Comparison of sequential and mixture injections of opioids and hyperbaric bupivacaine for subarachnoid block for lower segment caesarean section: a randomised controlled study.

INTRODUCTION: Opioids are commonly added to local anaesthetic for subarachnoid block for caesarean section due to their synergistic effects. The physiochemical characteristics of opioids suggest premixing with hyperbaric bupivacaine may limit their distribution within the CSF. We studied the effect of a separate injection with a combination of bupivacaine, morphine and fentanyl on block characteristics, haemodynamic changes, postoperative pain and patient satisfaction. METHOD: Following ethical approval and informed consent, a prospective double-blinded randomised controlled trial was performed in a university hospital. A total of 126 patients undergoing caesarean section were randomised to two groups. In group M, the premixed group, patients received 12 mg of hyperbaric bupivacaine, 20 mcg of fentanyl and 100 mcg of morphine injected as a single mixture. In group S, the separate injection group, patients received the same drugs in separate injections. Measurements included haemodynamics, block distribution, intra- and postoperative pain, as well as patient satisfaction. RESULTS: Patients in both groups had similar block height, time to maximum sensory block, time to block regression and motor block. However, haemodynamics were different between the groups. The proportion of systolic hypotension episodes was greater in group S [159/1320 (12.05%)] than group M [113/1452 (7.78%)], with P = 0.0002. Moreover, a greater amount of ephedrine was administered in group S than group M, with values 12.09 (8.1) and 9.09 (8.5) mg respectively (P = 0.001). Additionally, postoperative pain, as measured by the Visual Analogue Scale (VAS), was greater in group M, with a VAS of 4.6 (1.7), vs. group S, which recorded a VAS of 3.8 (2.0) (P = 0.017). CONCLUSION: Sequential injection of intrathecal opioids and hyperbaric bupivacaine resulted in greater early haemodynamic instability and slightly better postoperative analgesia without any difference in block height or patient satisfaction. CLINICAL TRIAL REGISTRATION: NCT04403724.

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

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

Evaluation of two doses (20 mL and 15 mL) of 0.25% bupivacaine in pericapsular nerve group block for patient positioning for sub-arachnoid block during hip fracture surgery: A single-centre, randomised comparative trial.

Background and Aims: Peri-capsular nerve group (PENG) block is a novel ultrasound (US)-guided technique to achieve regional analgesia in hip fractures. We compared the effectiveness of two doses of 0.25% bupivacaine (20 mL and 15 mL) in the US-guided PENG block for positioning patients for sub-arachnoid block (SAB) during hip fracture surgery. Methods: The randomised trial included 60 patients aged 40-90 years undergoing hip fracture surgery under SAB. PENG block was given by a US-guided approach with the patient in a supine position 20 minutes before SAB, and a total of 20 mL and 15 mL of bupivacaine (0.25%) were given in groups A and B, respectively. The primary outcome was to measure and compare the ease of positioning (EOP) of patients for the conduct of SAB. The secondary outcome was the pain assessment at rest and 15° leg raise position at baseline and 10 and 20 minutes post block using the verbal analogue scale (VAS). Continuous variables were compared using the t-test, and categorical variables were analysed using Pearson's Chi-square test or Fisher's exact test. Results: The mean (standard deviation) grade of EOP for SAB was significantly better in group A (2.47 (0.73) (95% confidence interval [CI]: 2.19-2.69)) than in group B (1.86 (0.62) (95% CI: 1.65-2.1)) (P = 0.001). The decrease in VAS scores was significantly higher in group A compared to group B at resting and 15° leg raise position at all-time points (P < 0.05). Conclusion: A dose of 20 mL of 0.25% bupivacaine shows better outcomes than 15 mL regarding the patient's positioning during the SAB.

TXNIP knockdown protects rats against bupivacaine-induced spinal neurotoxicity via the inhibition of oxidative stress and apoptosis.

