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 5 days. 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.

Comparative Analysis of Accuracy, Readability, Sentiment, and Actionability: Artificial Intelligence Chatbots (ChatGPT and Google Gemini) versus Traditional Patient Information Leaflets for Local Anesthesia in Eye Surgery.

Background and Aim: Eye surgeries often evoke strong negative emotions in patients, including fear and anxiety. Patient education material plays a crucial role in informing and empowering individuals. Traditional sources of medical information may not effectively address individual patient concerns or cater to varying levels of understanding. This study aims to conduct a comparative analysis of the accuracy, completeness, readability, tone, and understandability of patient education material generated by AI chatbots versus traditional Patient Information Leaflets (PILs), focusing on local anesthesia in eye surgery. Methods: Expert reviewers evaluated responses generated by AI chatbots (ChatGPT and Google Gemini) and a traditional PIL (Royal College of Anaesthetists' PIL) based on accuracy, completeness, readability, sentiment, and understandability. Statistical analyses, including ANOVA and Tukey HSD tests, were conducted to compare the performance of the sources. Results: Readability analysis showed variations in complexity among the sources, with AI chatbots offering simplified language and PILs maintaining better overall readability and accessibility. Sentiment analysis revealed differences in emotional tone, with Google Gemini exhibiting the most positive sentiment. AI chatbots demonstrated superior understandability and actionability, while PILs excelled in completeness. Overall, ChatGPT showed slightly higher accuracy (scores expressed as mean ± standard deviation) (4.71 ± 0.5 vs 4.61 ± 0.62) and completeness (4.55 ± 0.58 vs 4.47 ± 0.58) compared to Google Gemini, but PILs performed best (4.84 ± 0.37 vs 4.88 ± 0.33) in terms of both accuracy and completeness (p-value for completeness <0.05). Conclusion: AI chatbots show promise as innovative tools for patient education, complementing traditional PILs. By leveraging the strengths of both AI-driven technologies and human expertise, healthcare providers can enhance patient education and empower individuals to make informed decisions about their health and medical care.

Postoperative Analgesia With Modified Thoracoabdominal Nerve Block Through Perichondrial Approach in Neonatal and Infantile Abdominal Surgery.

Modified thoracoabdominal nerve block through the perichondrial approach (M-TAPA) is a novel strategy for peripheral nerve block in the abdomen. Its usefulness has been highlighted in adults, but no literature is currently available regarding its efficacy in infants. This report describes the cases of a one-day-old neonate in open abdominal surgery and a one-month-old infant in laparoscopic surgery who received M-TAPA. The postoperative condition of the infants was assessed through a neonate pain scale and the Face, Legs, Activity, Cry, and Consolability behavioral scale, respectively; both scales remained at 0 until discharge. Despite the need for special attention, M-TAPA may provide effective analgesia in neonatal and infant abdominal surgery in addition to adult cases, and its indications should be considered.

Analysis of the Effects of Epidural Anesthesia on the Nociception Level Index (NOL®) during Abdominal Surgery.

Background: The NOL® system (PMD-200™ Nociception Level Monitor; Medasense Ltd., Ramat Gan, Israel) is used for the real-time detection of physiological nociception in anesthetized patients by assessing the parameters indicative of sympathetic activity, such as photoplethysmography, skin conductance, peripheral temperature, and accelerometry, which are quantified into the NOL®-Index. This index is more sensitive than traditional clinical parameters in estimating pain and stress responses. While its effectiveness in general anesthesia is well documented, its efficacy in epidural anesthesia needs further investigation. Methods: This retrospective study analyzed NOL®-Index dynamics compared to conventional parameters after epidural administration of bupivacaine. Following ethics committee approval, 119 NOL® measurements were retrospectively analyzed after thoracic epidural catheter administration in 40 patients undergoing abdominal and urological surgery. The NOL-Index® was assessed at 0, 1, 3, and 5 min post application and compared to heart rate, blood pressure, and bispectral index dynamics. Results: This study showed a significant decrease in the NOL®-Index post-local-anesthetic administration with better sensitivity than classical clinical parameters (0 min = 38 ± 11; 1 min = 22 ± 13*; 3 min = 17 ± 11*; 5 min = 12 ± 10*). Higher doses of local anesthetics led to a significant, dose-dependent decrease in NOL®-Index (low dose, 5 min = 15 ± 10*; high dose, 5 min = 8 ± 8*). Conclusions: This study is the first to demonstrate the effectiveness of the NOL®-Index in measuring nociceptive effects following epidural administration, highlighting its potential superiority over conventional parameters and its sensitivity to dose variations.

