Bupivacaine HCl Research Articles

Entrapping bupivacaine-loaded emulsions in a crosslinked-hydrogel increases anesthetic effect and duration in a rat sciatic nerve block model.

The purpose of this research was to evaluate a novel long-acting bupivacaine delivery system for control of postoperative pain. Bupivacaine-loaded lipid emulsion (BLE) droplets were created by high-speed homogenization. The BLE droplets were then entrapped into a crosslinked-hyaluronic acid hydrogel system to create an injectable composite gel formulation (HA-BLE). Dynamic light scattering, rheological, and drug release techniques were used to characterize the formulations. A rat sciatic nerve block with a thermal nociceptive assay was used to evaluate the anesthetic effect in comparison to controls, bupivacaine HCl and liposomal bupivacaine. The BLE droplets had a zeta potential, droplet size, and polydispersity index of -40.8±0.66mV, 299±1.77nm, and 0.409±0.037, respectively. The HA-BLE formulation could be injected through 25g needles and had an elastic modulus of 372±23.7Pa. Approximately 80% and 100% of bupivacaine was released from the BLE and HA-BLE formulations by 20 and 68h, respectively. The HA-BLE formulation had a 5-times greater anesthetic area under the curve and an anesthetic duration that was twice as long as controls. Results indicate that incorporating the BLEs into the hydrogel significantly increased anesthetic effect by protecting the BLE droplets from the in vivo environment.

Neurotoxicity of bupivacaine and liposome bupivacaine after sciatic nerve block in healthy and streptozotocin-induced diabetic mice

BackgroundLong-acting local anaesthetics (e.g. bupivacaine hydrochloride) or sustained-release formulations of bupivacaine (e.g. liposomal bupivacaine) may be neurotoxic when applied in the setting of diabetic neuropathy. The aim of the study was to assess neurotoxicity of bupivacaine and liposome bupivacaine in streptozotocin (STZ) - induced diabetic mice after sciatic nerve block. We used the reduction in fibre density and decreased myelination assessed by G-ratio (defined as axon diameter divided by large fibre diameter) as indicators of local anaesthetic neurotoxicity.ResultsDiabetic mice had higher plasma levels of glucose (P < 0.001) and significant differences in the tail flick and plantar test thermal latencies compared to healthy controls (P < 0.001). In both diabetic and nondiabetic mice, sciatic nerve block with 0.25% bupivacaine HCl resulted in a significantly greater G-ratio and an axon diameter compared to nerves treated with 1.3% liposome bupivacaine or saline (0.9% sodium chloride) (P < 0.01). Moreover, sciatic nerve block with 0.25% bupivacaine HCl resulted in lower fibre density and higher large fibre and axon diameters compared to the control (untreated) sciatic nerves in both STZ-induced diabetic (P < 0.05) and nondiabetic mice (P < 0.01). No evidence of acute or chronic inflammation was observed in any of the treatment groups.ConclusionsIn our exploratory study the sciatic nerve block with bupivacaine HCl (7 mg/kg), but not liposome bupivacaine (35 mg/kg) or saline, resulted in histomorphometric indices of neurotoxicity. Histologic findings were similar in diabetic and healthy control mice.

A prospective randomized trial comparing liposomal bupivacaine vs standard bupivacaine wound infiltration in open gynecologic surgery on an enhanced recovery pathway

