Development of an Accelerated Rotator-based Drug Release Method for the Evaluation of Bupivacaine Multivesicular Liposomes.

PURPOSE: A multivesicular liposome (MVL) is a liposomal vehicle designed to achieve sustained release characteristics for drugs with short half-lives. For example, a commercial MVL formulation of bupivacaine has been approved by the U.S. Food and Drug Administration for local and regional analgesia. For complex formulations like those containing MVLs, challenges in developing an in vitro release testing (IVRT) method may hinder generic development and regulatory approval. In this study, we developed an accelerated rotator-based IVRT method with the ability to discriminate bupivacaine MVLs with different quality attributes. METHODS: Three IVRT experimental setups including mesh tube, horizontal shaker, and vertical rotator were screened to ensure that at least 50% of bupivacaine can release from MVLs in 24 h. Sample dilution factors, incubation temperature, and the release media pH were optimized for the IVRT. The reproducibility of the developed IVRT method was validated with commercial bupivacaine MVLs. The discriminative capacity was assessed via comparing commercial and compromised bupivacaine MVL formulations. RESULTS: The rotator-based release setup was chosen due to the capability to obtain 70% of drug release within 24 h. The optimized testing conditions were chosen with a 50-fold dilution factor, a temperature of 37ºC, and a media pH of 7.4. CONCLUSIONS: An accelerated rotator-based IVRT method for bupivacaine MVLs was developed in this study, with the discriminatory ability to distinguish between formulations of different qualities. The developed IVRT method was a robust tool for generic development of MVL based formulations.

The impact of timing, type, and method of instillation of intraperitoneal local anaesthetic in laparoscopic abdominal surgery: a systematic review and network meta-analysis.

BACKGROUND: Pain is common after laparoscopic abdominal surgery. Intraperitoneal local anaesthetic (IPLA) is effective in reducing pain and opioid use after laparoscopic surgery, although the optimum type, timing, and method of administration remains uncertain. We aimed to determine the optimal approach for delivering IPLA which minimises opioid consumption and pain after laparoscopic abdominal surgery. METHODS: MEDLINE, Embase, Scopus, and Cochrane Central Register of Controlled Trials (CENTRAL) databases were systematically searched for randomised controlled trials comparing different combinations of the type (bupivacaine vs lidocaine vs levobupivacaine vs ropivacaine), timing (pre-vs post-pneumoperitoneum at the beginning or end of surgery), and method (aerosol vs liquid) of IPLA instillation in patients undergoing any laparoscopic abdominal surgery. A network meta-analysis was conducted to ascertain the optimum approach for delivering IPLA resulting in the least cumulative opioid consumption and pain (overall and localising to the shoulder) 24 h after surgery. Certainty of evidence was evaluated using Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) assessments (PROSPERO ID: CRD42022307595). RESULTS: Twenty-five RCTs were included, among which 15 different combinations of delivering IPLA were analysed across 2401 participants. Aerosolised bupivacaine instilled at the end of surgery, before deflation of the pneumoperitoneum, was associated with significantly less postoperative opioid consumption compared with all other approaches for delivering IPLA (98.7% of comparisons; moderate certainty), aside from liquid levobupivacaine instilled before surgery and during or after creation of the pneumoperitoneum (mean difference -11.6, 95% credible interval: -26.1 to 2.5 i.v. morphine equivalent doses). There were no significant differences between different IPLA approaches regarding overall pain scores and incidence of shoulder pain up to 24 h after surgery. CONCLUSIONS: There are limited studies and low-quality evidence to conclude on the optimum method of delivering IPLA in laparoscopic abdominal surgery. While aerosolised bupivacaine instilled at the end of surgery but before deflation of the pneumoperitoneum minimises postoperative opioid consumption, pain scores up to 24 h did not differ between the different modalities of delivering IPLA. The generalisability of these results is limited by the lack of utilisation of non-opioid analgesics in most trials. SYSTEMATIC REVIEW PROTOCOL REGISTRATION: PROSPERO CRD42022307595.

The use of granisetron on bupivacaine induced sciatic nerve block in rats.

