underwent peripheral nerve blockade (PNB) with single-shot sciatic-popliteal (40.0%; n = 24), femoral (26.7%; n = 16), adductor canal (18.3%; n = 11), or fascia iliaca (1.7%; n = 1) block with ropivacaine. Ten patients received epidural analgesia (EA) with either single-shot spinal (11.7%; n = 7) blocks or continuous epidural (5.0%; n = 3). Additional baseline and treatment characteristics were recorded, including age, sex, race, body mass index (BMI), smoking, chronic opioid use, American Society of Anesthesiologists (ASA) score, injury mechanism, additional injuries, open injury, and additional inpatient surgery. Statistical models, including multivariable generalized linear models with propensity score weighting to adjust for baseline patient and treatment characteristics, were used to assess perioperative opioid demand with and without RA. RESULTS: RA was associated with reduced inpatient opioid usage from 0 to 24 hours postoperatively of approximately 5.2 oxycodone 5-mg equivalents (0.74 incident rate ratio [IRR]; 0.63-0.86 CI; P < .001) and from 24 to 48 hours postoperatively of approximately 2.9 oxycodone 5-mg equivalents (0.78 IRR; 0.64-0.95 CI; P = .014) but not at 48 to 72 hours postoperatively. From 1 month preoperatively to 2 weeks postoperatively, RA was associated with reduced outpatient opioid prescribing of approximately 24.0 oxycodone 5-mg equivalents (0.87; 0.75-0.99; P = .044) and from 1 month preoperatively to 90 days postoperatively of approximately 44.0 oxycodone 5-mg equivalents (0.83; 0.71-0.96; P = .011), although there was no significant difference from 1 month preoperatively to 6 weeks postoperatively. There were no cases of acute compartment syndrome in this cohort. CONCLUSIONS: In tibial plateau fracture surgery, RA was associated with reduced inpatient opioid consumption up to 48 hours postoperatively and reduced outpatient opioid demand up to 90 days postoperatively without an associated risk of acute compartment syndrome. RA should be considered for patients undergoing tibial plateau fracture fixation.

Ultrasound-guided genicular nerve blocks following total knee arthroplasty: a randomized, double-blind, placebo-controlled trial.

INTRODUCTION: Local anesthetic blockade of the genicular nerves, known targets of radiofrequency ablative techniques for knee pain, has not previously been studied in a randomized controlled trial evaluating acute pain after knee arthroplasty. We hypothesized that genicular nerve blockade added to an existing block regimen in total knee arthroplasty would result in a reduction in 24 hours opioid consumption. METHODS: Patients (American Society of Anesthesiologists 1-3, aged 18-85 years) undergoing primary total knee arthroplasty were randomized to receive single-injection nerve blocks of the superolateral, superomedial, and inferomedial genicular nerves with injectate (15 mL 0.25% bupivacaine and 2 mg dexamethasone or 15 mL saline placebo). All subjects received a standard oral analgesic regimen, spinal anesthetic with 12.5 mg isobaric bupivacaine, infiltration between the popliteal artery and capsule of the knee with 0.2% ropivacaine, and postoperative adductor canal perineural infusion with 0.2% ropivacaine. The primary outcome was 24 hours opioid consumption (measured in morphine milliequivalents). RESULTS: Forty (40) subjects were enrolled. Opioid consumption at 24 hours was significantly lower in the BLOCK group compared with the SHAM group (23±20 vs 58±35, p<0.001), and this difference remained significant at 48 hours (50±40 vs 98±56, p=0.004). Pain scores were reduced in the BLOCK group at time 6 hours (2.6±1.9 vs 4.3±2.2, p=0.012), but were otherwise similar at remaining time points. Patient satisfaction at 24 hours and 20 m walk test times were similar between groups. DISCUSSION: Genicular nerve blockade was associated with a reduction in opioid consumption at 24 hours in primary total knee arthroplasty patients. TRIAL REGISTRATION NUMBER: NCT03706313.