Bupivacaine (BUP) is an anesthetic commonly used in clinical practice that when used for spinal anesthesia, might exert neurotoxic effects. Thioredoxin-interacting protein (TXNIP) is a member of the α-arrestin protein superfamily that binds covalently to thioredoxin (TRX) to inhibit its function, leading to increased oxidative stress and activation of apoptosis. The role of TXNIP in BUP-induced oxidative stress and apoptosis remains to be elucidated. In this context, the present study aimed to explore the effects of TXNIP knockdown on BUP-induced oxidative stress and apoptosis in the spinal cord of rats and in PC12 cells through the transfection of adeno-associated virus-TXNIP short hairpin RNA (AAV-TXNIP shRNA) and siRNA-TXNIP, respectively. In vivo, a rat model of spinal neurotoxicity was established by intrathecally injecting rats with BUP. The BUP + TXNIP shRNA and the BUP + Control shRNA groups of rats were injected with an AAV carrying the TXNIP shRNA and the Control shRNA, respectively, into the subarachnoid space four weeks prior to BUP treatment. The Basso, Beattie & Bresnahan (BBB) locomotor rating score, % MPE of TFL, H&E staining, and Nissl staining analyses were conducted. In vitro, 0.8 mM BUP was determined by CCK-8 assay to establish a cytotoxicity model in PC12 cells. Transfection with siRNA-TXNIP was carried out to suppress TXNIP expression prior to exposing PC12 cells to BUP. The results revealed that BUP effectively induced neurological behavioral dysfunction and neuronal damage and death in the spinal cord of the rats. Similarly, BUP triggered cytotoxicity and apoptosis in PC12 cells. In addition, treated with BUP both in vitro and in vivo exhibited upregulated TXNIP expression and increased oxidative stress and apoptosis. Interestingly, TXNIP knockdown in the spinal cord of rats through transfection of AAV-TXNIP shRNA exerted a protective effect against BUP-induced spinal neurotoxicity by ameliorating behavioral and histological outcomes and promoting the survival of spinal cord neurons. Similarly, transfection with siRNA-TXNIP mitigated BUP-induced cytotoxicity in PC12 cells. In addition, TXNIP knockdown mitigated the upregulation of ROS, MDA, Bax, and cleaved caspase-3 and restored the downregulation of GSH, SOD, CAT, GPX4, and Bcl2 induced upon BUP exposure. These findings suggested that TXNIP knockdown protected against BUP-induced spinal neurotoxicity by suppressing oxidative stress and apoptosis. In summary, TXNIP could be a central signaling hub that positively regulates oxidative stress and apoptosis during neuronal damage, which renders TXNIP a promising target for treatment strategies against BUP-induced spinal neurotoxicity.

Apelin-13 reverses bupivacaine-induced cardiotoxicity: an experimental study.

INTRODUCTION: Cardiac arrest or arrhythmia caused by bupivacaine may be refractory to treatment. Apelin has been reported to directly increase the frequency of spontaneous activation and the propagation of action potentials, ultimately promoting cardiac contractility. This study aimed to investigate the effects of apelin-13 in reversing cardiac suppression induced by bupivacaine in rats. METHODS: A rat model of cardiac suppression was established by a 3-min continuous intravenous infusion of bupivacaine at the rate of 5 mg.kg-1.min-1, and serial doses of apelin-13 (50, 150 and 450 µg.kg-1) were administered to rescue cardiac suppression to identify its dose-response relationship. We used F13A, an inhibitor of Angiotensin Receptor-Like 1 (APJ), and Protein Kinase C (PKC) inhibitor chelerythrine to reverse the effects of apelin-13. Moreover, the protein expressions of PKC, Nav1.5, and APJ in ventricular tissues were measured using Western blotting and immunofluorescence assay. RESULTS: Compared to the control rats, the rats subjected to continuous intravenous administration of bupivacaine had impaired hemodynamic stability. Administration of apelin-13, in a dose-dependent manner, significantly improved hemodynamic parameters in rats with bupivacaine-induced cardiac suppression (p < 0.05), and apelin-13 treatment also significantly upregulated the protein expressions of p-PKC and Nav1.5 (p < 0.05), these effects were abrogated by F13A or chelerythrine (p < 0.05). CONCLUSION: Exogenous apelin-13, at least in part, activates the PKC signaling pathway through the apelin/APJ system to improve cardiac function in a rat model of bupivacaine-induced cardiac suppression.

To Compare the Effects of Post-tonsillectomy Intra-operative Infiltration of Ropivacaine Versus Bupivacaine in Tonsillar Fossa.