PURPOSE: The effects of the 5-hydroxytryptamine (5-HT3) receptor antagonists on regional anaesthesia are complex and unclear. The present study was designed to test the hypothesis that granisetron, a selective 5-HT3 receptor antagonist, would decrease the duration of motor block, sensory block, and proprioception in a dose-dependent fashion in a rat model of bupivacaine-induced sciatic nerve blockade. MATERIALS AND METHODS: Thirty-eight male Wistar Albino rats that received unilateral sciatic nerve blocks were randomly divided into five experimental groups. Group B received a perineural of 0.3 ml of bupivacaine alone; Group BG800 received perineural 0.3 ml of bupivacaine and 800 µg of granisetron 10 min later; Group BG1200 received perineural 0.3 ml of bupivacaine and 1200 µg of granisetron 10 min later; Group BG1200IP received a perineural 0.3 ml of bupivacaine and an intraperitoneal injection of 1200 µg of granisetron 10 min later; and Group S was sham operated. A blinded investigator assessed motor, sensory and proprioception function every 10 min until the return of normal function. RESULTS: The medians for recovery times in Group B, Group BG800, Group BG1200, and Group BG1200IP were 105, 64, 85, and 120 min for motor function, respectively; 80, 64, 84, and 104 min for sensory function; 80, 63, 85, and 108 min were calculated for the proprioception function. The time to the return of normal motor, sensory, and proprioception function was not statistically significantly different between the groups (p > 0.05). Motor block did not develop in any of the rats in Group S. CONCLUSIONS: Local and systemic application of granisetron was not significantly decrease the duration of bupivacaine induced motor, sensory, and proprioception block of sciatic nerve in rat.

Pain management after thoracotomy with dexamethasone and bupivacaine through a peripleural cather: a randomized controlled trial.

INTRODUCTION: Thoracotomy procedures can result in significant pain and cause nausea/vomiting. Glucocorticoids have anti-emetic and analgesic effects due to their anti-inflammatory and nerve-blocking properties. This study investigates the additive effect of local dexamethasone with bupivacaine as sole analgesic medication through a peripleural catheter after thoracotomy. METHOD: The study was conducted as a randomized control trial on 82 patients. Participants were allocated to receive either 2.5 mg/kg of bupivacaine plus 0.2 mg/kg of dexamethasone or 2.5 mg/kg of bupivacaine plus the same amount of normal saline as placebo through a 6 French peripleural catheter implemented above the parietal pleura and beneath the musculoskeletal structure of the chest wall. The primary outcome was the severity of pain 24 h after the operation in the visual analogue scale (VAS) score. Secondary outcomes were the incidence of nausea/vomiting, opioid consumption for pain control, and incidence of any adverse effects. RESULTS: A total of 50 participants were randomized to each group, and the baseline characteristics were similar between the groups. Median of VAS score (6 (3-8) vs. 8 (6-9), p < 0.001), postoperative opioid consumption (9 (36%) vs. 17 (68%) patients, p=0.024), and median length of hospital stay (4 (3-8) vs. 6 (3-12) days, p < 0.001) were significantly lower in the dexamethasone group. However, postoperative nausea/vomiting (p=0.26 for nausea and p=0.71 for vomiting) and surgical site infection (p = 0.55) were similar between the two groups. CONCLUSION: In thoracotomy patients, administering local dexamethasone + bupivacaine through a peripleural catheter can reduce postoperative pain, analgesic consumption, and length of hospital stay. TRIAL REGISTRATION: Iranian Registry of Clinical Trials (IRCT20220309054226N1, registration date: 3/21/2022.

The 90% effective dose of intrathecal hyperbaric bupivacaine for Cesarean delivery under combined spinal-epidural anesthesia in parturients with super obesity: an up-down sequential allocation study.

PURPOSE: To determine the 90% effective dose (ED90) of intrathecal hyperbaric bupivacaine for Cesarean delivery under combined spinal-epidural anesthesia (CSE) in parturients with super obesity (body mass index [BMI] ≥ 50 kg·m-2). METHODS: We enrolled parturients with BMI ≥ 50 kg·m-2 with term, singleton vertex pregnancies undergoing elective Cesarean delivery under CSE. An independent statistician generated the 0.75% hyperbaric bupivacaine dosing regimen in increments of 0.75 mg using a biased-coin up-down sequential allocation technique. This was combined with 15 µg fentanyl, 150 µg morphine, and normal saline to a volume of 2.05 mL. The initial and maximum doses were 9.75 mg and 12 mg, respectively. Participants, clinical team, and outcome assessors were blinded to the dose. The primary outcome was block success, defined as T6 block to pinprick within ten minutes and no intraoperative analgesic supplementation within 90 min of spinal injection. We determined the ED90 using logistic regression. RESULTS: We enrolled 45 parturients and included 42 in the analysis. All doses achieved a T6 level within ten minutes, and the primary outcome occurred in 0/1 (0%) of the 9.75-mg doses, 2/3 (67%) of the 10.5-mg doses, 21/27 (78%) of the 11.25-mg doses, and 11/11 (100%) of the 12-mg doses. The ED90 of hyperbaric bupivacaine was 11.56 mg (95% confidence interval, 11.16 to 11.99). Four parturients (9.5%) had sensory level higher than T2, but none was symptomatic or required general anesthesia. CONCLUSION: The estimated ED90 of hyperbaric bupivacaine with fentanyl and morphine in parturients with super obesity undergoing Cesarean delivery under CSE was approximately 11.5 mg. STUDY REGISTRATION: ClinicalTrials.gov (NCT03781388); first submitted 18 December 2018.

