Long-acting Local Anesthetic Research Articles

Ropivacaine and magnesium sulfate in sciatic nerve block at the popliteal level: randomized double-blind study.

Following surgical procedures, over 80% of patients experience acute pain, with half of them expressing dissatisfaction with pain relief. The modern approach to surgical treatment and pain management increasingly relies on implementing multimodal analgesia, which includes the use of adjuvants in addition to long-acting local anesthetics (such as ropivacaine). This double-blind randomized study evaluated the analgesic effect of magnesium sulfate added to ropivacaine in the sciatic nerve block at the popliteal level for bunion correction surgery. In this double-blind study, fifty patients were enrolled and randomized in a 1:1 ratio to receive ropivacaine and MgSO<inf>4</inf> 200 mg or ropivacaine and physiological solution. The primary endpoint was the duration of sensory block. A statistically significant difference was observed in the onset time for sensory block (9.2 minutes vs. 21.8 minutes, P<0.001) and its duration (18.2 hours vs. 13.9 hours, P<0.001) between the two groups. Between 12 and 24 hours postoperatively, the maximum NRS pain scores in the magnesium group were lower than those in the control group (IQR [range]) 2 (2-3.8 [0-6.5]) vs. 6.7 (5.6-7.9 [2.7-9.2], P<0.001). The need for additional opioids after 12-24 hours was significantly higher in patients in the physiological solution group compared to those in the magnesium group. Our results suggest that magnesium added to the local anesthetic extends sensory block duration, reduces postoperative pain, improves the quality of analgesia, decreases the need for additional opioids. Further studies are needed to confirm these preliminary findings.

Liposomal Bupivacaine in Managing Postoperative Pain Following Shoulder Surgery

To optimize postoperative analgesia following shoulder surgery, current literature recommends multimodal approaches, including the use of regional liposomal bupivacaine (LB), a long-acting local anesthetic. The liposomal formulation of bupivacaine affords it a longer duration of action without a substantial peak plasma concentration; this combined with 3% free bupivacaine provides patients with substantial, prolonged postoperative analgesia following shoulder surgery. The use of LB as part of a multimodal approach to postoperative pain results in diminished use of opioids, reduced pain, and decreased length of hospitalization. Current literature supports these effects following a wide variety of shoulder procedures; however, some studies describe no benefit and list drawbacks including higher costs when electing to use LB instead of comparable, more affordable treatment modalities. In the interest of reducing the number of opioid prescriptions following orthopedic procedures, it is imperative to continue investigating the efficacy of LB as an opioid-sparing pain reducer. Recent literature suggests certain patient populations may be less suitable for implementing this treatment modality; namely those with a history of opioid use, prior surgeries, substantial systemic illness, and existing cardiopulmonary compromise. Patient demographics may be an additional consideration when determining the potential utility of LB to optimize analgesia after shoulder surgery.

Effect of long-acting supplementary local anesthetic on intra and post operative pain in single visit root canal treatment: a randomized control trial

Effect of long-acting supplementary local anesthetic on intra and post operative pain in single visit root canal treatment: a randomized control trial

An injectable oleogel-based bupivacaine formulation for prolonged non-opioid post-operative analgesia.

Opioid-based medications remain the mainstay of post-operative pain management, even though they are associated with a plethora of adverse effects including addiction, nausea, constipation, cognitive impairment, respiratory depression, and accidental death due to overdose. Local anesthetics are effective at controlling the intense pain after surgery but their short duration of effect limits their clinical utility in post-operative pain management. In this manuscript, an optimized injectable oleogel-based formulation of bupivacaine for multi-day post-operative pain management was characterized on the benchtop and assessed in two clinically-relevant porcine post-operative pain models. Benchtop characterization verified the optimized oleogel-based bupivacaine formulation design, demonstrating a homogenous stable oleogel with sufficient injectability due to shear-thinning properties, high drug loading capacity and first-order drug release kinetics over 5days. In vivo assessment in two pig post-operative pain models demonstrated that the oleogel-based bupivacaine formulation can provide statistically significant multi-day analgesia in two routes of administration: local instillation directly into a surgical site and ultrasound-guided peripheral nerve block injection. Pharmacokinetic assessment of ALX005 found that Cmax values were not statistically different from the bupivacaine HCl control, with no clinical signs of local anesthetic systemic toxicity observed, when administering up to 2.7 and 8.1 times the control dose of bupivacaine HCl. This study demonstrates the pre-clinical safety and efficacy of an injectable oleogel-based bupivacaine formulation and explores its utility as a single-administration long-acting local anesthetic product for post-operative pain management that can be used in both local and regional anesthetic applications.

