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Peripheral nerve blockade (PNB) is a common treatment to relieve postoperative pain. However, local anesthetics alone have a short duration of action and severe side effects during postoperative analgesia. In order to overcome these limitations, the present study reported an injectable hydrogel with a drug slow‐release profile for regional nerve blockade. The injectable hydrogel was prepared by crosslinking with gelatin and NHS‐PEG‐NHS, which was degradable in the physiological environment and displayed sustainable release of anesthetics locally, thus improving the disadvantage of the high toxicity of local anesthetics. In this regard, we conducted a series of in vitro characterizations and proved that the hydrogel has a porous three‐dimensional mesh structure with high drug loading capability, and sustainable drug release profile. And cytotoxicity experiments confirmed the good biocompatibility of the hydrogel. It was shown that using the animal sciatic nerve block model, the analgesic effect was greatly improved in vivo, and there was no obvious evidence of permanent inflammation or nerve damage in the block site's sections. This locally slow‐release platform, combined with local anesthetics, is therefore a promising contender for long‐acting analgesia. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Patients with intrathecal catheters for pain medication infusion should be aware of the possible complication of acute flaccid paralysis. While exceedingly rare, it should prompt immediate medical attention to rule out compressive pathology requiring intervention. [ABSTRACT FROM AUTHOR]

Background: Persistent genital arousal disorder (PGAD) is a condition characterized by unwanted and potentially painful genital sensations or spontaneous orgasms without stimulation. We present a case of a 55‐year‐old woman with refractory genital arousal disorder that was treated with serial pudendal nerve blocks. Case: RW is a 55‐year‐old woman with chronic pelvic pain, pudendal neuralgia, MDD, SI, GAD, CRPS, and persistent genital arousal disorder for 11 years. Her PGAD was refractory to conservative management, physical therapy, and bilateral clitoral artery embolization. We performed bilateral pudendal nerve blocks with Kenalog and Bupivacaine, which provided almost complete relief for 2–3 months. We performed a bilateral pudendal nerve radiofrequency ablation; however, there was minimal benefit. RW continues to have significant relief with serial pudendal nerve blocks. Summary and Conclusion: Persistent genital arousal disorder is often refractory to medication and physical therapy requiring significant intervention such as entrapment surgery or artery embolization. Our case demonstrates pudendal nerve blocks as a potential treatment modality with minimal side effects. [ABSTRACT FROM AUTHOR]

Background: Transversus abdominis plane blocks are an established method of postoperative analgesia for abdominopelvic surgeries. Liposomal bupivacaine is an extended‐release formulation of bupivacaine providing up to 72 h of analgesia. This study aims to determine if transversus abdominis plane blocks performed with liposomal bupivacaine are associated with reduced opioid consumption and level of pain intensity compared to conventional bupivacaine in patients undergoing lower abdominal surgery. Methods: This retrospective cohort study was conducted at a single institution between December 2020 and December 2021. After institutional review board approval, we identified patients who underwent lower abdominopelvic surgery with transversus abdominis plane blocks done with liposomal or conventional bupivacaine and collected demographic, clinical, and procedural information for analysis. We compared total opioid consumption over 72‐h postoperatively in milligram morphine equivalents (MME), frequency of opioid utilization, and average level of pain intensity between groups. These outcomes were also evaluated after adjusting for covariates. Data were presented as mean ± SD, median [IQR] or frequency (%), as appropriate; p < 0.05 was accepted as significant. Results: A total of 178 patients met inclusion criteria, with 79 patients receiving an admixture of liposomal bupivacaine and conventional bupivacaine and 99 patients receiving conventional bupivacaine. The liposomal bupivacaine group had a median opioid consumption 72‐h postoperatively of 47.5 [18–91.8] MME compared to 88 [43.8–160] MME in the conventional bupivacaine group, p = 0.045. Differences in opioid consumption between the groups did not reach statistical significance after adjustment for demographic and clinical characteristics, p = 0.11. There was no significant difference in frequency of opioid use or average pain intensity. Conclusion: Transversus abdominis plane blocks using an admixture of liposomal bupivacaine conventional bupivacaine are not associated with decreased opioid consumption or reduced pain up to 72 h following elective abdominopelvic surgery. [ABSTRACT FROM AUTHOR]

We evaluated the effect of administration timing of meloxicam and robenacoxib on renal function, platelet cyclo‐oxygenase and perioperative analgesia in 60 cats undergoing ovariohysterectomy, in a prospective randomized blinded controlled study. Twelve cats were randomly allocated to one subcutaneous treatment group: meloxicam (0.2 mg/kg) or robenacoxib (2 mg/kg) at admission (MA, RA), at induction (MI, RI) and robenacoxib at the end of surgery (RE). All cats received the same anaesthesia protocol. Plasma renin activity (PRA), plasma creatinine, drug concentrations and serum thromboxane (TxB2) were measured sequentially. Anaesthesia significantly increased PRA, as activity at end of the surgery was higher than 2 h later (mean ± SD: 26.6 ± 2.8 versus 10.0 ± 3.9 ng/mL/h). PRA remained higher at 2 h post‐surgery in admission groups compared to induction groups (p =.01). Serum TxB2 was lower with meloxicam than robenacoxib (p =.001), and was lower in the MA than each robenacoxib group at catheter placement. Admission groups (16/24 from RA and MA groups) received earlier rescue analgesia than other groups (p =.033). In conclusion, the renin‐angiotensin system was activated during anaesthesia despite cyclo‐oxygenase inhibition, possibly due to hypotension or surgical stimulation. There was no effect of drug or timing on the markers of renal function but one cat receiving meloxicam at induction had suspected IRIS grade II acute kidney injury. [ABSTRACT FROM AUTHOR]

The objective of this study was to develop a population pharmacokinetic-pharmacodynamic model of subcutaneously administered bupivacaine in a novel extended-release microparticle formulation for postoperative pain management. Bupivacaine was administered subcutaneously in the lower leg to 28 healthy male subjects in doses from 150 to 600 mg in a phase 1 randomized, placebo-controlled, double-blind, dose-ascending study with two different microparticle formulations, LIQ865A and LIQ865B. Warmth detection threshold was used as a surrogate pharmacodynamic endpoint. Population pharmacokinetic-pharmacodynamic models were fitted to plasma concentration-effect-time data using non-linear mixed-effects modelling. The pharmacokinetics were best described by a two-compartment model with biphasic absorption as two parallel absorption processes: a fast, zero-order process and a slower, first-order process with two transit compartments. The slow absorption process was found to be dose-dependent and rate-limiting for elimination at higher doses. Apparent bupivacaine clearance and the transit rate constant describing the slow absorption process both appeared to decrease with increasing doses following a power function with a shared covariate effect. The pharmacokinetic-pharmacodynamic relationship between plasma concentrations and effect was best described by a linear function. This model gives new insight into the pharmacokinetics and pharmacodynamics of microparticle formulations of bupivacaine and the biphasic absorption seen for several local anaesthetics. [ABSTRACT FROM AUTHOR]

A novel microparticle-based extended-release local anaesthetic containing a bupivacaine/poly-lactic-co-glycolic acid (PLGA; LIQ865A) or plain bupivacaine (LIQ865B) was examined in a first-in-human trial. The objectives were to examine the dose safety/tolerability and pharmacodynamics. Randomized subcutaneous injections of LIQ865A (n = 16) or LIQ865B (n = 12) and diluent, contralaterally, were administered in a dose-ascending manner (150- to 600-mg bupivacaine). Subjects were admitted 24 h post-injection and followed for 30 days post-injection. The risk ratios (RRs; 95% CI) of erythematous reactions for LIQ865A versus diluent was 9.00 (1.81-52.23; P = 0.006) and for LIQ865B versus diluent 2.50 (0.69-9.94; P = 0.37). The RR for the development of hematomas (LIQ865A versus diluent) were 3.25 (1.52-8.16; P = 0.004) and 4.00 (0.72-24.89; P = 0.32) (LIQ865B versus diluent). Subcutaneous indurations persisting for 4-13 weeks were seen in 6/16 subjects receiving LIQ865A. One subject receiving LIQ865A (600-mg bupivacaine) developed intermittent central nervous system (CNS) symptoms of local anaesthetic systemic toxicity (85 min to 51 h post-injection) coinciding with plasma peak bupivacaine concentrations (490-533 ng/ml). Both LIQ865 formulations demonstrated dose-dependent hypoesthesia and hypoalgesia. The duration of analgesia ranged between 37 and 86 h. The overall number of local adverse events, however, prohibits clinical application without further pharmacological modifications. [ABSTRACT FROM AUTHOR]

