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.

Influence of Levobupivacaine Regional Scalp Block on Hemodynamic Stability, Intra- and Postoperative Opioid Consumption in Supratentorial Craniotomies: A Randomized Controlled Trial.

BACKGROUND: The anesthetic management of supratentorial craniotomy (CR) necessitates tight intraoperative hemodynamic control. This type of surgery may also be associated with substantial postoperative pain. We aimed at evaluating the influence of regional scalp block (SB) on hemodynamic stability during the noxious events of supratentorial craniotomies and total intravenous anesthesia, its influence on intraoperative anesthetic agents' consumption, and its effect on postoperative pain control. METHODS: Sixty patients scheduled for elective CR were prospectively enrolled. Patient, anesthesiologist, and neurosurgeon were blind to the random performance of SB with either levobupivacaine 0.33% (intervention group [group SB], n = 30) or the same volume of saline (control group [group CO], placebo group, n = 30). General anesthesia was induced and maintained using target-controlled infusions of remifentanil and propofol that were adjusted according to hemodynamic parameters and state entropy of the electroencephalogram (SE), respectively. Mean arterial blood pressure (MAP), heart rate (HR), SE, and propofol and remifentanil effect-site concentrations (Ce) were recorded at the time of scalp block performance (Baseline), and 0, 1, 3, and 5 minutes after skull-pin fixation (SP), skin incision (SI), CR, and dura-mater incision (DM). Morphine consumption and postoperative pain intensity (0-10 visual analog scale [VAS]) were recorded 1, 3, 6, 24, and 48 hours after surgery. Propofol and remifentanil overall infusion rates were also recorded. Data were analyzed using 2-tailed Student unpaired t tests, 2-way mixed-design analysis of variance (ANOVA), and Tukey's honestly significant difference (HSD) tests for post hoc comparisons as appropriate. RESULTS: Demographics and length of anesthetic procedure of group CO and SB were comparable. SP, SI, and CR were associated with a significantly higher MAP in group CO than in group SB, at least at one of the time points of recording surrounding those noxious events. This was not the case at DM. Similarly, HR was significantly higher in group CO than in group SB during SP and SI, at least at 1 of the points of recording, but not during CR and DM. Propofol and remifentanil Ce and overall infusion rates were significantly higher in group CO than in group SB, except for propofol Ce during SP. Postoperative pain VAS and cumulative morphine consumption were significantly higher in group CO than in group SB. CONCLUSIONS: In supratentorial craniotomies, SB improves hemodynamic control during noxious events and provides adequate and prolonged postoperative pain control as compared to placebo.

The 14-day repeated-dose toxicity study of a fixed-dose combination, QXOH/levobupivacaine, via subcutaneous injection in beagle dogs.

QXOH-Levobupivacaine (LB) is a fixed-dose combination of 35-mM QXOH and 10-mM LB. It was developed for perioperative analgesia because of its long-acting analgesic effect. The purpose of this study was to evaluate the potential toxicity of QXOH-LB in beagle dogs in accordance with the Guidance on the repeated-dose toxicity published by the China Food and Drug Administration. Groups of five male and five female beagle dogs received normal saline, QXOH-LB (2, 4, and 8 mg/kg, calculated as QXOH), QXOH (2, 4, and 8 mg/kg), or LB (2 mg/kg, equals the concentration of LB in 8-mg/kg QXOH-LB group) at the volume of 1 mL/kg once per day for 14 days through subcutaneous injection. No mortality was observed. Dogs in the control group as well as animals treated with 2-mg/kg QXOH or QXOH-LB exhibited normal behaviors. Clinical signs of toxicity in dogs treated with 4 and 8 mg/kg of QXOH or QXOH-LB included decreased activity, unsteady gait, jerks, tremors, vocalization, emesis, ataxia, lateral/sternal recumbency, deep/rapid respiration, and gasping. Additionally, neurological function was found to be affected by QXOH and QXOH-LB at the doses of 4 and 8 mg/kg. All clinical signs were recovered within 24 h. The no-observed-adverse-effect level of QXOH and QXOH-LB was considered to be 2 mg/kg. Toxicokinetic data showed that exposure to QXOH and LB increased as QXOH-LB doses were increased from 4 to 8 mg/kg. There was no evidence of drug accumulation or any effect of gender.

Efficacy of celecoxib as preemptive analgesia for patients undergoing laparoscopic inguinal hernia repair: a randomized trial.