Pharmacological Insights of Ropivacaine and Clinical Applications: A Narrative Review.

This review focuses on ropivacaine, a long-acting amide local anaesthetic, detailing its pharmacology and clinical applications. The article highlights its applications in providing analgesia, prolonging pain relief, and improving recovery outcomes in surgical settings. Ropivacaine is particularly effective for epidural labor analgesia in obstetrics, promoting stable hemodynamics and rapid onset when used with adjuvants. Its prolonged anesthetic effects reduce the need for postoperative opioids in peripheral nerve blocks. Intrathecal administration may enhance functional recovery and postoperative analgesia in various surgical procedures. While effective in treating acute pain, its role in chronic pain management remains unclear, indicating a need for further research. The review underscores the versatility and efficacy of ropivacaine in acute pain management and the importance of exploring its potential in chronic pain treatment.

Fascial Plane Blocks With Glucocorticoids or Liposomal Bupivacaine Versus Local Infiltration for Laparoscopic Non-donor Nephrectomy: A Propensity Score-Weighted Study.

Study objective The purpose of this study is to investigate the analgesic efficacy of ultrasound-guided fascial plane blocks (FPBs) versus local infiltration in patients undergoing laparoscopic non-donor nephrectomy. This study specifically compares the efficacy of FPBs with liposomal bupivacaine (LB) versus FPBs with dexamethasone sodium phosphate (DXP) and methylprednisolone acetate (MPA) versus surgical site local anesthetic infiltration without FPBs. Design This is a retrospective cohort study conducted over a five-year period (January 2018-December 2022). Setting The study was conducted in a tertiary care, academic, multi-hospital healthcare system. Participants Patients who underwent elective radical or partial laparoscopic non-donor nephrectomy were included in the study. Intervention Patients either received preoperative FPBs without intraoperative surgical site local anesthetic infiltration or received surgical site local anesthetic infiltration without FPBs (n = 141) at participating hospitals. Measurements The primary endpoint of this study was postoperative opioid use, measured as oral milligram morphine equivalents (MME). Secondary endpoints included postoperative pain scores, length of hospital stays, and significant adverse events within 30 days. The impact of medications utilized in FPBs was determined by univariate and multivariable analyses with covariates balancing propensity score weighting. Main results Patients undergoing non-donor laparoscopic radical or partial nephrectomy who received FPBs with bupivacaine or ropivacaine plus glucocorticoids DXP and MPA were more likely to be opioid-free 24-48 hours postoperatively compared to those who received FPBs with LB or surgical site local anesthetic infiltration without FPBs (40.5% vs. 30% vs. 13.9%, respectively; p = 0.017). Patients who received FPBs with glucocorticoids also reported the lowest pain scores at rest and with activity 0-12 hours postoperatively as compared to patients who received LB or local infiltration (p = 0.006 and p = 0.014, respectively). Additionally, patients who received FPBs with glucocorticoids received over 30% fewer opioids during the first 48 hours postoperatively compared to patients who received surgical site local anesthetic infiltration alone (30 MME vs. 44 MME, respectively). However, there was no significant difference in total opioid use during the first 48 hours postoperatively between patients who received FPBs with bupivacaine plus glucocorticoids and those who received FPBs with bupivacaine plus LB (mean ratio: 0.91, (95% CI: 0.05 ~ 15.97); p = 0.948). There was also no difference in the length of hospital stays or rate of adverse events between the groups. Conclusion Perioperative FPBs for non-donor laparoscopic nephrectomy using glucocorticoids as an adjuvant to long-acting local anesthetics may decrease postoperative opioid use and reduce pain scores as compared to FPBs with LB or surgical site local anesthetic infiltration. Bupivacaine or ropivacaine combined with DXP and MPA is a safe and effective alternative to LB for FPBs in laparoscopic nephrectomy.