No previous studies have investigated the systemic absorption of bupivacaine when used topically for posttonsillectomy pain. The present study was undertaken to investigate the pharmacokinetics of bupivacaine after administration by a swab in the tonsillar fossae over 4 min after tonsillectomy. Eleven adult patients undergoing elective tonsillectomy were recruited. After removal of both tonsils, each of the two tonsillar fossae was covered with a swab moistened with 2 mL of bupivacaine 5 mg/mL, that is, a total of 20 mg bupivacaine. Blood samples were drawn after 0, 5, 10, 20, 30, 45, and 60 min. Bupivacaine was analyzed with an ultra‐high‐performance liquid chromatography–tandem mass spectrometry method. The highest single measured bupivacaine serum concentration was 23.2 ng/mL and took place 10 min after drug administration. Mean (±SD) Cmax was 11.4 ± 6.0 ng/mL and mean tmax was 11.3 ± 4.7 min. Mean t1/2 was 31.6 ± 9.3 min. As the toxic concentration threshold has been reported to be in the interval 1500–4500 ng/mL, the concentrations measured were well below 2% of the lowest cited toxic threshold. In conclusion, this study shows that applying 4 mL of bupivacaine 5 mg/mL by a swab in the tonsillar fossae posttonsillectomy yields very low plasma concentrations, suggesting its safe application without any risk of systemic toxic effects. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Summary: A 7‐day‐old, 60 kg, Purebred Spanish Horse filly was referred with the mare to Complutense University of Madrid, Veterinary teaching hospital for elective omphalectomy. Upon admission, clinical examination was unremarkable except for a thickening of the umbilical area. Haematology and biochemistry values were within the normal range. On abdominal ultrasound (US) examination, a well‐defined, rounded (24 mm of diameter) area that contained heterogeneous material with numerous hyperechoic foci with acoustic shadowing was seen within the inner portion of the umbilical pedicle, between both umbilical arteries. Surgical correction with omphalectomy was scheduled. To provide perioperative analgesia, the transversus abdominis plane (TAP) block was considered. Under general anaesthesia, TAP block was performed in both left and right hemi‐abdominal walls with a modified subcostal approach with two‐site injections. A spinal needle was inserted under US guidance. During surgery, end‐tidal concentration of isoflurane was maintained at 0.7%–0.9%. Surgery was completed uneventfully and no signs of nociceptive input were observed, suggesting an adequate level of analgesia. Therefore, this TAP block technique may be considered to provide analgesia for surgical procedures involving the abdominal wall in foals. [ABSTRACT FROM AUTHOR]

Summary: Optimal pain management after open abdominal surgery is essential but can be difficult to achieve. The effects of inadequate analgesia go beyond the first few postoperative days; severe acute postoperative pain may contribute to the development of chronic postsurgical pain. Thoracic epidural analgesia is a traditional approach to the management of acute pain after open abdominal surgery but has multiple possible contraindications and can be technically challenging. In our hospital, we typically offer ultrasound‐guided rectus sheath blocks with catheters when epidural analgesia is not feasible. However, the recent registration of long‐acting liposomal bupivacaine in the Netherlands as well as logistical and equipment‐related issues have led us to consider liposomal bupivacaine as an alternative to the use of catheters. Here, we present a short case series to describe our first clinical experiences with the use of liposomal bupivacaine in ultrasound‐guided rectus sheath blocks after midline laparotomy for three patients in whom epidural insertion was contraindicated. [ABSTRACT FROM AUTHOR]

1‐Azaspiro[3.3]heptanes were synthesized, characterized, and validated biologically as bioisosteres of piperidine. The key synthesis step was thermal [2+2] cycloaddition between endocyclic alkenes and the Graf isocyanate, ClO2S−NCO, to give spirocyclic β‐lactams. Reduction of the β‐lactam ring with alane produced 1‐azaspiro[3.3]heptanes. Incorporation of this core into the anesthetic drug bupivacaine instead of the piperidine fragment resulted in a new patent‐free analogue with high activity. [ABSTRACT FROM AUTHOR]

Background: The first metatarsophalangeal joint is the most common site of osteoarthritis (OA) in the foot and ankle. Intra-articular corticosteroid injections are widely used for this condition, but little is known about their use in practice. This study explored current practice within the UK National Health Service (NHS) relating to the administration of intra-articular corticosteroids for people with painful first metatarsophalangeal joint (MTPJ) OA. Methods: A cross-sectional survey using Qualtrics online survey platform (Qualtrics, Provo, UT, USA), distributed through professional bodies, special interest groups, and social media. Results: One hundred forty-four healthcare professionals responded, including podiatrists (53/144; 39%), orthopaedic surgeons (28/144; 19%), podiatric surgeons (26/144; 17%) and physiotherapists (24/144; 16%). Half of respondents administered up to 25 corticosteroid injections per year (67/136; 49%) but some administered more than fifty (21/136; 15%). Injections were administered across the healthcare system but were most common in hospital settings (64/136; 44%) followed by community (38/136; 26%), with less delivered in primary care (11/136; 8%). Half of respondents routinely used image-guidance, either ultrasound or x-ray/fluoroscopy (65/136; 48%) although over one third used none (52/136; 38%). Imaging guidance was more common amongst medical professionals (21/31; 68%) compared to non-medical health professionals (45/105; 43%). Overall, methylprednisolone acetate was the most common corticosteroid used. Medical professionals mostly injected methylprednisolone acetate (n = 15/27; 56%) or triamcinolone acetonide (n = 11/27; 41%), whereas premixed methylprednisolone acetate with lidocaine hydrochloride was the most common preparation used by non-medical health professionals (41/85; 48%). When injecting non premixed steroid, lidocaine hydrochloride (15/35; 43%) was the most common choice of local anaesthetic for non-medical health professionals but medical professionals showed more variation between lidocaine hydrochloride (8/23; 35%) levobupivacaine hydrochloride (9/23; 39%) and bupivacaine hydrochloride (5/23; 22%). Conclusions: Multiple professional groups regularly administer intra-articular corticosteroids for symptomatic first MTPJ OA across a range of NHS healthcare settings. Overall, methylprednisolone acetate was the most commonly administered steroid and lidocaine hydrochloride the most common local anaesthetic. There was large variation in the use of imaging guidance, type and dose of steroid, local anaesthetic, and clinical pathways used in the intra-articular injection of corticosteroids for people with first MTPJ OA. [ABSTRACT FROM AUTHOR]

Opioid and local anaesthetic receptors are abundantly concentrated in different layers of the skin. Therefore, simultaneous targeting of these receptors can produce more potent dermal anaesthesia. Herein, we developed lipid‐based nanovesicles for the co‐delivery of buprenorphine and bupivacaine to efficiently target skin‐concentrated pain receptors. Invasomes incorporating two drugs were prepared by ethanol injection method. Subsequently, the size, zeta potential, encapsulation efficiency, morphology, and in‐vitro drug release of vesicles were characterized. Ex‐vivo penetration features of vesicles were then investigated by the franz diffusion cell on the full‐thickness human skin. Wherein, it was demonstrated that invasomes penetrated the skin deeper and delivered bupivacaine more effectively than buprenorphine to the target site. The superiority of invasome penetration was further evidenced by the results of ex‐vivo fluorescent dye tracking. Estimation of in‐vivo pain responses by the tail‐flick test revealed that compared with the liposomal group, the group receiving invasomal formulation and drug‐free invasomal formulation (only containing menthol) displayed increased analgesia in the initial times of 5 and 10 min. Also, no signs of oedema or erythema were observed in the Daze test in any of the rats receiving the invasome formulation. Finally, ex‐vivo and in‐vivo assays demonstrated efficiency in delivering both drugs into deeper layers of skin and exposing them to the located pain receptors, which improves the time of onset and the analgesic effects. Hence, this formulation appears to be a promising candidate for tremendous development in the clinical setting. [ABSTRACT FROM AUTHOR]