Femoral artery block (FAB) attenuates thigh tourniquet-induced hypertension: a prospective randomized, double-blind, placebo-controlled trial.

INTRODUCTION: Prolonged tourniquet inflation during surgery frequently leads to tourniquet hypertension (TH), which is thought to arise from compression of A-δ fibers leading to sympathetically mediated C fiber activation. In the lower extremity, C fibers and other sympathetic nerve fibers are carried along the femoral artery. We hypothesized that blockade of these fibers at the femoral artery would decrease the incidence of TH. METHODS: Thirty American Society of Anesthesia 1-3 patients aged 18-75 undergoing total ankle arthroplasty were randomized to receive 15 mL of injectate (mepivacaine 1.5% or saline placebo) at the anteromedial aspect of the common femoral artery at the level of the inguinal crease under ultrasound guidance. Both groups received preoperative popliteal sciatic and saphenous nerve blocks for analgesia and a standardized general anesthetic. Esmolol was administered if systolic blood pressure rose >30% above baseline. Incidence of TH was the primary outcome. RESULTS: TH was present in 93.3% of sham patients versus 33.3% of block patients. Mean systolic pressure at 120 min and 150 min of tourniquet time was significantly higher in the sham group compared with the block group. Esmolol requirement (95.3+107.6 v 8.0+14.2, p=<0.001) was also significantly higher in the sham group. No differences were noted in pain scores or opioid consumption, and no patient experienced sensory or motor block of the femoral nerve. DISCUSSION: Under these experimental conditions, injection of local anesthetic around the femoral artery reduced the incidence of TH and intraoperative esmolol requirement. TRIAL REGISTRATION NUMBER: www.clinicaltrials.gov (NCT03390426; December 28, 2017).

Transversus Abdominis Plane Block With Liposomal Bupivacaine for Pain After Cesarean Delivery in a Multicenter, Randomized, Double-Blind, Controlled Trial.

BACKGROUND: In women undergoing cesarean delivery under spinal anesthesia with intrathecal morphine, transversus abdominis plane (TAP) block with bupivacaine hydrochloride (HCl) may not improve postsurgical analgesia. This lack of benefit could be related to the short duration of action of bupivacaine HCl. A retrospective study reported that TAP block with long-acting liposomal bupivacaine (LB) reduced opioid consumption and improved analgesia following cesarean delivery. Therefore, we performed a prospective multicenter, randomized, double-blind trial examining efficacy and safety of TAP block with LB plus bupivacaine HCl versus bupivacaine HCl alone. METHODS: Women (n = 186) with term pregnancies undergoing elective cesarean delivery under spinal anesthesia were randomized (1:1) to TAP block with LB 266 mg plus bupivacaine HCl 50 mg or bupivacaine HCl 50 mg alone. Efficacy was evaluated in a protocol-compliant analysis (PCA) set that was defined a priori. The primary end point was total postsurgical opioid consumption (oral morphine equivalent dosing [MED]) through 72 hours. Pain intensity was measured using a visual analog scale. Adverse events (AEs) after treatment were recorded through day 14. RESULTS: Total opioid consumption through 72 hours was reduced with LB plus bupivacaine HCl versus bupivacaine HCl alone (least squares mean [LSM] [standard error (SE)] MED, 15.5 mg [6.67 mg] vs 32.0 mg [6.25 mg]). This corresponded to an LSM treatment difference of -16.5 mg (95% confidence interval [CI], -30.8 to -2.2 mg; P = .012). The area under the curve of imputed pain intensity scores through 72 hours supported noninferiority of LB plus bupivacaine HCl versus bupivacaine HCl alone (LSM [SE], 147.9 [21.13] vs 178.5 [19.78]; LSM treatment difference, -30.6; 95% CI, -75.9 to 14.7), with a prespecified noninferiority margin of 36 (P = .002). In an analysis of all treated patients, including those not meeting criteria for inclusion in the PCA, there was no difference in postsurgical opioid consumption between groups. In the LB plus bupivacaine HCl group, 63.6% of patients experienced an AE after treatment versus 56.2% in the bupivacaine HCl-alone group. Serious AEs after treatment were rare (≈3% in both groups). CONCLUSIONS: TAP block using LB plus bupivacaine HCl as part of a multimodal analgesia protocol incorporating intrathecal morphine resulted in reduced opioid consumption after cesarean delivery in the PCA set. Results suggest that with correct TAP block placement and adherence to a multimodal postsurgical analgesic regimen, there is an opioid-reducing benefit of adding LB to bupivacaine TAP blocks after cesarean delivery (ClinicalTrials.gov identifier: NCT03176459).

