Cost-effectiveness of Transforaminal epidural steroid injections for patients with ACUTE sciatica: a randomized controlled trial.

BACKGROUND: Transforaminal epidural injections with steroids (TESI) are increasingly being used in patients sciatica. The STAR (steroids against radiculopathy)-trial aimed to evaluate the (cost-) effectiveness of TESI in patients with acute sciatica (< 8 weeks). This article contains the economic evaluation of the STAR-trial. METHODS: Participants were randomized to one of three study arms: Usual Care (UC), that is oral pain medication with or without physiotherapy, n = 45); intervention group 1: UC and transforaminal epidural steroid injection (TESI) 1 ml of 0.5% Levobupivacaine and 1 ml of 40 mg/ml Methylprednisolone and intervention group 2: UC and transforaminal epidural injection (TEI) with 1 ml of 0,5% Levobupivacaine and 1 ml of 0.9% NaCl (n = 50). The primary effect measure was health-related quality of life. Secondary outcomes were pain, functioning, and recovery. Costs were measured from a societal perspective, meaning that all costs were included, irrespective of who paid or benefited. Missing data were imputed using multiple imputation, and bootstrapping was used to estimate statistical uncertainty. RESULTS: None of the between-group differences in effects were statistically significant for any of the outcomes (QALY, back pain, leg pain, functioning, and global perceived effect) at the 26-weeks follow-up. The adjusted mean difference in total societal costs was €1718 (95% confidence interval [CI]: - 3020 to 6052) for comparison 1 (intervention group 1 versus usual care), €1640 (95%CI: - 3354 to 6106) for comparison 2 (intervention group 1 versus intervention group 2), and €770 (95%CI: - 3758 to 5702) for comparison 3 (intervention group 2 versus usual care). Except for the intervention costs, none of the aggregate and disaggregate cost differences were statistically significant. The maximum probability of all interventions being cost-effective compared to the control was low (< 0.7) for all effect measures. CONCLUSION: These results suggest that adding TESI (or TEI) to usual care is not cost-effective compared to usual care in patients with acute sciatica (< 8 weeks) from a societal perspective in a Dutch healthcare setting. TRIAL REGISTRATION: Dutch National trial register: NTR4457 (March, 6th, 2014).

Pre-incisional local infiltration with levobupivacaine in laparoscopic cholecystectomy: a randomized and clinical trial.

OBJECTIVE: Laparoscopic cholecystectomy (LC), despite its minimally invasive nature, requires effective control of post-operative pain. The use of local anesthetics (LA) has been studied, but the level of evidence is low, and there is little information on important parameters such as health-related quality of life (HRQoL) or return to work. The objective of the study was to evaluate the efficacy of 0.50% levobupivacaine infiltration of incisional sites in reducing POP after LC. METHODS: This was a prospective, randomized, double-blind study. Patients undergoing elective LC were randomized into two groups: no infiltration (control group) and port infiltration (intervention group). POP intensity (numerical rating scale, NRS), need for rescue with opioid drugs, PONV incidence, HRQoL, and return to work data, among others, were studied. RESULTS: Two hundred and twelve patients were randomized and analyzed: 105 (control group) and 107 (intervention group). A significant difference was observed in the NRS values (control group mean NRS score: 3.41 ± 1.82 vs. 2.56 ± 1.96) (p < 0.05) and in the incidence of PONV (31.4% vs. 19.6%) (p = 0.049). CONCLUSIONS: Levobupivacaine infiltration is safe and effective in reducing POP, although this does not lead to a shorter hospital stay and does not influence HRQoL, return to work, or overall patient satisfaction.

OBJETIVO: la colecistectomía laparoscópica (CL), a pesar de su carácter mínimamente invasivo, requiere un control efectivo del dolor postoperatorio (POP). El uso de anestésicos locales (AL) ha sido estudiado pero el nivel de evidencia es bajo y existe poca información acerca de parámetros relevantes como la calidad de vida relacionada con la salud (CVRS) o la reincorporación laboral. El objetivo de este estudio es analizar la eficacia de la infiltración de los sitios incisionales con levobupivacaína 0,50% en la reducción del dolor postoperatorio tras la CL. MATERIAL Y MÉTODOS: estudio prospectivo, aleatorizado y doble ciego. Pacientes sometidos a CL programada fueron aleatorizados en dos grupos: sin infiltración (grupo control) y con infiltración preincisional (grupo intervención). La intensidad del dolor (escala de puntuación numérica, NRS), la necesidad de rescates con opioides, la incidencia de náuseas o vómitos postoperatorios (NVPO) y datos de CVRS o reincorporación laboral, entre otros, fueron recogidos. RESULTADOS: 212 pacientes fueron aleatorizados y analizados: 105 en el grupo control y 107 en el grupo de intervención. Se observó una diferencia estadísticamente significativa en la intensidad del dolor (puntuación media NRS: 3.41 ± 1.82 vs. 2.56 ± 1.96) (p < 0.05) y en la incidencia de NVPO (31.4% vs. 19.6%) (p = 0.049). CONCLUSIONES: La infiltración con levobupivacaína es segura y efectiva en la reducción del dolor postoperatorio, aunque esto no conlleva una menor estancia hospitalaria y no influye en los resultados de CVRS, reincorporación laboral o satisfacción del paciente.