Background: Liposomal local anaesthetic solutions may provide extended‐duration analgesia postoperatively but have not been assessed following intra‐peritoneal local infiltration in any species. Objectives: To evaluate two doses of 1.33% liposomal bupivacaine (LB) versus 0.75% bupivacaine HCL (BHCl) for analgesia following laparoscopic ovariectomy in mares. Study design: Prospective cohort study. Methods: Fifteen healthy Quarter Horse mares (age 2–20 years) with normal bilateral ovarian palpation and appearance were enrolled. Horses were restrained in standing stocks and administered an α‐2 agonist, butorphanol, and flunixin meglumine, followed by a variable rate infusion of sedation with α‐2 agonists. Bilateral paralumbar fossa ovariectomies were performed. Treatment with either 30 ml 0.75% BHCl followed by 20 or 40 ml LB 13.3% (LB20 and LB40) volume expanded with saline to 80 ml total (n = 6/group) or 80 ml BHCl alone (n = 3, BCHL) was infused around incision sites and each mesovarium (LB or BHCl) prior to ovariectomy. Horses were monitored for 72 h by physical examination, algometry, and pain scoring (composite pain scale by Bussieres et al., Horse Grimace Scale). Abdominocentesis with peritoneal fluid analysis was performed at 72 h. Results: Analgesia achieved with all treatment protocols allowed completion of ovariectomy procedures. Pressure algometry scores were lower in BHCl‐treated horses versus both LB groups overall. Pain scores were improved with LB‐treated horses in a dose‐dependent fashion (Horse Grimace Scale scores LB40 < LB20 < BHCL; composite pain scale scores LB40 < BHCL, LB20 < BHCL, BHCL, and LB20 did not differ). Peritoneal fluid total protein was lower in LB40 versus LB20 and BHCL horses. No complications from LB administration were appreciated. Main limitations: Small patient sample size, lack of follow‐up past 72 h or histopathology. Conclusions: Analgesia duration was extended and pain scores improved postoperatively with LB versus BHCl in a dose‐dependent fashion. Further clinical evaluation of extended‐duration local anaesthetics in horses for improved postoperative pain management is warranted. [ABSTRACT FROM AUTHOR]

Animals with impaired hepatic metabolism may experience reduced effect from some anaesthetic drugs and are more prone to developing unwanted side effects. Due to reduced blood flow to the liver, it is important to carefully select anaesthetic drugs in patients with extrahepatic shunt. We present the case in which a dog was submitted for surgical attenuation of congenital extrahepatic portosystemic shunt through placement of an ameroid constrictor. A multimodal regimen was designed in order to provide an opioid‐free anaesthesia, relying on analgesia through a locoregional quadratus lumborum block with bupivacaine. Dexmedetomidine was administered intramuscularly as pre‐anaesthetic medication, propofol was used for the induction and anaesthesia was maintained with isoflurane. The present case describes the first case in which an extrahepatic portosystemic shunt was surgically treated using an opioid‐free anaesthesia in a dog. [ABSTRACT FROM AUTHOR]

This study was aimed at examining the anesthetic effects and spinal cord injuries in the rats by intrathecal injection of levobupivacaine at different concentrations. Rats with successful intrathecal cannulation were selected and randomly divided into six groups (n = 72), and administered 0.1 mL of 0.125%, 0.25%, 0.5%, or 0.75% levobupivacaine, saline or 5% lidocaine via intrathecal catheters. The potency of levobupivacaine was evaluated by walking behavior. To identify the motor and sensory function, walking behavior and paw withdrawal thresholds (PWTs) were measured once a day. After 7 days, the L4–5 spinal cord segments were removed for histological examination. The onset time of 0.125% levobupivacaine intrathecal injection was 70.0 ± 8.9 s, and the maintenance time was 9.5 ± 1.8 min. The onset time of 0.75% levobupivacaine intrathecal injection was significantly shortened to 31.0 ± 5.5 s, and the maintenance time was significantly extended to 31.3 ± 5.4 min. The severe injury was observed in the 5% lidocaine group, while milder injury was observed in the 0.75% levobupivacaine group. The damage in the 0.5% levobupivacaine group was mild, and there were no histological abnormalities in the 0.125%, 0.25% levobupivacaine and saline groups. The neurotoxicity of intrathecally administered levobupivacaine was concentration dependent. In addition, higher concentrations of levobupivacaine were associated with shorter onset and longer maintenance times. The clinical concentration of levobupivacaine should not exceed 0.5% to avoid potential damage. [ABSTRACT FROM AUTHOR]

Background: Limited data exist concerning the management of postoperative pain after robotic‐assisted surgery. The present study was performed to investigate the efficacy of intrathecal morphine and bupivacaine to treat postoperative pain in adult women undergoing robot‐assisted laparoscopic hysterectomy. Methods: The primary outcomes of this study were opioid consumption and pain scores during and after robotic surgery. 96 patients were prospectively enrolled and randomized to a nonspinal group (n = 48) and a spinal group (n = 48). The intrathecal regimen consisted of 100 μg morphine and 15 mg of bupivacaine. The numeric rating scale scores (NRS) were assessed every 15 min in the postoperative care unit (PACU) and pain was treated with iv fentanyl or morphine when NRS was above 5 and orally oxycodone when NRS was 3–5. Cumulative iv opioid‐consumption and NRS scores were compared. Results: Intrathecal morphine and bupivacaine resulted in a significantly lower cumulative total iv opioid (morphine equivalents) consumption (9.4 ± 3.9 vs. 22.8 ± 6.1 mg equivalents). Highest recorded NRS scores in the PACU were also significantly lower in the spinal group (2.0 ± 2.6 vs. 5.3 ± 3.2). Conclusion: Intrathecal morphine and bupivacaine to treat postoperative pain after robotic‐assisted laparoscopic hysterectomy decrease total opioid consumption and NRS pain scores. This might be of great importance to diminish the rate of other serious disadvantages related to opioids. [ABSTRACT FROM AUTHOR]

Background: Bupivacaine lioposomal suspension has recently emerged in the veterinary field for local analgesia. Objective: To describe the extra‐label administration of bupivacaine liposomal suspension at the incision site of dogs undergoing limb amputation and characterize any complications. Study Design: Nonblinded retrospective study. Animals: Client‐owned dogs undergoing limb amputation from 2016 to 2020. Methods: Medical records of dogs undergoing limb amputation with concurrent use of long‐acting liposomal bupivacaine suspension were reviewed for incisional complications, adverse effects, hospitalization length, and time to alimentation. Data were compared to a control group (CG) of dogs who underwent a limb amputation procedure without concurrent use of liposomal bupivacaine suspension. Results: Forty‐six dogs were included in the liposomal bupivacaine group (LBG) and 44 cases in the CG. The CG had 15 incidences of incisional complications (34%) compared to 6 within the LBG (13%). Four dogs required revisional surgery in the CG (9%) whereas none of the dogs required revisional surgery in the LBG. Time from surgery to discharge was statistically higher in the CG compared to the LBG (p = 0.025). First time to alimentation was statistically higher in the CG (p value = 0.0002). The total number of rechecks needed postoperatively revealed the CG having a statistically significant increase in recheck evaluations (p = 0.001). Conclusions: Extra‐label administration of liposomal bupivacaine suspension was well‐tolerated in dogs undergoing limb amputation. Liposomal bupivacaine usage did not increase incisional complication rates and its use allowed for a quicker time to discharge. Clinical significance: Surgeons should consider inclusion of extra‐label administration of liposomal bupivacaine in analgesic regimens for dogs undergoing limb amputation. [ABSTRACT FROM AUTHOR]