Value in healthcare is reflected by patient-centered outcomes of care per health dollar expended. Although liposomal bupivacaine is more expensive, it has been shown to provide prolonged analgesia (up to 72 hours). This study aimed to evaluate whether the addition of liposomal bupivacaine to standard bupivacaine could decrease opioid intake and improve pain control after laparotomy for gynecologic surgery compared with standard bupivacaine alone in an enhanced recovery after surgery pathway. A prospective randomized controlled single-blinded trial of wound infiltration with liposomal bupivacaine plus 0.25% bupivacaine (study arm) vs 0.25% bupivacaine (control arm) was performed at a National Cancer Institute-designated tertiary referral cancer center. Participants were patients aged ≥18 years undergoing exploratory laparotomy for a gynecologic indication. All patients were treated on an enhanced recovery pathway including local wound infiltration before closure. In this study, 266 mg of liposomal bupivacaine (free base; equal to 300 mg bupivacaine HCL)+150 mg of bupivacaine mixed in the same syringe was used in the study arm, and 150 mg of bupivacaine was used in the control arm. The primary outcome was the proportion of patients who were opioid-free within 48 hours after surgery. Secondary outcomes included number of opioid-free days from postoperative day 0 to postoperative day 3, days to first opioid administration, morphine equivalent daily dose, and patient-reported outcomes collected with the MD Anderson Symptom Inventory. The MD Anderson Symptom Inventory was administered as a preoperative baseline, daily while hospitalized, and at least weekly for 8 weeks after discharge. All outcomes were prespecified before data collection. In this study, 102 patients were evaluated. Among them, 16.7% of patients in the study arm received no opioids up to 48 hours compared with 14.8% in the control arm (P=.99). There were no significant differences in the amount of intraoperative opioids administered or days to first opioid use. There was no significant difference between the 2 arms in median cumulative morphine equivalent daily dose (21.3 [study arm] vs 33.8 [control arm]; P=.36) or between the groups in morphine equivalent daily dose per individual day. There were no significant differences in patient-reported pain or interference with walking between the 2 arms or other patient-reported outcomes. Within an enhanced recovery after surgery pathway, adding liposomal bupivacaine to 0.25% bupivacaine wound infiltration did not decrease the proportion of patients who were opioid-free within 48 hours after surgery, did not decrease opioid intake, or did not improve patient's self-reported pain and functional recovery compared with standard bupivacaine.

Comparison of analgesic and tissue effects of subcutaneous perineural injection of liposomal bupivacaine and bupivacaine hydrochloride in horses with forelimb lameness induced via circumferential clamp.

To evaluate the analgesic and tissue effects of liposomal bupivacaine administered SC as an abaxial sesamoid nerve block in horses with experimentally induced lameness. 6 healthy mature light-breed horses. In a randomized crossover study, a circumferential hoof clamp was applied to a forelimb to induce reversible lameness. An abaxial sesamoid nerve block of the lame forelimb was performed by SC perineural injection of 10 mg of liposomal bupivacaine or bupivacaine HCl/site. Quantitative gait data were objectively obtained with a body-mounted inertial sensor system before (baseline) and at 30-minute intervals after treatment. Time to return to 85% of baseline lameness was determined. After a minimum 4-day washout period, procedures were repeated with the alternate limb and treatment. Lastly, the palmar digital nerves and perineural tissues were collected and examined histologically. SC perineural injection of liposomal bupivacaine ameliorated forelimb lameness in 5 of 6 horses. The median duration of analgesia was not significantly different between liposomal bupivacaine (4.5 hours) and bupivacaine HCl (3.0 hours). Histologically, mild inflammation was noted in 3 of 10 sites injected with liposomal bupivacaine and in none of the sites injected with bupivacaine HCl. SC perineural injection of 10 mg of liposomal bupivacaine/site ameliorated experimentally induced forelimb lameness in some horses. At milligram-equivalent doses, liposomal bupivacaine had a similar duration of analgesia to that of bupivacaine HCl. Further investigation is required before recommending clinical use of liposomal bupivacaine for nerve blocks in horses.

PAIN trial: phase II, single-center, double-blinded RCT comparing the efficacy of high dose of liposomal bupivacaine and standard bupivacaine periarticular injection in relieving immediate postoperative pain after total knee arthroplasty. Study protocol