PURPOSE: To investigate the efficacy and safety of preemptive analgesia with a transversus abdominis plane (TAP) block versus celecoxib for patients undergoing laparoscopic transabdominal preperitoneal inguinal hernia repair (LTAPP). METHODS: Sixty patients scheduled for LTAPP were randomized into three groups: a celecoxib group, given 200 mg celecoxib 2 h before surgery; a celecoxib/diclofenac group, given 200 mg celecoxib 2 h before surgery and 50 mg rectal diclofenac sodium on recovery from general anesthesia; and a block group, given a TAP block with 60 mL 0.25% levobupivacaine after general anesthesia. We assessed the numerical rating scale (NRS) scores for pain at rest and with movement 24 h after surgery. Postoperative analgesia use and adverse events were also evaluated. RESULTS: The NRS scores for pain at rest and with movement were lower in the celecoxib group than in the block group, 24 h postoperatively. The time to first request for analgesia tended to be longer in the block group than in the celecoxib group. No significant between-group differences were noted in analgesic use or adverse events. CONCLUSIONS: Celecoxib was not inferior to the TAP block as preemptive analgesia. Thus, celecoxib could be given as simple preemptive analgesia for LTAPP by considering a multimodal analgesic strategy in the early postoperative period.

Levobupivacaine-Loaded Liposome Associated with Thermogel for Prolonged Analgesia.

Pain is a phenomenon present in the majority of the population, affecting, among others, the elderly, overweight people, and especially recently operated patients, analgesia being necessary. In the specific case of relief of postoperative pain, different kinds of anesthetics are being used, among them bupivacaine, a widely used drug which promotes long-lasting analgesic effects. However, cardiotoxicity and neurotoxicity are related to its repetitive use. To overcome these shortcomings, Novabupi® (a racemic mixture) was developed and is marketed as an injectable solution. This formulation contains an enantiomeric excess of the levogyre isomer, which has reduced toxicity effects. Seeking to rationalize its use by extending the duration of effect and reducing the number of applications, the objectives of this work were to develop and evaluate liposomes containing Novabupi (LBPV), followed by incorporation into thermogel. Liposomes were prepared using the lipid hydration method, followed by size reduction using sonication, and the developed formulations were characterized by hydrodynamic diameter, polydispersity index (PDI), surface zeta potential, and encapsulation efficiency. The selected optimal liposomal formulation was successfully incorporated into a thermogel without loss of thermoresponsive properties, being suitable for administration as a subcutaneous injection. In the ex vivo permeation studies with fresh rodent skin, the thermogel with liposomes loaded with 0.5% LBPV (T-gel formulation 3) showed higher permeation rates compared to the starting formulation, thermogel with 0.5% LBPV (T-Gel 1), which will probably translate into better therapeutic benefits for treatment of postoperative analgesia, especially with regard to the number of doses applied.

Quadratus lumborum block for analgesia after caesarean section: a randomised controlled trial.

Quadratus lumborum block has been shown to provide satisfactory analgesia after caesarean section performed under neuraxial anaesthesia. However, its efficacy has not been demonstrated in patients who have received intrathecal morphine. The aim of this study was to assess the efficacy of quadratus lumborum block as part of a multimodal analgesic regimen including intrathecal morphine. This was a prospective, double-blind, placebo-controlled trial. Participants were randomly allocated to receive bilateral quadratus lumborum block (40 ml levobupivacaine 0.25%) or sham block (control) after undergoing elective caesarean section under spinal anaesthesia. The primary outcome was 24-h morphine consumption measured by patient-controlled analgesia. Secondary outcomes included pain scores and quality of recovery. Data from 86 women were analysed. Median (IQR [range]) 24-h morphine consumption was similar in patients receiving quadratus lumborum block and sham block (12 (8-29 [0-68]) mg vs. 14 (5-25 [0-90]) mg, respectively; p = 0.986). There was a reduction in median (IQR [range]) visual analogue scale pain scores at 6 h with quadratus lumborum block compared with sham block both at rest (6 (0-14 [0-98]) mm vs. 14 (3-23 [0-64]) mm (p = 0.019); and on movement: 23 (10-51 [0-99]) mm vs. 44 (27-61 [2-94]) mm; (p = 0.014)). There was no difference in pain scores at any other time-point up to 48 h. When used in conjunction with intrathecal morphine and spinal anaesthesia, bilateral quadratus lumborum block does not reduce 24-h morphine consumption after caesarean section.

Sustained Release of Levobupivacaine, Lidocaine, and Acemetacin from Electrosprayed Microparticles: In Vitro and In Vivo Studies.

