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.

Comparison of the effect of adding midazolam versus fentanyl to intrathecal levobupivacaine in patients undergoing cesarean section: double-blind, randomized clinical trial

Abstract Background: Many adjuvants are added to prolong the effects of spinal analgesia. We investigated the postoperative analgesic efficacy of the addition of midazolam or fentanyl to intrathe-cal levobupivacaine in women undergoing cesarean delivery. Methods: Eighty patients were randomly assigned to two groups (n = 40). Group M received 10 mg of 0.5% levobupivacaine plus 2 mg of midazolam. Group F received 10 mg of 0.5% levobupivacaine plus 25 μg of fentanyl. Assessments included motor and sensory block, APGAR score, time to first request for analgesia, postoperative pain score, total consumption of rescue analgesics, and adverse effects. Results: Sensory blockade was prolonged in Group M compared with Group F (215.58 ± 27.94 vs. 199.43 ± 19.77 min; p = 0.004), with no differences in other characteristics of the spinal block in intraoperative hemodynamics or APGAR score. The mean time to first request for rescue analgesia was longer in Group M (351.45 ± 11.05 min) than in Group F (268.83 ± 10.35 min; p = 0.000). The median total consumption of rescue analgesics in the first 24 hours postoperatively was 30 mg in Group M vs. 60 mg in Group F (p = 0.003). The median Visual Analog Scale (VAS) scores were lower in Group Ethan in Group F from the 8th to the 12th hour postoperatively, with no differences between the groups at other time points. The incidence of adverse effects was higher in Group F than in Group M. Conclusion: Intrathecal midazolam (2 mg) was superior to intrathecal fentanyl (25 μg) in increasing the duration of the sensory blockade and postoperative analgesia with lower postoperative pain scores and decreasing the incidence of adverse effects.

Comparison of the effect of adding midazolam versus fentanyl to intrathecal levobupivacaine in patients undergoing cesarean section: double-blind, randomized clinical trial.

BACKGROUND: Many adjuvants are added to prolong the effects of spinal analgesia. We investigated the postoperative analgesic efficacy of the addition of midazolam or fentanyl to intrathecal levobupivacaine in women undergoing cesarean delivery. METHODS: Eighty patients were randomly assigned to two groups (n = 40). Group M received 10 mg of 0.5% levobupivacaine plus 2 mg of midazolam. Group F received 10 mg of 0.5% levobupivacaine plus 25 µg of fentanyl. Assessments included motor and sensory block, APGAR score, time to first request for analgesia, postoperative pain score, total consumption of rescue analgesics, and adverse effects. RESULTS: Sensory blockade was prolonged in Group M compared with Group F (215.58 ± 27.94 vs. 199.43 ± 19.77 min; p = 0.004), with no differences in other characteristics of the spinal block in intraoperative hemodynamics or APGAR score. The mean time to first request for rescue analgesia was longer in Group M (351.45 ± 11.05 min) than in Group F (268.83 ± 10.35 min; p = 0.000). The median total consumption of rescue analgesics in the first 24 hours postoperatively was 30 mg in Group M vs. 60 mg in Group F (p = 0.003). The median Visual Analog Scale (VAS) scores were lower in Group Ethan in Group F from the 8th to the 12th hour postoperatively, with no differences between the groups at other time points. The incidence of adverse effects was higher in Group F than in Group M. CONCLUSION: Intrathecal midazolam (2 mg) was superior to intrathecal fentanyl (25 µg) in increasing the duration of the sensory blockade and postoperative analgesia with lower postoperative pain scores and decreasing the incidence of adverse effects.

Infiltração de anestésicos locais na ferida cirúrgica: efeito sobre a inflamação e cicatriz fibrosa em ratos / Infiltration of local anesthetics into the surgical wound: effect on inflammation and fibrous scar in rats