Introduction: Anesthetic strategies to improve postoperative pain management after Total Knee Arthroplasty (TKA) include multimodal pain management to minimize opiate requirements. Postoperatively, subcutaneous standard bupivacaine HCl is often used. Recent studies have suggested that high dose liposomal bupivacaine may result in improved outcomes. Objectives: This study aims to compare periarticular injection of 399mg (high dose) Liposomal Bupivacaine to Standard Bupivacaine in patients undergoing Total Knee Arthroplasty. Methods: We propose a phase II, single-institution, randomized, controlled, double-blinded, superiority trial with two parallel arms with a 1:1 allocation ratio. The two arms of the study will be standard bupivacaine and liposomal bupivacaine at 399mg dose. We will include patients with age >50 years, with primary knee osteoarthritis requiring TKA, ASA status 1 and 2, without opioid consumption in the last 3 months, and with signed informed consent. Exclusion criteria are history of substance abuse, uncontrolled psychiatric disorder, hepatic cirrhosis, renal failure, rheumatoid arthritis, immune arthritis, post-traumatic osteoarthritis, active malignancy or oncologic disease, pregnancy, synchronic surgical intervention, and morbid obesity with Body Mass Index (BMI) equal or greater than 40kg/m2. The primary outcome is time to first opioid rescue. Secondary outcomes include total opioid consumption, VAS scale, adverse events, GROC score, arc of motion, bupivacaine serum levels, length of stay, and mobilization. Discussion: Improving total knee arthroplasty postoperative pain without opioids decreases opioid-related side effects, reduces costs, and improves outcomes. By decreasing opiate use and complications related to them, Liposomal Bupivacaine may improve patient satisfaction as well as functional outcomes.

ROLE OF LOCAL INFILTRATION OF INJECTION BUPIVACAINE IN REDUCING EARLY POST-OPERATIVE PAIN

ABSTRACT:&#x0D; BACKGROUND &amp; OBJECTIVE:&#x0D; Intolerable morbidity occurs after major thoracic, orthopedic or abdominal surgeries due to post-operative pain. Inadequately controlled pain leads to patient displeasure and major morbidities like postoperative pulmonary dysfunctions and cardiac ischemic changes. Various techniques are presently used to treat this pain and opiods are the most regularly used medications by parenteral or neuraxial route. Intolerable morbidity occurs post-operatively due to inadequately controlled pain. The objective of this study was to compare the mean pain scores in patients undergoing laparotomy with and without local infiltration of injection bupivacaine at surgical incision site in post-operative period.&#x0D; METHODOLOGY: This randomized controlled trial was conducted at surgical department Allied hospital Faisalabad from June 2017 to December 2017.Total 80 patient were included in this study that were randomly divided into two groups using random number tables. In post-operative period, patients of both groups were given treatment as per requirement of their respective diseases. They received a baseline analgesia using Inj. Toradol (ketorolac) 30mg/1ml intravenously every 8 hours, first dose given during the surgery. The study group was additionally given 10ml Inj. Bupivacaine HCl 0.5% diluted with 10ml saline injected into the subcutaneous plane around the incision immediately after the closure of skin and time was noted. No further difference in the treatment of patients of both groups required for the purpose of this study. The patients in both groups were compared for the degree of pain experienced by them in early post-operative period. This information was collected using Numeric pain scale, 10 being worst pain and 1 meaning least appreciable pain. These assessments were done 2 and 4 hours after surgery.&#x0D; RESULTS: We recorded pain score 3.0+0.75 in study and 5.2+0.72 in control group, p-value was &lt; 0.001 showing a significant difference.&#x0D; CONCLUSION: We concluded that there is significantly lower pain in patients infiltrated with injection bupivacaine around surgical incision in early post-operative period as compared to those who had only intravenous analgesics.

Bupivacaine Extended-Release Liposomal Injection Versus Bupivacaine HCl for Early Postoperative Pain Control Following Wrist Operations: A Prospective, Randomized Control Trial