Kaempferol (KA), a widely recognized anti‐oxidation and anti‐inflammation agent, has been reported to have neuroprotective effects. This work aimed to investigate whether KA protects mouse dorsal root ganglia (DRG) neurons against bupivacaine (BU)‐stimulated neurotoxicity and explore the underlying mechanisms. In this study, BU treatment suppressed DRG neuron viability and promoted LDH leakage, which was partially abated by KA. Besides, BU‐triggered DRG neuron apoptosis, and changes in Bax and Bcl‐2 levels were attenuated by KA treatment. In addition, pretreatment with KA substantially reduced interleukin (IL)‐6, IL‐1β, and tumor necrosis factor (TNF)‐α levels in BU‐treated DRG neurons. In addition, KA administration abrogated BU‐induced decline in CAT, SOD, and GSH‐Px levels, as well as the increase in the malondialdehyde level. Interestingly, we found that KA significantly attenuated BU‐induced TNF receptor‐associated factor 6 (TRAF6) upregulation as well as NF‐κB activation. Furthermore, oe‐TRAF6‐mediated TRAF6 overexpression promoted NF‐κB activation and partly abolished KA‐induced protection against BU‐triggered neurotoxic effects on DRG neurons. Our results revealed that KA mitigated BU‐induced neurotoxic effects on DRG neurons by deactivating the TRAF6/NF‐κB signaling. [ABSTRACT FROM AUTHOR]

Summary: Posterior reversible encephalopathy syndrome is a rare and serious condition that presents with acute neurological symptoms with characteristic changes on imaging. It can lead to substantial morbidity and mortality, but can be reversible if recognised and treated. Here, we report a case of posterior reversible encephalopathy syndrome in a child post‐splenectomy under general anaesthesia with spinal anaesthesia. As far as we are aware, this condition has not previously been described in relation to spinal anaesthesia in the paediatric population. This case demonstrates the importance of recognising blood pressure changes in children, which can be challenging due to age‐, sex‐ and height‐related centiles for blood pressure measurements. Posterior reversible encephalopathy syndrome should be considered as a differential diagnosis for headache in a patient that has had a spinal anaesthesia. [ABSTRACT FROM AUTHOR]

Infusion of lipid emulsion for drug overdose arose as a treatment for local anaesthetic systemic toxicity (LAST) initially based on laboratory results in animal models with the subsequent support of favourable case reports. Following successful translation to the clinic, practitioners also incorporated lipid emulsion as a treatment for non‐local anaesthetic toxicities but without formal clinical trials. Recent clinical trials demonstrate a benefit of lipid emulsion in antipsychotic, pesticide, metoprolol and tramadol overdoses. Formal trials of lipid emulsion in LAST may never occur, but alternative analytic tools indicate strong support for its efficacy in this indication; for example, lipid emulsion has obviated the need for cardiopulmonary bypass in most cases of LAST. Herein, we describe the pre‐clinical support for lipid emulsion, evaluate the most recent clinical studies of lipid emulsion for toxicity, identify a possible dose‐based requirement for efficacy and discuss the limitations to uncontrolled studies in the field. [ABSTRACT FROM AUTHOR]

Liposomal bupivacaine (LB) has consistently been considered a potential analgesic for surgical wound infiltration. However, the evidence of its analgesic effectiveness remains unclear. In this meta‐analysis, we attempted to identify the potential clinical role of LB wound infiltration in different surgical procedures. Randomised controlled trials (RCTs) comparing LB with non‐liposomal local anaesthetics and placebos were retrieved from six electronic databases. The primary outcome was cumulative morphine equivalent consumption within 24, 48, and 72 hours after surgery. Approximately 2659 patients from 22 studies were included in the meta‐analysis. Compared to the control, LB‐wound infiltration did not reduce the postoperative morphine consumption at 24 hours (weighted mean difference [WMD], −0.60 mg; 97.5% confidence interval [CI], −2.78 to 1.59 mg; P = 0.54), 48 hours (WMD, −1.00 mg; 97.5% CI, −3.23 to 1.24; P = 0.32) or 72 hours (WMD, 0.50 mg; 97.5% CI, −0.67 to 1.67; P = 0.33). Similarly, secondary outcome analysis did not reveal any additional benefits of LB in any other pain‐related outcomes. LB was not associated with any adverse effects. Overall, LB does not appear to improve the postoperative analgesic, rehabilitation, or safety outcomes. Current evidence does not support the routine use of LB for wound infiltration following surgical procedures. [ABSTRACT FROM AUTHOR]

Pain is common in the acute phase of Guillain–Barré Syndrome and can be severe and refractory. Pain in GBS may not always respond to contemporary pain therapy. An epidural can potentially be considered for the treatment of refractory pain after a careful patient‐centered discussion with the patient about risks. [ABSTRACT FROM AUTHOR]

Local anesthetics have anti‐inflammatory effects. Because most previous experiments were performed with supra‐therapeutic concentrations, we measured the effects of clinically relevant concentrations of bupivacaine on the Toll like receptor 4 (TLR4)‐ and TLR2‐myeloid differentiation primary response 88 (MyD88)‐nuclear factor kappa‐light‐chain‐enhancer of activated B cell (NF‐κB) pathways. We measured tumor necrosis factor alpha (TNF‐α) and prostaglandin E2 (PGE2) release, p38 mitogen‐activated protein kinase (MAP‐kinase) phosphorylation and translocation of NF‐κB in human peripheral blood mononuclear cells (hPBMCs) and human monocytes challenged with lipopolysaccharide (LPS) or tripalmitoylated lipopeptide Pam3CysSerLys4 (Pam3CSK4) in the presence or absence of bupivacaine. Similarly, we measured the effect of bupivacaine on HEK293 cells expressing the hTLR4 and the hTLR2 genes and challenged with LPS or Pam3CSK4. Finally, molecular docking simulations of R(+)‐ and S(−)‐bupivacaine binding to the TLR4‐myeloid differentiation protein 2 (MD‐2) complex and to the TLR2/TLR1 heterodimer were performed. In PBMCs, bupivacaine from 0.1 to 100 μM inhibited LPS‐induced TNF‐α and PGE2 secretion, phosphorylation of p38 and nuclear translocation of NF‐κB in monocytes. Bupivacaine similarly inhibited the effects of Pam3CSK4 on TNF‐α secretion. Bupivacaine inhibited the effect of LPS on HEK293 cells expressing the human TLR4 receptor and the effect of Pam3CSK4 on HEK293 cells expressing the human TLR2 receptor. Molecular docking showed that bupivacaine binds to the MD‐2 co‐receptor of TLR4 and to the TLR2 receptor. Contrary to numerous experiments performed with supratherapeutic doses, our results were obtained with concentrations of bupivacaine as low as 0.1 μM. We conclude that bupivacaine modulates the inflammatory reactions such as those observed after surgery or trauma, at least partly by inhibiting the TLR4‐ and TLR2‐NF‐κB pathways. [ABSTRACT FROM AUTHOR]

In postoperative patients with head and neck cancer, scar tissue formation may interfere with the healing process, resulting in incomplete functional recovery and a reduced quality of life. Percutaneous application of carbon dioxide (CO2) has been reported to improve hypoxia, stimulate angiogenesis, and promote fracture repair and muscle damage. However, gaseous CO2 cannot be applied to the head and neck regions. Previously, we developed a paste that holds non‐gaseous CO2 in a carrier and can be administered transdermally. Here, we investigated whether this paste could prevent excessive scarring and promote muscle regeneration using a bupivacaine‐induced rat model of muscle injury. Forty‐eight Sprague Dawley rats were randomly assigned to either a control group or a CO2 group. Both groups underwent surgery to induce muscle injury, but the control group received no treatment, whereas the CO2 group received the CO2 paste daily after surgery. Then, samples of the experimental sites were taken on days 3, 7, 14, and 21 post‐surgery to examine the following: (1) inflammatory (interleukin [IL]‐1β, IL‐6), and transforming growth factor (TGF)‐β and myogenic (MyoD and myogenin) gene expression by polymerase chain reaction, (2) muscle regeneration with haematoxylin and eosin staining, and (3) MyoD and myogenin protein expression using immunohistochemical staining. Rats in the CO2 group showed higher MyoD and myogenin expression and lower IL‐1β, IL‐6, and TGF‐β expression than the control rats. In addition, treated rats showed evidence of accelerated muscle regeneration. Our study demonstrated that the CO2 paste prevents excessive scarring and accelerates muscle regeneration. This action may be exerted through the induction of an artificial Bohr effect, which leads to the upregulation of MyoD and myogenin, and the downregulation of IL‐1β, IL‐6, and TGF‐β. The paste is inexpensive and non‐invasive. Thus, it may be the treatment of choice for patients with muscle damage. [ABSTRACT FROM AUTHOR]