Role of Dexmedetomidine and Clonidine With Hyperbaric Ropivacaine in Subarachnoid Block: A Comprehensive Review.

Subarachnoid block (SAB), a fundamental technique in regional anesthesia, offers efficient anesthesia for various surgical procedures with advantages including rapid onset, reliable anesthesia, and reduced systemic effects compared to general anesthesia. Hyperbaric ropivacaine, a long-acting local anesthetic, has gained popularity due to its favorable pharmacokinetic profile and safety profile. However, to extend the duration and enhance the quality of anesthesia provided by hyperbaric ropivacaine, adjuvants such as dexmedetomidine and clonidine are frequently employed. This comprehensive review explores the roles of dexmedetomidine and clonidine as adjuvants to hyperbaric ropivacaine in SAB. It examines their pharmacological mechanisms, clinical efficacy, safety profiles, and comparative effectiveness in prolonging analgesia and enhancing anesthesia. The review synthesizes evidence from clinical studies to delineate the synergistic effects of these adjuvants, their impact on patient outcomes, and their potential advantages over traditional anesthesia techniques. Through a detailed analysis of current literature and clinical practices, this review aims to provide insights into optimizing the use of dexmedetomidine and clonidine in SAB protocols. It discusses clinical implications, offers recommendations for practice, and identifies future research directions to further enhance the efficacy and safety of SAB using these adjuvants.

Ultra-Sound Guided Quadratus Lamborum Block Using Dexamethasone and Bupivacaine versus Dexmedetomidine and Bupivacaine for Post-Operative Analgesia after Labaroscopic Cholecystectomy

Abstract Background The goal of postoperative pain management is provision of comfort, early mobilization and improved respiratory function without causing inadequate sedation and respiratory compromise, which can be achieved through using regional anethesia. Transversus abdominis plane (TAP) block has been increasedly used for postoperative pain relief after lower abdominal surgeries. The main advantage of quadratus lumborum block (QLB) compared to TAP block is the extension of local anesthetic agent beyond the transversus abdominis plane to the thoracic paravertebral space. The wider spread of the local anesthetic agents may produce extensive analgesia and prolonged action of the injected local anesthetic solution. Objective To assess the analgesic effect of addition dexamethasone or Dexmedetomidine with bupivacaine in ultrasound-guided QLB to prolong it’s duration in patients undergoing laparscopic abdominal surgeries in the early postoperative period regarding pain relief, provision of comfort, and improved respiratory functions. Patients and Methods After approval of anesthesiology department scientific and ethical committees in Ain Shams University Hospitals, patients undergoing laparscopic abdominal surgeries were included in the study, and were divided into two groups (n = 10; each); group A and B . Where in group A patients(n = 10) received 20 ml bupivacaine 0.5% plus 100 μg Dexmedetomidine diluted in 5ml 0.9% NaCl (the total volume injected in all patients is 25 ml), and group B patients (n = 10) received 20 ml bupivacaine 0.25% plus 8 mg dexamethasone (2 ml) plus 3 ml 0.9% NaCl . Results The thesis proved that the addition of either Dexmedetomidine or dexamethasone to bupivacaine 0.25% in ultrasound guided QLB for laparscopic abdominal (cholecystectomy) surgeries hastened the onset, prolonged the duration of sensory block, increased post-operative analgesia and decreased rescue analgesia needed without increasing the risk of adverse effects, with Dexmedetomidine showing better results. Conclusion The addition of either 100 μg Dexmedetomidine diluted in 5 ml 0.9% NaCl or 8 mg dexamethasone to 20 ml bupivacaine 0.25% in ultrasound guided quadratus lumborum block for laparscopic abdominal surgery prolonged the duration of analgesia significantly and decreased the postoperative analgesic requirement. Hence, our study suggests that either Dexmedetomidine or dexamethasone may be a useful alternative as an adjuvant to long-acting local anesthetics for quadratus lumborum nerve block with Dexmedetomidine showing better results.