Tonsillectomy is one of the most common surgical procedures practiced in Otorhinolaryngology. A significant obstacle for the speedy and smooth recovery is early post- operative pain. Pain leads to negative outcomes such as poor intake, tachycardia, anxiety, delayed wound healing and insomnia. Aim to assess and compare the effect of post-incisional infiltration of 0.75% Ropivacaine v/s 0.5% Bupivacaine on post tonsillectomy pain, the on start of oral intake and stay in hospital and to investigate any complications that can arise due to infiltration of the said drugs. 60 Patients above the age of 5 years were posted for tonsillectomy or adenotonsillectomy under general anesthesia. Patients were blinded about the group in which they will be enrolled. Group A received Inj. ropivacaine (0.75%) 2 ml and Group B: received Inj. Bupivacaine (0.50%) 2 ml in each fossa. After surgery, no analgesics were given & patients were observed for the intensity of post-operative pain in the immediate post-operative period, at 2, 4, 6, 12, 24, 48 h and further if not discharged using VISUAL ANALOGUE SCORE (VAS) and VERBAL RATING SCALE(VRS). Post-operative pain assessment was done using VAS and VRS at 2nd, 4th, 6th, 12th, 24th and 48th hour which was found to be lower in Group 'A'. Patients in Group 'A' also started their oral intake sooner, had lesser hospitalization days than group 'B' patients. Longer time for Rescue analgesic and reduced total dose of analgesic required was seen in Group A compared to Group B. This comparative study on Post-incisional infiltration of 2 ml 0.75% Ropivacaine v/s 2 ml 0.5% Bupivacaine has shown that Ropivacaine is a more effective drug in reducing post-operative pain in comparison to Bupivacaine, proven statistically.

Reduced Opioid Use Among Patients Who Received Liposomal Bupivacaine Brachial Plexus Block for Total Shoulder Arthroplasty.

Purpose This retrospective cohort explores the efficacy of regional shoulder blocks using Exparel™ in patients undergoing total shoulder arthroplasty (TSA)/reverse total shoulder arthroplasty (RSA) to reduce total opioid prescription, refills, and length of stay in the acute care setting. Methods Patients who underwent TSA/RSA by a single surgeon in a three-year period were evaluated. Patients in the case group received liposomal bupivacaine 1.3% brachial plexus block while the control group received ropivacaine 0.5% interscalene brachial plexus block. Outcomes of the study included the number of opioids taken, opioids prescribed, and length of hospital stay. Results Thirty-six patients underwent TSA/RSA between January 2017 and March 2020. Patients who received an Exparel brachial plexus block had decreased opioid use within the first 24 hours after surgery compared to the ropivacaine group, 9.00 ± 14.10 and 26.20 ± 24.8 morphine milligram equivalent (MME), respectively (p=0.0213). Patients who received an Exparel brachial plexus block had decreased opioid prescriptions over the entire postoperative follow-up, 411.00 ± 200.74 MME in the case group and 593.07 ± 297.57 MME in the control group (p=0.0314). Lastly, patients who received an Exparel brachial plexus block had a shorter length of hospital stay, 1.28 ± 0.91 days as compared to the control group's 2.15 ± 1.49 days (p=0.0451). Conclusion This study demonstrates a significant reduction in opioid prescribing and use in patients who receive Exparel brachial plexus nerve blocks compared to non-liposomal local anesthetics, as well as a significant reduction in the length of hospital stay. The data suggest that Exparel use may decrease the risks associated with opioid use while providing adequate analgesia in patients undergoing shoulder arthroplasty.

Efficacy of Peripheral Nerve Stimulator Guided Pectoral Nerve Block-1 and Serratus Anterior Plane Block for Post-operative Analgesia in Modified Radical Mastectomy: A Randomized Controlled Study.

BACKGROUND: Breast carcinoma is one of the most common cancers in present-day women worldwide, hence surgical intervention for the same is inevitable. General anesthesia being the preferred technique, the selection of appropriate postoperative pain management is a major concern in which superficial fascial plane chest wall blocks play a pivotal role. We aimed to prove the efficacy of peripheral nerve stimulator-guided pectoral nerve-1 (PEC 1) block and serratus anterior plane (SAP) block for postoperative analgesia in modified radical mastectomy. METHODS: This prospective randomized controlled clinical study comprised 60 females undergoing modified radical mastectomy and was randomly allocated to two groups. Group A patients received general anesthesia while, in addition to general anesthesia, group B patients received PEC 1 and SAP blocks. Postoperatively the active and passive visual analog score (VAS), duration of analgesia, cumulative requirement of rescue analgesics in the first 24 hours and associated perioperative complications were noted. All quantitative data were analyzed by student t-test and qualitative data by chi-square test using MedCalc software 12.5. RESULTS: VAS score for first 24 hours in group B was lower at rest, on pressure over the surgical site as well as on movements compared with the patients in group A with the p-value being < 0.0001 at all time intervals. Time for receiving first rescue analgesia was shorter (1.25±0.56hour vs 20.05±7.78hour, p<0.001) with the significantly higher requirement of cumulative doses of tramadol in the first 24 hours in patients belonging to group A (233.33±47.95mg vs 110±31.62 mg, p<0.001). CONCLUSION: PEC 1 and SAP blocks given under peripheral nerve stimulator guidance have a high success rate and are reliable in providing adequate postoperative analgesia for patients undergoing modified radical mastectomy.