Total joint arthroplasty is one of the most common surgeries in the United States, with almost a million procedures performed annually. Periprosthetic joint infections (PJI) remain the most devastating complications associated with total joint replacement. Effective antibacterial prophylaxis after primary arthroplasty could substantially reduce incidence rate of PJI. In the present study we propose to provide post‐arthroplasty prophylaxis via dual‐analgesic loaded ultra‐high molecular weight polyethylene (UHMWPE). Our approach is based on previous studies that showed pronounced antibacterial activity of analgesic‐ and NSAID‐loaded UHMWPE against Staphylococci. Here, we prepared bupivacaine/tolfenamic acid‐loaded UHMWPE and assessed its antibacterial activity against Staphylococcus aureus and Staphylococcus epidermidis. Dual‐drug loaded UHMWPE yielded an additional 1–2 log reduction of bacteria, when compared with single‐drug loaded UHMWPE. Analysis of the drug elution kinetics suggested that the observed increase in antibacterial activity is due to the increased tolfenamic acid elution from dual‐drug loaded UHMWPE. We showed that the increased fractal dimension of the drug domains in UHMWPE could be associated with increased drug elution, leading to higher antibacterial activity. Dual‐analgesic loaded UHMWPE proposed here can be used as part of multi‐modal antibacterial prophylaxis and promises substantial reduction in post‐arthroplasty mortality and morbidity. [ABSTRACT FROM AUTHOR]

Purpose: Various sustained-release formulations incorporate high bupivacaine concentrations but data on local toxicity is lacking. This study explores local toxic effects of highly concentrated (5%) bupivacaine compared to clinically used concentrations in vivo following skeletal surgery, to assess the safety of sustained-release formulations with high bupivacaine concentrations. Methods: Sixteen rats underwent surgery, in which screws with catheters affixed were implanted in the spine or femur in a factorial experimental design, allowing single-shot or continuous 72 h local administration of 0.5%, 2.5% or 5.0% bupivacaine hydrochloride. During the 30-day follow-up, animal weight was recorded and blood samples were obtained. Implantation sites underwent histopathological scoring for muscle damage, inflammation, necrosis, periosteal reaction/thickening and osteoblast activity. Effects of bupivacaine concentration, administration mode and implantation site on local toxicity scores were analyzed. Results: Chi-squared tests for score frequencies revealed a concentration-dependent decrease in osteoblast count. Moreover, spinal screw implantation led to significantly more muscle fibrosis but less bone damage than femoral screw implantation, reflecting the more invasive muscle dissection and shorter drilling times related to the spinal procedure. No differences between bupivacaine administration modes regarding histological scoring or body weight changes were observed. Weight increased, while CK levels and leukocyte counts decreased significantly during follow-up, reflecting postoperative recovery. No significant differences in weight, leukocyte count and CK were found between interventional groups. Conclusion: This pilot study found limited concentration-dependent local tissue effects of bupivacaine solutions concentrated up to 5.0% following musculoskeletal surgery in the rat study population. [ABSTRACT FROM AUTHOR]

Multimodal analgesia is the foundation of opioid‐sparing analgesia protocols in major surgery, being locoregional anaesthesia their keystone. Its aim is to provide adequate analgesia while minimising opioid requirements, and thus opioid‐related adverse effects. The blossoming of ultrasound‐guided fascial plane blocks offers a new spectrum of safer and simpler alternatives to traditional locoregional anaesthesia techniques. This report describes the anaesthetic management of a dog and a cat that underwent bilateral thoracotomy for treatment of chylothorax. The multimodal analgesia protocol consisted of preoperative methadone, ultrasound‐guided serratus plane and erector spinae plane blocks, and epidural catheter for postoperative analgesia management. The combination of these techniques allowed for a reduction of perioperative opioid requirements, good‐quality recovery and opioid‐free analgesia in the postoperative period. [ABSTRACT FROM AUTHOR]

Introduction and Hypothesis: The primary aim of this study was to compare the effect of bladder instillations using dimethyl sulfoxide (DMSO) with triamcinolone versus bupivacaine, triamcinolone, and heparin (BTH) in women with newly diagnosed interstitial cystitis/painful bladder syndrome. The primary outcome was improvement in symptoms measured using the O'Leary‐Sant Interstitial Cystitis Symptoms Index (ICSI) score. Secondary comparisons included changes in urinary frequency, nocturia, and bladder capacity. Materials and Methods: This was a prospective, randomized study. Patients with a recent diagnosis of interstitial cystitis/painful bladder syndrome (IC/PBS) were randomized 1:1 to treatment with either 6 weekly bladder instillations of DMSO with triamcinolone or BTH. During follow‐up visits, patients completed the ICSI questionnaire, and bladder capacity was determined through the retrograde filling of the bladder. The χ2 test or Student's t test were used for data analysis. Results: A total of 83 patients were randomized, and final analysis included 70 participants who completed the 6 weekly instillations (42 DMSO, 28 BTH). The groups were similar in baseline demographics and clinical characteristics, except for cystometric maximum capacity (DMSO 338.62± 139.44 mL, BTH 447.43 ± 180.38 mL, p = 0.01). In the DMSO group, 63% of patients had a greater than 29.5% reduction in total ICSI score versus 43% in the BTH group (p = 0.15). Nocturia and pain were significantly reduced in the DMSO group. There was a significant increase from baseline in bladder capacity for both groups. Conclusion: In women with newly diagnosed IC/PBS, bladder instillations with DMSO and triamcinolone provide greater improvement in pain and nocturia compared to BTH. [ABSTRACT FROM AUTHOR]

This article, published in Equine Veterinary Education, discusses the use of a caudal intercostal block for perioperative analgesia in horses undergoing surgery for colic. The study aims to evaluate the safety and efficacy of this technique compared to a saline block. The results indicate that the caudal intercostal block is technically simple, can be safely performed with minimal training, and may lead to improved recovery time and quality in horses. Additionally, horses receiving the caudal intercostal block had lower mean visceral pain scores compared to those receiving the saline block. However, it is important to note that the data analysis is preliminary and further analysis is pending. [Extracted from the article]

Objective: This study was undertaken to determine the efficacy of ultrasound‐guided genicular nerve block (GNB) for the management of knee pain in patients with knee osteoarthritis. Methods: We performed a 12‐week parallel‐group, placebo‐controlled randomized trial of GNB. Within 2 weeks of randomization, patients with knee osteoarthritis in the active arm received 3 injections of 5.7 mg celestone chronodose (1 ml) and 0.5% bupivacaine (3 ml) to the inferomedial, superomedial, and superolateral genicular nerves; patients with knee osteoarthritis in the placebo arm received injections of normal saline. At baseline and at weeks 2, 4, 8, and 12, patients recorded their pain and disability on a 100‐mm visual analog scale (VAS) (the primary outcome measure), the Western Ontario and McMasters Universities Osteoarthritis Index (WOMAC), and the Intermittent and Constant Osteoarthritis Pain scale. Statistical significance was set at a 2‐sided Type I error of α = 0.0125 for comparisons at each of the 4 time points. We used a global perceived effect scale to measure patient satisfaction. Results: The 59 patients (36 female, 23 male) who completed the trial had a mean ± SD age of 68.2 ± 8.6 years. Patients in the active group reported improvements in pain scores at 2, 4, 8, and 12 weeks with a diminution of the effect over time. VAS scores at baseline and at weeks 2, 4, 8, and 12 in the active group (n = 31) versus placebo group (n = 28) were 6.2 versus 5.3 (P = 0.294), 2.7 versus 4.7 (P < 0.001), 3.2 versus 5.1 (P < 0.001), 3.9 versus 4.9 (P < 0.001), and 4.6 versus 5.1 (P = 0.055), respectively. Total WOMAC scores at baseline and at weeks 2, 4, 6, 8, and 12 in the active group versus the placebo group were 54.5 versus 48.1 (P = 0.177), 32.9 versus 44.4 (P < 0.001), 33.7 versus 45.8 (P < 0.001), 39.2 versus 44.8 (P = 0.001), and 42.65 versus 45.1 (P = 0.012), respectively. Conclusion: GNB offers short‐term pain relief for knee osteoarthritis. [ABSTRACT FROM AUTHOR]

