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.

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).

Retrospective comparison between low-volume high-concentration and high-volume low-concentration levobupivacaine for bilateral erector spinae plane block in dogs undergoing hemilaminectomy.

OBJECTIVE: To compare the analgesic effect of a bilateral ultrasound-guided erector spinae plane block (ESPB) in dogs undergoing hemilaminectomy using either a low-volume high-concentration (LV-HC) or a high-volume low-concentration (HV-LC) local anaesthetic solution. STUDY DESIGN: Retrospective observational equivalence trial. ANIMALS: A total of 391 client-owned dogs undergoing hemilaminectomy. METHODS: Dogs were assigned to group LV-HC or HV-LC depending on whether 0.2-0.25% levobupivacaine (0.4-0.5 mL kg-1) or 0.125-0.15% levobupivacaine (0.8-1 mL kg-1) was used to perform the ESPB, respectively. The number of dogs in which intraoperative rescue fentanyl boluses were administered, the total dose of fentanyl administered, the overall methadone consumption during the first 24 hours postoperatively and anaesthetic complications were recorded. Univariate and multivariate statistical analyses were performed considering p < 0.05 significant. RESULTS: A total of 248 and 143 dogs were assigned to groups LV-HC and HV-LC, respectively. In group HV-LC, the number of dogs requiring fentanyl intraoperatively (64.3%) was higher (p = 0.0001) than that in group LV-HC (43.5%). The overall intraoperative fentanyl consumption was higher in group HV-LC between the first skin incision and the end of the lamina drilling (p = 0.028). According to the regression analysis, the group allocation was the best variable to predict the intraoperative fentanyl consumption (p < 0.001). Antimuscarinic drugs were administered more frequently in group LV-HC (p < 0.02). However, the prevalence of hypotension and other pharmacological cardiovascular interventions did not differ between groups. No differences in methadone consumption during the first 24 hours postoperatively were found between the groups. CONCLUSIONSAND CLINICAL RELEVANCE: When performing a bilateral ESPB in dogs undergoing hemilaminectomy, compared with HV-LC, the use of LV-HC local anaesthetic solution reduces the intraoperative fentanyl consumption without affecting the postoperative methadone requirement.

[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.

Postoperative recovery with continuous erector spinae plane block or video-assisted paravertebral block after minimally invasive thoracic surgery: a prospective, randomised controlled trial.

BACKGROUND: PROcedure SPECific Postoperative Pain ManagemenT (PROSPECT) guidelines recommend erector spinae plane (ESP) block or paravertebral block (PVB) for postoperative analgesia after video-assisted thoracoscopic surgery (VATS). However, there are few trials comparing the effectiveness of these techniques on patient-centric outcomes, and none evaluating chronic postsurgical pain (CPSP). Furthermore, there are no available trials comparing ultrasound-guided ESP with surgically placed PVB in this patient cohort. METHODS: We conducted a two-centre, prospective, randomised, double-blind, controlled trial, comparing anaesthesiologist-administered, ultrasound-guided ESP catheter with surgeon-administered, video-assisted PVB catheter analgesia among 80 adult patients undergoing VATS. Participants received a 20 ml bolus of levobupivacaine 0.375% followed by infusion of levobupivacaine 0.15% (10-15 ml h-1) for 48 h. Primary outcome was Quality of Recovery-15 score (QoR-15) at 24 h. Secondary outcomes included QoR-15 at 48 h, peak inspiratory flow (ml s-1) at 24 h and 48 h, area under the pain verbal response score vs time curve (AUC), opioid consumption, Comprehensive Complication Index, length of stay, and CPSP at 3 months after surgery. RESULTS: Median (25-75%) QoR-15 at 24 h was higher in ESP (n=37) compared with PVB (n=37): 118 (106-134) vs 110 (89-121) (P=0.03) and at 48 h: 131 (121-139) vs 120 (111-133) (P=0.03). There were no differences in peak inspiratory flow, AUC, Comprehensive Complication Index, length of hospital stay, and opioid consumption. Incidence of CPSP at 3 months was 12 (34%) for ESP and 11 (31%) for PVB (P=0.7). CONCLUSIONS: Compared with video-assisted, surgeon-placed paravertebral catheter, erector spinae catheter improved overall QoR-15 scores at 24 h and 48 h but without differences in pain or opioid consumption after minimally invasive thoracic surgery. CLINICAL TRIAL REGISTRATION: NCT04729712.