Background factors for intra-operative hypotension during hip fracture repair surgery in the elderly under spinal anesthesia managed by orthopedic surgeons: A retrospective case-control study.

BACKGROUND: Spinal anesthesia is used for femoral trochanteric fracture surgery, but frequently induces hypotension and the causative factors remain unclear. We examined background factors for the use of an intraoperative vasopressor in elderly patients receiving spinal anesthesia for femoral trochanteric fracture surgery. METHODS: We retrospectively analyzed 203 patients >75 years (mean age, 87.9 years) with femoral trochanteric fractures who underwent short nail fixation under orthopedically managed spinal anesthesia at our hospital between April 2020 and July 2023. Patients were divided into two groups: group A (intraoperative vasopressor) and group B (no vasopressor). The following data were compared: age, sex, height, weight, body mass index, antihypertensive medication, years of experience as a primary surgeon, bupivacaine dose, puncture level, anesthesia time, operation time, hemoglobin level and blood urea nitrogen/creatinine ratio on the day of surgery, brain natriuretic peptide level, left ventricular ejection fraction, and percentage of patients operated on the day of transport. RESULTS: There were 65 patients in group A and 138 in group B. The average dose of bupivacaine was 11.7 mg. In a univariate analysis, group A was slightly younger (87.0 vs. 88.3 years), had a higher blood urea nitrogen/creatinine ratio (27.1 vs. 24.5), more frequently received ß-blockers (14.1% vs. 5.8 %) and diuretic medications (21.9% vs. 11.6 %), and had a higher puncture level. A logistic regression analysis identified younger age (p = 0.02) and diuretic medication (p = 0.001) as independent risk factors in group A. Vasopressor use was more frequent at a higher puncture level in group A (57 % for L2/3, 33 % for L3/4, 15 % for L4/5, 0 % for L5/S). CONCLUSIONS: Spinal anesthesia-induced hypotension is attributed to volume deficit or extensive sympathetic blockade and may be prevented by avoiding high puncture levels and increasing preoperative fluid supplementation in patients on diuretics. There is currently no consensus on anesthetic dosages.

Blood bupivacaine concentrations after pecto-serratus and serratus anterior plane injections of plain and liposomal bupivacaine in robotically-assisted mitral valve surgery: Sub-study of a randomized trial.

STUDY OBJECTIVE: To investigate the timing of peak blood concentrations and potential toxicity when using a combination of plain and liposomal bupivacaine for thoracic fascial plane blocks. DESIGN: Pharmacokinetic analysis. SETTING: Operating room. PATIENTS: Eighteen adult patients undergoing robotically-assisted mitral valve surgery. INTERVENTIONS: Ultrasound-guided pecto-serratus and serratus anterior plane blocks using a mixture of 0.5% bupivacaine HCl up to 2.5 mg/kg and liposomal bupivacaine up to 266 mg. MEASUREMENTS: Arterial plasma bupivacaine concentration. MAIN RESULTS: Samples from 13 participants were analyzed. There was substantial inter-patient variability in plasma concentrations. A geometric mean maximum bupivacaine concentration was 1492 ng/ml (range 660 to 4650 ng/ml) at median time of 30 min after injection. In 4/13 (31%) patients, plasma bupivacaine concentrations exceeded our predefined 2000 ng/ml toxic threshold. A second much smaller peak was observed about 32 h after the injection. No obvious signs of local anesthetic toxicity were observed. CONCLUSIONS: Combined injection of plain and liposomal bupivacaine for pecto-serratus/serratus anterior plane blocks produced a biphasic pattern, with the highest arterial plasma concentrations observed within 30 min. Maximum concentrations exceeded the potential toxic threshold in nearly a third of patients, but without clinical evidence of toxicity. Clinicians should not assume that routine combinations of plain and liposomal bupivacaine for thoracic fascial plane blocks are inherently safe.

Comparison of Postoperative Analgesia Between Intrathecal Nalbuphine and Intrathecal Fentanyl in Infraumbilical Surgeries: A Double-Blind Randomized Controlled Trial.