This study evaluated pain control after wrist operations using a long-acting local anesthetic, liposomal bupivacaine, compared with the standard local anesthetic, bupivacaine HCl. Patients undergoing elective carpometacarpal joint arthroplasty and proximal row carpectomy were eligible. Those meeting inclusion criteria were enrolled before surgery and were randomized to receive an intraoperative injection of liposomal bupivacaine or bupivacaine HCl. Primary outcomes included intraoperative and postoperative opioid requirements and pain levels. On the first 4 postoperative days, phone contact assessed pain level by numeric rating scale, number of opioids taken in each 24-hour period, and efficacy of anesthesia and opioid side effects with overall benefit of analgesia score. Postoperative pain scores for 52 patients measured by numeric rating scale demonstrated that liposomal bupivacaine and bupivacaine HCl were similar for pain control. Painscores and opioid use were similar during the first 4 postoperative days. Opioid use on day 1 was slightly lower with liposomal bupivacaine. There were no statistically significant differences in any postoperative outcome between groups. Liposomal bupivacaine and bupivacaine HCl have similar effects in the treatment of early postoperative pain after trapeziometacarpal suspension arthroplasty and proximal row carpectomy. Neither drug demonstrated a clear advantage in this study. Therapeutic II.

Comparison of Therapeutic Benefit of Bupivacaine HCl Transversus Abdominis Plane (TAP) Block as Part of an Enhanced Recovery Pathway versus Traditional Oral and Intravenous Pain Control after Minimally Invasive Colorectal Surgery: A Prospective, Randomized, Double-Blind Trial

Enhanced recovery pathways (ERPs), when combined with transversus abdominis plane (TAP) blocks, have been proven to reduce the length of stay (LOS) and improve quality outcomes. Nonopioid pain management is an essential component of this pathway, leading to a reduction in immobility, postoperative ileus, and an increase in patient satisfaction. TAP block variations have been studied in general and gynecologic surgery. This study evaluates the effectiveness of laparoscopic TAP blocks in conjunction with the benefit of an ERP. One hundred thirty-seven consecutive laparoscopic and robotic-assisted Colorectal Surgery patients received TAP blocks under laparoscopic guidance while under anesthesia, randomized to a placebo, bupivacaine TAP block, or bupivacaine TAP block with an ERP arm of the trial. Patient demographics, operative techniques, and postoperative outcomes were analyzed using statistical analysis software. Our main objective was to determine short-term benefits of TAP blocks on reducing total narcotic consumption. Secondary objectives included effects of TAP blocks on time to ambulation, time to bowel function, and LOS. To isolate the effect of the TAP blocks, no efforts were made to control nursing or patient education in patients managed without an ERP. Of 137 patients, 14 were withdrawn. All cases were elective, with the main diagnosis colon cancer or dysplastic polyps (47.1%). The median age in each group was comparable (P = 0.12), with female majority in both groups (58.5%). Most procedures were segmental colon resections (74.7%). Thirty-one patients received a placebo, 41 bupivacaine TAP, and 51 bupivacaine TAP plus ERP. In terms of primary endpoints, the bupivacaine plus ERP arm used statistically significant less IV narcotics on postoperative day 1 and in total (P = 0.001, P = 0.008). All patients ambulated on average within the first 24 hours postoperatively, with the TAP plus ERP group approximately 0.5 days sooner (P = 0.001). The TAP plus ERP group also had a return of bowel function and LOS approximately 24 hours early (P = 0.001 and P = 0.001). This study shows that a laparoscopically placed bupivacaine TAP block when used as part of an ERP can reduce LOS, postoperative narcotics, time to ambulation and bowel function, and LOS. Defined pain regimens with auxiliary staff teaching can add to the improvement in quality outcomes in laparoscopic colorectal surgery and, with the addition of the TAP block, can add to patient satisfaction and lower hospital costs.

Liposomal encapsulated bupivacaine provides longer duration analgesia than bupivacaine HCl when administered as an abaxial sesamoid block in horses

Liposomal encapsulated bupivacaine provides longer duration analgesia than bupivacaine HCl when administered as an abaxial sesamoid block in horses

Laparoscopic-assisted Transversus Abdominis Plane (TAP) Block in Patient Undergoing Laparoscopic Gynecologic Surgery: Randomized Controlled Trial