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.

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.

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.

'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.

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.

0.125% 8 ml/h v.s. 0.25% 8 ml/h of levobupivacaine in continuous paravertebral block for postoperative analgesia in video-assisted thoracoscopic surgery: a randomized, controlled, double-blind study.

PURPOSE: Research has shown that a higher dose of bupivacaine administered in continuous paravertebral block (CPVB) provides a greater analgesic effect after video-assisted thoracoscopic surgery (VATS). In this randomized, controlled, double-blind study, we hypothesized that 0.25% 8 ml/h of levobupivacaine administered in CPVB after VATS provides a greater analgesic effect than 0.125% 8 ml/h. METHODS: Fifty patients who underwent unilateral VATS were randomized to receive a postoperative continuous infusion of 0.125% (low group, n = 25) or 0.25% (high group, n = 25) levobupivacaine at 8 mL/h for CPVB. The primary outcome was the visual analog scale (VAS) score during coughing on the morning of postoperative day (POD) 1. The secondary outcomes were the VAS scores at rest and during coughing on POD 2, the number of anesthetized dermatomes, the frequency of rescue analgesics, postoperative nausea and vomiting, patient satisfaction, and adverse events and complications. RESULTS: There was no significant difference in the VAS score during coughing on the morning of POD 1 between the low and high groups [median, 37.5 (interquartile range 21-50) vs. 40.0 (interquartile range 21-50), respectively; p = 0.79]. Similarly, there were no significant differences in any secondary outcomes between the two groups. CONCLUSIONS: Levobupivacaine at 0.25% 8 ml/h in CPVB did not provide better analgesia after VATS over 0.125% 8 ml/h. CLINICAL TRIAL REGISTRATION NUMBER: UMIN000037930.

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.

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.

Plasma concentrations of levobupivacaine in neonates during caudal epidural analgesia maintained over 48 hours.

BACKGROUND: Differences in neonatal pharmacokinetics are known to cause systemic accumulation of levobupivacaine with adverse effects during epidural analgesia. Therefore, it is not recommended to surpass 48 hours of administration in neonates. Free and total levobupivacaine levels are considered as predictors of toxicity. OBJECTIVE: The aim of the LEVON pilot study was to detect the accumulation of levobupivacaine during epidural analgesia exceeding 48 hours in neonates. METHODS: Ten neonates received a loading dose of levobupivacaine (1.25 mg/kg) followed by a continuous infusion (0.2 mg/kg/hour) epidurally. Free and total levobupivacaine concentrations were measured 0.5, 1, 6, 12, 36, 72 and 144 hours after the start of infusion. Cumulative doses of levobupivacaine, pain scores and clinical signs of toxicity were used for assessing efficacy and safety. RESULTS: The median concentrations of total levobupivacaine were 586.0, 563.0, 837.5, 957.0, 1930.0, 708.5 and 357.5 ng/ml. The median concentrations of free levobupivacaine were 4.0, 3.6, 5.5, 3.6, 5.5, 0.8 and 0.0 ng/ml. Three patients reached concerning concentrations of total levobupivacaine. Levels of free levobupivacaine remained low. No signs of toxicity were observed. CONCLUSION: Caudal epidural analgesia with levobupivacaine lasting longer than 48 hours appears to be safe providing that free levobupivacaine levels are below the presumed threshold for toxicity (Tab. 1, Fig. 1, Ref. 29). Text in PDF www.elis.sk Keywords: free levobupivacaine, total levobupivacaine, neonate, caudal continuous epidural analgesia, postoperative pain.