RéSUMé: OBJECTIF: Notre objectif était de déterminer la dose efficace à 90 % (DE90) de bupivacaïne hyperbare intrathécale pour l'accouchement par césarienne sous péri-rachianesthésie combinée (PRC) chez les personnes parturientes atteintes de super obésité (indice de masse corporelle [IMC] ≥ 50 kg·m−2). MéTHODE: Nous avons recruté des personnes parturientes ayant un IMC ≥ 50 kg·m−2 présentant des grossesses uniques à terme, en présentation céphalique et bénéficiant d'un accouchement par césarienne programmée sous PRC. Un·e statisticien·ne indépendant·e a généré le schéma posologique de bupivacaïne hyperbare à 0,75 % par incréments de 0,75 mg à l'aide d'une technique d'allocation séquentielle en escalier. La bupivacaïne a été combinée à 15 µg de fentanyl, 150 µg de morphine et à une solution physiologique salée jusqu'à un volume de 2,05 mL. Les doses initiale et maximale étaient respectivement de 9,75 mg et 12 mg. Les participant·es, l'équipe clinique et les personnes évaluant les résultats n'avaient pas connaissance de la dose. Le critère d'évaluation principal était la réussite du bloc, définie comme un bloc à T6 à la piqûre dans les dix minutes et aucune supplémentation analgésique peropératoire dans les 90 minutes suivant l'injection rachidienne. Nous avons déterminé la DE90 à l'aide d'une méthode de régression logistique. RéSULTATS: Nous avons recruté 45 personnes parturientes et en avons inclus 42 dans l'analyse. Toutes les doses ont atteint le niveau T6 en dix minutes, et le critère d'évaluation principal a été obtenu pour 0/1 (0 %) des doses de 9,75 mg, 2/3 (67 %) des doses de 10,5 mg, 21/27 (78 %) des doses de 11,25 mg et 11/11 (100 %) des doses de 12 mg. La DE90 de bupivacaïne hyperbare était de 11,56 mg (intervalle de confiance à 95 %, 11,16 à 11,99). Quatre personnes parturientes (9,5 %) ont affiché un niveau sensoriel supérieur à T2, mais aucune n'était symptomatique ni n'a nécessité d'anesthésie générale. CONCLUSION: La DE90 estimée de bupivacaïne hyperbare avec fentanyl et morphine chez les personnes parturientes hyperobèses bénéficiant d'une césarienne sous PRC était d'environ 11,5 mg. ENREGISTREMENT DE L'éTUDE: ClinicalTrials.gov (NCT03781388); soumis pour la première fois le 18 décembre 2018.

Super-refractory status epilepticus, rhabdomyolysis, central hyperthermia and cardiomyopathy attributable to spinal anesthesia: a case report and review of literature.

BACKGROUND: There are only six past reports of super-refractory status epilepticus induced by spinal anesthesia. None of those patients have died. Only < 15 mg of bupivacaine was administered to all six of them and to our case. Pathophysiology ensuing such cases remains unclear. CASE PRESENTATION: A 27 year old gravida 2, para 1, mother at 37 weeks of gestation came to the operating theater for an elective cesarean section. She had no significant medical history other than controlled hypothyroidism and one episode of food allergy. Her current pregnancy was uneventful. Her American Society of Anesthesiologists (ASA) grade was 2. She underwent spinal anesthesia and adequate anesthesia was achieved. After 5-7 min she developed a progressive myoclonus. After delivery of a healthy baby, she developed generalized tonic clonic seizures that continued despite the induction of general anesthesia. She had rhabdomyolysis, one brief cardiac arrest and resuscitation, followed by stress cardiomyopathy and central hyperthermia. She died on day four. There were no significant macroscopic or histopathological changes in her brain that explain her super refractory status epilepticus. Heavy bupivacaine samples of the same batch used for this patient were analyzed by two specialized laboratories. National Medicines Quality Assurance Laboratory of Sri Lanka reported that samples failed to confirm United States Pharmacopeia (USP) dextrose specifications and passed other tests. Subsequently, Therapeutic Goods Administration of Australia reported that the drug passed all standard USP quality tests applied to it. Nonetheless, they have detected an unidentified impurity in the medicine. CONCLUSIONS: After reviewing relevant literature, we believe that direct neurotoxicity by bupivacaine is the most probable cause of super-refractory status epilepticus. Super-refractory status epilepticus would have led to her other complications and death. We discuss probable patient factors that would have made her susceptible to neurotoxicity. The impurity in the drug detected by one laboratory also would have contributed to her status epilepticus. We propose several possible mechanisms that would have led to status epilepticus and her death. We discuss the factors that shall guide investigators on future such cases. We suggest ways to minimize similar future incidents. This is an idiosyncratic reaction as well.

Association Between Single-Injection Regional Analgesia and Postoperative Pain in Cardiac Surgery Patients: A Single-Center Retrospective Cohort Study.