Aim: To compare local anesthetic wound infiltration with intraperitoneal instillation of local anesthetic for analgesia after cesarean section under spinal anesthesia. Methods: This study was conducted on 150 pregnant women undergoing elective cesarean section under spinal anesthesia. Spinal anesthesia was performed with 7 mg isobaric bupivacaine and 15 μcg fentanyl. The patients were randomized into three groups of 50 patients each: Group local anesthetic wound infiltration (LWI): 20 ml local anesthetic solution (10 ml 0.5% bupivacaine and 10 ml 2% lidocaine mixture) was administered subcutaneous wound infiltration at the end of surgery prior to skin closure and 20 ml saline was instilled into the uterine peritoneal area before fascia closure. Group intraperitoneal local anesthetic (IPLA): 20 ml local anesthetic solution (10 ml 0.5% bupivacaine and 10 ml 2% lidocaine mixture) was instilled into the uterine peritoneal area and 20 ml saline was administered subcutaneous wound infiltration. Group Placebo: 20 ml saline was instilled into the uterine peritoneal area and 20 ml saline was administered local subcutaneous wound infiltration. Pain scores at rest and on movement, total fentanyl consumption at 24 h, maternal satisfaction, and the time to first analgesic request were recorded. Results: No statistically significant difference was observed in the postoperative pain scores at rest at 2, 12, and 24 h (p = 0.314, 0.343, and 0.735, respectively) and on movement at 12 and 24 h (p = 0.318 and 0.642, respectively) between the groups. The pain scores on movement at 2 h were significantly lower in Group IPLA compared with Group Placebo (p = 0.047). There were no significant differences between the groups in terms of total fentanyl consumption and the time to first analgesic request. Conclusion: The use of intraperitoneal instillation of bupivacaine and lidocaine reduces early the pain score on movement in women undergoing cesarean section under spinal anesthesia. [ABSTRACT FROM AUTHOR]

Objectives: To compare the duration of regional anesthesia of the pelvic limb using bupivacaine with and without a temperature‐responsive hydrogel (TRH) in dogs. Methods: Under anesthesia using medetomidine (10 μg·kg−1), alfaxalone (2 mg·kg−1), and isoflurane, seven healthy male Beagles received four injections of 0.5% bupivacaine (1 mg·kg−1 with 5 μg·ml−1 epinephrine) to block the femoral and sciatic nerves bilaterally via ultrasound with nerve stimulation guidance. Bupivacaine was used on one pelvic limb (Bup treatment), and bupivacaine with TRH was used on the contralateral limb (Bup‐TRH treatment). The nerve block was considered successful upon the absence of responses to pinching the digital pads and mid‐tibial skin of both pelvic limbs with mosquito forceps; the pinch, proprioception, and locomotion tests were performed before (baseline) and at each hour after the nerve block until sensory and motor functions returned to baseline. The effect of TRH on nerve blocks was analyzed using a linear mixed model. Results: The duration of the sensory nerve block at the digital pads and mid‐tibial skin was longer with Bup‐TRH (8.0 ± 1.6 h and 10.9 ± 1.6 h, respectively) than with Bup treatment (3.7 ± 2.0 h and 8.0 ± 1.6 h, respectively). Motor block times of proprioception and locomotion were longer with Bup‐TRH (9.3 ± 1.6 and 12.7 ± 1.5 h, respectively) than with Bup treatment (4.6 ± 1.9 and 9.6 ± 1.5 h, respectively). No complications were observed. Clinical significance: TRH extended the duration of regional anesthesia of the pelvic limb using bupivacaine. [ABSTRACT FROM AUTHOR]

Aim: A single caudal anesthetic at the start of lower abdominal surgery is unlikely to provide prolonged analgesia. A second caudal at the end of the procedure extends the analgesia duration but total plasma concentrations may be associated with toxicity. Our aim was to measure total plasma levobupivacaine concentrations after repeat caudal anesthesia in infants and to generate a pharmacokinetic model for prediction of plasma concentrations after repeat caudal anesthesia in neonates, infants and children. Methods: Infants undergoing definitive repair of anorectal malformations or Hirschsprung's disease received a second caudal anesthesia at the end of the procedure. Total levobupivacaine concentrations were assayed 3–4 times in the first 6 h after the initial caudal. These data were pooled with data from four studies describing plasma concentrations after levobupivacaine caudal or spinal anesthesia. Population pharmacokinetic parameters were estimated using nonlinear mixed‐effects models. Covariates included postmenstrual age and body weight. Parameter estimates were used to simulate concentrations after a repeat levobupivacaine 2.5 mg kg−1 caudal at 3 or 4 h following an initial levobupivacaine 2.5 mg kg−1 caudal. Results: Twenty‐one infants (postnatal age 11–32 weeks, gestation 37–39 weeks, weight 5.2–8.6 kg) were included. The measured peak plasma concentration after repeat caudal levobupivacaine 2.5 mg kg−1 4 h after initial caudal was 1.38 mg L−1 (95% prediction interval 0.60–2.6 mg L−1) and 3 h after initial caudal was 1.46 mg L−1 (0.60–2.80) mg L−1. Simulation of total plasma concentrations in neonates (7 kg, 57 weeks postmenstrual age) given caudal levobupivacaine 4 h after the initial caudal were 1.76 mg L−1 (0.68–3.50) mg L−1 if 2.5 mg kg−1 levobupivacaine was used and 0.88 mg L−1 (0.34–1.73) mg L−1 if 1.25 mg kg−1 of 0.125% levobupivacaine was used. In simulated older children (20 kg, 6 years), the mean maximum concentration was 1.43 mg L−1 (0.60–2.70) mg L−1 if 2.5 mg kg−1 levobupivacaine was repeated at 3 h. Conclusion: Repeat caudal levobupivacaine 2.5 mg kg−1 at 3 h after an initial 2.5 mg kg−1 dose does not exceed the concentration associated with systemic local anesthetic toxicity. In 2.5% of simulated neonates (weight 3.8 kg, PMA 40 weeks), repeat caudal anesthesia demonstrates broaching of the lower concentration limit associated with toxicity at both 3 and 4 h after initial caudal. [ABSTRACT FROM AUTHOR]

Extended‐release liposomal bupivacaine is frequently used in surgical infiltration for postoperative pain control. The manufacturer recommends against subsequent local anesthetics within 96 hours. We administered epidural bupivacaine one day after local liposomal bupivacaine infiltration for staged hemipelvectomy without symptoms of LAST. Further pharmacokinetic and clinical safety studies are needed. Further pharmacokinetic and clinical safety studies are needed regarding the use of different local anesthetics within 96 h of patients receiving liposomal bupivacaine. [ABSTRACT FROM AUTHOR]