Epidermal growth factor receptor phosphorylation contributes to levobupivacaine-induced contraction in isolated rat aorta.

Vasoconstriction induced by levobupivacaine, a local anesthetic, is mediated by increased levels of calcium, tyrosine kinase, c-Jun NH2-terminal kinase (JNK), and phospholipase D, which are associated with prolonged local anesthesia. Epidermal growth factor receptor (EGFR) phosphorylation is associated with vasoconstriction. However, its role in levobupivacaine-induced contractions remains unknown. We determined whether EGFR phosphorylation is associated with levobupivacaine-induced contractions in isolated rat thoracic aortas and identified the underlying cellular signaling pathways. The effects of various inhibitors and a calcium-free solution alone or in combination on levobupivacaine-induced contractions were then assessed. Furthermore, we examined the effects of various inhibitors on levobupivacaine-induced EGFR and JNK phosphorylation and calcium levels in vascular smooth muscle cells (VSMCs) of rat aortas. The EGFR tyrosine kinase inhibitor AG1478, matrix metalloproteinase (MMP) inhibitor GM6001, Src kinase inhibitors PP1 and PP2, and JNK inhibitor SP600125 attenuated levobupivacaine-induced contractions. Moreover, although the calcium-free solution abolished levobupivacaine-induced contractions, calcium reversed this inhibitory effect. The magnitude of the calcium-mediated reversal of abolished levobupivacaine-induced contractions was lower in the combination treatment with calcium-free solution and AG1478 than in the treatment with calcium-free solution alone. Levobupivacaine induced EGFR and JNK phosphorylation. However, AG1478, GM6001, and PP2 attenuated levobupivacaine-induced EGFR and JNK phosphorylation. Moreover, although levobupivacaine induced JNK phosphorylation in control siRNA-transfected VSMCs, EGFR siRNA inhibited levobupivacaine-induced JNK phosphorylation. Furthermore, AG1478 inhibited levobupivacaine-induced calcium increases in VSMCs. Collectively, these findings suggest that levobupivacaine-induced EGFR phosphorylation, which may occur via the Src kinase-MMP pathway, contributes to vasoconstriction via JNK phosphorylation and increased calcium levels.

Safety of blood reinfusion drains after local infiltration analgesia in total joint replacement.

BACKGROUND: Local infiltration analgesia (LIA) is frequently administered to patient undergoing joint replacement surgical procedures. The aim of the present research was to verify the safety of collected shed blood to be reinfused postoperatively, by measuring levobupivacaine levels in drainage blood in patients undergoing LIA during knee replacement surgery. PATIENTS AND METHODS: 24 patients who underwent total knee arthroplasty (TKA) and 12 scheduled for total hip arthroplasty (THA) who received intraoperative LIA were considered. Blood samples were collected from shed blood which was present in drainage 2 and 5 hours after surgery and serum was analysed by liquid chromatography-tandem mass spectrometry. RESULTS: At 2 hours postoperatively, the median levobupivacaine serum concentration in the collected shed blood was 1.2 mg/L (SD: 4.2) for TKA and 17.13 mg/L (SD: 24.4) for THA. At 5 hours, levobupivacaine concentration was 1.84 mg/L (SD: 2.2) for TKA and 17.5 mg/L (SD: 25.2) for THA. Higher values of average serum levobupivacaine concentration were reported in drains collected from patients who had undergone THA compared to TKA (p<0.001). BMI significantly influenced levels of serum drug, that resulted to be higher in patients with BMI<25 (p= 0.01). CONCLUSION: Levobupivacaine from collected shed blood that would have been returned to the patient, was below toxicity level at 2 and 5 hours after LIA during total joint replacement. The average serum levobupivacaine concentration was found to be higher in drains taken from THA patients than TKA patients. Patients with lower BMI demonstrated the highest levels of levobupivacaine in shed blood and a lower blood volume needed for central nervous system toxicity. Therefore, in patients with a lower BMI undergoing THA, anaesthetic dosage should be reduced or autotransfusion should be avoided to prevent potential risks of toxicity.

[Efficacy and safety analysis of bupivacaine liposome for pericapsular nerve group block for postoperative analgesia in elderly patients with hip replacement].