OBJECTIVES: Effective pain control after cardiac surgery may facilitate recovery. This study aimed to assess the use and association of ultrasound-guided single-injection chest wall blocks with liposomal bupivacaine on postoperative pain scores and short-term opioid requirements after cardiothoracic surgery at a single institution. DESIGN: Retrospective cohort study. SETTING: Midwestern academic hospital. PARTICIPANTS: Adult patients who underwent cardiothoracic surgery between July 1, 2020, and June 30, 2022. INTERVENTIONS: Ultrasound-guided single-injection chest wall block with liposomal bupivacaine. MEASUREMENTS AND MAIN RESULTS: Of the 1,038 patients included in this study, 301 (29%) received a perioperative nerve block for postoperative sternotomy pain, and 737 (71%) did not. Most of the single-shot blocks were bilateral parasternal intercostal plane blocks (n = 294 [98%]) performed after induction and before surgical incision (n = 280 [93%]). After adjusting for age, gender, American Society of Anesthesiologists status, select comorbidities, and surgical procedure type, mean postoperative pain scores were not significantly different between groups in the immediate postoperative period at all time points assessed (12 ± 2 hours, 24 ± 4 hours, 48 ± 8 hours, and 72 ± 12 hours). Similarly, there was no difference in mean opioid requirements (milligram morphine equivalents) at 72 hours between groups (68.6 [95% confidence interval, 56.3-83.4] vs 62.9 [95% confidence interval, 52.8-74.9], p = 0.195). CONCLUSIONS: In this retrospective study, the implementation of single-shot chest wall nerve blocks with liposomal bupivacaine was not associated with decreased postoperative pain scores or opioid consumption at 72 hours in select cardiac surgical patients at one institution.

Bupivacaine pleural effusion mimicking a hemothorax after a thoracoscopic microdiscectomy with epidural anesthesia.

PURPOSE: Post-operative pain after video-assisted thoracoscopic surgery is often treated using thoracic epidural analgesics or thoracic paravertebral analgesics. This article describes a case where a thoracic disc herniation is treated with a thoracoscopic microdiscectomy with post-operative thoracic epidural analgesics. The patient developed a bupivacaine pleural effusion which mimicked a hemothorax on computed tomography (CT). METHODS: The presence of bupivacaine in the pleural effusion was confirmed using a high performance liquid chromatography method. RESULTS: The patient underwent a re-exploration to relieve the pleural effusion. The patient showed a long-term recovery similar to what can be expected from an uncomplicated thoracoscopic microdiscectomy. CONCLUSION: A pleural effusion may occur when thoracic epidural analgesics are used in patents with a corridor between the pleural cavity and epidural space.

Intra-obturator bupivacaine injection and post-operative pain following the trans-obturator tension-free vaginal tape procedure: randomized study.

PURPOSE: To assess the effectiveness of a long-acting anesthetic injection into the obturator membrane for pain relief in women undergoing trans-obturator tension-free vaginal tape. METHODS: A total of 22 women were randomized for the intra-operative injection of bupivacaine into one of their obturator membranes: the left or right side. All the participants were asked to define their groin pain on a visual analog scale (scored 0-10 cm) at 1, 6, 12, and 24 h post-operative. For each woman, pain scores were compared between the local anesthetic-injected side and the opposite side. RESULTS: Statistically significant differences were not observed in groin pain scores between the bupivacaine injection side and the no injection side at 1 h (p = 0.76), 6 h (p = 1), 12 h (p = 0.95), and 24 h (p = 0.82) post-operative. CONCLUSION: In women who undergo trans-obturator tension-free vaginal tape procedures, intra-operative intra-obturator injection of local anesthetics is not effective in alleviating the characteristic post-operative groin pain. TRIAL REGISTRATION: This study is registered on ClinicalTrials.gov (NCT03479996).

Is transoral sphenopalatine ganglion blockade more effective on postoperative pain than endoscopic sphenopalatine ganglion blockade?

PURPOSE: In this study, we aimed to examine and compare the effects of endoscopic SPGB and transoral SPGB on postoperative pain control and patient satisfaction in patients undergoing septoplasty. METHODS: Participants were randomly divided into three groups, no blockade (n:20), endoscopic SPGB (n:20), and transoral SPGB (n:20). Those who had no blockage were included in the control group. Demographic data of patients, such as age and sex, VAS (visual analogue scale) and postoperative pain scores (PPS) [determined at arrival in the post-anesthesia care unit (PACU) and after 2, 6, 12, and 24 h], general analgesic use (24 and 168 h after surgery) and postoperative Quality of Recovery (QoR-15) values were recorded and compare them. RESULTS: The PPS PACU of 2 h, 6 h, 12 h, and 24-h values of the transoral group were lower than the endoscopic and control groups (p < 0.001).The values of 24 h and 168 h of analgesic use in the transoral group were lower than in the control and endoscopic groups (p < 0.001).The average recovery QoR-15 scores at 12 h and 24 h differed according to the groups (p < 0.001) and the highest values were in the transoral group (p < 0.001). CONCLUSION: Transoral SPGB is more effective in postoperative pain control than endoscopic SPGB, it decreases the use of postoperative analgesics and improves postoperative recovery scores.