Application of propofol-remifentanil intravenous general anesthesia combined with regional block in pediatric ophthalmic surgery

ObjectiveThe aim of this study is to observe the anesthetic effect and safety of intravenous anesthesia without muscle relaxant with propofol-remifentanil combined with regional block under laryngeal mask airway in pediatric ophthalmologic surgery.MethodsA total of 90 undergoing ophthalmic surgery were anesthetized with general anesthesia using the laryngeal mask airway without muscle relaxant. They were randomly divided into two groups: 45 children who received propofol-remifentanil intravenous anesthesia combined with regional block (LG group), and 45 children who received total intravenous anesthesia (G group). The peri-operative circulatory indicators, awakening time after general anesthesia, postoperative analgesic effect and the incidence of anesthesia-related adverse events were respectively compared between the two groups.ResultsAll the children successfully underwent the surgical procedure. The awakening time after general anesthesia and removal time of laryngeal mask were significantly shorter in the LG group than in the G group (P < 0.05). There was no statistically significant difference in the heart rates in the perioperative period between the two groups (P > 0.05). There was no statistically significant difference in the incidence of intraoperative physical response, respiratory depression, postoperative nausea and vomiting (PONV) and emergence agitation (EA) between the two groups (P > 0.05). The pain score at the postoperative hour 2 was lower in the LG group than in the G group (P < 0.05).ConclusionPropofol-remifentanil intravenous anesthesia combined with long-acting local anesthetic regional block anesthesia, combined with laryngeal mask ventilation technology without muscle relaxants, can be safely used in pediatric eye surgery to achieve rapid and smooth recovery from general anesthesia and better postoperative analgesia. This anesthesia scheme can improve the comfort and safety of children in perioperative period, and has a certain clinical popularization value.

Effectiveness of Postoperative Single-shot and Continuous Transverse Abdominis Plane Block Compared to Conventional Analgesia in Hand-assisted Laparoscopic Live-donor Nephrectomy.

Few studies have evaluated the efficacy of transverse abdominis plane (TAP) block in patients undergoing hand-assisted laparoscopic live-donor nephrectomy (HALN). We aimed to evaluate the analgesic effectiveness of TAP block as part of a multimodal pain management regimen in patients undergoing HALN. We retrospectively reviewed the medical records of living kidney donors at our center between June 2016 and February 2020. HALNs were performed via a transperitoneal approach through a suprapubic incision. Additional laparoscopic ports were used in the upper midabdomen. In consenting donors, TAP block was performed postoperatively under ultrasound guidance with either a single-shot or continuous infusion of long-acting local anesthetic (0.2%-0.5% ropivacaine). All the patients received postoperative around-the-clock ketorolac and acetaminophen. Overall, 72 donors received the block (block group, 38 single-shot, 34 continuous), whereas 86 donors did not receive the block (control group). Baseline characteristics were comparable between the groups except for body weight (control: 71.8 ± 13.3 versus block: 77.8 ± 17.3 kg; P = 0.01) and intraoperative opioid dose (32.1 ± 9.6 versus 26.6 ± 10.7 morphine milligram equivalents; P < 0.001). After adjusting for baseline differences, postoperative opioid requirements were similar between the groups. When the baseline pain scale was adjusted for, there was no difference in the overall pain scale scores between the groups (P = 0.242). Subgroup analyses comparing single-shot or continuous TAP versus control did not show any differences. With the caveat of the retrospective nature of the study, the adjunctive effect of TAP block after transabdominal HALN was limited when other multimodal analgesia was used.