Objective: To investigate the efficacy and safety of bupivacaine liposome for pericapsular nerve group block (PENGB) for postoperative analgesia in elderly patients with total hip replacement. Methods: A total of 42 elderly patients underwent total hip replacement were selected in the Second Affiliated Hospital of Wenzhou Medical University from May to July in 2023, including 19 males and 23 females, aged (68.8±6.3) years, the American Society of Anesthesiologists (ASA) grade Ⅰ to Ⅲ. They were divided into bupivacaine liposome group (observation group) and levobupivacaine hydrochloride group (control group) according to random number table, with 21 cases in each group. All the patients were anesthetized by lumbar anesthesia combined with PENGB. During PENGB, the observation group was injected with 10 ml (133 mg) bupivacaine liposome+5 ml normal saline, and the control group was injected with 10 ml (75 mg) levobupivacaine hydrochloride+5 ml normal saline. The primary outcome measures included the rest and movement visual analogue scale (VAS) scores at 6, 12, 24, 36, 48, 60, and 72 h after operation, the sufentanil consumption in analgesic pump, the numbers of analgesic pump compressions, and the rates of additional parexib sodium use in ward. The secondary outcome measures were the changes in lower limb muscle strength, the length of hospital stay and the occurrence of adverse reactions. Results: There was no significant difference in the rest and movement VAS scores between the two groups at pre-operation and at 6 h after operation (P>0.05);but the rest and movement VAS scores at 12, 24, 36, 48, 60 and 72 h after operation in observation group were significantly lower than those in control group (P<0.05); the rest and movement VAS scores at 6, 12, 24, 36, 48, 60 and 72 h after operation were lower than those at pre-operation in two group (P<0.05). The consumption of sufentanil in analgesic pump and parexib sodium usage in observation group were lower than those in control group at 12, 24, 36 and 48 h after operation (P<0.05). The total number of analgesic pump compressions, the number of effective compressions and the number of ineffective compressions in 48 h in observation group were lower than those in control group (P<0.05). The muscle strength of the lower limbs of all patients were able to move against gravity at 12 h after operation. The incidence of nausea in 48 h after operation in observation group was 9.5% (2/21), which was lower than 42.9% (9/21) in control group (P=0.014). No postoperative vomiting occurred in all patients. The length of the hospital stay was (9.3±2.2) d in observation group and (8.9±1.9) d in control group, and there was no significant difference between the two groups (P=0.500). Conclusion: Compared with levobupivacaine hydrochloride, liposomal bupivacaine in PENGB provides analgesic effects for up to 72 h after total hip replacement in elderly patients, reduces postoperative opioid and other analgesics usage, decreases the incidence of postoperative nausea, and has a minor effect on lower limb movement without prolonging hospitalization.

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

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

Efficacy of ultrasound-guided infiltration with levobupivacaine and triamcinolone for myofascial pain syndrome of the quadratus lumborum: a retrospective observational study

Abstract Introduction and objectives: Myofascial Pain Syndrome (MPS) of the Quadratus Lumborum muscle (QL) is a frequent cause of chronic low back pain. With this study, we aimed to assess the efficacy of ultrasound-guided infiltration with 0.25% levobupivacaine and 40 mg triamcinolone for MPS of the QL. Methods: Observational and retrospective study of participants submitted to ultrasound-guided infiltration of the QL muscle from January 1, 2015 to June 31, 2019. Pain intensity was assessed using the five-point pain Numeric Rating Scale (NRS): pre-intervention, at 72 hours, 1 month, 3 months and 6 months post-intervention. Additional data collected were demographic characteristics, opioid consumption, and adverse effects. Results: We assessed 90 participants with mean age of 55.2 years. Sixty-eight percent of participants were female. Compared to the pre-intervention assessment, there was an improvement in pain at 72 hours (Mean Difference [MD = 3.085]; 95% CI: 2.200-3.970, p < 0.05), at the 1st month (MD = 2.644; 95% CI: 1.667-3.621, p < 0.05), at the 3rdmonth (MD = 2.017; 95% CI: 0.202-2.729, p < 0.05) and at the 6th month (MD = 1.339; 95% CI 0.378-2.300, p < 0.05), post-intervention. No statistically significant differences in opioid consumption were observed. No adverse effects associated with the technique were reported. Conclusions: Ultrasound-guided infiltration of the QL muscle is a safe and effective procedure for the treatment of pain in the QL MPS within 6 months post-intervention.

Comparative retrospective review of perioperative analgesia using ultrasound-guided programmed intermittent erector spinae plane block for video-assisted thoracoscopic lobectomy.

BACKGROUND: The retrospective cohort study was conducted to estimate the opioid-sparing anesthesia and limited side-effects with ultrasound (US)-guided ESPB using programmed intermittent bolus (PIB) or continuous infusion (CI) and standard opioid-based anesthesia in patients undergoing video-assisted thoracoscopic lobectomy (VATS). METHODS: Patients underwent VATS were stratified into either control group or one of the two ESPB groups in a 1:2:2 ratio depending on whether PIB was implemented or not. The primary endpoint was intra- and post-operative opioids consumption over the first 48 h following surgery. RESULTS: A total of 180 cases were included in the analysis. Cumulative perioperative opioid administration was found to be significantly different between PIB, CI and control group (both p < 0.001), and between PIB and CI group (p = 0.028). More specifically, the mean was 305.30 ± 51.35 mg, 339.68 ± 56.07 mg and 468.91 ± 79.84 mg in PIB, CI and control group. NRS scores at rest across all postoperative times were comparable in two ESPB groups, while significantly lower than control group, however, scores during exercising at postoperative 3, 6, 12 h were significantly lower in PIB group as compared to CI group. A wider anesthetized dermatomes with PIB was observed at 6, 24 and 48 h as opposed to the CI. The mean of levobupivacaine plasma concentration was significantly lower for PIB at postoperative 0.5, 12, 24 and 48 h after initiation than CI. However, local anesthetic toxicity was not observed in any of the two ESPB groups. CONCLUSIONS: When US-guided ESPB using PIB was performed preoperatively, it contributed to the minimization of intra- and post-operative opioid consumption due to better analgesia with a wider anesthetic dermatome opposed to conventional CI, whereas, it was also associated with lower risk of local anesthetic toxicity because of lower plasma concentration of levobupivacaine.