Does Ultrasonographic Measurement of Gastric Content Influence Airway Management Decisions?

The presence of gastric content before induction of general anesthesia is the primary modifiable risk factor in the prevention of pulmonary aspiration. The purpose of this project was to determine if ultrasonography could be routinely used to measure gastric content and assign aspiration risk in patients undergoing general anesthesia. Preoperative gastric ultrasonography was performed in a convenience sample of 100 patients. A group of Certified Registered Nurse Anesthetists, anesthesia residents, and anesthesiologists were asked their plan for airway management before and after receiving the results of the patients' gastric ultrasonogram, to determine if the scan would alter the plan. In 14% of patients scanned, solid gastric content was observed, 7% had clear liquids present, and 79% had an empty stomach. Of the patients with clear liquids present, 3 had substantial (> 100 mL) gastric content despite following fasting guidelines. Overall, there was a 9% change in airway management from standard induction: 6% changed to modified rapid sequence intubation (no ventilation, no cricoid pressure), and 3% changed to rapid sequence intubation with cricoid pressure. The number of changes to the airway management plan and identification of several patients with substantial gastric content demonstrate the value of preoperative gastric ultrasonography in airway management decision making.

A protocol to reduce self-reported pain scores and adverse events following lumbar punctures in older adults.

OBJECTIVE: Lumbar punctures (LPs) are important for obtaining CSF in neurology studies but are associated with adverse events and feared by many patients. We determined adverse event rates and pain scores in patients prospectively enrolled in two cohort studies who underwent LPs using a standardized protocol and 25 g needle. METHODS: Eight hundred and nine LPs performed in 262 patients age ≥ 60 years in the MADCO-PC and INTUIT studies were analyzed. Medical records were monitored for LP-related adverse events, and patients were queried about subjective complaints. We analyzed adverse event rates, including headaches and pain scores. RESULTS: There were 22 adverse events among 809 LPs performed, a rate of 2.72% (95% CI 1.71-4.09%). Patient hospital stay did not increase due to adverse events. Four patients (0.49%) developed a post-lumbar puncture headache (PLPH). Twelve patients (1.48%) developed nausea, vasovagal responses, or headaches that did not meet PLPH criteria. Six patients (0.74%) reported lower back pain at the LP site not associated with muscular weakness or paresthesia. The median pain score was 1 [0, 3]; the mode was 0 out of 10. CONCLUSIONS: The LP protocol described herein may reduce adverse event rates and improve patient comfort in future studies.

Brachial Plexus Block with Liposomal Bupivacaine for Shoulder Surgery Improves Analgesia and Reduces Opioid Consumption: Results from a Multicenter, Randomized, Double-Blind, Controlled Trial.