Study Objective To compare the analgesic efficacy of laparoscopic-assisted posterior Transversus Abdominis Plane (TAP) block versus lateral TAP block for post-operative pain control in patients undergoing laparoscopic gynecologic surgeries. Design Prospective randomized trial. Setting Patients undergoing laparoscopic/robotic gynecology surgeries. Patients or Participants 80 patients were randomly assigned to laparoscopic-assisted lateral (mid-axillary) TAP block and posterior TAP block. Total sample size of 80 patients with considering 10 % drop out rate, gives 85 % power (two-sided alpha =0. 05) to detect a difference of 0.7 in pain score. Interventions Laparoscopic-assisted TAP block with liposomal Bupivacaine and Bupivacaine HCL 0.5% mixed in ratio of 1:2 in milligram. We randomized patients posterior approach injection was applied in triangle of petit versus in lateral TAP block injection was performed in mid axillary line between iliac crest and lower coastal margin. Opioid consumption and Numeric Pain Rating Score (NPRS 0 to 10) were recorded at 6, 12, 24, 48 and 72 hours post-operatively. Measurements and Main Results patients in the posterior TAP block group was older than the lateral TAP block group (P-Value: 0.03). There was no difference in terms of race, BMI, ASA classification and comorbidities between two groups. Length of surgery was longer in lateral group (P-value: 0.02). There was no difference in terms of type of procedure. Patients in posterior group had less pain score at 6 h, 12h, 24h, 48h and 72 h post-operative, and they significantly used less narcotic during the first 3 days after surgery (p-value:0.009) Conclusion Laparoscopic-assisted TAP block is a new and safe technique for multimodal pain management. Posterior TAP block provides better analgesia than lateral TAP block for laparoscopy gynecologic surgeries. Posterior TAP block significantly reduces the total amount of narcotics used by patients in post-operative course.

Role of the G-Protein-Coupled Receptor Signaling Pathway in Insecticide Resistance

The G-protein-coupled receptor (GPCR) regulated intracellular signaling pathway is known to be involved in the development of insecticide resistance in the mosquito, Culex quinquefasciatus. To elucidate the specific role of each effector in the GPCR regulating pathway, we initially expressed a GPCR, G-protein alpha subunit (Gαs), adenylate cyclase (AC), and protein kinase A (PKA) in insect Spodoptera frugiperda (Sf9) cells and investigated their regulation function on cyclic AMP (cAMP) production and PKA activity. GPCR, Gαs, and AC individually expressed Sf9 cells showed higher cAMP production as the expression of each effector increased. All the effector-expressed cell lines showed increased PKA activity however. Moreover, Sf9 cytochrome P450 gene expression and cell tolerance to permethrin were examined. The relative expression of CYP9A32gene in Sf9 cells tested was significantly increased in all effector-expressed cell lines compared to a control cell line; these effector-expressed cell lines also showed significantly higher tolerance to permethrin. Inhibitor treatments on each effector-expressed cell line revealed that Bupivacaine HCl and H89 2HCl robustly inhibited cAMP production and PKA activity, respectively, resulting in decreased tolerance to permethrin in all cell lines. The synergistic functions of Bupivacaine HCl and H89 2HCl with permethrin were further examined in Culex mosquito larvae, providing a valuable new information for mosquito control strategies.

Surgical site infiltration: A neuroanatomical approach.

Local anaesthetic administration into a surgical wound blocks the noxious stimuli that result from surgical insult at the site of origin. Surgical site infiltration (also known as local infiltration analgesia) is easy to perform, safe and inexpensive. In addition, it avoids motor blockade, which is particularly relevant for lower limb surgery. The best approach to surgical site infiltration includes meticulous, systematic and extensive surgical site local anaesthetic infiltration in the various tissue planes under direct visualisation before closure of the surgical wound. Local anaesthetic solutions that could be used include bupivacaine HCl, ropivacaine or liposomal bupivacaine diluted with preservative-free normal (0.9%) saline to a total volume depending on the size of the incision. Bupivacaine and ropivacaine are sometimes combined with additives, which have controversial benefits. Continuous wound infusion with preperitoneal wound catheters is an effective pain modality in abdominal surgery and can be used as an alternative for neuraxial analgesia. It is essential that surgical site infiltration is combined with other non-opioid analgesics such as paracetamol and non-steroidal anti-inflammatory drugs to attain the maximum analgesic efficacy.