Background: Prostatectomy is associated with relevant acute postoperative pain. Optimal analgesic techniques to minimize pain and enhance recovery are still under investigation. We aimed to compare the effect of three different analgesic techniques on quality of recovery.Methods: This investigator-initiated, prospective, randomized, three-arm, parallel-group, active-controlled, interventional superiority trial was performed in a Swiss teaching hospital from 2018 to 2021. Consecutive patients undergoing open or robotic-assisted radical prostatectomy were randomized to spinal anaesthesia (SSS, bupivacaine 0.5% + fentanyl), bilateral transversus abdominis plane block (TAP, ropivacaine 0.375% + clonidine) or systemic administration of lidocaine (SA, lidocaine 1%) in addition to general anaesthesia. Primary outcome was quality of recovery 15 (QoR-15) score on postoperative day one compared to baseline. Secondary outcomes were QoR-15 at discharge, postoperative nausea and vomiting, pain scores, return of gastrointestinal function and use of rescue analgesia.Results: From 133 patients, 40 received spinal anaesthesia, 45 TAP block and 48 systemic analgesia. QoR-15 scores did not differ on day 1 (p = 0.301) or at discharge (p = 0.309) when compared to baseline. QoR-15 changes were similar in all groups. At discharge, median QoR-15 scores were considered as good (>122) in all groups: SSS 134 [IQR 128-138]; TAP 129 [IQR 122-136] and SA 128 [IQR 123-136]. There were no significant differences in the other secondary outcomes.Conclusions: Quality of recovery on postoperative day one compared to baseline did not differ if spinal anaesthesia, TAP block or systemic administration of lidocaine was added to general anaesthesia.Significance: Optimal analgesic techniques to enhance recovery after prostatectomy are still under investigation. In this 3-arm randomized controlled trial, addition of spinal anaesthesia or transversus abdominis plane block to general anaesthesia did not improve quality of recovery after radical prostatectomy compared to less invasive intravenous lidocaine infusion (standard of care/control group). Quality of recovery at the time of discharge was considered as good in all three groups. [ABSTRACT FROM AUTHOR]

This paper discusses the use of a peribulbar local block with bupivacaine in a rabbit presenting for enucleation and represents an alternative locoregional technique to a retrobulbar block, which is challenging to perform in rabbits due to the presence of a venous sinus behind the globe. A peribulbar block is comparatively easy to perform, and it provided excellent perioperative and postoperative analgesia in the case reported. Clinicians should consider a peribulbar block as part of a multimodal anaesthetic plan where indicated. [ABSTRACT FROM AUTHOR]

Summary: Tuberous sclerosis complex is a genetic disease that can affect multiple organs, commonly the renal, central nervous, cardiac and respiratory systems. Here, we present the peripartum management of a woman with a new diagnosis of tuberous sclerosis complex associated with massive renal angiomyolipomas. There was significant risk of catastrophic haemorrhage from the angiomyolipomas during pregnancy. This created a challenging scenario for the anaesthetists, obstetricians, urologists and interventional radiologists involved in their care, necessitating collaborative working, numerous investigations and honest patient‐centred discussions. Evidence for the management of tuberous sclerosis and angiomyolipomas in pregnancy does not appear to have been previously reported. After much consideration, arterial embolisation of the most vascular area of the angiomyolipoma was completed at 28 weeks gestation under remifentanil sedation. An elective caesarean section under combined spinal epidural anaesthesia was completed at 37 + 3 weeks gestation. Central nervous system involvement must always be considered; benign tumours within the brain and spinal cord may contraindicate neuraxial techniques. Early multidisciplinary involvement is essential due to the diverse and complex nature of tuberous sclerosis. Individuals differ in their presentation and disease severity; therefore, they must be assessed on an individual basis with management tailored accordingly. [ABSTRACT FROM AUTHOR]

Background: Erector spinae plane block (ESPB) in pediatric patients presenting for hip surgery may improve the postoperative analgesia. Aim: The study aimed to investigate the effect of ultrasound‐guided ESPB on postoperative analgesia after a pediatric hip surgery. Methods: Forty children scheduled for hip surgeries were included in this trial and randomly distributed into; Control group, patients received sham ultrasound‐guided ESPB at the level of L3 or ESPB group, patients received real ultrasound‐guided ESPB at the level of L3 with an injection of 0.4 ml/kg of plain bupivacaine 0.25%. The time for the first call of rescue analgesia, intraoperative fentanyl consumption, postoperative morphine consumption, Children's Hospital Eastern Ontario Pain Scale (CHEOPS), and Objective Behavioral Pain score (OPS) were recorded. Results: As compared to the control group, the use of ESPB significantly prolonged the time for first request of rescue analgesia from 170.50 ± 44.066 to 256.50 ± 66.434 min (p < 0.0001), decreased the intraoperative fentanyl consumption from 1.025 ± 0.379 to 0.775 ± 0.343 μg/kg (p = 0.035), decreased the postoperative morphine consumption from 0.105 ± 0.036 to 0.065 ± 0.023 mg/kg (p = 0.0002). Also, it significantly decreased postoperative CHEOPS and OPS scores 2, 4, and 6 h after the surgery (p < 0.05) with an insignificant difference between the two groups at all other time intervals (p ˃ 0.05). Conclusion: The use of ESPB in pediatric patients undergoing hip surgery prolonged the time for the first call of analgesia, decreased the intraoperative and postoperative opioid consumption, and decreased the postoperative pain. [ABSTRACT FROM AUTHOR]

Introduction: The sesamoid disease is a cause of lameness in dogs, and there is limited literature relating to diagnosis, treatment and outcome of treatment in dogs with the sesamoid disease. Our aim was to compare the efficacy of intra‐articular metacarpophalangeal/metatarsophalangeal joint injection with methylprednisolone and bupivacaine (IMPB) or conservative management with nonsteroidal anti‐inflammatories and rest (CMNR) for treatment of this disease. Materials and methods: We conducted a retrospective survey of dogs treated for the sesamoid disease with IMPB or CMNR. The medical records of all dogs that received IMPB or were recommended CMNR for treatment of sesamoid pain were reviewed, and a client questionnaire was delivered to owners. Response to treatment, rapidity of response, length of resolution and recurrence of clinical signs associated with the sesamoid disease were assessed. Results: A total of 78 dogs were included in the study. One week after IMPB, 52/58 (89.7%) dogs demonstrated resolution of lameness compared with 1 week of CMNR, 0/18 (P < 0.001). There was limited statistical evidence in client satisfaction between treatment groups, IMPB 36/53 (67.9%) and CMNR 16/17 (94%) (P = 0.052). Dogs presenting with the sesamoid disease had comorbidities in 51/78 (65.4%) of cases. Elbow disease was the most common comorbidity 29/78 (37.2%). Conclusion: Our results support the use of IMPB for short‐term (1 week) resolution of lameness associated with sesamoid disease in dogs. Dogs treated with CMNR had slower improvement; however, there was no difference in lameness or client satisfaction between treatment groups at long‐term follow‐up (12 months). [ABSTRACT FROM AUTHOR]

Background: Despite increased attention, acute and persistent post‐operative pain are not treated efficiently and interventions against acute pain are therefore of clinical importance and should be welcomed. Aims and objectives: To evaluate the effectiveness of wound infiltration with 0.5% bupivacaine for pain management in the immediate post‐operative period in patients that underwent cardiac surgery with sternotomy. Design: The study was performed employing a single‐centre nonrandomized experimental design to evaluate a prospective cohort of patients recruited from June to December of 2017. Methods: A single‐centre study with a non‐randomized experimental design compared the pain perceived by 137 patients undergoing to cardiac surgery within which 68 patients who received infiltration of bupivacaine and 69 patients received infiltration with saline solution. Pain measures were made with the numeric rating scale (NRS) at 2, 12, 24, and 48 hours. Socio‐demographic and clinical variables were included too and descriptive, bivariate, and multivariate logistic regression analyses were performed. Results: A statistically significant difference was found between the means of the NRS scores in favour of the intervention group. Cohen's d showed a significant effect size. NRS scores were grouped into NRS ≥4 or NRS <4 and similar results were found. Multivariate logistic regression analyses showed the absence of confounding factors that could call results into question. Conclusion: Subcutaneous infiltration of 0.5% bupivacaine in the surgical site of patients who have undergone cardiac surgery showed clinically and statistically significant pain relief compared with patients who received saline infiltration throughout the first 12 hours after surgery. This intervention provides promising preliminary results that, alone or in conjunction with other nursing interventions, could constitute an important therapeutic tool for this area of nursing clinical practice. [ABSTRACT FROM AUTHOR]