Preventing Local Anesthetic Systemic Toxicity After Administration of Long-Acting Local Anesthetics.

Preventing Local Anesthetic Systemic Toxicity After Administration of Long-Acting Local Anesthetics.

Contamination of liposomal bupivacaine during multi-dose usage in a clinical setting evaluated by culture and PCR.

Liposomal bupivacaine, a long-acting local anesthetic, is sold in single-dose vials at a cost of approximately $200/20 mL vial. As many veterinary patients are not dosed an entire vial, the vials have been used for multiple doses at our institution to provide cost savings. Multiple punctures of a vial can lead to increased opportunity for contamination of the contents. This study aims to describe our institutional procedure for multi-dose use of single-dose liposomal bupivacaine vials and to evaluate clinically utilized liposomal bupivacaine for bacterial and fungal contamination using molecular and bacteriological methods. The first (Control) and last (Sample B) 0.5 mL from each vial were collected and submitted for bacterial and fungal PCR, anaerobic and aerobic bacterial culture, and opportunistic fungal culture. All 40 bacterial cultures yielded no growth; Bacterial or fungal DNA was identified in 19 samples (50%). Of the 19 samples in which bacterial or fungal DNA was identified, 10 (52.6%) were from Control, and 9 (47.4%) were from Sample B. PCR does not appear to be useful in detecting bacterial or fungal contamination from liposomal bupivacaine. Results support the aseptic handling protocol described in this article is successful in preventing detectable bacterial and fungal contamination of liposomal bupivacaine vials for up to 7 individual punctures and vials open for up to 5 days.

Efficacy of Levobupivacaine in Regional Anaesthesia - A Narrative Review

Background: The pursuit of safer and more effective anesthetic agents continues to be a key focus in anesthesiology. Levobupivacaine, a purified derivative of bupivacaine, has emerged as a preferable alternative for regional anesthesia due to its enhanced safety profile. Clinical studies have shown that levobupivacaine provides similar efficacy to bupivacaine but with a more favorable pharmacokinetic profile. It has been well-tolerated in various regional anesthesia techniques, including bolus administration and continuous postoperative infusion, with few adverse drug reactions, typically linked to incorrect administration or pharmacological effects. Allergic reactions are rare. Comparative studies indicate that levobupivacaine and bupivacaine offer comparable surgical sensory blocks, adverse effects, and labour analgesia outcomes, with similar safety profiles for both maternal and fetal health. Objectives: This review aims to examine the pharmacokinetic and pharmacological benefits of levobupivacaine, highlighting its safety and clinical applications based on current evidence. Results: Levobupivacaine is generally more powerful than ropivacaine but less strong than bupivacaine, according to the majority of clinical investigations. A total of 60 studies were discovered. Some studies, such as those with unavailable full-text publications, were eliminated. Finally, 26 publications were chosen and studied since they were relevant to the current review aims. Sushma examined, in 60 patients receiving axillary block utilizing the nerve stimulation technique, the effects of 30 ml of 1.5% lidocaine with adrenaline compared to 30 ml of 0.333% levobupivacaine. Agarwal compared the effectiveness of bupivacaine and levobupivacaine in 56 patients receiving supraclavicular brachial plexus block. Levobupivacaine, according to the study, caused both motor and sensory blocks to start more quickly. Conclusion: Levobupivacaine is a long-acting local anesthetic that closely resembles bupivacaine in its clinical effects, but it offers specific advantages such as reduced cardiotoxicity.

Sustainable synthesis of long-acting local anesthetics ropivacaine and levobupivacaine under batch and continuous flow via asymmetric hydrogenation

A sustainable synthesis method was developed for long-acting local anesthetics, ropivacaine and levobupivacaine, using both batch and continuous flow processes via asymmetric hydrogenation.

YTHDF1-mediated sphingosine kinase 2 upregulation alleviates bupivacaine-induced neurotoxicity via the PI3K/AKT axis.