A Comparative Study of Plain and Hyperbaric Solutions of Bupivacaine HCl During Spinal Anaesthesia

A Comparative Study of Plain and Hyperbaric Solutions of Bupivacaine HCl During Spinal Anaesthesia

Local Infiltration Analgesia With Liposomal Bupivacaine Improves Early Outcomes After Total Knee Arthroplasty: 24-Hour Data From the PILLAR Study

BackgroundEnhanced postoperative care pathways have shifted total knee arthroplasty (TKA) to outpatient and short-stay settings, placing greater emphasis on predischarge outcomes. In this study, we report prespecified secondary and tertiary end points of the PILLAR study within 24 hours after TKA in patients receiving local infiltration analgesia (LIA) with or without liposomal bupivacaine (LB). MethodsPatients with knee osteoarthritis were randomized 1:1 to receive LIA with LB 266 mg/20 mL admixed with bupivacaine HCl 0.5% 20 mL (n = 70) or bupivacaine HCl alone (n = 69). End points (0-24 hours postsurgery) were proportion of opioid-free patients, opioid consumption, areas under the curve of visual analog scale pain intensity scores, patient satisfaction, discharge readiness, and ambulation. Safety was also assessed. ResultsPatients receiving LIA with LB were 16% less likely to require opioid rescue within 24 hours postsurgery (17.1% vs 1.4%; relative risk, 0.085; 95% confidence interval, 0.011-0.633). LIA with LB was associated with a 91% reduction in opioid consumption (P = .0009) and 19% reduction in pain intensity (P = .0142). Significantly more patients receiving LB were discharge ready (42.9% vs 27.5%; P = .0449) and satisfied with pain treatment (84.6% vs 69.2%; P = .0306). A numerically lower but not significantly different proportion achieved steady gait/no dizziness with LIA with LB (42.9% vs 52.2%). Adverse event incidence was similar between groups. ConclusionLIA with LB 266 mg plus bupivacaine HCl significantly reduced opioid requirements and pain intensity and significantly improved discharge readiness and satisfaction 0-24 hours after TKA compared with bupivacaine HCl alone. These findings support the use of LIA with LB for TKA when early discharge is the goal.

Safety and Efficacy of Bupivacaine HCl Collagen-Matrix Implant (INL-001) in Open Inguinal Hernia Repair: Results from Two Randomized Controlled Trials.

IntroductionSurgical site infiltration with bupivacaine results in short-lived analgesia. The MATRIX-1 and MATRIX-2 studies examined the efficacy and safety of the bioresorbable bupivacaine HCl collagen-matrix implant (INL-001) for postsurgical pain after open inguinal hernia repair. INL-001, designed to provide early and extended delivery of bupivacaine, provides prolonged duration of perioperative analgesia.MethodsIn two phase 3 double-blind studies [MATRIX-1 (ClinicalTrials.gov identifier, NCT02523599) and MATRIX-2 (ClinicalTrials.gov identifier, NCT02525133)], patients undergoing open tension-free mesh inguinal hernia repair were randomized to receive 300-mg bupivacaine (three INL-001 100-mg bupivacaine HCl collagen-matrix implants) (MATRIX-1 n = 204; MATRIX-2 n = 213) or three placebo collagen-matrix implants (MATRIX-1 n = 101; MATRIX-2 n = 106) during surgery. Postsurgical medication included scheduled acetaminophen and as-needed opioids.ResultsPatients who received INL-001 in both studies reported statistically significantly lower pain intensity (P ≤ 0.004; primary end point) and opioid analgesic use (P < 0.0001) through 24-h post-surgery versus those who received a placebo collagen-matrix. Patients who received INL-001 reported lower pain intensity through 72 h (P = 0.0441) for the two pooled studies. In both studies, more of the patients (28–42%) who received INL-001 used no opioid medication 0–24, 0–48, and 0–72 h post-surgery versus those who received a placebo collagen-matrix (12–22%). Among patients who needed opioid medication, patients receiving INL-001 used fewer opioids than those who received a placebo collagen-matrix through 24 h in both studies (P < 0.0001) and through 48 h in MATRIX-2 (P = 0.0003). Most adverse events were mild or moderate, without evidence of bupivacaine toxicity or deleterious effects on wound healing.ConclusionThese findings indicate that INL-001 results in post-inguinal hernia repair analgesia that is temporally aligned with the period of maximal postsurgical pain and may reduce the need for opioids while offering a favorable safety profile.Trial RegistrationClinicalTrials.gov identifiers, NCT02523599; NCT02525133.FundingInnocoll Pharmaceuticals.Plain Language SummaryPlain language summary available for this article.