Opioid analgesics are commonly used post‐lung transplant, but have many side effects and are associated with worse outcomes. We conducted a retrospective review of all lung transplant recipients who were treated with a multimodal opioid‐sparing pain protocol. The use of liposomal bupivacaine intercostal nerve block was variable due to hospital restrictions. The primary objective was to describe opioid requirements and patient‐reported pain scores early post‐lung transplant and to assess the impact of intraoperative liposomal bupivacaine intercostal nerve block. We treated 64 lung transplant recipients with our protocol. Opioid utilization decreased to a mean of 43 milligram oral morphine equivalents by postoperative day 4. Median pain scores peaked at 4 on postoperative day 1 and decreased thereafter. Only three patients were discharged home with opioids, all of whom were taking opioid agonist therapy pre‐transplant for opioid use disorder. Patients who received liposomal bupivacaine intercostal nerve block in the operating room had a significant reduction in opioid consumption over postoperative day 1 through 4 (228 mg vs. 517 mg, P=.032). A multimodal opioid‐sparing pain management protocol is feasible and resulted in weaning of opioids prior to hospital discharge. [ABSTRACT FROM AUTHOR]

Objective comparative evidence of the time to onset and duration of effect provided by local anaesthetic (LA) agents for perineural blocks in the horse is lacking. Clear knowledge of these properties is required to guide clinically appropriate agent selection and aid interpretation of response to diagnostic blocks for lameness examinations. An interventional study, with complete, randomised crossover design was used to compare time to onset and duration of skin desensitisation provided by four LA agents applied to palmar digital nerve blocks in 12 horses. Effect at each time point was determined using a pressure gauge to measure the mechanical nociceptive threshold (MNT) over the heel bulbs. Complete desensitisation was defined when MNT was greater than four times the pre‐block baseline. Onset and duration of complete desensitisation were recorded and compared across agents using a mixed linear model. When significant (P ≤ 0.05), post‐hoc paired comparisons between agents were performed against a Tukey's corrected P ≤ 0.05. Onset of complete skin desensitisation for each agent was <5 min. Duration for lidocaine (mean 25 min; 95% confidence interval [CI] 9–42) was shorter than bupivacaine (53 min; 95% CI 39–65), which was shorter than both prilocaine (102 min; 95% CI 81–123) and mepivacaine (107 min; 95% CI 92–121), which were not different. Although onset of complete skin desensitisation was not different for the LA agents tested, duration varied from 25 min to nearly 2 h. Prilocaine and mepivacaine provided the most prolonged duration of effect, both exceeding bupivacaine. [ABSTRACT FROM AUTHOR]

A 9‐year‐old male neutered domestic short hair cat was referred to our practice after a road traffic accident. On presentation, the cat was obtunded, with bilateral hindlimb fractures. The fractures were surgically repaired, and an epidural catheter was placed for perioperative pain management. Postoperative analgesia consisted of bupivacaine administered intermittently through the epidural catheter. In the days after surgery, the cat became duller and more obtunded, and marked bilateral mydriasis with absence of a pupillary reflex was noted. After ruling out different causes for mydriasis and weaning the cat from systemic opioids, local anaesthetic systemic toxicity (LAST) emerged the primary differential diagnosis. Bupivacaine plasma concentrations were measured and found a fourfold increase in concentration over that reported after a perineural block. Mydriasis and absent pupillary light reflex, among other clinical signs, could be early indicators of LAST secondary to accumulation of the local anaesthetic in patients with an epidural catheter. [ABSTRACT FROM AUTHOR]

In the present study, we developed a simple and rapid analytical method for the quantification of bupivacaine hydrochloride in human biopsy samples of adipose, muscle, neural, connective and cartilage tissue using liquid chromatography‐mass spectrometry. Anesthetics were extracted from the tissue samples using 0.1% formic acid in acetonitrile for protein denaturation and hexane for removal of lipophilic impurities. Analytes were separated adequately on Phenomenex Luna Omega polar C18 column using a gradient mobile phase 0.1% formic acid in water and 0.1% formic acid in acetonitrile. The lower limits of quantification were ≤ 97 ng g−1 tissue for all studied tissues. Intra‐day recoveries were between 48.2% and 82.1% with relative standard deviations (RSDs) between 1.47% and 14.28%, whereas inter‐day recoveries were between 52.2% and 77.6% with RSDs between 2.98% and 14.79%. The calibration curve showed a linear fit with R2 higher than 0.99 in the concentration range from 0.16 to 100 μg g−1. Lidocaine hydrochloride was tested as internal standard because its recoveries and matrix effects were comparable to bupivacaine hydrochloride. Post‐analytical corrections of measured bupivacaine tissue concentrations can accordingly be made based on recovery of lidocaine as internal standard, with recoveries between 51.2% and 86.9% and RSDs between 1.99% and 16.88%. The developed method could be used to study time‐dependent spread of bupivacaine locally or to more distant locations across tissue barriers. [ABSTRACT FROM AUTHOR]

Wounds resulting from surgeries, implantation of medical devices, and musculoskeletal trauma result in pain and can also result in infection of damaged tissue. Up to 80% of these infections are due to biofilm formation either on the surface of implanted devices or on surrounding wounded tissue. Bacteria within a biofilm have intrinsic growth and development characteristics that allow them to withstand up to 1,000 times the minimum inhibitory concentration of antibiotics, demonstrating the need for new therapeutics to prevent and treat these infections. Cis‐2‐decenoic acid (C2DA) is known to disperse preformed biofilms and can prevent biofilm formation entirely for some strains of bacteria. Additionally, local anesthetics like bupivacaine have been shown to have antimicrobial effects against multiple bacterial strains. This study sought to evaluate hexanoic acid‐treated electrospun chitosan membranes (HA‐ESCM) as wound dressings that release C2DA and bupivacaine to simultaneously prevent infection and alleviate pain associated with musculoskeletal trauma. Release profiles of both therapeutics were evaluated, and membranes were tested in vitro against Methicillin‐resistant Staphylococcus aureus (MRSA) to determine efficacy in preventing biofilm infection and bacterial growth. Results indicate that membranes release both therapeutics for 72 hr, and release profile can be tailored by loading concentration. Membranes were effective in preventing biofilm growth but were toxic to fibroblasts when loaded with 2.5 or 5 mg of bupivacaine. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is a leading cause of cancer‐related death worldwide. Retrospective studies suggest that using local/regional anesthetic (LA/RA) is associated with better outcomes in primary HCC patients. In this study, we evaluated the effects of LA/RA bupivacaine in HCC cells and the underlying molecular mechanisms. The biological functions of bupivacaine in HCC cells were evaluated by transcriptome RNA sequencing, cell viability assay, bromodeoxyuridine incorporation assay, colony formation assay, flow cytometry, western blot, wound healing assay, transwell cell migration assay, tumor xenograft formation, and lung metastasis assay. Bupivacaine suppressed proliferation and induced apoptosis of HepG2 and SNU‐449 cells in a time‐ and dose‐dependent manner. Bupivacaine treatment also decreased colony formation, migration, and invasion of HepG2 and SNU‐449 cells. In mouse models, bupivacaine repressed tumor xenograft growth and lung metastasis of HepG2 cells. Transcriptome sequencing of HepG2 cells suggested that PI3K/Akt and MAPK signaling pathways were suppressed by bupivacaine treatment. In western blot analysis, bupivacaine reduced the expression of total and phosphorylated Akt, mTOR, and MAPK. Furthermore, reactivated PI3K/Akt and MAPK signaling by EGF or NRG1 partially reversed the effects of bupivacaine on cell growth, colony formation, and invasion of HCC cells. Local anesthetic bupivacaine suppressed proliferation, migration and invasion, and induced apoptosis of HCC cells. Our results provided novel insights into the local anesthetic bupivacaine in the therapy of HCC patients. [ABSTRACT FROM AUTHOR]