Bupivacaine (BUP), a long-acting local anesthetic, has been widely used in analgesia and anesthesia. However, evidence strongly suggests that excessive application of BUP may lead to neurotoxicity in neurons. Sphingosine kinase 2 (SPHK2) has been reported to exert neuroprotective effects. In this study, we intended to investigate the potential role and mechanism of SPHK2 in BUP-induced neurotoxicity in dorsal root ganglion (DRG) neurons. DRG neurons were cultured with BUP to simulate BUP-induced neurotoxicityin vitro. CCK-8, LDH, and flow cytometry assays were performed to detect the viability, LDH activity, and apoptosis of DRG neurons. RT-qPCR and western blotting was applied to measure gene and protein expression. Levels. MeRIP-qPCR was applied for quantification of m6A modification. RIP-qPCR was used to analyze the interaction between SPHK2 and YTHDF1. SPHK2 expression significantly declined in DRG neurons upon exposure to BUP. BUP challenge substantially reduced the cell viability and increased the apoptosis rate in DRG neurons, which was partly abolished by SPHK2 upregulation. YTHDF1, an N6-methyladenosine (m6A) reader, promoted SPHK2 expression in BUP-treated DRG neurons in an m6A-dependent manner. YTHDF1 knockdown partly eliminated the increase in SPHK2 protein level and the protection against BUP-triggered neurotoxicity in DRG neurons mediated by SPHK2 overexpression. Moreover, SPHK2 activated the PI3K/AKT signaling to protect against BUP-induced cytotoxic effects on DRG neurons. In sum, YTHDF1-mediated SPHK2 upregulation ameliorated BUP-induced neurotoxicity in DRG neurons via promoting activation of the PI3K/AKT signaling pathway.

Size control of ropivacaine nano/micro-particles by soft-coating with peptide nanosheets for long-acting analgesia.

Rationale: To meet the need of long-acting analgesia in postoperative pain management, slow-releasing formulations of local anesthetics (LAs) have been extensively investigated. However, challenges still remain in obtaining such formulations in a facile and cost-effective way, and a mechanism for controlling the release rate to achieve an optimal duration is still missing. Methods: In this study, nanosheets formed by a self-assembling peptide were used to encapsulate ropivacaine in a soft-coating manner. By adjusting the ratio between the peptide and ropivacaine, ropivacaine particles with different size were prepared. Releasing profile of particles with different size were studied in vitro and in vivo. The influence of particle size and ropivacaine concentration on effective duration and toxicity were evaluated in rat models. Results: Our results showed that drug release rate became slower as the particle size increased, with particles of medium size (2.96 ± 0.04 μm) exhibiting a moderate release rate and generating an optimal anesthetic duration. Based on this size, formulations at different ropivacaine concentrations generated anesthetic effect with different durations in rat sciatic nerve block model, with the 6% formulation generated anesthetic duration of over 35 h. Long-acting analgesia up to 48 h of this formulation was also confirmed in a rat total knee arthroplasty model. Conclusion: This study provided a facile strategy to prepare LA particles of different size and revealed the relationship between particle size, release rate and anesthetic duration, which provided both technical and theoretical supports for developing long-acting LA formulations with promising clinical application.

A national survey of UK practice for day-case vaginal prolapse surgery: Unrealistic expectations?