Infiltration Techniques for Local Infiltration Analgesia With Liposomal Bupivacaine in Extracapsular and Intracapsular Hip Fracture Surgery: Expert Panel Opinion.

Liposomal bupivacaine (LB) has demonstrated efficacy in improving pain scores and reducing opioid consumption across a variety of surgical settings, including orthopaedic surgery. However, meticulous infiltration techniques combined with a multimodal approach are important to optimizing outcomes. A panel of 4 orthopaedic surgeons and 3 anesthesiologists convened on April 1, 2017, to discuss current practices and develop a consensus statement regarding local infiltration analgesia with LB for extracapsular and intracapsular hip fracture surgery, including LB infiltration techniques. Optimizing surgical outcomes with LB in hip fracture surgery requires an understanding of the neuroanatomy of the surgical site and the pharmacology of the drug. Meticulous infiltration technique is critical to achieve optimal results with LB given its viscosity and reduced diffusion compared with bupivacaine HCl. For extracapsular procedures, a total injection volume of 120 mL is recommended, whereas intracapsular procedures typically require a lower volume (∼80 mL). In both cases, infiltration is best achieved using a 22-gauge needle and applying a tracking and/or fanning technique. To ensure optimal placement, LB should be infiltrated using multiple, small-volume (1- to 5-mL) injections spaced at 1.0-cm intervals. These consensus recommendations regarding LB infiltration techniques can serve as a resource for designing clinical studies to evaluate outcomes using periarticular infiltration of LB in extracapsular and intracapsular hip fracture surgery as part of a multimodal pain management approach. Level V.

Current Practices for Multimodal Pain Management Using Liposomal Bupivacaine in Extracapsular and Intracapsular Hip Fracture Surgery: Expert Panel Opinion.

Liposomal bupivacaine (LB) has demonstrated efficacy across a range of surgical settings, including shoulder, knee, and hip surgery. However, data are limited on the use of LB as part of a multimodal pain management approach in hip fracture surgery. On April 1, 2017, 4 orthopaedic surgeons and 3 anesthesiologists convened to discuss current practices and develop a consensus statement related to local infiltration analgesia with LB for hip fracture surgical procedures within the context of a multimodal opioid-sparing pain management approach. Separate workshops addressed intracapsular and extracapsular hip fracture surgery. Multimodal strategies before, during, and after hip fracture surgery are paramount to optimizing pain control and minimizing opioid requirements. LB infiltration should occur intraoperatively near the time of closing the incision. For both intracapsular and extracapsular procedures, oral or intravenous acetaminophen, a nonsteroidal anti-inflammatory drug (NSAID) of choice, and tramadol should be given preoperatively. Presurgical fascia iliaca block with bupivacaine HCl may help bridge the period before LB takes effect. After both procedures, patients should receive 1 dose of intravenous acetaminophen, an NSAID, and opioid rescue medication as needed, starting with tramadol. Postoperative NSAIDs may help minimize opioid use. Patient and provider education are integral to managing patient expectations and alleviating concerns about pain and opioid use. Standardized, validated, and appropriately timed pain assessments are also necessary to optimize postsurgical pain management. These consensus recommendations regarding multimodal pain management protocols incorporating local infiltration analgesia with LB for extracapsular and intracapsular hip fracture procedures serve as a basis for additional research. Level V.

Multimodal Pain Strategies Including Liposomal Bupivacaine for Isolated Acetabular Fracture Surgery.