■ RESUMO Introdução: O alívio da dor após a cirurgia continua sendo um dos desafios médicos mais significativos, principalmente na cirurgia estética. A infiltração da incisão cirúrgica com anestésicos locais tem sido cada vez mais utilizada para reduzir a dor e o uso de analgésicos. No entanto, pouco se sabe sobre o efeito desta injeção na cicatrização. O objetivo é avaliar a interferência dos anestésicos locais na área de infiltrado inflamatório e cicatriz de fibrose em ratos. Métodos: Duas incisões lineares foram feitas cada uma na região dorsal de 40 ratos Wistar. A incisão esquerda foi infiltrada com doses de 1,8ml de bupivacaína, levobupivacaína, ropivacaína ou solução salina 0,9%. A incisão direita não recebeu infiltração, servindo como grupo controle. Após sete dias, amostras das incisões foram coletadas para avaliação morfométrica histológica. Resultados: Quando comparada com os grupos controle, a área de infiltrado inflamatório encontrada foi maior nos grupos bupivacaína, ropivacaína e levobupivacaína. O grupo bupivacaína apresentou um infiltrado inflamatório maior do que a levobupivacaína e a ropivacaína. A área da cicatriz fibrosa foi maior nos grupos levobupivacaína e ropivacaína. Não houve diferença entre os grupos que receberam anestésico e solução salina. Conclusão: Como não houve diferença entre os grupos de anestésico e soro fisiológico, o volume aplicado ou o trauma podem ter sido a causa das maiores áreas de infiltração e cicatriz associadas à aplicação dos anestésicos locais.

■ ABSTRACT Introduction: Pain relief after surgery remains one of the most significant medical challenges, mainly in aesthetic surgery. The infiltration of the surgical incision with local anesthetics has been increasingly used to reduce pain and other analgesic use. However, little is known about the effect of this injection on healing. The objective is to evaluate the interference of local anesthetics in the area of inflammatory infiltrate and fibrosis scar in rats. Methods: Two linear incisions each were made on the dorsal region of 40 Wistar rats. The left incision was infiltrated with doses of 1.8ml of bupivacaine, levobupivacaine, ropivacaine, or 0,9% saline solution infiltration. The right incision did not receive infiltration, serving as a control group. After seven days, samples of the incisions were collected for histological morphometric evaluation. Results: When compared with the control groups, the area of inflammatory infiltrate was found larger in the bupivacaine, ropivacaine, and levobupivacaine groups. The bupivacaine group presented a larger inflammatory infiltrate than the levobupivacaine and ropivacaine. The fibrous scar area was larger in the levobupivacaine and ropivacaine groups. There was no difference between the groups that received anesthetic and saline solution. Conclusion: As there was no difference between the anesthetics and saline solution groups, the volume applied, or the trauma may have been the cause of the larger areas of infiltrating and scar associated with local anesthetics application.

Paravertebral block using levobupivacaine or dexmedetomidine-levobupivacaine for analgesia after cholecystectomy: a randomized double-blind trial.

BACKGROUND: Thoracic paravertebral block (TPVB) has emerged as an effective and feasible mode of providing analgesia in laparoscopic cholecystectomy. Though a variety of local anaesthetic combinations are used for providing TPVB, literature is sparse on use of dexmedetomidine in TPVB. We aimed to compare levobupivacaine and levobupivacaine-dexmedetomidine combination in ultrasound guided TPVB in patients undergoing laparoscopic cholecystectomy. METHODOLOGY: 70 ASA I/II patients, aged 18-60 years, scheduled to undergo laparoscopic cholecystectomy under general anaesthesia were enrolled and divided into two groups. Before anaesthesia induction, group A patients received unilateral right sided ultrasound guided TPVB with 15 ml 0.25% levobupivacaine plus 2 ml normal saline while group B patients received unilateral right sided ultrasound guided TPVB with 15 ml 0.25% levobupivacaine plus 2 ml solution containing dexmedetomidine 1 µg.kg-1. Patients were monitored for pain using Numeric Rating Scale (NRS) at rest, on movement, coughing and comfort scores post surgery. Total analgesic consumption in first 48 hour postoperative period, time to first request analgesic and pain scores were recorded. RESULTS: Total amount of rescue analgesia (injection tramadol plus injection tramadol intravenous equivalent dose) consumed during 48 hours postoperatively in group A was 146.55 mg while in group B was 111.30 mg (p = 0.026). Mean time for demanding rescue analgesia was 273 minutes in group A while in group B was 340 minutes (p = 0.00). CONCLUSION: TPVB using dexmedetomidine 1 µg.kg-1 added to levobupivacaine 0.25% in patients undergoing laparoscopic cholecystectomy significantly reduced total analgesic consumption in first 48 hours and provided longer duration of analgesia postoperatively compared to levobupivacaine 0.25% alone.