A comparison of intra and postoperative analgesic effects of sacrococcygeal and lumbosacral epidural levobupivacaine in cats undergoing ovariohysterectomy.

The aim of this study was to compare the intra and postoperative analgesic effects of sacrococcygeal epidural levobupivacaine with those of lumbosacral levobupivacaine in feline ovariohysterectomy. Thirty-six cats were premedicated with intramuscular acepromazine (0.05 mg/kg) and meperidine (6 mg/kg). Anesthesia was induced with intravenous propofol and maintained with isoflurane in oxygen. The cats were randomly assigned one of the three treatments receiving 0.33% levobupivacaine (0.3 mL/kg) into the sacrococcygeal (S-C group, n=12) or lumbosacral (L-S group, n=12) epidural space, or the same volume of 0.9% saline solution into one of the epidural approaches (Control group, n=12). Intraoperatively, cardiorespiratory variables, end-tidal isoflurane concentration (FE´ISO), and fentanyl requirements were recorded. Postoperative pain was assessed by the UNESP (Universidade Estadual Paulista)-Botucatu multidimensional composite pain scale and the Glasgow feline composite measure pain scale up to 8 hr post-extubation. Morphine was administered as rescue analgesia. Overall FE´ISO and fentanyl requirements were lower in the L-S and S-C compared to the Control (P=0.002-0.048, respectively). There was no significant difference in the cardiorespiratory variables during anesthesia, postoperative pain and rescue analgesia among groups. The time to standing after anesthesia was prolonged in the L-S and S-C groups than in the Control (P<0.001). Lumbosacral and sacrococcygeal epidural levobupivacaine resulted in similar decreases in isoflurane requirements and intraoperative fentanyl supplementation in the cats, with no postoperative benefits.

Effect of Transforaminal Epidural Corticosteroid Injections in Acute Sciatica: A Randomized Controlled Trial.

OBJECTIVE: Transforaminal epidural steroid injections (TESIs) are widely administered for sciatica. The aim of this trial was to evaluate the effectiveness of TESIs in patients with acute sciatica (<8 wk). METHODS: This study was conducted in 2 Dutch hospitals. Participants (n=141) were randomly assigned to (1) usual care and TESI of 1 ml of 40 mg/ml Methylprednisolone plus 1 ml of 0.5% Levobupivacaine (intervention 1); (2) usual care and transforaminal epidural injection with 1 ml of 0.5% Levobupivacaine and 1 ml NaCl 0.9% (intervention 2); (3) usual care consisting of oral pain medication with or without physiotherapy (control). Co-primary outcomes were back pain and leg pain intensity, physical functioning, and recovery measured during 6-month follow-up. RESULTS: There were no statistically significant mean differences in co-primary outcomes between groups during follow-up, except for leg pain when comparing intervention group 1 with control (-0.96 95%CI:-1.83 to -0.09). For secondary outcomes, some statistical significant between-group differences were found for treatment satisfaction and surgery, but only when comparing intervention group 2 to control. Post hoc analyses showed a statistically significant difference in response [50% improvement of leg pain (yes/no)] between intervention 1 and the control group at 3 months and that both intervention groups used less opioids. DISCUSSION: Except for a statistically significant effect of TESI on leg pain for patients with acute sciatica compared with usual care, there were no differences in co-primary outcomes. Nonetheless, transforaminal epidural injections seem to be associated with less opioid use, which warrants further exploration.

'Walking epidural': comparison of the analgesic efficacy of levobupivacaine 0.0625% + fentanyl 2mcg/mL versus ropivacaine 0.075% + fentanyl 2mcg/mL.