In this study, we explored the release characteristics of analgesics, namely levobupivacaine, lidocaine, and acemetacin, from electrosprayed poly(D,L-lactide-co-glycolide) (PLGA) microparticles. The drug-loaded particles were prepared using electrospraying techniques and evaluated for their morphology, drug release kinetics, and pain relief activity. The morphology of the produced microparticles elucidated by scanning electron microscopy revealed that the optimal parameters for electrospraying were 9 kV, 1 mL/h, and 10 cm for voltage, flow rate, and travel distance, respectively. Fourier-transform infrared spectrometry indicated that the analgesics had been successfully incorporated into the PLGA microparticles. The analgesic-loaded microparticles possessed low toxicity against human fibroblasts and were able to sustainably elute levobupivacaine, lidocaine, and acemetacin in vitro. Furthermore, electrosprayed microparticles were found to release high levels of lidocaine and acemetacin (well over the minimum therapeutic concentrations) and levobupivacaine at the fracture site of rats for more than 28 days and 12 days, respectively. Analgesic-loaded microparticles demonstrated their effectiveness and sustained performance for pain relief in fracture injuries.

Peripheral nerve block versus systemic analgesia in dogs undergoing tibial plateau levelling osteotomy: Analgesic efficacy and pharmacoeconomics comparison.

OBJECTIVE: To compare the perioperative effects and pharmacoeconomics of peripheral nerve blocks (PNBs) versus fentanyl target-controlled infusion (fTCI) in dogs undergoing tibial plateau levelling osteotomy (TPLO). STUDY DESIGN: Randomized clinical study. ANIMALS: A total of 39 dogs undergoing unilateral TPLO. METHODS: After acepromazine and methadone, anaesthesia was induced with propofol and maintained with isoflurane. Dogs were allocated to group fTCI [target plasma concentration (TPC) 1 ng mL-1] or group PNB (nerve stimulator-guided femoral-sciatic block using 0.2 and 0.1 mL kg-1 of levobupivacaine 0.5%, respectively). If nociceptive response occurred, isoflurane was increased by 0.1%, and TPC was increased by 0.5 ng mL-1 in group fTCI; a fentanyl bolus (1 µg kg-1) was administered in group PNB. During the first 24 postoperative hours, methadone (0.2 mg kg-1) was administered intramuscularly according to the Short Form Glasgow Composite Pain Scale, or if pain was equal to 5/24 or 4/20 for two consecutive assessments, or if the dog was non-weight bearing. The area under the curve (AUC) of pain scores, cumulative postoperative methadone requirement, food intake and pharmacoeconomic implications were calculated. RESULTS: Incidence of bradycardia (p = 0.025), nociceptive response to surgery (p = 0.041) and AUC of pain scores (p < 0.0001) were greater in group fTCI. Postoperatively, 16/19 (84.2%) and eight/20 (40%) dogs in groups fTCI and PNB, respectively, were given at least one dose of methadone (p = 0.0079). Food intake was greater in group PNB (p = 0.049). Although total cost was not different (p = 0.083), PNB was more cost-effective in dogs weighing >15 kg. CONCLUSIONS AND CLINICAL RELEVANCE: Compared with group fTCI, incidence of bradycardia, nociceptive response to surgery, postoperative pain scores, cumulative methadone requirement were lower, and food intake was greater in group PNB, with an economic advantage in dogs weighing >15 kg.

Effects of bupivacaine or levobupivacaine on cerebral oxygenation during spinal anesthesia in elderly patients undergoing orthopedic surgery for hip fracture: a randomized controlled trial.