OBJECTIVE: The utility of single-injection and continuous peripheral nerve blocks is limited by short duration of analgesia and catheter-related complications, respectively. This double-blind, multicenter trial evaluated the efficacy, safety, and pharmacokinetics of single-injection, ultrasound-guided brachial plexus block (BPB) with liposomal bupivacaine (LB) added to a standardized pain management protocol for shoulder surgery. METHODS: Adults undergoing total shoulder arthroplasty or rotator cuff repair were randomized to receive LB 133 mg, LB 266 mg (pharmacokinetic and safety analyses only), or placebo, added to a standardized analgesia protocol. The primary end point was area under the curve (AUC) of visual analog scale pain intensity scores through 48 hours postsurgery. Secondary end points were total opioid consumption, percentage of opioid-free patients, and time to first opioid rescue through 48 hours. Pharmacokinetic samples were collected through 120 hours and on days 7 and 10. Adverse events were documented. RESULTS: One hundred fifty-five patients received treatment (LB 133 mg, N = 69; LB 266 mg, N = 15; placebo, N = 71). BPB with LB 133 mg was associated with significantly improved AUC of pain scores (least squares mean [SE] = 136.4 [12.09] vs 254.1 [11.77], P < 0.0001), opioid consumption (least squares mean [SE] = 12.0 [2.27] vs 54.3 [10.05] mg, P < 0.0001), median time to opioid rescue (4.2 vs 0.6 h, P < 0.0001), and percentage of opioid-free patients (treatment difference = 0.166, 95% confidence interval = 0.032-0.200, P = 0.008) through 48 hours vs placebo. Adverse event incidence was comparable between groups. CONCLUSIONS: Single-injection BPB with LB 133 mg provided analgesia through 48 hours postsurgery with reduced opioid use compared with placebo after shoulder surgery.

Use of Near-Infrared Spectroscopy to Measure Tissue Oxygen Saturation During Total Knee Arthroplasty With Use of a Tourniquet.

The primary purpose of this proof-of-concept quality improvement effort was to evaluate the practicality of using near-infrared spectroscopy (NIRS) to measure tissue oxygen saturation (Sto2) during total knee arthroplasty (TKA) with use of a tourniquet. NIRS sensors were applied to the biceps femoris (BF) and gastrocnemius (GS) muscles of both lower extremities of patients undergoing TKA procedures. For a convenience sample of 15 patients, measurement of Sto2 was attempted at baseline, following subarachnoid block administration, and after tourniquet inflation and deflation. Mean baseline Sto2 (SD) was 71% (6%) in the BF muscle and 66% (7%) in the GS muscle. Significant changes in Sto2 values were observed following subarachnoid block, tourniquet inflation, and tourniquet deflation. The Sto2 returned to or above baseline in the BF muscle but did not return to baseline in the GS muscle following tourniquet deflation. Changes in tissue oxygen saturation resulting from use of a tourniquet can be continuously monitored with the use of an NIRS device. Further evaluation of the use of NIRS should be undertaken to determine if it could be used to guide safe duration and pressure limits for tourniquet inflation.

Multimodal Analgesia in Breast Surgical Procedures: Technical and Pharmacological Considerations for Liposomal Bupivacaine Use.

Enhanced recovery after surgery is a multidisciplinary perioperative clinical pathway that uses evidence-based interventions to improve the patient experience as well as increase satisfaction, reduce costs, mitigate the surgical stress response, accelerate functional recovery, and decrease perioperative complications. One of the most important elements of enhanced recovery pathways is multimodal pain management. Herein, aspects relating to multimodal analgesia following breast surgical procedures are discussed with the understanding that treatment decisions should be individualized and guided by sound clinical judgment. A review of liposomal bupivacaine, a prolonged-release formulation of bupivacaine, in the management of postoperative pain following breast surgical procedures is presented, and technical guidance regarding optimal administration of liposomal bupivacaine is provided.

Pectoral Fascial (PECS) I and II Blocks as Rescue Analgesia in a Patient Undergoing Minimally Invasive Cardiac Surgery.