Retro superior costotransverse ligament space block as an effective analgesia after laparoscopic gastrectomy -a case report.

BACKGROUND: The retro superior costotransverse ligament space (RSS) block, reported as a novel target in paraspinal block, involves the spreading of local anesthetics into the thoracic paravertebral space through slits around the superior costotransverse ligament . This blocks not only the dorsal rami but also the ventral rami, achieving a reliable complete sensory blockade. CASE: We performed an RSS block at the T5, T7, and T9 levels on both sides for postoperative analgesia in two patients who underwent laparoscopic gastrectomy. Both patients showed complete sensory blockade from T4 to L1 on the anterior, lateral, and posterior chest walls in the recovery room. The resting and dynamic pain scores were 0 at 30 min and 6 h postoperatively. The pain score consistently remained below 3 throughout postoperative period. CONCLUSIONS: The RSS block provided effective postoperative analgesia in laparoscopic gastrectomy through definitive complete sensory blockade.

EMLA cream in burns: A systematic review of safety, analgesic efficacy, and effects on burn pathophysiology.

AIM: Management of procedural pain in burn care is challenging. Lidocaine-prilocaine cream 5%, eutectic mixture of local anesthetics (EMLA®), is a widely used, effective local anesthetic cream approved for normal intact skin, genital mucosa for superficial surgical procedures, and debridement of chronic leg ulcers. This comprehensive review aimed to determine the safety, analgesic efficacy, and effects of EMLA on burn pathophysiology to provide evidence-based clinical recommendations for introducing the topical anesthetic into burn care. METHODS: The PRISMA guidelines were followed for conducting a systematic PubMed search to include all relevant preclinical and clinical studies, according to pre-specified eligibility criteria. RESULTS: Fifteen studies were included in a qualitative synthesis, among which nine were human and six were animal studies. To date, safety and pharmacokinetic data on EMLA application in burns have been limited. Nevertheless, human studies indicated that EMLA is safe and provides adequate procedural-pain relief in adults when applied to smaller burns. Caution should be exercised when using EMLA in younger children, as systemic toxicity, pertaining to prilocaine-induced methemoglobinemia, has been reported owing to overdosing (high doses applied over large burn areas). Furthermore, animal studies demonstrate the potential beneficial effects of EMLA on burn pathophysiology such as anti-inflammatory, decreased capillary permeability to plasma proteins and edema formation, and improved tissue perfusion, which are factors that may impact burn wound progression. CONCLUSION: Current data on EMLA use in the management of procedural pain in small burns are sparse but suggest that EMLA is safe and effective in adults. Further clinical pharmacokinetic studies are warranted, especially for application on larger burn areas.

Use of wound infusion catheters for delivery of local anesthetic following standing partial ostectomy of thoracolumbar vertebral spinous processes in horses is not associated with increased surgical site infections.