INTRODUCTION: Epidural infusion with low local anesthetic concentrations with opiates decrease the severity of the motor blockade associated. The present study aims to compare the analgesic efficacy and the motor blockade between two local anesthetic epidural infusions: levobupivacaine 0.0625% + fentanyl 2mcg/mL versus ropivacaine 0.075% + fentanyl 2mcg/mL. MATERIALS AND METHODS: In a single-blind prospective randomized study, 60 laboring parturient had continuous epidural analgesia as follows: 30 of them received levobupivacaine 0.0625% + fentanyl 2mcg/mL and 30 of them received ropivacaine 0.075% + fentanyl 2mcg/mL and rates of infusion were adjusted to the height. Analgesic, motor blockade and satisfaction records were collected as well as maternal and neonate adverse events. RESULTS: After 2 h of the catheter placement, patients who received levobupivacaine showed a mean VAS of 3.2 [1.8-4.6] versus 1.8 [1.2-2.5] (p = 0.05) in patients who received ropivacaine. In addition, patients who received levobupivacaine showed a punctuation in Bromage scale of 0.0 [0.0-1.0] versus 0.0 [0.0-0.0] (p = 0.04) in patients who received ropivacaine. Finally, the parturient who received levobupivacaine scored a mean satisfaction index of 8.1 [7.3-8.9] versus 9.3 [8.7-9.8] (p = 0.02) in those who received ropivacaine. We did not register maternal nor neonate adverse events. CONCLUSION: Both infusions (levobupivacaine 0.0625% + fentanyl 2mcg/mL and ropivacaine 0.075% + fentanyl 2mcg/mL) are effective for labor analgesia. However, ropivacaine would present a better pharmacodynamic profile with less motor blockade and decreased need for analgesic rescue hence improving patient's satisfaction.

The potencies and neurotoxicity of intrathecal levobupivacaine in a rat spinal model: Effects of concentration.

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.

Chronological changes in plasma levobupivacaine concentrations after bilateral modified thoracoabdominal nerve block through perichondrial approach.

The local anesthetic (LA) systemic toxicity of trunk blocks is a major concern. Recently, modified thoracoabdominal nerve block through perichondrial approach (M-TAPA) has attracted attention; however, plasma LA level is unknown. We tested whether the peak plasma LA concentration following M-TAPA, using 25 mL of 0.25% levobupivacaine mixed with epinephrine on each side, would be below the toxic level (2.6 µg/mL). We recruited 10 patients undergoing abdominal surgery with planned M-TAPA between November 2021 and February 2022. In all patients, 25 mL of 0.25% levobupivacaine mixed with 1:200,000 epinephrine was administered on each side. Blood samples were obtained at 10, 20, 30, 45, 60, and 120 min after the block. The highest individual peak and the mean peak plasma LA concentrations were 1.03 and 0.73 µg/mL, respectively. We could not capture the peak in five patients; however, the highest concentrations in all patients were significantly lower than the toxic level. A negative correlation between the peak level and body weight was observed. Our results indicated that the plasma LA concentration following M-TAPA using total of 50 mL of 0.25% levobupivacaine with epinephrine remains below the toxic level. Further research is required due to the small sample size of this study.Trial registry number: UMIN000045406.

Extrapleural infusion of levobupivacaine versus levobupivacaine-sufentanil-adrenaline after video-assisted thoracoscopic surgery (VATS): A randomised controlled trial.

BACKGROUND: Peripheral blocks are increasingly used for analgesia after video-assisted thoracic surgery (VATS). We hypothesised that addition of sufentanil and adrenaline to levobupivacaine would improve the analgesic effect of a continuous extrapleural block. METHODS: We randomised 60 patients undergoing VATS to a 5-mL h-1 extrapleural infusion of levobupivacaine at 2.7 mg mL-1 (LB group) or levobupivacaine at 1.25 mg mL-1 , sufentanil at 0.5 µg mL-1 , and adrenaline at 2 µg mL-1 (LBSA group). The primary outcome was the cumulative morphine dose administered as patient-controlled analgesia (PCA-morphine) at 48 and 72 h. The secondary outcomes were pain according to numerical rating scale (NRS) at rest and after two deep breaths twice daily, peak expiratory flow (PEF) daily, quality of recovery (QoR)-15 score at 1 day and 3 weeks postoperatively, serum levobupivacaine concentrations at 1 h after the start and at the end of the intervention, and adverse events. RESULTS: At 48 h, the median cumulative PCA-morphine dose for the LB group was 6 mg (IQR, 2-10 mg) and for the LBSA group 7 mg (IQR, 3-13.5 mg; p = .378). At 72 h, morphine doses were 10 mg (IQR, 3-22 mg) and 12.5 mg (IQR, 4-21 mg; p = .738), respectively. Median NRS score at rest and after two deep breaths was 3 or lower at all time points for both treatment groups. PEF did not differ between groups. Three weeks postoperatively, only the LB group returned to baseline QoR-15 score. The LB group had higher, but well below toxic, levobupivacaine concentrations at 48 and 72 h. The incidence of nausea, dizziness, pruritus and headache was equally low overall. CONCLUSION: For a continuous extrapleural block, and compared to plain levobupivacaine at 13.5 mg h-1 , levobupivacaine at 6.25 mg h-1 with addition of sufentanil and adrenaline did not decrease postoperative morphine consumption. The levobupivacaine serum concentrations after 48 and 72 h of infusion were well below toxic levels, therefore our findings support the use of the maximally recommended dose of levobupivacaine for a 2- to 3-day continuous extrapleural block.

Automated mandatory bolus versus basal infusion for maintenance of epidural analgesia in labour.