Comparative analysis of low-dose bupivacaine and ropivacaine combined with spinal-epidural anesthesia in cesarean sections for pregnant women with coexisting mental illness.

OBJECTIVE: To analyze the application effects of low-dose bupivacaine and ropivacaine combined with epidural anesthesia. METHODS: The primary outcome measure was the anesthesia effect, assessed by the excellent anesthesia rate. Secondary outcomes included the occurrence of adverse reactions, blood pressure, and serum prolactin levels at different time points. The anesthesia effect, serum prolactin levels, occurrence of adverse reactions, and MAP at various time points [before anesthesia (T0), 5 min after anesthesia (T1), at the start of surgery (T2), at delivery of the fetus (T3), and at closure of the abdomen (T4)] were compared between the two groups. RESULTS: ① Anesthesia effect: The excellent anesthesia rate was 71.88% in the control group and 93.94% in the observation group, with a significantly higher rate in the observation group than in the control group (p = 0.017). ② Serum prolactin levels: The serum prolactin levels in both groups increased significantly after surgery compared to before surgery (p < 0.001); however, there was no statistically significant difference in serum prolactin levels between the two groups before and after surgery (p = 0.651). ③ Occurrence of adverse reactions: The occurrence rate of adverse reactions was 28.13% in the control group and 9.09% in the observation group, with a significantly lower rate in the observation group than in the control group (p = 0.048). CONCLUSION: In cesarean sections for pregnant women with coexisting mental illness, low-dose ropivacaine demonstrates significantly better anesthesia efficacy, blood pressure stability, and anesthesia safety compared to low-dose bupivacaine. Both low-dose bupivacaine and ropivacaine result in increased prolactin levels postpartum.

Does Addition of a Longer Acting Local Anesthetic Improve Postoperative Pain After Carpal Tunnel Release? A Randomized Controlled Trial.

PURPOSE: Carpal tunnel release (CTR) is a simple and effective treatment for carpal tunnel syndrome in patients who have failed nonsurgical management. This surgery is often performed in the ambulatory clinic under local anesthesia, with lidocaine, a short-acting agent. Few studies have investigated the use of longer acting agents, such as bupivacaine, for outpatient CTR. Therefore, the aim of our study was to compare the postoperative pain experience after CTR with the use of either our standard lidocaine solution (control) or a mixture consisting of lidocaine and bupivacaine in equal amounts (intervention). METHODS: Patients undergoing CTR were randomized into control or intervention groups. Postoperative pain severity and numbness were recorded at several timepoints within the first 72 hours. The timing and quantity of postoperative analgesic use (acetaminophen and/or ibuprofen) was also documented. Both patients and assessor were blinded to allocation. RESULTS: Our study cohort included 139 patients: 67 in the control group and 72 in the intervention group. Postoperative pain scores were significantly lower in the intervention group at 6 hours (2.3 vs 3.2) and 8 hours (2.9 vs 3.9). Additionally, patients in the intervention group reported longer time to first analgesic use than those in the control group (5.2 hours vs 3.7 hours). A greater proportion of patients in the intervention group reported postoperative numbness at nearly all time points, compared to the control group. CONCLUSIONS: Our study shows that a mixture of bupivacaine and lidocaine improves early postoperative pain but causes prolonged finger numbness when compared to lidocaine alone. As both medications are effective and feasible for outpatient CTR, surgeon and patient preference should guide local anesthetic choice. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic Ib.

Effect of dexmedetomidine added to retrobulbar blockade with lignocaine and bupivacaine in dogs undergoing enucleation surgery.