Background: Wound infusion catheters (WICs) have been used in humans and some veterinary species for post-operative local anesthetic administration following a variety of surgical procedures, aiming to reduce post-operative analgesia requirements and improve patient comfort. Benefit in reduction in pain, post-operative analgesia requirements and length of hospital stay are well documented in humans, but use of WICs may not have been widely adopted in veterinary species due to the concern of increased complications, such as dehiscence or surgical site infection (SSI), creating a barrier to their use. This study aimed to evaluate the use of WICs in horses undergoing standing partial ostectomy surgeries, document complications and investigate if the incidence of SSI was equivalent between those horses that did and did not have a WIC. Methods: Clinical records were searched between January 2010-December 2023 for horses undergoing standing partial ostectomy surgery of thoracolumbar vertebral spinous processes at one institution. Population variables (age, breed, bodyweight), placement of a WIC or not, post-operative complications, analgesia protocols and surgical time were recorded. Horses received up to 0.1 mg kg-1 bupivacaine (0.5 mg mL-1) every 6-8 h via the WIC where one was placed. To compare SSI complication incidence between using or not using a WIC, a proportional independent equivalence test was used. Results: There were 64 horses included in the final analysis with a WIC placed in 29/64 horses (45.3%) and 35/64 (54.7%) having no WIC placed at surgery. Incidence of short-term SSI was 11.4% (no WIC used) and 13.8% (WIC used), respectively. The difference in proportion of SSI between the presence or absence of a WIC was not significant [-0.024 (90% CI -0.181; 0.133); p = 0.94]. Conclusion: The incidence of SSIs was equivalent between groups whether a WIC was used or not. WICs should be considered as part of a multi-modal analgesic approach in the post-operative period. Further research into local anesthetic dosing and its impact on rescue analgesia requirements and pain-scores is warranted.

Efficacy of dexmedetomidine as an adjuvant to local anesthetics in peribulbar block: a meta-analysis with trial-sequential analysis.

PURPOSE: To assess the role of dexmedetomidine as an adjuvant to local anesthetics (LA) in enhancing the duration and quality of peribulbar blocks for ophthalmic surgeries. DESIGN: Systematic review with meta-analysis and trial sequential analysis Methods: We systematically searched MEDLINE, Embase, and Cochrane for randomized controlled trials (RCTs) involving adult patients undergoing ophthalmic surgery under peribulbar block, comparing LA alone versus LA + dexmedetomidine. Risk ratios (RR) and mean differences (MD) with 95% confidence intervals (CI) were computed using a random effects model. Sensitivity and trial-sequential analyses (TSA) were performed to assess inconsistencies, weight type II and II errors, and estimate the required information size of the samples for all endpoints. RESULTS: Sixteen RCTs (1,220 patients) were included. Compared with LA alone, dexmedetomidine was associated with prolonged (1) motor block duration (MD 65.01 minutes, p<0.001) and (2) sensory block duration (MD 81.94 minutes, p<0.001); (3) reduced intraocular pressure (IOP) (MD -2.6 mmHg, p<0.001), and (4) decreased need for supplemental injections (RR 0.44, p=0.007). Additionally, dexmedetomidine showed (5) longer time to analgesic request (MD 97.15 minutes, p<0.001) and (6) increased surgeon satisfaction (RR 1.52, p=0.01). Sensitivity analyses and TSA were consistent across all endpoints, and the required information size was achieved for most endpoints, indicating that pooled analyses were reliable and sample sizes were sufficient. CONCLUSIONS: Compared with LA alone, dexmedetomidine significantly prolonged sensory and motor block duration and the time to the first analgesic request; decreased IOP and the need for supplemental injections, while increasing surgeon satisfaction.

Extended Release of Bupivacaine from Temperature-Responsive PNDJ Hydrogels Improves Postoperative Weight-Bearing in Rabbits Following Knee Surgery.