BACKGROUND: Bupivacaine and levobupivacaine have similar pharmacokinetic and pharmacodynamic characteristics, and are used regularly in spinal anesthesia. Whether potential differences in their hemodynamic and anesthetic profiles could determine a differential risk of complications in elderly subjects, is controversial. The main objective was to compare the effects of intrathecally administered levobupivacaine (LB) versus bupivacaine (B), on regional cerebral O2 saturation during spinal anesthesia, cognitive status and neurological complications in elderly patients undergoing surgery for hip fracture. METHODS: This was a randomized, controlled, single blind study. 58 patients aged 70 or older undergoing surgery for hip fracture with spinal anesthesia were allocated with a 1:1 ratio to receive LB or B, combined with fentanyl 15 µg, by intrathecal route. The primary outcome was the proportion of intraoperative time with regional cerebral desaturation (≥20% reduction in regional cerebral oxygen saturation from baseline), monitored by near -infrared spectroscopy. Secondary endpoints included hemodynamic parameters, level of sensory and motor block, changes in Short Portable Mental Status Questionnaire (SPMSQ), and neurological complications. RESULTS: The mean percentage of intraoperative time with desaturation in the B group was 6.1% (SD: 17.5) and 4.7% (SD: 11.9) in the left and right hemisphere respectively; in the LB group the mean was 4.8% (SD: 11.4) in the left hemisphere and 2.4% (SD: 8.3) in the right one. No statistically significant differences were found between treatment groups. The level of sensory block at the start of surgery was lower for LB than for B (Th10 vs Th8, p:0.047) and motor block at 15 min was lower for LB (2.5 vs 3, p:0.009). No differences in postoperative SPMSQ were observed. Neurological complications such as confusional state, agitation or disorientation were reported in 50% of patients in the B group and 21.4% of patients in the LB group, p = 0.05. CONCLUSIONS: No statistically significant differences in regional cerebral oxygen saturation or hemodynamic parameters were observed between both treatment groups. Bupivacaine and levobupivacaine differed in sensory and motor block achieved. While no differences were observed in cognitive impairment measured by the SPMSQ between treatment groups neurological complications reported by the physician were more frequent with bupivacaine. TRIAL REGISTRATION: European Union Clinical Trials Register ( EudraCT 2013-000846 -20 ) (April 9th, 2013). ClinicalTrials.gov ( NCT01960543 ) (September 23rd, 2013).

The influence of the infusion of ephedrine and phenylephrine on the hemodynamic stability after subarachnoid anesthesia in senior adults - a controlled randomized trial.

BACKGROUND: We studied the influence of ephedrine or phenylephrine infusion administered immediately after spinal anesthesia (SA) on hemodynamics in elderly orthopedic patients. METHODS: A prospective, randomized, double-blind, placebo-controlled study. After a subarachnoid injection of 15 mg of levobupivacaine, the participants received an infusion of either ephedrine 20 mg (E group), phenylephrine 250 mcg (P group) or saline (C group) within 30 min. We measured blood pressure, cardiac index (CI) and heart rate (HR) from 15 min before to 30 min after SA. RESULTS: Seventy patients were included in the final analysis. At the end of measurements, mean arterial pressure (MAP) decreased significantly after SA in comparison to the baseline value in the C group but was maintained in the P and E group, with no significant differences between the groups. CI decreased after SA in the C group, was maintained in the P group, and increased significantly in the E group with significant differences between the C and E group (p = 0.049) also between the P and E (p = 0.01) group at the end of measurements. HR decreased significantly after SA in the C and P group but was maintained in the E group, with significant differences between the P and E group (p = 0.033) at the end of measurements. CONCLUSIONS: Hemodynamic changes after SA in elderly orthopedic patients can be prevented by an immediate infusion of phenylephrine or ephedrine. In addition to maintaining blood pressure, the ephedrine infusion also maintains HR and increases CI after SA. TRIAL REGISTRATION: ISRCTN registry with registration number ISRCTN44377602, retrospectively registered on 15 June 2017.

A study of the dosage and duration for levobupivacaine infusion by the caudal-epidural route in infants aged 3-6 months.

BACKGROUND: The local anesthetic, levobupivacaine, is the safer enantiomer of racemic bupivacaine. Present protocols for levobupivacaine are based on studies and pharmacokinetic modeling with racemic bupivacaine. AIMS: The aim is to investigate total serum levobupivacaine concentrations after a caudalepidural loading dose followed by a maintenance infusion over 48 hours in infants aged 3-6 months. METHODS: The clinical trial was conducted in eight infants aged 3-6 months, undergoing bladder exstrophy repair. Pharmacokinetic modeling allowed optimization of clinical sampling to measure total levobupivacaine and α1 -acid glycoprotein and prediction of the effect of α1 -acid glycoprotein on levobupivacaine plasma protein binding. RESULTS: The observed median total levobupivacaine serum concentration was 0.30 mg/L (range: 0.20-0.70 mg/L) at 1 hour after the loading dose of 2 mg/kg. The median total levobupivacaine concentration after 47 hours of infusion, at 0.2 mg/kg/h, was 1.21 mg/L (0.07-1.85 mg/L). Concentrations of α1 -acid glycoprotein were found to rise throughout the study period. Pharmacokinetic modeling suggested that unbound levobupivacaine quickly reached steady state at a concentration of approximately 0.03 mg/L. CONCLUSION: The study allows the development of a pharmacokinetic model, combining levobupivacaine and α1 -acid glycoprotein data. Modeling indicates that unbound levobupivacaine quickly reaches steady state once the infusion is started. Simulations suggest that it may be possible to continue the infusion beyond 48 hours.