OBJECTIVE: To investigate the effect of the addition of dexmedetomidine (BLD) to retrobulbar blockade with combined lignocaine and bupivacaine on nociception. ANIMALS: A total of 17 eyes from 15 dogs. METHODS: Prospective, randomized, masked clinical comparison study. Dogs undergoing unilateral enucleation were randomly assigned into two groups; a retrobulbar administration of lignocaine and bupivacaine in a 1:2 volume ratio combined with either BLD or 0.9% saline (BLS). The total volume of the intraconal injection was calculated at 0.1 mL/cm cranial length. Intraoperative parameters were recorded: heart rate (HR), respiratory rate (RR), end-tidal CO2 (EtCO2 ) arterial blood pressure (BP), and inspired isoflurane concentration (ISOinsp). Pain scores, heart rate and RR were recorded postoperatively. RESULTS: Dogs receiving BLD (n = 8) had significantly lower intraoperative RR (p = 0.007), and significantly lower ISOinsp (p = 0.037) than dogs in the BLS group (n = 9). Postoperatively heart rate was significantly lower in the BLD group at 1 min (p = 0.025) and 1 h (p = 0.022). There were no other significant differences in intraoperative or postoperative parameters, or in postoperative pain scores (p = 0.354). Dogs receiving BLD had a higher rate of anesthetic events of bradycardia and hypertension (p = 0.027). Analgesic rescue was not needed in either group. CONCLUSIONS: The addition of BLD to retrobulbar anesthesia did not result in a detectable difference in pain scores relative to blockade with lignocaine and bupivacaine alone. Dogs receiving retrobulbar BLD had a significantly lower intraoperative RR and isoflurane requirement and an increased incidence of intraoperative bradycardia and hypertension.

Single Shot Interscalene Block with Liposomal Bupivacaine versus Non-Liposomal Bupivacaine in Shoulder Arthroplasty.

BACKGROUND: Regional anesthesia is a valuable component of multimodal pain control in total shoulder arthroplasty (TSA), and multiple interscalene block anesthetic options exist, including non-liposomal interscalene bupivacaine (NLIB) and liposomal interscalene bupivacaine (LIB). The purpose of the current of study was to compare pain control and opioid consumption within 48 hours postoperative in those undergoing TSA with either LIB or NLIB. METHODS: This was a retrospective cohort study at a single academic medical center including consecutive patients undergoing inpatient (>23-hour hospitalization) primary anatomic or reverse TSA from 2016 to 2020 who received either LIB or a NLIB for perioperative pain control. Perioperative patient outcomes were collected including pain levels and opioid usage, as well as 30- and 90-day ED visits or readmissions. The primary outcome was postoperative pain and opioid use. RESULTS: Overall, 489 patients were included in this study (316 LIB and 173 NLIB). Pain scores at 3, 6, 12, and 48 hours postoperatively were not statistically significantly different (p>0.05 for all). However, the LIB group had improved pain scores at 24- and 36-hours postoperative (p<0.05 all). There was no difference in the incidence of severe postoperative pain, defined as a 9 or 10 NRS-11 score, between the two anesthesia groups after adjusting for preoperative pain and baseline opioid use (OR: 1.25; 95% CI: 0.57-2.74; p=0.57). Overall, 99/316 (31.3%) of patients receiving LIB did not require any postoperative opioids compared with 38/173 (22.0%) receiving NLIB; however, this difference was not statistically significant after adjusting for prior opioid use and preoperative pain (p=0.33). No statistically significant differences in postoperative total morphine equivalents or mean daily morphine equivalents consumed between the groups were found during their hospital stays (p>0.05 for both). Finally, no significant differences in 30- and 90-day ED visits or readmission rates were found (all p>0.05). CONCLUSION: LIB and NLIB demonstrated differences in patient reported pain scores at 24- and 36-hours post operation, although these did not reach clinical significance. There were no statistically significant differences in opioid consumption during the hospital stay, including opioid use, total morphine equivalents and daily mean morphine equivalents consumed during the hospital stay. Additionally, no differences were observed in 30- and 90-day ED visits or readmission rates.

Liposomal bupivacaine versus conventional anesthetic or placebo for hemorrhoidectomy: a systematic review and meta-analysis.

BACKGROUND: Liposome bupivacaine (LB) is a long-acting anesthetic to enhance postoperative analgesia. Studies evaluating the efficacy of the LB against an active comparator (bupivacaine or placebo) on acute postoperative pain control in hemorrhoidectomy procedures are few and heterogeneous. Therefore, we performed a systematic review and meta-analysis comparing LB's analgesic efficacy and side effects to conventional/placebo anesthetic in hemorrhoidectomy patients. METHODS: We performed a systematic review and meta-analysis of randomised controlled trials investigating the use of LB after haemorrhoidectomy. We searched the literature published from the time of inception of the datasets to August 19, 2022. The electronic databases included English publications in Ovid MEDLINE In-Process & Other Non-Indexed Citations, Ovid MEDLINE, Ovid EMBASE, and Scopus. RESULTS: A total of 338 patients who underwent a hemorrhoidectomy procedure enrolled in three randomized clinical trials were included. The overall mean age was 45.84 years (SD ± 11.43), and there was a male predominance (53.55% male). In total 194 patients (52.2%) received LB and 144 (47.8%) received either bupivacaine or placebo. Pain scores at 72 h in the LB (199, 266, and 300 mg) were significantly lower than in the bupivacaine HCl group (p = 0.002). Compared to the bupivacaine/placebo group, the time to first use of opioids in the LB group was significantly longer at LB 199 mg (11 h vs. 9 h), LB 266 mg (19 h vs. 9 h), and LB 300 mg (19 h vs. 8 h) (p < 0.05). Moreover, compared to the bupivacaine/epinephrine group, it was significantly lower in the LB 266 mg group (3.7 vs. 10.2 mg) and at LB 300 mg (13 vs. 33 mg) (p < 0.05). Finally, regarding adverse effects, the conventional anesthetic/placebo group reported more pain in bowel movement than LB groups (OR 2.60, 95% CI 1.31-5.16). CONCLUSIONS: Comparing LB to conventional anesthetic/placebo anesthetic for hemorrhoidectomy, we found a statistically significant reduction in pain through 72 h, decreased opioid requirements, and delayed time to first opioid use. Moreover, the conventional anesthetic/placebo group reported more pain in bowel movement than LB groups.