Effective treatment of postoperative pain lasting for multiple days without opioids is an important clinical need. We previously reported analgesia lasting up to 96 h in a porcine soft tissue model of postoperative pain using SBG004, an extended-release formulation of bupivacaine based on the temperature-responsive polymer poly(N-isopropylacrylamide-co-dimethylbutyrolactone acrylamide-co-Jeffamine M-1000 acrylamide) [PNDJ]. Orthopaedic surgical sites such as the knee can involve complex sensory innervation which presents a distinct challenge to local anesthetic delivery. The purpose of this work was to evaluate the pharmacokinetics and efficacy of SBG004 in an orthopaedic surgical model in comparison to currently available local anesthetics. Pharmacokinetics following periarticular (PA) or intraarticular (IA) injection of SBG004 were compared against liposomal bupivacaine (Lip-Bupi) PA in New Zealand White rabbits (all doses 14.5 mg/kg). Analgesic efficacy of SBG004 (IA, PA, or IA + PA), three active comparators, and saline was evaluated following knee surgery in New Zealand White rabbits. Analgesia was assessed via weight-bearing on the operated limb during spontaneous large steps in video recordings. Systemic bupivacaine exposure lasted at least 7 days for SBG004 PA, 4 days for SBG004 IA, and 2 days for Lip-Bupi PA. In the analgesia study, weight-bearing in all active groups except SBG004 IA was more frequent versus saline through 8 h postoperatively (p < 0.05). Only SBG004 IA + PA resulted in a higher proportion of weight-bearing rabbits at 24 h versus saline (6/7 versus 2/10, p = 0.015). Analysis of pooled data from 24-72 h showed significantly greater frequency of weight-bearing in rabbits receiving SBG004 IA + PA (71%) versus saline (37%), ropivacaine cocktail (41%), and Lip-Bupi PA (36%). The results indicate that the release profile from SBG004 PA or IA coincides reasonably with the time course of postoperative pain, and SBG004 may produce longer duration of analgesia than local anesthetics currently used in knee surgery, including during the period of 24-72 h recognized as a target for extended-release local anesthetics.

Lidocaine-Associated CNS Toxicity at Therapeutic Dosage: A Case Report and Literature Review.

Lidocaine is a commonly used anesthetic. High doses or intravenous administration of lidocaine, as well as other local anesthetics, may result in systemic effects involving the cardiovascular and neurologic systems. Typically, effects are dependent on the serum concentrations of the offending agent. This is a case where a patient presented with symptoms of systemic lidocaine toxicity despite therapeutic dosage and an undetectable serum lidocaine concentration. A 47-year-old Caucasian male received a lumbar medial branch injection of lidocaine and presented with symptoms of perioral numbness, seizure-like activity, and confusion. The patient had a workup, including a CT head without acute findings and an undetectable serum lidocaine level. Due to symptoms consistent with systemic local anesthetic toxicity, intravenous lipid emulsion (ILE) was administered with resolution and without recurrence of symptoms. There should be a low threshold of suspicion for local anesthetic systemic toxicity when patients have neurologic or cardiovascular symptoms following exposure. Toxicity may be present despite therapeutic dosages and low serum concentrations. ILE may be beneficial and should be considered.

Evaluation of the Effect of Benzydamine Hydrochloride on the Intensity of Gag Reflex: A Randomized Single-Blind Clinical Trial.

Statement of the Problem: Gag reflex is among the most common problems during dental and endoscopic procedures. Benzydamine hydrochloride is a non-steroidal anti-inflammatory medication and a local anesthetic that might be useful in reducing the gag reflex. Purpose: This study aimed to evaluate the effects of benzydamine hydrochloride mouthwash on the intensity of the gag reflex. Materials and Method: In this randomized clinical trial study, 30 participants aged 21-26 with a gag trigger point index (GTPI) higher than 2 were divided into 2 groups. In the case group, 15 ml of 0.15% benzydamine hydrochloride mouthwash was gargled for 1 minute, and after 10 minutes GTPI test was conducted. In the control group, 4 puffs of 10% lidocaine spray were applied to the mucosa of the targeted area, and after 5 minutes, GTPI was measured. Participants were asked about the taste and smell of the medications. Results: GTPI was significantly reduced in both groups. In the lidocaine group, the GTPI score changed from 4.47 to 2.00 (p< 0.001), and that for the benzydamine group was 4.20 to 1.47 (p< 0.001). The variance rate of the gag reflex was -2.73 and -2.47 in the benzydamine group and lidocaine group, respectively. However, this reduction was not statistically significant between the two groups. Moreover, benzydamine mouthwash has a significantly better taste and smell than lidocaine (p= 0.001). Conclusion: The results of this study showed that benzydamine mouthwash could be used quite effectively in reducing the gag reflex.