Does programmed intermittent epidural bolus improve childbirth conditions of nulliparous women compared with patient-controlled epidural analgesia?: A multicentre, randomised, controlled, triple-blind study.

BACKGROUND: Epidural analgesia may change the mechanics of childbirth. These changes are related to the concentration of the local anaesthetic used epidurally but probably also to its mode of delivery into the epidural space. OBJECTIVE: To determine whether the administration of programmed intermittent epidural boluses (PIEB) improves the mechanics of second-stage labour compared with patient-controlled epidural analgesia (PCEA) with a background infusion. DESIGN: A randomised, controlled, triple-blind study. SETTING: Multicentre study including four level III maternity units, January 2014 until June 2016. PATIENTS: A total of 298 nulliparous patients in spontaneous labour were randomised to a PIEB or PCEA group. INTERVENTION: After epidural initiation with 15 ml of 0.1% levobupivacaine containing 10 µg of sufentanil, patients received either an hourly bolus of 8 ml (PIEB) or a continuous rate infusion of 8 ml h (PCEA): the drug mixture used was levobupivacaine 0.1% and sufentanil 0.36 µg ml. MAIN OUTCOME MEASURES: The primary outcome was a composite endpoint of objective labour events: a posterior occiput position in the second stage, an occiput position at birth, waiting time at full cervical dilatation before active maternal pushing more than 3 h, maternal active pushing duration more than 40 min, and foetal heart rate alterations. Vaginal instrumental delivery rates, analgesia and motor blockade scores were also recorded. RESULTS: From the 298 patients randomised, data from 249 (124 PIEB, 125 PCEA) were analysed. No difference was found in the primary outcome: 48.0% (PIEB) and 45.5% (PCEA) of patients, P = 0.70. In addition, no difference was observed between the groups for each of the individual events of the composite endpoint, nor in the instrumental vaginal delivery rate, nor in the degree of motor blockade. Despite an equivalent volume of medication in the groups, a significantly higher analgesia score at full dilatation was observed in the PIEB group, odds-ratio = 1.9 (95% confidence interval, 1.0 to 3.5), P = 0.04. CONCLUSION: The mechanics of the second stage did not differ whether PIEB or PCEA was used. Analgesic conditions appeared to be superior with PIEB, especially at full dilation. TRIAL REGISTRATION: NCT01856166.

Programmed intermittent bolus infusion versus continuous infusion of 0.2% levobupivacaine after ultrasound-guided thoracic paravertebral block for video-assisted thoracoscopic surgery: A randomised controlled trial.

BACKGROUND: The analgesic benefits of programmed intermittent bolus infusion for thoracic paravertebral block remain unknown. OBJECTIVE: The aim of this study was to compare the analgesia from intermittent bolus infusion with that of a continuous infusion after thoracic paravertebral block. DESIGN: A randomised controlled study. SETTING: A single centre between December 2016 and November 2017. Seventy patients scheduled for video-assisted thoracoscopic surgery were included in the study. INTERVENTION(S): Patients were randomly assigned to receive 0.2% levobupivacaine via continuous infusion (5 ml h, continuous group) or programmed intermittent bolus infusion (15 ml every 3 h, bolus group) after an initial 15-ml bolus injection of 0.2% levobupivacaine. MAIN OUTCOME MEASURES: The main outcome was the amount of rescue fentanyl (per kg of body weight) consumed within 24 h after surgery. Secondary outcomes were postoperative pain scores, plasma levobupivacaine concentrations and the number of dermatomes anaesthetised. RESULTS: There was no significant difference between the continuous and bolus groups in the postoperative consumption of fentanyl (median [interquartile range] 5.5 [4 to 9.5] µg kg versus 6 [3.5 to 9] µg kg respectively, P = 0.45) and postoperative pain scores within 24 h. At 20 h after initiating the infusions, there was no statistically significant difference between the two groups in terms of the plasma levobupivacaine concentration. The number of dermatomes anaesthetised to pinprick and cold testing was significantly greater in the bolus group. CONCLUSION: Our findings suggest that postoperative pain and opioid usage are similar with either programmed intermittent bolus infusion or continuous infusion after thoracic paravertebral block. Programmed intermittent bolus infusion provides a wider sensory blockade and could benefit patients requiring a wider extent of anaesthesia. TRIAL REGISTRATION: UMIN Clinical Trials Registry (UMIN-CTR; URL: http://umin.ac.jp/ctr/, ID: UMIN000023378).

Patient intermittent epidural boluses (PIEB) plus very low continuous epidural infusion (CEI) versus patient-controlled epidural analgesia (PCEA) plus continuous epidural infusion (CEI) in primiparous labour: a randomized trial.