INTRODUCTION: Patients undergoing minimally invasive cardiac surgery have the potential for significant pain from the thoracotomy site. We report the successful use of pectoral nerve block types I and II (Pecs I and II) as rescue analgesia in a patient undergoing minimally invasive mitral valve repair. CASE REPORT: In this case, a 78-year-old man, with no history of chronic pain, underwent mitral valve repair via right anterior thoracotomy for severe mitral regurgitation. After extubation, he complained of 10/10 pain at the incision site that was minimally responsive to intravenous opioids. He required supplemental oxygen because of poor pulmonary mechanics, with shallow breathing and splinting due to pain, and subsequent intensive care unit readmission. Ultrasound-guided Pecs I and II blocks were performed on the right side with 30 mL of 0.2% ropivacaine with 1:400,000 epinephrine. The blocks resulted in near-complete chest wall analgesia and improved pulmonary mechanics for approximately 24 hours. After the single-injection blocks regressed, a second set of blocks was performed with 266 mg of liposomal bupivacaine mixed with bupivacaine. This second set of blocks provided extended analgesia for an additional 48 hours. The patient was weaned rapidly from supplemental oxygen after the blocks because of improved analgesia. CONCLUSIONS: Pectoral nerve blocks have been described in the setting of breast surgery to provide chest wall analgesia. We report the first successful use of Pecs blocks to provide effective chest wall analgesia for a patient undergoing minimally invasive cardiac surgery with thoracotomy. We believe that these blocks may provide an important nonopioid option for the management of pain during recovery from minimally invasive cardiac surgery.

Essentials of Our Current Understanding: Abdominal Wall Blocks.

Abdominal wall blocks rely on the spread of local anesthetic within musculofascial planes to anesthetize multiple small nerves or plexuses, rather than targeting specific nerve structures. Ultrasonography is primarily responsible for the widespread adoption of techniques including transversus abdominis plane and rectus sheath blocks, as well as the introduction of novel techniques such as quadratus lumborum and transversalis fascia blocks. These blocks are technically straightforward and relatively safe and reduce pain and opioid requirements in many clinical settings. The data supporting these outcomes, however, can be inconsistent because of heterogeneity of study design. The extent of sensory blockade is also somewhat variable, because it depends on the achieved spread of local anesthetic and the anatomical course of the nerves being targeted. The blocks mainly provide somatic analgesia and are best used as part of a multimodal analgesic regimen. This review summarizes the anatomical, sonographic, and technical aspects of the abdominal wall blocks in current use, examining the current evidence for the efficacy and safety of each.

Time to Analgesia Onset and Pharmacokinetics After Separate and Combined Administration of Liposome Bupivacaine and Bupivacaine HCl: Considerations for Clinicians.

BACKGROUND: Liposome bupivacaine is a prolonged-release bupivacaine formulation indicated for single-dose administration into the surgical site to produce postsurgical analgesia. METHODS: An overview of time to onset of analgesia observed with liposome bupivacaine in human studies is provided, as well as a summary of data from pharmacokinetic studies including those that assessed pharmacokinetics after separate versus coadministration of liposome bupivacaine and bupivacaine HCl. RESULTS: Data from multiple studies show that local administration of liposome bupivacaine is associated with rapid onset and effective analgesia after surgery. However, the efficacy profile observed in controlled settings may not replicate the profile observed in clinical practice; time to onset may be impacted by nonpharmacologic factors, such as amount of drug given, location and relative vascularity, and variances in surgical techniques. Some clinicians coadminister or admix bupivacaine HCl and liposome bupivacaine based on the supposition that adjuvant use will result in more rapid onset of efficacy. To date, no clinical studies have been conducted comparing pain-related outcomes following coadministration versus liposome bupivacaine alone. Preclinical pharmacokinetic studies have assessed the potential impact of combined use, which resulted in predictable, additive systemic exposure without compromising the prolonged-release profile of liposome bupivacaine, and without signs of toxicity. CONCLUSION: Based on available data and approved package insert, in the setting of wound infiltration, clinicians have the flexibility to administer liposome bupivacaine alone, coadminister separately with bupivacaine HCl, or admix with bupivacaine HCl prior to injection, providing the bupivacaine HCl dose does not exceed 50% of the liposome bupivacaine dose.