Acute Pain Management in a Multi-site Trauma Patient.

Pain management is often difficult in the setting of multi-site trauma such as that caused by motor vehicle accidents (MVA), which is especially compounded in the setting of polysubstance abuse. This often results in patients with poor pain tolerance requiring escalating doses of opioid therapy, which creates a vicious cycle. The use of peripheral nerve blocks (PNB) has been shown to decrease overall opioid consumption and can be used effectively to manage postoperative pain in this patient population. Our case report aims to highlight the importance of PNBs as part of a multimodal approach to pain management in patients with polytrauma in the setting of polysubstance abuse.

Fresh Carrier for an Old Topical Local Anesthetic: Benzocaine in Nanostructured Lipid Carriers.

Nanostructured lipid carriers (NLC) have emerged as innovative drug delivery systems, offering distinct advantages over other lipid-based carriers, such as liposomes and solid lipid nanoparticles. Benzocaine (BZC), the oldest topical local anesthetic in use, undergoes metabolism by pseudocholinesterase, leading to the formation of p-aminobenzoic acid, a causative agent for allergic reactions associated with prolonged BZC usage. In order to mitigate adverse effects and enhance bioavailability, BZC was encapsulated within NLC. Utilizing a 23 factorial design, formulations comprising cetyl palmitate (solid lipid), propylene glycol monocaprylate (liquid lipid), and Pluronic F68 as surfactants were systematically prepared, with variations in the solid/liquid lipid mass ratios (60:40-80:20%), total lipid contents (15-25%), and BZC concentrations (1-3%). The optimized formulation underwent characterization by dynamic light scattering, differential scanning calorimetry, Raman imaging, X-ray diffraction, small-angle neutron scattering, nanotracking analysis, and transmission electron microscopy (TEM)/cryo-TEM, providing insights into the nanoparticle structure and the incorporation of BZC into its lipid matrix. NLCBZC exhibited a noteworthy encapsulation efficiency (%EE = 96%) and a 1 year stability when stored at 25 °C. In vitro kinetic studies and in vivo antinociceptive tests conducted in mice revealed that NLCBZC effectively sustained drug release for over 20 h and prolonged the anesthetic effect of BZC for up to 18 h. We therefore propose the use of NLCBZC to diminish the effective anesthetic concentration of benzocaine (from 20 to 3% or less), thus minimizing allergic reactions that follow the topical administration of this anesthetic and, potentially, paving the way for new routes of BZC administration in pain management.

Ultrasound-guided sciatic nerve block injections in barred owl (Strix varia) cadavers.