Epidural maintenance technique for labour analgesia updates constantly. Thanks to infusion pumps, the recently developed programmed intermittent epidural bolus (PIEB) may reduce the use of anesthetic drugs and minimize unintended consequences such as cardio or neurotoxicity. Nevertheless, it is not yet a general practice. So far, there are no comparative studies in the literature that address levobupivacaine-based CEI + PCEA versus CEI + PIEB + PCEA. A randomized double-blind trial was carried out to evaluate if PIEB could reduce local anesthetic use compare to PCEA. Primiparous pregnant patients were divided into two groups: PIEB group (continuous infusion plus intermittent automatic doses) and PCEA group (continuous infusion plus PCEA). The primary objective was to analyze the differences between both groups regarding levobupivacaine total dose. The secondary objectives were to find out the differences concerning pain control, motor blockage, satisfaction score, labour time and delivery outcomes. Statistical analyses were done by protocol. The study recruited 200 patients (103 PIEB, 97 PCEA). The total dose administered was significantly higher in PIEB group: PCEA group 52.97 mg, IC 95% 45.65-60.28 mg and PIEB group 62.04 mg, IC 95% 55.46-68.61 mg (p = 0.021). PIEB group required fewer top up boluses (median value1; range 0-2) than CEI + PCEA group (median value 6; range 3-9) p < 0.05. Satisfaction scores were higher in PIEB group (p = 0.039, CI 95% 1.23-1.42). CEI + PIEB was found to be a good alternative to CEI + PCEA with very high rates of satisfaction in both groups although it was higher in PIEB group. PIEB group required fewer PCEA boluses. Further studies are needed to determine the best approach for epidural pain management.Clinical Trial Number and Registry URL: NCT03133091 ( https://clinicaltrials.gov/ct2/show/NCT03133091?term=MB+Rodriguez&rank=1) .

Sciatic nerve block in dogs: description and evaluation of a modified ultrasound-guided parasacral approach.

OBJECTIVE: To develop a modified ultrasound-guided parasacral approach to the sciatic nerve and compare the effects of a volume of 0.2 mL kg-1 of 0.5% levobupivacaine with an equivalent volume of 0.9% saline injected near the sciatic nerve. STUDY DESIGN: Cadaveric and experimental, blinded, randomized study. ANIMALS: Seven canine cadavers and seven experimental Beagle dogs. METHODS: Both sciatic nerves of seven cadavers were identified using a modified in-plane ultrasound-guided approach. Methylene blue solution (0.2 mL) was injected perineurally, and success was evaluated through dissection. The same approach was repeated in seven Beagle dogs sedated with dexmedetomidine (50 µg kg-1) injected intramuscularly (IM). After randomization, 0.2 mL kg-1 of 0.5% levobupivacaine (limb L) and 0.2 mL kg-1 of 0.9% saline (limb C) were injected perineurally on either right or left limb. Block success was determined by sensory deficits every hour for 8 hours after an atipamezole injection (0.2 mg kg-1) IM. Reaction to pinprick (binary score) over the course of the sciatic nerve (four locations) and locomotion were assessed. RESULTS: The overall sciatic nerve block success was 93% in cadavers and 86% in sedated dogs. It was impossible to localize the sciatic nerves in one obese sedated dog. Significant differences between limb L and limb C were observed for pinprick at great trochanter, caudal thigh and lateral tarsal joint (p < 0.0001). Reaction to pinprick was absent in all dogs at great trochanter and caudal thigh up to at least 3 hours on limb L. Locomotion was impaired in all but one dog for 60 (30-210) minutes (median; interquartile range). No complications were observed. CONCLUSIONS AND CLINICAL RELEVANCE: A volume of ≥0.2 mL kg-1 and a concentration of 0.5% levobupivacaine can be recommended when using a modified ultrasound-guided parasacral approach to the sciatic nerve in dogs.

Single-shot pectoral plane (PECs I and PECs II) blocks versus continuous local anaesthetic infusion analgesia or both after non-ambulatory breast-cancer surgery: a prospective, randomised, double-blind trial.