INTRODUCTION: Spinal anesthesia is a widely used regional anesthesia technique for surgeries below the umbilicus, but postoperative analgesia is of major concern due to the relatively short duration of the local anesthetic. Various drugs were used as an additive to local anesthetic to prolong the duration of postoperative analgesia. This study aims to compare the efficacy of nalbuphine and fentanyl as an intrathecal additive along with local anesthetic. METHODOLOGY: A total of 166 patients aged between 18 and 65 years belonging to the American Society of Anesthesiologists (ASA) I and II undergoing elective infraumbilical surgeries were included in the prospective double-blind randomized controlled trial. The patients were allocated into two groups of 83 each. Group N was given 2.5 mL of 0.5% bupivacaine + 1 mg of nalbuphine (0.5 mL), and group F received 2.5 mL of 0.5% bupivacaine + 25 mcg fentanyl (0.5 mL). Both groups were compared for postoperative analgesia, onset and duration of both sensory and motor blockade, intraoperative hemodynamics, and side effects. RESULTS: All demographic data, hemodynamic parameters, and side effects were not statistically significant among the two groups. However, other parameters, such as the mean duration of analgesia, which was 267.27 ± 172.099 minutes in group N and 161.35 ± 14.957 minutes in group F; meantime for the onset of sensory blockade, which was 3.94 ± 1.769 minutes in group N and 5.94 ± 0.929 minutes in group F; onset of complete motor blockade, which was 7.10 ± 1.858 minutes in group N and 11.61 ± 1.218 minutes in group F; duration of motor blockade, which was 182.57 ± 13.011 minutes in group N and 112.53 ± 7.389 minutes in group F; and mean time taken for two-segment regression, which was 118.20 ± 12.61 minutes in group N and 113.72 ± 8.84 minutes in group F, were all comparable between the two groups. CONCLUSION: Nalbuphine was found to be more efficacious for prolongation of postoperative analgesia with better hemodynamic stability.

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

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

Spinal Anaesthesia Using Hypobaric Drugs: A Review of Current Evidence.

Spinal anesthesia is one of the most widely used techniques in modern anesthesia practice. It involves the injection of local anesthetic drugs into the cerebrospinal fluid (CSF) within the subarachnoid space. The choice of drug, its concentration, and baricity play a crucial role in determining the characteristics of the spinal block and has evolved over the years with continuous advancements in drug formulations and administration methods. Spinal anesthesia with hypobaric drugs represents a valuable technique in the armamentarium of anesthesiologists, offering distinct advantages in terms of targeted action, reduced systemic toxicity, and enhanced hemodynamic stability. This review aims to scan the characteristics of hypobaric drugs, factors influencing their spread within the spinal canal, challenges associated with their use, clinical applications in various surgical scenarios, and potential implications for patient outcomes and healthcare practice. PubMed and Google Scholar databases were searched for relevant articles and a total of 23 relevant articles were selected for the review based on inclusion and exclusion criteria. Hypobaric drugs have many advantages in high-risk morbidly ill patients for some select surgical procedures and daycare surgeries. The concentration and volume of hypobaric drugs need to be selected according to the extensiveness of the surgery and the desired block can be achieved by giving spinal injection in specific positions. The dynamic field of anesthesiology encompasses the integration of emerging technologies and evidence-based practices, which will contribute to further refining the safety and efficacy of spinal anesthesia with hypobaric drugs.

Absorption and pharmacokinetics of bupivacaine after bilateral topical administration in tonsillar fossae for posttonsillectomy pain relief.

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.

Liposomal bupivacaine intercostal block placed under direct vision reduces morphine use in thoracic surgery.