OBJECTIVE: To describe an ultrasound-guided approach to the sciatic nerve and the distribution of nerve staining using two injectate volumes of dye in barred owls. STUDY DESIGN: Descriptive, randomized, assessor-blinded, cadaveric study. ANIMALS: Twelve barred owl cadavers. METHODS: The sciatic nerve was visualized with a 13-6 MHz linear ultrasound probe placed on the medial aspect of the proximal femur in barred owl cadavers. A needle was inserted at the proximal caudal thigh, and cranially advanced in-plane until the tip was immediately adjacent and ventral to the sciatic nerve. Eleven owls were injected bilaterally with a 1:1 solution of 1% methylene blue and 0.5% ropivacaine, with high-volume (HV; 0.4 mL kg-1) and low-volume (LV; 0.2 mL kg-1) treatments. Nerve staining ≥ 1 cm circumferentially was determined by dissection 15 minutes post-injection. The coelom was then opened to inspect for aberrant dye spread. In one barred owl cadaver, a 1:1 solution of 1% methylene blue and 74% ioversol contrast was injected, and computed tomography was performed immediately before and 15 minutes after injection for evaluation of injectate spread. RESULTS: The HV treatment (0.4 mL kg-1) resulted in successful nerve staining in 100% of injections, whereas the LV treatment (0.2 mL kg-1) resulted in successful nerve staining in 91% of injections. There was no leakage of injectate into undesired locations (e.g. coelomic cavity) in any cadaver. CONCLUSIONS AND CLINICAL RELEVANCE: In barred owls, the sciatic nerve can be visualized with ultrasound and injecting a ropivacaine/dye solution under ultrasound guidance successfully stained the sciatic nerve in the majority of cases. This technique holds potential for providing analgesia distal to the stifle joint; however, further investigations are necessary to evaluate its practical application in a clinical setting.

A review of local anesthetic-induced heart toxicity using human induced pluripotent stem cell-derived cardiomyocytes.

Local anesthetic (LA) cardiotoxicity is one of the main health problems in anesthesiology and pain management. This study reviewed the reported LA-induced cardiac toxicity types, risk factors, management, and mechanisms, with attention to the use of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) in heart toxicity research. Important scientific databases were searched to find relevant articles. We briefly assessed the reported cardiotoxic effects of different types of LA drugs, including ester- and amide-linked LA agents. Furthermore, cardiotoxic effects and clinical manifestations, strategies for preventing and managing LA-induced cardiotoxic effects, pharmacokinetics, pharmacodynamics, and sodium channel dynamics regarding individual variability and genetic influences were discussed in this review. The applications and importance of hiPSC-CMs cellular model for evaluating the cardiotoxic effects of LA drugs were discussed in detail. This review also explored hiPSC-CMs' potential in risk assessment, drug screening, and developing targeted therapies. The main mechanisms underlying LA-induced cardiotoxicity included perturbation in sodium channels, ROS production, and disorders in the immune system response due to the presence of LA drugs. Furthermore, drug-specific characteristics including pharmacokinetics and pharmacodynamics are important determinants after LA drug injection. In addition, individual patient factors such as age, comorbidities, and genetic variability emphasize the need for a personalized approach to mitigate risks and enhance patient safety. The strategies outlined for the prevention and management of LA cardiotoxicity underscore the importance of careful dosing, continuous monitoring, and the immediate availability of resuscitation equipment. This comprehensive review can be used to guide future investigations into better understanding LA cardiac toxicities and improving patient safety.

A single center descriptive study of local anesthetic dose in knee arthroplasty: Was there evidence of local anesthetic systemic toxicity?

STUDY OBJECTIVE: Describe dosing of local anesthetic when both a periarticular injection (PAI) and peripheral nerve block (PNB) are utilized for knee arthroplasty analgesia, and compare the dosing of local to suggested maximum dosing, and look for evidence of local anesthetic systemic toxicity (LAST). DESIGN: A single center retrospective cohort study between May 2018 and November 2022. SETTING: A major academic hospital. PATIENTS: Patients who had both a PAI and PNB while undergoing primary, revision, total, partial, unilateral, or bilateral knee arthroplasty. INTERVENTIONS: None. MEASUREMENTS: Calculate the dose of local anesthetic given via PAI, PNB, and both routes combined as based on lean body weight and compare that to the suggested maximum dosing. Look for medications, clinical interventions, and critical event notes suggestive of a LAST event. MAIN RESULTS: There were 4527 knee arthroplasties where both a PAI and PNB were performed during the study period. When combining PAI and PNB doses, >75% of patients received more than the suggested maximum dose of 3 mg/kg lean body weight. The median local anesthetic dosing over the study period, 4.4 mg/kg (IQR 3.5,5.9), was 147% of the suggested maximum dose (IQR 117,197). There was no conclusive evidence of LAST among any of the patients in the study. CONCLUSIONS: Over the course of our study, we had 4527 knee arthroplasties with a median PAI and PNB local anesthetic dose that was 147% of the suggested maximum without any clear clinical evidence of a LAST event.