BACKGROUND: Pectoral plane blocks (PECs) are increasingly used in analgesia for patients undergoing breast surgery, and were recently found to be at least equivalent to single-shot paravertebral anaesthesia. However, there are no data comparing PECs with the popular practice of continuous local anaesthetic wound infusion (LA infusion) analgesia for breast surgery. Therefore, we compared the efficacy and safety of PECs blocks with LA infusion, or a combination of both in patients undergoing non-ambulatory breast-cancer surgery. METHODS: This single-centre, prospective, randomised, double-blind trial analysed 45 women to receive either PECs blocks [levobupivacaine 0.25%, 10 ml PECs I and levobupivacaine 0.25%, 20 ml PECs II (PECs group); LA infusion catheter (levobupivacaine 0.1% at 10 ml h-1 for 24 h (LA infusion group); or both (PECs and LA infusion)]. The primary outcome measure was area under the curve of the pain verbal rating score whilst moving vs time (AUC) over 24 h. Secondary outcomes included total opioid consumption at 24 h. RESULTS: AUC moving was mean (SD) 71 (34) mm h-1vs 58 (41) vs 23 (20) in PECs, LA infusion, and both, respectively; P=0.002. AUC at rest was also significantly lower in patients receiving both. The total 24 h opioid consumption [median (25-75%)] was 14 mg (9-26) vs 11 (8-24) vs 9 (5-11); P=0.4. No adverse events were observed. CONCLUSIONS: The combination of both pre-incisional PECs blocks and postoperative LA infusion provides better analgesia over 24 h than either technique alone after non-ambulatory breast-cancer surgery. CLINICAL TRIAL REGISTRATION: NCT 03024697.

Opioid analgesia and the somatosensory memory of neonatal surgical injury in the adult rat.

BACKGROUND: Nociceptive input during early development can produce somatosensory memory that influences future pain response. Hind-paw incision during the 1st postnatal week in the rat enhances re-incision hyperalgesia in adulthood. We now evaluate its modulation by neonatal analgesia. METHODS: Neonatal rats [Postnatal Day 3 (P3)] received saline, intrathecal morphine 0.1 mg kg-1 (IT), subcutaneous morphine 1 mg kg-1 (SC), or sciatic levobupivacaine block (LA) before and after plantar hind-paw incision (three×2 hourly injections). Six weeks later, behavioural thresholds and electromyography (EMG) measures of re-incision hyperalgesia were compared with an age-matched adult-only incision (IN) group. Morphine effects on spontaneous (conditioned place preference) and evoked (EMG sensitivity) pain after adult incision were compared with prior neonatal incision and saline or morphine groups. The acute neonatal effects of incision and analgesia on behavioural hyperalgesia at P3 were also evaluated. RESULTS: Adult re-incision hyperalgesia was not prevented by neonatal peri-incision morphine (saline, IT, and SC groups > IN; P<0.05-0.01). Neonatal sciatic block, but not morphine, prevented the enhanced re-incision reflex sensitivity in adulthood (LA < saline and morphine groups, P<0.01; LA vs IN, not significant). Morphine efficacy in adulthood was altered after morphine alone in the neonatal period, but not when administered with neonatal incision. Morphine prevented the acute incision-induced hyperalgesia in neonatal rats, but only sciatic block had a preventive analgesic effect at 24 h. CONCLUSIONS: Long-term effects after neonatal injury highlight the need for preventive strategies. Despite effective analgesia at the time of neonatal incision, morphine as a sole analgesic did not alter the somatosensory memory of early-life surgical injury.

Combined thoracic paravertebral and pectoral nerve blocks for breast surgery under sedation: a prospective observational case series.

Avoidance of general anaesthesia for breast surgery may be because of clinical reasons or patient choice. There is emerging evidence that the use of regional anaesthesia and the avoidance of volatile anaesthetics and opioid analgesia may have beneficial effects on oncological outcomes. We conducted a prospective observational case series of 16 breast cancer surgeries performed under thoracic paravertebral plus pectoral nerve block with propofol sedation to demonstrate feasibility of technique, patient acceptability and surgeon satisfaction. Fifteen out of 16 cases were successfully completed under sedation and regional anaesthesia, with one conversion to general anaesthesia. Eleven out of 16 cases required low-dose intra-operative opioid analgesia. Out of the 15 surgical procedures completed under regional anaesthesia with sedation, all patients experienced either no or minimal intra-operative pain, and all would choose this anaesthetic technique again. Surgeon-reported operating conditions were 'indistinguishable from general anaesthesia' in most cases, and surgeons were 'extremely satisfied' or 'satisfied' with the technique after every procedure. Combined thoracic paravertebral plus pectoral nerve block with intra-operative sedation is a feasible technique for breast surgery.

A randomized comparison between interscalene and combined infraclavicular-suprascapular blocks for arthroscopic shoulder surgery.