The incidence of isolated acetabular fractures has been increasing, particularly in older adult patients. These fractures can be debilitating and may require prolonged immobilization and/or complex surgical reconstruction. Liposomal bupivacaine (LB) is a prolonged-release form of bupivacaine demonstrated to be effective in orthopaedic surgery. Defining a multimodal pain management plan, which incorporates optimized techniques for use of LB in acetabular surgery, may improve outcomes for patients. Two orthopaedic surgeons specializing in orthopaedic traumatology discussed best practices for infiltration of LB and recommendations for perioperative use of LB plus other anesthetics/analgesics for isolated acetabular fracture surgery. Consensus techniques for isolated posterior and anterior acetabular fractures were developed. LB (266 mg/20 mL) should be expanded with 50 mL of bupivacaine HCl 0.25% and saline to a total volume of 120 or 300 mL for the posterior or anterior techniques, respectively. A 3.5-inch spinal needle is inserted tangentially, infiltrating 1 mL/cm into the fracture site, periosteum, muscle fascia, subcutaneous tissue, and skin. Patients receive acetaminophen, celecoxib, gabapentin, and opioids before surgery, adjusting appropriately for patient comorbidities and potential drug-drug interactions. At the end of the surgery, before closure, LB is infiltrated and patients receive a dose of intravenous acetaminophen. Presurgical medications are continued after surgery for approximately 10-14 days, after which opioids are only considered to treat breakthrough pain. These recommendations can be used to optimize and streamline care for patients with isolated acetabular fractures and act as a foundation for additional clinical research. Therapeutic Level V.

Local sustained delivery of bupivacaine HCl from a new castor oil-based nanoemulsion system.

Bupivacaine HCl (1-butyl-2',6'-pipecoloxylidide hydrochloride), an amide local anesthetic compound, is a local anesthetic drug utilized for intraoperative local anesthesia, post-operative analgesia and in the treatment of chronic pain. However, its utility is limited by the relative short duration of analgesia after local administration (approximately 9h after direct injection) and risk for side effects. This work is aimed to develop a nanoemulsion of bupivacaine HCl with sustained local anesthetics release kinetics for improved pain management, by exhibiting extended analgesic action and providing reduced peak levels in the circulation to minimize side effects. Herein, biodegradable oils were evaluated for use in nanoemulsions to enable sustained release kinetics of bupivacaine HCl. Only with castor oil, a clear and stable nanoemulsion was obtained without the occurrence of phase separation over a period of 3months. High loading of bupivacaine HCl into the castor oil-based nanoemulsion system was achieved with about 98% entrapment efficiency and the resulting formulation showed high stability under stress conditions (accelerated stability test) regarding changes in visual appearance, drug content, and droplet size. We show herein that the in vitro release and in vivo pharmacokinetic profiles as well as pharmacodynamic outcome (pain relief test) after subcutaneous administration in rats correlate well and clearly demonstrate the prolonged release and extended duration of activity of our novel nanoformulation. In addition, the lower Cmax value achieved in the blood compartment suggests the possibility that the risk for systemic side effects is reduced. We conclude that castor oil-based nanomulsion represents an attractive pain treatment possibility to achieve prolonged local action of bupivacaine HCl.

Bupivacaine Versus Liposomal Bupivacaine For Pain Control.

Local infiltrations and regional blocks have been some of the effective ways employed to manage and control post-operative pain. One of the limitations of administration of local anesthesia drugs in post-operative conditions is its inability to act for a longer period of time. Multi-vesicular liposomes made up of bupivacaine have been progressively used for their increased duration of action. Compared to bupivacaine HCL, local infiltration of liposomal bupivacaine have shown to have a significantly increase the duration and delay in peak plasma concentration. In this article, we attempt to compare liposomal bupivacaine and bupivacaine based on available clinical literatures. Liposomal bupivacaine has been demonstrated to have promising implications in post- operative pain control resulting in increased patient satisfaction; reduced hospital admission and opioid induced adverse events. Clinical studies have identified liposomal bupivacaine to be effective in delivering increased post-operative pain control. The purpose of this review is to give a comprehensive comparison between bupivacaine liposomal and conventional bupivacaine based on reported clinical trials.