Peripheral nerve blocks for analgesia following cesarean delivery A narrative review.

Spinal and epidural blocks are commonly employed for pain relief during and following cesarean section. Intrathecal morphine (ITM) has been the gold standard for the same for many years. In recent times, many peripheral nerve blocks (PNBs) have been tried for postoperative analgesia following cesarean delivery (PACD). This article has reviewed the common PNBs used for PACD. The role of PNBs along with ITM has been studied and the current best strategy for PACD has also been explored. Currently, Ilio-inguinal nerve and anterior transversus abdominis plane block in conjunction with intrathecal morphine have been found to be the most effective strategy, providing lower rest pain at 6 hours as compared to ITM alone. In patients not receiving intrathecal morphine, recommended PNBs are lateral transversus abdominis plane block, single shot local anesthetic wound infiltration, or continuous wound infiltration with catheter below rectus fascia. PNBs are recommended for PACD. They have an opioid-sparing effect and are devoid of adverse effects associated with central neuraxial blocks such as hypotension, bradycardia, and urine retention. However, caution must be observed with PNBs for possible local anesthetic toxicity due to the large volumes of drug required.

Serum Levels of Bupivacaine After Bilateral Ultrasound-Guided Deep Parasternal Intercostal Plane Block in Cardiac Surgery with Median Sternotomy.

OBJECTIVE: To evaluate systemic levels of bupivacaine after bilateral ultrasound-guided deep parasternal intercostal plan (PIP) block in cardiac surgical patients undergoing median sternotomy. DESIGN: Prospective, observational study SETTING: Single institution; academic university hospital PARTICIPANTS: Twenty-eight adult patients undergoing cardiac surgery with median sternotomy received a PIP block with 2.5 mg/kg bupivacaine with or without dexamethasone and dexmedetomidine. MEASUREMENTS: Arterial blood samples were analyzed for total serum bupivacaine concentration at 5, 15, 30, 45, 60, 90, 120, and 150 minutes after placement of PIP. Local anesthetic volume, local anesthetic adjuncts, time to extubation, postoperative pain scores, and opioid consumption were recorded. MAIN RESULTS: The mean peak bupivacaine concentration was 0.60 ± 0.62 µg/mL, and the mean time to maximum concentration (Tmax) was 16.92 ± 12.97 minutes. Two patients (7.1%) had a concentration >2.0 µg/mL within 15 minutes of block placement. The mean Tmax of bupivacaine was significantly greater in patients who did not receive additives compared to those patients who did (22.86 ± 14.77 minutes v 10.0 ± 5.22 minutes; p = .004). The times to extubation and postoperative pain were not improved with additives. CONCLUSIONS: Bilateral PIP placed at the end of cardiac surgery resulted in low systemic bupivacaine levels. The inclusion of additives shortened Tmax without improving outcome.

Dexmedetomidine with different concentrations added to local anesthetics in erector spinae plane block: a meta-analysis of randomized controlled trials.