Liposomal bupivacaine provides superior pain control compared to bupivacaine with adjuvants in interscalene block for total shoulder replacement: a prospective double-blinded, randomized controlled trial.

INTRODUCTION: Optimal pain control methods after total shoulder arthroplasty (TSA) achieve reduced opioid consumption, shortened hospital stay, and improved patient satisfaction in addition to adequate analgesia. Interscalene brachial plexus block is the gold standard for TSA, yet it typically does not provide pain relief lasting beyond 24 hours. Liposomal bupivacaine (LB) purportedly provides prolonged analgesia, yet it has been minimally explored for interscalene block, and it is significantly more expensive than standard bupivacaine. METHODS: This is a prospective, 2-arm, double-blinded randomized controlled trial. Subjects presenting for anatomic or reverse TSA were randomized in a 1:1 ratio to receive interscalene brachial plexus block with either LB plus bupivacaine (LBB group) or bupivacaine plus dexamethasone and epinephrine (BDE group). The primary outcome was 120-hour postoperative opioid consumption. Secondary outcomes were pain scores up to 96 hours postoperatively, pain control satisfaction, complications, level of distress from block numbness, and hospital stay. RESULTS: Ninety patients, 45 per group, were included in the intention-to-treat analysis and randomized. Because of withdrawal of consent and loss to follow-up, 40 in each group completed enrollment through postoperative day 60. Total 120-hour postoperative opioid consumption was similar between groups (P = .127), with no differences within 24- or 48-hour time intervals. Postoperative pain scores at 24-48 hours, 48-72 hours, 72-96 hours, and day 60 were significantly lower for the LBB group. DISCUSSION: LB interscalene brachial plexus block before total shoulder arthroplasty did not reduce 120-hour postoperative opioid consumption but significantly reduced postoperative pain between 24 and 96 hours and at postoperative day 60.

A Network Meta-Analysis of Randomized Controlled Trials Assessing Intraoperative Anesthetic Therapies for Analgesic Efficacy and Morphine Consumption Following Total Knee Arthroplasty.

BACKGROUND: The purpose of this study was to compare intraoperative anesthetic therapies for total knee arthroplasty (TKA) regarding postoperative analgesic efficacy and morphine consumption by conducting a systematic literature search. METHODS: Randomized controlled trials of TKA using various anesthetic therapies were identified from various databases from conception through December 31, 2021. A network meta-analysis of relevant literature was performed to investigate which treatment showed better outcomes. In total, 40 trials were included in this study. RESULTS: Surface under the cumulative ranking curve showed local infiltration anesthesia (LIA) with saphenous nerve block (SNB) to produce the best pain relief on postoperative days (PODs) 1 and 2 and the best reduction of morphine consumption on PODs 1 and 3. However, femoral nerve block showed the largest effect on pain relief on POD 3, and liposomal bupivacaine showed the largest effect on reduction of morphine consumption on POD 2. CONCLUSIONS: According to this network meta-analysis, surface under the cumulative ranking curve percentage showed that LIA with SNB provided the best analgesic effect after TKA. Furthermore, patients receiving LIA with SNB had the lowest consumption of morphine. Although femoral nerve block resulted in better pain relief on POD 3, LIA with SNB could be selected first when trying to reduce morphine consumption or increase early ambulation.

Toxic effects of local anesthetics on rat fibroblasts: An in-vitro study.