Effects of an Intrathecal Drug Delivery System Connected to a Subcutaneous Port on Pain, Mood and Quality of Life in End Stage Cancer Patients: An Observational Study.

BACKGROUND: In cancer patients with limited life expectancy, an implant of an intrathecal (IT) drug delivery system connected to a subcutaneous port (IDDS-SP) has been proposed as a successful strategy, but conflicting results are reported on quality of life (QoL). The aim of this prospective observational study is to report the effects on pain, mood and QoL of an IT combination therapy delivered by an IDDS-SP in malignant refractory pain. METHODS: Adult patients in which IT therapy was recommended were recruited. An IT therapy with morphine and levobupivacaine was started: VASPI score, depression and anxiety (evaluated by the Edmonton Symptom Assessment System -ESAS-), the Pittsburgh Sleep Quality Index (PSQI), the 5-level EuroQol 5D version (EQ-5D-5L) and the requirements of breakthrough cancer pain (BTcP) medications were registered, with adverse events rate and the satisfaction of patients scored as Patient Global Impression of Change (PGIC). RESULTS: Fifty patients, (16 F/34 M) were enrolled (age 69 ± 12). All had advanced cancer with metastasis. The median daily VASPI score was 75, the median depression score was 6, and the median anxiety score was 4, median PSQI was 16. At 28 days, a significant reduction in VASPI score was registered as well as in depression and anxiety item. Also, PSQI decreased significantly. The EQ-5D-5 L showed a significant improvement in all components at 14 and 28 days. Patient Global Impression of Change scores showed high level of satisfaction. A low incidence of adverse events and a reduction in BTCP episodes were also registered. CONCLUSION: Intrathecal combination therapy delivered by an IDDS-SP could ensure adequate control of cancer related symptoms, such as pain, depression, anxiety and sleep disturbances. These effects, with low rate of AEs and reduced BTcP episodes, could explain the improvement in QoL and the overall high levels of patients' satisfaction.

Wound Infusion of 0.35% Levobupivacaine Reduces Mechanical Secondary Hyperalgesia and Opioid Consumption After Cesarean Delivery: A Prospective, Randomized, Triple-Blind, Placebo-Controlled Trial.

BACKGROUND: Some patients still report moderate-to-severe postoperative pain after cesarean delivery. Local anesthetic wound infusion improves acute pain and might act on peripheral and central sensitization mechanisms; however, no studies have proved this hypothesis. We evaluated the potential benefits of continuous wound infusion of levobupivacaine after cesarean delivery on secondary hyperalgesia (primary end point) and primary hyperalgesia, pain relief, persistent pain, and inflammatory and metabolic stress response. METHODS: Healthy women scheduled for elective cesarean delivery participated in this prospective, randomized, triple-blind, placebo-controlled trial (NCT01458431). All patients received spinal anesthesia with 0.5% hyperbaric bupivacaine with fentanyl and a multiholed wound catheter placed under the fascia. Women were randomized to receive continuous wound infusion (0.35% levobupivacaine 7 mL/h for 48 hours; group L) or an equal volume of saline (group S). Secondary hyperalgesia to punctate mechanical stimuli was evaluated using dynamic tests, and primary hyperalgesia was evaluated using an electronic von Frey anesthesiometer; both were assessed at 24, 48, and 72 hours. The following variables were collected: intensity of postoperative parietal and visceral pain at rest and on movement rated on a visual analog scale >72 hours, time to first bolus of patient-controlled analgesia (PCA), cumulative dose of rescue morphine (PCA) and acetaminophen, ability to sleep and sleep quality, and patient satisfaction. Persistent postoperative pain was evaluated during a telephone interview at 1, 3, 6, and 12 months after surgery. C-reactive protein, acid glycoprotein, preprandial glucose, insulin, cortisol, prolactin, growth hormone, and interleukin-6 were measured before cesarean delivery and at 8, 24, and 48 hours. Adverse events and patient outcomes were recorded. RESULTS: Seventy women were included. In group L, the area of secondary hyperalgesia was significantly reduced (43.4 [18.5-80] vs 68.4 [39.0-136] cm2 and 45.1 [0.9-89.8] vs 67.3 [31.3-175] cm2 at 24 and 48 hours, respectively; group:time interaction P value < .001), the mechanical pain threshold was significantly higher at 24 hours (633 [441-802] vs 417 [300-572] g.mm-2; P = .001), and morphine consumption was significantly lower at 24 hours (4 [2-11] vs 11[6-23]; P = .003) compared with group S. Levobupivacaine had no effect on persistent postoperative pain at 1, 3, 6, and 12 months. Plasma insulin levels in the immediate postoperative period and at 8, 24, and 48 hours were significantly lower in group L (P < .001). There were no significant differences in other biochemical parameters of inflammatory and endocrine-metabolic response. CONCLUSIONS: Levobupivacaine wound infusion provides adequate analgesia and might be an effective antihyperalgesic adjunct.