ObjectiveThe UK NHS Getting It Right First Time report (2021) recommended that a significant proportion of native tissue vaginal prolapse operations should be undertaken as day-case procedures (target: 80% anterior compartment, 70% posterior compartment, 60% combined anterior/posterior compartment). The evidence for perioperative care, options for anaesthesia and outcomes of day-case vaginal prolapse surgery is limited. This study aimed to establish current practice amongst UK gynaecologists and explore perceived barriers to implementing day-case surgery for pelvic organ prolapse.Study designA pre-tested 16-item survey was emailed to British Society of Urogynaecology members in July 2022. This survey recorded rates of day-case prolapse surgeries, barriers to implementation and practices for managing urethral catheters, vaginal packs, intraoperative anaesthetics and perioperative care. Responses to free-text questions were independently analysed by two of the authors and underwent thematic analysis. Results121 eligible responses were received (28 % response-rate): 41 % never undertook day-case prolapse repair, 16 % undertook < 5 per year and 26 % undertook > 20 cases per year. There was no significant difference in training level or hospital setting between those groups. Reasons cited for not undertaking day-case prolapse surgery included concerns about vaginal packs and urinary catheters (92 %) postoperative complications (67 %), early discharge of elderly patients (60 %) and a lack of published evidence (39 %) or national guidance (35 %). For those currently undertaking day-case prolapse surgery; 67 % used general anaesthesia, 15 % spinal with short-acting local anaesthetic, 14 % spinal with long-acting local anaesthetic and 3 % local anaesthetic alone. Vaginal packs and self-retaining urethral catheters were used by 68 % and 70 % respectively. Concerns regarding the management of vaginal packs and urinary catheters were the most frequently cited barrier to implementing day-case surgery for pelvic organ prolapse amongst free-text responses. There were wide variations in managing catheters and packs, and in managing readmissions. ConclusionsThere is significant variation in uptake and practice for day-case prolapse surgery in the UK, with legitimate clinical concerns a barrier to its implementation. Further evaluation and development of robust, evidence-based management pathways are required to make day-case prolapse surgery consistent, feasible and defensible in clinical practice.

Effect of Pharmacoprophylaxis on Postoperative Outcomes in Adult Elective Colorectal Surgery: A Multi-Center Retrospective Cohort Study within an Enhanced Recovery after Surgery Framework.

The application of enhanced recovery after surgery principles decreases postoperative complications (POCs), length of stay (LOS), and readmissions. Pharmacoprophylaxis decreases morbidity, but the effect of specific regimens on clinical outcomes is unclear. Records of 476 randomly selected adult patients who underwent elective colorectal surgeries (ECRS) at 10 US hospitals were abstracted. Primary outcomes were surgical site infection (SSI), venous thromboembolism (VTE), postoperative nausea and vomiting (PONV), pain, and ileus rates. Secondary outcomes included LOS and 7- and 30-day readmission rates. POC rates were SSI (3.4%), VTE (1.5%), PONV (47.9%), pain (58.1%), and ileus (16.1%). Cefazolin 2 g/metronidazole 500 mg and ertapenem 1 g were associated with the shortest LOS; cefotetan 2 g and cefoxitin 2 g with the longest LOS. No SSI occurred with ertapenem and cefotetan. More Caucasians than Blacks received oral antibiotics before intravenous antibiotics without impact. Enoxaparin 40 mg subcutaneously daily was the most common inpatient and discharge VTE prophylaxis. All in-hospital VTEs occurred with unfractionated heparin. Most received rescue rather than around-the-clock antiemetics. Scopolamine patches, spinal opioids, and IV lidocaine continuous infusion were associated with lower PONV. Transversus abdominis plane block with long-acting local anesthetics, celecoxib, non-anesthetic ketamine bolus, ketorolac IV, lidocaine IV, and pregabalin were associated with lower in-hospital pain severity rates. Gabapentinoids and alvimopan were associated with lower ileus rates. Acetaminophen, alvimopan, famotidine, and lidocaine patches were associated with shorter LOS. Significant differences in pharmacotherapy regimens that may improve primary and secondary outcomes in ECRS were identified. In adult ECRS, cefotetan or ertapenem may be better regimens for preventing in-hospital SSI, while ertapenem or C/M may lead to shorter LOS. The value of OA to prevent SSI was not demonstrated. Inpatient enoxaparin, compared to UFH, may reduce VTE rates with a similar LOS. A minority of patients had a documented PONV risk assessment, and a majority used as-needed rather than around-the-clock strategies. Preoperative scopolamine patches continued postoperatively may lower PONV and PDNV severity and shorter LOS. Alvimopan may reduce ileus and shorten LOS. Anesthesia that includes TAP block, ketorolac IV, and pregabalin use may lead to reduced pain rates. Acetaminophen, alvimopan, famotidine, and lidocaine patches may shorten LOS. Given the challenges of pain management and the incidence of PONV/PDNV found in this study, additional studies should be conducted to determine optimal opioid-free anesthesia and the benefit of newer antiemetics on patient outcomes. Moreover, future research should identify latent pharmacotherapy variables that impact patient outcomes, correlate pertinent laboratory results, and examine the impact of order or care sets used for ECRS at study hospitals.