BACKGROUND: This randomized trial aimed to evaluate combined infraclavicular-suprascapular blocks (ICB-SSBs) as a diaphragm-sparing alternative to interscalene blocks (ISBs) for arthroscopic shoulder surgery. We hypothesized that ICB-SSB would provide equivalent postoperative analgesia to ISB 30 min after surgery without the risk of hemidiaphragmatic paralysis. METHODS: Following research ethics board approval and written informed consent, participants in the ISB group received an ultrasound-guided ISB with 20 mL of levobupivacaine 0.25% and epinephrine 5 µg·mL-1. In the ICB-SSB group, ultrasound-guided ICB (20 mL) and SSB (10 mL) were carried out using the same local anesthetic. Thirty minutes after the block was performed, a blinded investigator assessed the presence of hemidiaphragmatic paralysis. Subsequently, all patients underwent general anesthesia. Postoperatively, a blinded investigator recorded pain scores at rest at 0.5, 1, 2, 3, 6, 12 and 24 hr. Consumption of intra- and postoperative narcotics was also tabulated. RESULTS: Compared to its ICB-SSB counterpart, the ISB group displayed non-equivalent (i.e., lower) postoperative pain scores at 30 min (difference of the medians, -4; 99% confidence interval [CI], -6 to -3), required less cumulative morphine iv at 24 hr (difference of the means, -6.1 mg; 95% CI, -10.5 to -1.6), and resulted in a higher incidence of hemidiaphragmatic paralysis (18/20 vs 0/20 patients, respectively; P < 0.001). Although postoperative pain scores at one, two, and three hours appeared lower in the ISB group, the upper bounds of the 99% CIs did not exceed the equivalence margin. CONCLUSION: Compared with ICB-SSB, ISB provided non-equivalent (i.e., lower) postoperative pain scores 30 min after arthroscopic shoulder surgery. Thereafter, postoperative analgesia was comparable between the two groups. Further trials are required to compare ISB with ICB-SSB using a proximal (i.e., costoclavicular) technique for ICB. TRIAL REGISTRATION: www.clinicaltrials.gov , NCT02993939. Registered 12 December 2016.

Efficacy of continuous in-wound infusion of levobupivacaine and ketorolac for post-caesarean section analgesia: a prospective, randomised, double-blind, placebo-controlled trial.

BACKGROUND: In-wound catheters for infusion of local anaesthetic for post-caesarean section analgesia are well tolerated in parturients. Few studies have examined continuous in-wound infusion of a combination of local anaesthetic and non-steroidal anti-inflammatory drug for post-caesarean section analgesia. This single centre study evaluated post-operative analgesic efficacy and piritramide-sparing effects of continuous in-wound infusion of either local anaesthetic or non-steroidal anti-inflammatory agent, or the combination of both, versus saline placebo, when added to systemic analgesia with paracetamol. METHODS: After National Ethical Board approval, 59 pregnant women scheduled for non-emergency caesarean section were included in this prospective, randomised, double-blind, placebo-controlled study. The parturients received spinal anaesthesia with levobupivacaine and fentanyl. Post-operative analgesia to 48 h included paracetamol 1000 mg intravenously every 6 h, with the studied agents as in-wound infusions. Rescue analgesia with piritramide was available as needed, titrated to 2 mg intravenously. Four groups were compared, using a subcutaneous multi-holed catheter connected to an elastomeric pump running at 5 mL/h over 48 h. The different in-wound infusions were: levobupivacaine 0.25% alone; ketorolac tromethamine 0.08% alone; levobupivacaine 0.25% plus ketorolac tromethamine 0.08%; or saline placebo. The primary outcome was total rescue piritramide used at 24 h and 48 h post-operatively, under maintained optimal post-caesarean section analgesia. RESULTS: Compared to placebo in-wound infusions, ketorolac alone and levobupivacaine plus ketorolac in-wound infusions both significantly reduced post-operative piritramide consumption at 24 h (p = 0.003; p < 0.001, respectively) and 48 h (p = 0.001; p < 0.001). Compared to levobupivacaine, levobupivacaine plus ketorolac significantly reduced post-operative piritramide consumption at 24 h (p = 0.015) and 48 h (p = 0.021). For levobupivacaine versus ketorolac, no significant differences were seen for post-operative piritramide consumption at 24 h and 48 h (p = 0.141; p = 0.054). CONCLUSION: Continuous in-wound infusion with levobupivacaine plus ketorolac provides greater opioid-sparing effects than continuous in-wound infusion with levobupivacaine alone. TRIAL REGISTRATION: German Clinical Trials Register: retrospectively registered on 30 July, 2014, DRKS 00006559 .