Background: Thoracic epidural analgesia (TEA) and liposomal bupivacaine (LB) are two methods used for postoperative pain control after thoracic surgery. Some studies have compared LB to standard bupivacaine. However, data comparing the outcomes of LB to TEA after minimally invasive lung resection is limited. Therefore, the objective of our study was to compare postoperative pain, opioid usage, and outcomes between patients who received TEA vs. LB. Methods: We conducted a retrospective chart review of patients who underwent minimally invasive lung resections over an 8-month period. Intraoperatively, patients received either LB under direct vision or a TEA. Pain scores were obtained in the post-anesthesia care unit (PACU) and at 12, 24, and 48 hours postoperatively. Morphine milligram equivalents (MMEs) were calculated at 24 and 48 hours postoperatively. Postoperative outcomes were then compared between groups. Results: In total, 391 patients underwent minimally invasive lung resection: 236 (60%) wedge resections, 51 (13%) segmentectomies, and 104 (27%) lobectomies. Of these, 326 (83%) received LB intraoperatively. Fewer patients in the LB group experienced postoperative complications (18% vs. 34%, P=0.004). LB patients also had lower median pain scores at 24 (P=0.03) and 48 hours (P=0.001) postoperatively. There was no difference in MMEs at 24 hours (P=0.49). However, at 48 hours, patients who received LB required less narcotics (P=0.02). Median hospital length of stay (LOS) was significantly shorter in patients who received LB (2 vs. 4 days, P<0.001). On multivariable analysis, increasing age, postoperative complications, and use of TEA were independently associated with a longer hospital LOS. Conclusions: Compared to TEA, LB intercostal block placed under direct vision reduced morphine use 48 hours after thoracic surgery. It was also associated with fewer postoperative complications and shorter median hospital LOS. LB is a good alternative to TEA for pain management after minimally invasive lung resection.

Chitosan Membranes Stabilized with Varying Acyl Lengths Release Cis-2-Decenoic Acid and Bupivacaine at Controlled Rates and Inhibit Pathogenic Biofilm.

BACKGROUND: Adherence of complex bacterial biofilm communities to burned tissue creates a challenge for treatment, with infection causing 51% of burn victim deaths. This study evaluated the release of therapeutics from wound care biomaterials and their antimicrobial activity against pathogens Staphylococcus aureus, Acinetobacter baumannii, and Pseudomonas aeruginosa. METHODS: Electrospun chitosan membranes (ESCMs) were fabricated and acylated with chain lengths ranging from 6-10 carbons then loaded with 0.15 mg of anti-biofilm agent, cis-2-decenoic acid (C2DA), and 0.5 mg of local anesthetic, bupivacaine. RESULTS: Combinations of therapeutics released from modified ESCMs at a cumulative amount of 45-70% of bupivacaine and less than 20% of C2DA. Results from bacterial studies suggest that this combination reduced biofilm 10-fold for S. aureus, 2-fold for Acinetobacter baumannii, and 2-3-fold for Pseudomonas aeruginosa by 24 hours. Additionally, dual loaded groups reduced planktonic Staphylococcus aureus ~4-fold by 24 hours as well as Acinetobacter baumannii ~3-fold by 48 hours. CONCLUSIONS: The combination of therapeutics used has a significant role in biofilm prevention for selected strains via direct contact or diffusion in aqueous solutions.

Liposomal bupivacaine for ultrasound-guided rectus sheath blocks after midline laparotomy.

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.

Ultrasound-guided and 'blind' sciatic nerve injection techniques: Comparison in rat cadavers.

OBJECTIVE: To compare the success rate and extent of sciatic nerve staining with a bupivacaine-dye solution using two injection techniques: 'blind' or ultrasound-guided approach. STUDY DESIGN: Prospective, experimental, randomized, cadaveric study. ANIMALS: Adult female Wistar rat cadavers [n = 24, mass 352 g (323-374)]. METHODS: Each sciatic nerve was randomly allocated to one of two groups: 'blind' (group B) or ultrasound-guided approach (group US) to injection. Following injection of bupivacaine-dye solution (0.1 mL), gross anatomical dissection was performed to visualize nerve staining, categorizing it as either positive or negative. The length of nerve staining was then measured and visual inspection conducted to identify potential nerve damage. Fisher's exact test was used to compare positive or negative nerve staining, and the Wilcoxon signed rank test used to compare the length of nerve staining between groups. RESULTS: In group B, the bupivacaine-dye solution stained 16/24 sciatic nerves (67% success). In group US, staining was successfully observed in all 24 nerves (100% success, p < 0.004). The length of nerve staining [median (interquartile range)] was 2 (2-3) mm in group B and 5 (4-6) mm in group US (p < 0.001). One sciatic nerve in group B had injectate distributed over 16 mm, suggestive of an intraneural injection. No signs of laceration or nerve damage were visible under 6× magnification in either group. CONCLUSIONS AND CLINICAL RELEVANCE: The ultrasound-guided approach for sciatic nerve injection demonstrated a higher success rate with superior injectate distribution when compared with the 'blind' approach. Ultrasound guidance is recommended over a 'blind' approach for sciatic nerve block in rats when possible.

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

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

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

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

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