BACKGROUND: Epidural analgesia is often used for pain relief during labour and childbirth, and involves administration of local anaesthetics (LA) into the epidural space resulting in sensory blockade of the abdomen, pelvis, and perineum. Epidural opioids are often co-administered to improve analgesia. Administration of epidural medications can be accomplished by basal infusion (BI) or automated mandatory bolus (AMB). With BI, medications are administered continuously, while AMB involves injecting medications at set time intervals. Patient-controlled epidural analgesia (PCEA) on top of AMB or BI enables patients to initiate additional boluses of epidural medications.  The superior method of delivering epidural medications would result in lower incidence of pain requiring anaesthesiologist intervention (breakthrough pain). Also, it should be associated with lower incidence of epidural-related adverse effects including caesarean delivery, instrumental delivery (use of forceps or vacuum devices), prolonged duration of labour analgesia, and LA consumption. However, clear evidence of the superiority of one technique over the other is lacking. Also, differences in the initiation of epidural analgesia such as combined spinal-epidural (CSE) (medications given into the intrathecal space in addition to the epidural space) compared to epidural only, and medications used (types and doses of LA or opioids) may not have been accounted for in previous reviews.  Our prior systematic review suggested that AMB reduces the incidence of breakthrough pain compared to BI with no significant difference in the incidence of caesarean delivery or instrumental delivery, duration of labour analgesia, and LA consumption. However, several studies comparing AMB and BI have been performed since then, and inclusion of their data may improve the precision of our effect estimates. OBJECTIVES: To assess the benefits and harms of AMB versus BI for maintaining labour epidural analgesia in women at term. SEARCH METHODS: We searched CENTRAL, Wiley Cochrane Library), MEDLINE, (National Library of Medicine), Embase(Elseiver), Web of Science (Clarivate), the WHO-ICTRP (World Health Organization) and ClinicalTrials.gov (National Library of Medicine) on 31 December 2022. Additionally, we screened the reference lists of relevant trials and reviews for eligible citations, and we contacted authors of included studies to identify unpublished research and ongoing trials. SELECTION CRITERIA: We included all randomised controlled studies that compared bolus dosing AMB with continuous BI during epidural analgesia. We excluded studies of women in preterm labour, with multiple pregnancies, with fetal malposition, intrathecal catheters, those that did not use automated delivery of medications, and those where AMB and BI were combined. DATA COLLECTION AND ANALYSIS: We used standard methodology for systematic review and meta-analysis described by Cochrane. Primary outcomes included: incidence of breakthrough pain requiring anaesthesiologist intervention; incidence of caesarean delivery; and incidence of instrumental delivery. Secondly, we assessed the duration of labour; hourly LA consumption in bupivacaine equivalents, maternal satisfaction after fetal delivery, and neonatal Apgar scores.  The following subgroup analyses were chosen a priori: epidural alone versus CSE technique; regimens that used PCEA versus those that did not; and nulliparous versus combination of nulli- and multi-parous women. We used the GRADE system to assess the certainty of evidence associated with our outcome measures. MAIN RESULTS: We included 18 studies of 4590 women, of which 13 enrolled healthy nulliparous women and five included healthy nulli- and multiparous women. All studies excluded women with preterm or complicated pregnancies. Techniques used to initiate epidural analgesia differed between the studies: seven used combined spinal epidural, 10 used epidural, and one used dural puncture epidural (DPE). There was also variation in analgesics used. Eight studies utilised ropivacaine with fentanyl, three used ropivacaine with sufentanil, two utilised levobupivacaine with sufentanil, one used levobupivacaine with fentanyl, and four utilised bupivacaine with fentanyl. Most of the studies were assessed to have low risk of randomisation, blinding, attrition, and reporting biases, except for allocation concealment where eight studies were assessed to have uncertain risk and three with high risk. Our results showed that AMB was associated with lower incidence of breakthrough pain compared to BI (risk ratio (RR) 0.71; 95% confidence interval (CI) 0.55 to 0.91; I2 = 57%) (16 studies, 1528 participants), and lower hourly LA consumption in bupivacaine equivalents (mean difference (MD) -0.84 mg/h; 95% CI -1.29 to -0.38, I2 = 87%) (16 studies, 1642 participants), both with moderate certainty. AMB was associated with an estimated reduction in breakthrough pain incidence of 29.1% (incidence 202 per 1000, 95% CI 157 to 259), and was therefore considered clinically significant. The incidence of caesarean delivery (RR 0.85; 95% CI 0.69 to 1.06; I2 = 0%) (16 studies, 1735 participants) and instrumental delivery (RR 0.85; 95% CI 0.71 to 1.01; I2 = 0%) (17 studies, 4550 participants) were not significantly, both with moderate certainty. There was no significant difference in duration of labour analgesia (MD -8.81 min; 95% CI -19.38 to 1.77; I2 = 50%) (17 studies, 4544 participants) with moderate certainty. Due to differences in the methods and timing of outcome measurements, we did not pool data for maternal satisfaction and Apgar scores. Results reported narratively suggest AMB may be associated with increased maternal satisfaction (eight studies reported increased satisfaction and six reported no difference), and all studies showed no difference in Apgar scores. WIth the exception of epidural alone versus CSE which found significant subgroup differences in LA consumption between AMB and BI, no significant differences were detected in the remaining subgroup analyses. AUTHORS' CONCLUSIONS: Overall, AMB is associated with lower incidence of breakthrough pain, reduced LA consumption, and may improve maternal satisfaction. There were no significant differences between AMB and BI in the incidence of caesarean delivery, instrumental delivery, duration of labour analgesia, and Apgar scores. Larger studies assessing the incidence of caesarean and instrumental delivery are required.