Effects of dexmedetomidine as an adjuvant to ropivacaine or ropivacaine alone on duration of postoperative analgesia: A systematic review and meta-analysis of randomized controlled trials.

Ropivacaine is a long-acting local anesthetic that is used to treat postoperative pain. Adjuvant use of dexmedetomidine in regional anesthesia may prolong the duration of analgesia. The objective of this systematic review and meta-analysis was to investigate the duration and effect of ropivacaine alone vs. ropivacaine in combination with dexmedetomidine for postoperative analgesia. The PubMed, EMBASE, Web of Science, and Google Scholar databases were searched for randomized controlled trials (RCTs) of ropivacaine alone or ropivacaine in combination with dexmedetomidine for regional anesthesia. The primary outcome was duration of analgesia, defined as the time from onset of the block to the time of the first analgesic request or initial pain report. Secondary outcomes were duration of sensory block, duration of motor block, consumption of sufentanil for analgesia, length of hospital stay, and incidence of postoperative nausea and vomiting. Eighteen studies with 1148 patients were included. Overall quality of the RCTs, as assessed by the Jadad scale, was high. The meta-analysis demonstrated that ropivacaine combined with dexmedetomidine significantly prolonged the duration of postoperative analgesia from local anesthetics compared to ropivacaine alone (WMD: 4.14h; 95%CI: 3.29~5.0h; P<0.00001; I2 = 99%). There was evidence of high heterogeneity between studies. The duration of sensory and motor block was significantly increased, and consumption of sufentanil for analgesia and the incidence of postoperative nausea and vomiting were significantly reduced in patients who received ropivacaine combined with dexmedetomidine compared to ropivacaine alone. There was no significant difference in length of hospital stay. Compared to ropivacaine alone, ropivacaine combined with dexmedetomidine significantly prolonged the duration of postoperative analgesia and sensory and motor block, and reduced consumption of sufentanil for analgesia and the incidence of postoperative nausea and vomiting, across an array of surgeries.

Tetracaine downregulates matrix metalloproteinase activity and inhibits invasiveness of strongly metastatic MDA-MB-231 human breast cancer cells

Tetracaine, a long-acting amino ester-type local anesthetic, prevents the initiation and propagation of action potentials by reversibly blocking voltage-gated sodium channels (VGSCs). These channels, which are highly expressed in several carcinomas (e.g. breast, prostate, colon and lung cancers) have been implicated in promoting metastatic behaviours. Recent evidence suggests that local anesthetics can suppress cancer progression. In this paper, we aimed to explore whether tetracaine would reduce the invasive characteristics of breast cancer cells. In a comparative approach, we used two cell lines of contracting metastatic potential: MDA-MB-231 (strongly metastatic) and MCF-7 (weakly metastatic). Tetracaine (50 μM and 75 μM) did not affect the proliferation of both MDA-MB-231 and MCF-7 cells. Importantly, tetracaine suppressed the migratory, invasive, and adhesive capacities of MDA-MB-231 cells; there was no effect on the motility of MCF-7 cells. Tetracaine treatment also significantly decreased the expression and activity levels of MMP-2 and MMP-9, whilst increasing TIMP-2 expression in MDA-MB-231 cells. On the other hand, VGSC α/Nav1.5 and VGSC-β1 mRNA and protein expression levels were not affected. We conclude that tetracaine has anti-invasive effects on breast cancer cells and may be exploited clinically, for example, in surgery and/or in combination therapies.