Intensity-adjustable pain management with prolonged duration based on phase-transitional nanoparticles-assisted ultrasound imaging-guided nerve blockade.

BACKGROUND: The lack of a satisfactory strategy for postoperative pain management significantly impairs the quality of life for many patients. However, existing nanoplatforms cannot provide a longer duration of nerve blockage with intensity-adjustable characteristics under imaging guidance for clinical applications. RESULTS: To overcome this challenge, we proposed a biocompatible nanoplatform that enables high-definition ultrasound imaging-guided, intensity-adjustable, and long-lasting analgesia in a postoperative pain management model in awake mice. The nanoplatform was constructed by incorporating perfluoropentane and levobupivacaine with red blood cell membranes decorated liposomes. The fabricated nanoplatform can achieve gas-producing and can finely escape from immune surveillance in vivo to maximize the anesthetic effect. The analgesia effect was assessed from both motor reactions and pain-related histological markers. The findings demonstrated that the duration of intensity-adjustable analgesia in our platform is more than 20 times longer than free levobupivacaine injection with pain relief for around 3 days straight. Moreover, the pain relief was strengthened by repeatable ultrasound irradiation to effectively manage postoperative pain in an intensity-adjustable manner. No apparent systemic and local tissue injury was detected under different treatments. CONCLUSION: Our results suggest that nanoplatform can provide an effective strategy for ultrasound imaging-guided intensity-adjustable pain management with prolonged analgesia duration and show considerable transformation prospects.

A randomised controlled trial in patients undergoing arthroscopic shoulder surgery comparing interscalene block with either 10 ml or 20 ml levobupivacaine 0.25.

The interscalene brachial plexus block is recommended for analgesia after shoulder surgery but it may cause hemidiaphragmatic dysfunction. We tested whether ipsilateral hemidiaphragmatic contraction was better after a smaller dose of local anaesthetic without impairing analgesic effect. We randomly allocated 48 adults to 10 ml or 20 ml levobupivacaine 0.25% before arthroscopic shoulder surgery. The primary outcome was hemidiaphragmatic paralysis, defined as inspiratory thickness < 1.2 times expiratory thickness, measured by ultrasound 4 h after block. Hemidiaphragmatic paralysis was recorded for 6/24 vs. 23/24 supine participants after 10 ml vs. 20 ml levobupivacaine 0.25%, respectively, and for 4/24 vs. 23/24 sitting participants, respectively, p < 0.001 for both. Pain scores after 10 ml injectate were not worse than after 20 ml injectate. Median (IQR [range]) morphine doses in the first 24 postoperative hours after 10 ml and 20 ml levobupivacaine 0.25% were 2 (0-6 [0-23]) mg vs. 1 (0-2 [0-11]) mg, respectively, p = 0.12. No participant had a complication after 10 ml interscalene levobupivacaine, whereas seven had complications after 20 ml levobupivacaine, p = 0.009. Hemidiaphragmatic function was better after 10 ml vs. 20 ml interscalene levobupivacaine 0.25% without impairing analgesia for 24 postoperative hours.