Hemodynamic Safety and Effect of Dexmedetomidine on Superficial Cervical Block Quality for Carotid Endarterectomy: A Prospective Study.

OBJECTIVE: Dexmedetomidine as an adjuvant to local anesthetics (LAs) in regional anesthesia has demonstrated a positive effect on the quality of regional blocks, but there are no studies on usage in superficial cervical block (SCB) for carotid endarterectomy (CEA), in which the management of mean arterial pressure is essential. The authors designed a prospective, randomized, double-blinded study to investigate the effects of the addition of dexmedetomidine on the hemodynamic management and quality of SCB. DESIGN: A prospective, randomized, double-blinded study. SETTING: A single-center study at a university hospital center. PARTICIPANTS: Ultrasound-guided SCB was performed on 60 patients classified as American Society of Anesthesiologists Grades II and III undergoing elective CEA surgery who were assigned into 2 groups randomly. INTERVENTION(S): Both groups received 2 mg/kg of 0.5% levobupivacaine with 2 mg/kg of 2% lidocaine. The intervention group additionally received 50 µg of dexmedetomidine. MEASUREMENTS AND MAIN RESULTS: The onset and duration of sensory block and analgesia, hemodynamic parameters, and adverse effects were recorded. There were minimum effects on hemodynamic parameters and no differences in the incidence of adverse effects. The time to first analgesia was longer in the intervention group than in the control group (N = 30). There was no difference in the duration of the sensory block between groups. The log-rank test indicated a significant difference in the probability of the Numeric Pain Rating Scale <3. CONCLUSION: The addition of 50 µg of dexmedetomidine to 0.5% levobupivacaine and 2% lidocaine for SCB did not influence the hemodynamics and frequency of adverse effects. The median sensory block duration time showed no statistical difference between the groups, but the quality of analgesia postoperatively was much improved in the study group.

Sustained release of levobupivacaine from temperature-sensitive injectable hydrogel for long-term local anesthesia in postoperative pain management.

Postoperative pain is a major concern for most of the surgical patients, and an inadequate postoperative pain control may cause a series of complications. With an effective pain control and lesser side effects, local anesthetics are preferred for use in postoperative pain management. However, the action duration of current local anesthetics is too short to meet the requirements of postoperative analgesia. In this study, an injectable levobupivacaine (LB)-loaded thermo-sensitive hydrogel system based on biodegradable poly(D,L-lactide)-poly(ethylene glycol)-poly(D,L-lactide) (PLEL) was developed for long-acting local anesthetic, in which the soluble charged cation form of LB (LB HCl) was partly alkalified to the poorly soluble base form (LB base). This hybrid LB loaded PLEL system (hLB/PLEL) is a free flowable liquid at room temperature and changes into a semi-solid hydrogel once injection in response to the physiological temperature. Then, the dissolved LB HCl could release firstly from the hydrogel contributing to a quick work, and the insoluble LB base dissolved and released gradually as the decrease of the pH during the biodegradation of PLEL hydrogel, resulting in a long-term LB release in local. The drug release behavior, pharmacokinetic, and biocompatibility of the thermo-sensitive hLB/PLEL were studied in vitro and in vivo. The anesthetic effects of hLB/PLEL system were evaluated in the rat models of sciatic nerve block, subcutaneous infiltration anesthesia and postoperative pain as well. This hLB/PLEL system generated a significantly prolonged analgesic effect in rat models, which produced approximately 7 times longer duration than 0.75% LB HCl and effectively relieved the spontaneous pain for 3 days. In general, the presented hLB/PLEL system can not only achieve a fast-acting but also sustainably release LB to block the nerve and significantly extend the effect of local analgesia, which means a promising candidate for long-acting postoperative pain management.

Local Anesthetic Systemic Toxicity Following Inadvertent Intravenous Levobupivacaine Infusion in Infants: A Case Report.