BACKGROUND: Infusion catheters facilitate a controlled infusion of local anesthetic (LA) for pain control after surgery. However, their potential effects on healing fibroblasts are unspecified. METHODS: Rat synovial fibroblasts were cultured in 12-well plates. Dilutions were prepared in a solution containing reduced-serum media and 0.9% sodium chloride in 1:1 concentration. Each well was treated with 500 µl of the appropriate LA dilution or normal saline for 15- or 30-min. LA dilutions included: 0.5% ropivacaine HCl, 0.2% ropivacaine HCl, 1% lidocaine HCl and epinephrine 1:100,000, 1% lidocaine HCl, 0.5% bupivacaine HCl and epinephrine 1:200,000, and 0.5% bupivacaine HCl. This was replicated three times. Dilution of each LA whereby 50% of the cells were unviable (Lethal dose 50 [LD50]) was analyzed. RESULTS: LD50 was reached for lidocaine and bupivacaine, but not ropivacaine. Lidocaine 1% with epinephrine is toxic at 30-min at 1/4 and 1/2 sample dilutions. Bupivacaine 0.5% was found to be toxic at 30-min at 1/2 sample dilution. Bupivacaine 0.5% with epinephrine was found to be toxic at 15- and 30-min at 1/4 sample dilution. Lidocaine 1% was found to be toxic at 15- and 30-min at 1/2 sample dilution. Ropivacaine 0.2% and 0.5% remained below LD50 at all time-points and concentrations, with 0.2% demonstrating the least cell death. CONCLUSIONS: Though pain pumps are generally efficacious, LAs may inhibit fibroblasts, including perineural fibroblast and endoneurial fibroblast-like cells, which may contribute to persistent nerve deficits, delayed neurogenic pain, and negatively impact healing. Should a continuous infusion be used, our data supports ropivacaine 0.2%. LEVEL OF EVIDENCE: Basic Science Study; Animal model.

Physicochemical Stability Study of the Morphine-Bupivacaine-Ziconotide Association.

OBJECTIVE: The aim of this study was to investigate the physicochemical stability of morphine-bupivacaine-ziconotide mixtures used in intrathecal analgesia in polypropylene syringes and intrathecal pumps. MATERIALS AND METHODS: The stability study method was conceived according to International Council for Harmonisation guidelines. For propylene syringes, six different mixtures of morphine-bupivacaine and ziconotide were assessed over seven days. Two storage temperatures were tested (5 °C ± 3 °C and 25 °C ± 2 °C). For implantable pumps, nine different mixtures were assessed over 60 days and stored at 37 °C. Assays were performed using ultrahigh-pressure liquid chromatography. Turbidity and pH also were measured throughout the study. RESULTS: Results confirmed excellent physicochemical stability for morphine and bupivacaine in the study for all conditions investigated (pumps at 37 °C, polypropylene syringes at 5 °C ± 3 °C and 25 °C ± 2 °C). Concerning ziconotide, after seven days, our study showed that every 95% confidence interval calculated had lower bounds >90% for all mixtures stored in polypropylene syringes. In implantable pumps, a decrease of the concentration was observed in all the mixtures studied. Moreover, the appearance of a degradation product confirmed the ziconotide degradation. CONCLUSION: All results are in favor with a physicochemical stable preparation for six mixture profiles when stored in polypropylene syringes at 5 °C ± 3 °C and 25 °C ± 2 °C. For mixtures stored in implantable pumps, the efficacy should decrease over time owing to the degradation of ziconotide. A trade-off between high morphine concentration and increased refill interval will need to be found by clinicians.

Ultrasound-guided sciatic nerve block in Wistar rat cadavers: Relevant anatomy and injection distribution.

OBJECTIVE: To investigate the feasibility of an ultrasound-guided sciatic nerve block by describing the sonoanatomy and comparing the distribution of two volumes of bupivacaine dye solution for nerve staining. STUDY DESIGN: Randomized, experimental, assessor-blinded cadaveric study. ANIMALS: A total of 40 adult female Wistar rat cadavers. METHODS: After studying the sonoanatomy of the sciatic nerve and adjacent structures using a high-resolution linear transducer (19-5 MHz), rat cadavers were randomly divided into two groups that were administered either 0.1 mL (group 0.1) or 0.2 mL (group 0.2) of bupivacaine dye solution per nerve, delivered via an in-plane technique. The extent of nerve staining was subsequently evaluated following dissection. Statistical analysis consisted of assessing data distribution using the Shapiro-Wilk test, followed by paired t-tests for continuous data, Mann-Whitney U test and McNemar's test for categorical data. Statistical significance was defined as p < 0.05. RESULTS: The sciatic nerve was identified bilaterally as a double ellipsoid-shaped image, surrounded by a hyperechoic fascia separating the biceps femoris from the adductor muscle. The hypoechoic structure formed by the bupivacaine dye solution around the nerve was effectively visualized using ultrasound imaging. Sciatic nerve staining was successfully achieved in all pelvic limbs, with dye spread of 4.82 ± 1.55 mm and 5.47 ± 2.18 mm in groups 0.1 and 0.2, respectively (p = 0.128). CONCLUSIONS AND CLINICAL RELEVANCE: This study achieved a detailed understanding of the sonoanatomy of the sciatic nerve and its adjacent structures, highlighting the feasibility of the ultrasound-guided technique for injection in Wistar rats. Furthermore, the results show a comparable distribution of dye solution in both groups. Use of the ultrasound-guided sciatic nerve block technique in rats not only exhibits substantial potential for regional anesthesia but also opens avenues for translational studies.