Comparison of the efficacy of two doses of dexmedetomidine as an adjunct to levobupivacaine in infraclavicular brachial plexus block: prospective double-blinded randomized controlled trial.

BACKGROUND: This prospective, double-blind, randomized, controlled trial compared the efficacy of two dexmedetomidine doses (50 and 100-µg) combined with levobupivacaine on sensory block duration in infraclavicular brachial plexus block. We hypothesized that perineural dexmedetomidine would extend sensory block duration dose-dependently. METHODS: The study included 60 patients aged 20 to 60 years of both sex with an ASA I/II undergoing forearm and hand surgery. The patients were randomly assigned into three equal groups (n = 20) for ultrasound-guided infraclavicular brachial plexus block. The L group received 35-mL 0.5% levobupivacaine plus normal saline, the LD50 group received 35-mL 0.5% levobupivacaine plus 50-µg dexmedetomidine, and the LD100 group received 35-mL 0.5% levobupivacaine plus 100-µg dexmedetomidine. Patients were investigated for onset and duration of sensory blockade, time to first postoperative rescue analgesia, and the total 24-h postoperative morphine requirement. RESULTS: The LD100 group had a longer sensory block duration (15.55 ± 1.1 h; 95% confidence interval (CI), 15.04-16.06) than the LD50 group (12.8 ± 1.2 h; 95% CI, 12.24-13.36 h) (p < 0.001) or the L group (9.95 ± 1.05 h; 95% CI, 9.46-10.44 h) (p < 0.001). The LD100 group took longer to request postoperative rescue analgesia and required fewer postoperative morphine doses than the LD50 and L groups (P < 0.001). CONCLUSIONS: Sensory block duration was longer with perineural 100-µg dexmedetomidine as an adjunct to levobupivacaine than with 50-µg dexmedetomidine. TRIAL REGISTRATION: This study was approved by the Ethics Committee of Aswan University Hospital (approval number: aswu/125/4/17) (date of registration: 04/04/2017). Furthermore, the trial was retrospectively registered at ClinicalTrial.gov (NCT04729868) with a verification date of January 2021.

Comparison of plasma levobupivacaine concentrations with and without epinephrine following erector spinae plane block for breast cancer surgery: a randomized controlled trial.

BACKGROUND: The erector spinae plane (ESP) block requires a large volume of local anesthetic to provide effective analgesia, which has the potential to cause local anesthetic systemic toxicity (LAST). Adjunctive epinephrine slows the entry of local anesthetic into the plasma and decreases its toxic effect on vulnerable tissues. We compared plasma levobupivacaine concentrations with and without epinephrine after ESP blocks for breast cancer surgery. METHODS: In this prospective, double-blinded, randomized controlled trial, 35 patients who underwent elective unilateral partial mastectomy with sentinel lymph node biopsy were enrolled. The patients were randomized to group L (ESP block with 2 mg/kg levobupivacaine) or LE (ESP block with 2 mg/kg levobupivacaine and 5 µg/mL epinephrine). Blood samples were obtained at 2.5, 5, 7.5, 10, 12.5, 15, 30, 60, and 120 min after the ESP block, and plasma concentrations of levobupivacaine were compared. RESULTS: Twenty-nine patients were included in the analysis. The maximum plasma concentration (Cmax) and the time to maximum concentration (Tmax) were, respectively, 1.24 µg/mL and 6.0 min in group L and 0.62 µg/mL and 7.2 min in group LE. The two groups showed no significant differences in the numerical rating scale scores immediately after extubation and 5 and 9 h after the ESP block, or in the interval from the ESP block to the first rescue analgesia. No patient developed symptoms suggestive of LAST. CONCLUSIONS: A single bolus of 2 mg/kg levobupivacaine in the ESP block resulted in a short Tmax with high Cmax. Adding epinephrine to levobupivacaine decreased the Cmax and delayed the Tmax after ESP blocks but had no effect on postoperative analgesia. TRIAL REGISTRATION: UMIN Clinical Trials Registry, UMIN000034479 . The trial was retrospectively registered on October 13, 2018.