Background and objectives: Local anesthetic systemic toxicity (LAST) in children is extremely rare, occurring at an estimated rate of 0.76 cases per 10,000 procedures. However, among reported cases of LAST in the pediatric population, infants and neonates represent approximately 54% of reported LAST cases. We aim to present and discuss the clinical case of LAST with full clinical recovery due to accidental levobupivacaine intravenous infusion in a healthy 1.5-month-old patient, resulting in cardiac arrest necessitating resuscitation. Case presentation: A 4-kilogram, 1.5-month-old female infant, ASA I, presented to the hospital for elective herniorrhaphy surgery. Combined anesthesia was planned, involving general endotracheal and caudal anesthesia. After anesthesia induction, cardiovascular collapse was noticed, resulting in bradycardia and later cardiac arrest with EMD (Electromechanical Dissociation). It was noticed that during induction, levobupivacaine was accidentally infused intravenously. A local anesthetic was prepared for caudal anesthesia. LET (lipid emulsion therapy) was started immediately. Cardiopulmonary resuscitation was carried out according to the EMD algorithm, which lasted 12 min until spontaneous circulation was confirmed and the patient was transferred to the ICU. In ICU, the girl was extubated the second day, and the third day she was transferred to the regular pediatric unit. Finally, the patient was discharged home after a total of five days of hospitalization with full clinical recovery. A four-week follow-up has revealed that the patient recovered without any neurological or cardiac sequelae. Conclusions: The clinical presentation of LAST in children usually begins with cardiovascular symptoms because pediatric patients are already under general anesthesia when anesthetics are being used, as was the case in our case. Treatment and management of LAST involve cessation of local anesthetic infusion, stabilization of the airway, breathing, and hemodynamics, as well as lipid emulsion therapy. Early recognition of LAST as well as immediate CPR if needed and targeted treatment for LAST can lead to good outcomes.

Spinal Dexamethasone Effect on Cognitive Disorders After Hip Surgery.

Background: Proximal femoral fractures (PrFF) are one of the most common causes of emergency admission in the elderly population. The majority of patients have pre-existing conditions that get worsened by unplanned surgery. Objective: Purpose of this article was to evaluate if a is single shot of dexamethasone with levobupivacaine administered intrathecally reduces postoperative pain and cognitive complications in patients with proximal femoral fractures. Methods: The study was performed at a level II trauma center which is a part of a teaching hospital with a catchment population of around 300,000 patients, the first author's affiliation. Around 500 PrFF are performed yearly in the center. All participants gave oral and written informed consent before randomization. Results: In total, 60 patients with a PrFF, ASA status 2 or 3 were randomized into two groups for spinal anaesthesia as DLSA study group (received 8 mg of dexamethasone and 12.5 mg of 0.5 % levobupivacaine) or LSA control group (received 12.5 mg of 0,5 % levobupivacaine). Postoperative cognitive disturbance was evaluated using simplified Confusion Assessment Method (CAM) scale, pain intensity was measured using Visual Analogue Scale (VAS) and blood samples for defining cortisol concentrations were taken before and after the surgical procedure. The primary outcomes were effects of intrathecal dexamethasone on plasma cortisol affecting cognitive disturbances. Secondary outcomes included pain scores and length of hospital stay. The DLSA group demonstrated a reduced incidence of postoperative cognitive dysfunction (POCD), p=0.043, longer analgesia duration, p<0.001, decreased cortisol levels and shorter hospitalization p=0.045. Intrathecal dexamethasone was the only significant predictor of postoperative delirium, OR 7.76, p=0.019. Conclusion: Single shot intrathecal administration of dexamethasone with levobupivacaine used in anaesthesia for proximal femoral fractures reduces the stress response by decreasing plasma cortisol concentrations prolonging analgesia. Complications such as delirium and POCD occurred with significantly lower frequency allowing better postoperative rehabilitation and shortening the hospitalization.

In vitro chondrotoxicity of bupivacaine, levobupivacaine and ropivacaine and their effects on caspase activity in cultured canine articular chondrocytes.

Bupivacaine, levobupivacaine and ropivacaine are potent, long acting, amide-type local anesthetics that have several clinical applications including intra-articular administration. The objectives of this study were to evaluate their in vitro effects on cell viability and caspase activity to elucidate whether they activate the extrinsic or intrinsic pathways of apoptosis in canine articular chondrocytes. Chondrocytes in monolayer culture were treated with culture medium as the control, or with 0.062% (0.62 mg/mL) bupivacaine, 0.062% levobupivacaine, and 0.062% ropivacaine for 24 hr. Cell viability was evaluated using the live/dead, 3-(4,5-dimehylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT), and Cell Counting Kit-8 (CCK-8) assays. Evaluation of caspase-3, caspase-8, and caspase-9 activity was performed using colorimetric assays. The MTT and CCK-8 assays were used to evaluate the effect of caspase inhibitors on local anesthetic chondrotoxicity. All three local anesthetics decreased chondrocyte viability after 24 hr (P<0.001). Apoptosis was induced through both the extrinsic and intrinsic pathways. Bupivacaine increased caspase-3, caspase-8, and caspase-9 activity (P<0.001). Levobupivacaine increased caspase-3 (P=0.03) while ropivacaine did not significantly upregulate activity for all three caspases. Caspase inhibition did not suppress bupivacaine chondrotoxicity whereas inhibition of caspase-8 and caspase-9 decreased ropivacaine chondrotoxicity and mildly attenuated levobupivacaine chondrotoxicity. In summary, the level of chondrotoxicity, the type of caspase activated, the level of caspase activation, and the response to caspase inhibitors was dependent on the type of local anesthetic. Therefore, ropivacaine may be a safer choice for intra-articular administration compared to levobupivacaine and bupivacaine.