Background: Dexmedetomidine has been used as a perineural local anesthetic (LA) adjuvant to facilitate the potency of erector spinal plane block (ESPB). This quantitative review aimed to evaluate whether perineural dexmedetomidine for ESPB can improve the effects of analgesia compared to LA alone. Methods: Randomized controlled trials (RCTs) that investigated the addition of dexmedetomidine to LA compared to LA alone in ESPB were included. The pain scores, duration of sensory block, the time to first analgesia requirement, postoperative morphine consumption, rescue analgesia, and dexmedetomidine-related side effects were analyzed and combined using random-effects models. Results: A total of 823 patients from 13 RCTs were analyzed. Dexmedetomidine was used at the concentration of 0.5 µg/kg in three trials and 1 µg/kg in nine trials, and both in one trial. Both concentrations of dexmedetomidine perineurally administrated significantly reduced the rest VAS scores postoperatively at 12 h (0.5 µg/kg dexmedetomidine: MD = -0.86; 95% CI: -1.59 to -0.12; p = 0.02; 1 µg/kg dexmedetomidine: MD = -0.49; 95% CI: -0.83 to -0.16; p = 0.004), and 24 h (0.5 µg/kg dexmedetomidine: MD = -0.43; 95% CI: -0.74 to -0.13; p = 0.005; 1 µg/kg dexmedetomidine: MD = -0.62; 95% CI: -0.84 to -0.41; p < 0.00001). Both concentrations of dexmedetomidine added in LAs improved the dynamic VAS scores postoperatively at 12 h (0.5 µg/kg dexmedetomidine: MD = -0.55; 95% CI: -0.95 to -0.15; p = 0.007; 1 µg/kg dexmedetomidine: MD = -0.66; 95% CI: -1.05 to -0.28; p = 0.0006) and 24 h (0.5 µg/kg dexmedetomidine: MD = -0.52; 95% CI: -0.94 to -0.10; p = 0.01; 1 µg/kg dexmedetomidine: MD = -0.46; 95% CI: -0.75 to -0.16; p = 0.002). Furthermore, perineural dexmedetomidine prolonged the duration of the sensory block and the time to first analgesia requirement, reduced postoperative morphine consumption, and lowered the incidence of rescue analgesia and chronic pain. Conclusion: The meta-analysis showed that using perineural dexmedetomidine at either 0.5 µg/kg or 1 µg/kg doses in ESPB can effectively and safely enhance pain relief. Systematic review registration: PROSPERO (CRD42023424532: https://www.crd.york.ac.uk/PROSPERO/).

CPL-01, an investigational long-acting ropivacaine, demonstrates safety and efficacy in open inguinal hernia repair.

BACKGROUND: There is an unmet medical need for effective nonopioid analgesics that can decrease pain while reducing systemic opioid use. CPL-01, an extended-release injectable formulation of ropivacaine, is designed to safely provide analgesia and reduce or eliminate opioid use in the postoperative period. METHODS: Subjects undergoing open inguinal hernia with mesh were prospectively randomized to 1 of 3 doses of CPL-01 (10, 20, or 30 ml of 2% CPL-01, n = 14, 12, and 14, respectively), Naropin (150 mg, n = 40), or saline placebo (n = 13) infiltrated into the surgical site prior to closure. Pain and rescue medication usage was assessed, and Numeric Rating Scale (NRS) pain scores were adjusted for opioid usage using windowed worst observation carried forward (wWOCF) imputation. The primary efficacy endpoint was the mean area under the curve (AUC) of the NRS pain intensity scores with activity. RESULTS: Ninety-three subjects were treated, and 91 subjects completed 72 h of post-operative monitoring. Subjects who received the highest dose of CPL-01 in Cohort 3 showed a clinically meaningful reduction in postoperative pain intensity scores, which was the lowest value for any treatment in all cohorts, showing a trend towards statistical significance as compared to the pooled placebo group (p = 0.08), and numerically better than the 40 subjects who received Naropin. Opioid use through 72 h in subjects who received CPL-01 in Cohort 3 was approximately half of that shown in the placebo and Naropin groups; approximately 2/3 of the CPL-01 subjects (9/14) required no opioids at all through the first 72 h after the operation. More CPL-01 subjects avoided severe pain and were ready for discharge earlier than other groups. CPL-01 was safe and well-tolerated, with no clinically meaningful safety signals, and showed predictable and consistent extended-release pharmacokinetics. CONCLUSION: Results suggest that CPL-01 may be the first long-acting ropivacaine to address postoperative pain while reducing the need for opioids.