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.

Management of urethral obstruction in a cat with epidural sacrococcygeal anesthesia guided by electrical neurostimulation

Background: The treatment for urethral obstruction in cats consists of catheterization, and for this, the cat must be sedated or anesthetized. Sacococcygeal epidural block has the advantage of being close to receptors related to nociception located in the spinal cord and it is safer because it represents lower risk of spinal cord injury or inadvertent application in the subarachnoid space, when compared to the lumbosacral epidural. Nerve stimulation through the neurolocator to identify the epidural space increases the accuracy of this technique. Thus, the objective is to report a case of epidural anesthesia with a sacrococcygeal approach guided by neurostimulation in a cat with urethral obstruction. Case: A 4-year-old male Siamese cat, weighing 4 kg, was referred to the veterinary care with a history of apathy and anorexia for 2 days. From the physical exam, the clinical diagnosis of urethral obstruction was made, and to desobstruction, we chose to perform sacrococcygeal epidural block. Initially, the patient was anesthetized with propofol (4 mg/kg) and midazolam (0.3 mg/kg). To perform the anesthetic block, the cat was placed in sternal decubitus with the hind limbs extended cranially to perform sacrococcygeal epidural block. The positive pole (cathode) was connected to the skin of the right inguinal region at the caudal aspect of the thigh and the neurostimulator was turned on and adjusted to 0.7 mA of stimulating current intensity, 0.1 ms duration and 1 Hz frequency. The needle for electrical neurolocation was introduced in the dorsal midline, perpendicular to the skin surface, between the spinous processes of S3-Cd1 in the skin. The exact injection point was obtained observed by the muscular response of the middle and distal third of the animal's tail with the neurostimulator adjusted to 0.3 mA of intensity, in the same duration and frequency as before. The total volume of 0.9 mL (0.22 mL/kg) of solution containing the combination of 0.6 mL of 0.75% levobupivacaine and 0.3 mL of 2% lidocaine was injected. The success of the block was confirmed by the loss of reflexes of the pelvic limbs and anal sphincter 10 min after the administration of the anesthetic solution. Discussion: In this case, the use of the neurolocator helped to perform an effective sacrococcygeal block, allowing urethral catheterization without the addition of other analgesic agents. This technique desensitizes and relaxes muscles in the regions of the perineum, anus, distal colon and penis, being useful for performing urethral catheterization. The use of smaller anaesthetic volumes to perform sacrococcygeal block makes it possible to achieve a more localized anesthesia, without affecting the motor function of the pelvic limbs. However, in our report, using a combination of levobupivacaine and lidocaine, the pelvic limb block was also verified despite the low volume applied. A hypothesis that could justify the different responses in relation to the pelvic limb block compared to other studies would be due to the different physicalchemical properties of the drugs used. Lidocaine is known to be less fat-soluble than bupivacaine, so it tends to spread more through the epidural space, in order to result in more extensive blocks. The use of a neurostimulator using a fixed electric current of 0.7 mA, pulse 0.1 ms and a frequency of 1 Hz allowed the correct identification of the needle position for the application of the anesthetic.

Evaluation of intraperitoneal and incisional bupivacaine or levobupivacaine for postoperative analgesia in ovariohysterectomized dogs

Background: Ovariohysterectomy (OHE) is the most commonly performed elective surgical procedure in companionanimals. OHE offers benefits of control of population and decreased risk of potentially life-threatening diseases such asmammarian tumours and pyometra. Traditional OHE intervention causes inflammation and pain due to trauma duringorgan manipulation. The purpose of this study was to compare the effect of intraperitoneal and incisional administrationof bupivacaine (BP) or levobupivacaine (LP) on postoperative analgesia in dogs undergoing the OHE procedure.Materials, Methods & Results: A total of 24 mix-breed bitches aged between 1 - 3 years and weighed 19 - 20 kg wereused in this study. The animals were divided into three groups as control (n = 8), BP (n = 8) and LP group (n = 8). Theanimals were kept under surveillance at the hospitalisation unit of the animal hospital for one day before the elective OHE.The dogs were fasted for 12 h before the surgery, with adlib water consumption. Atropine sulphate 0.045 mg/kg was administered subcutaneously approximately 30 min before general anaesthesia. Midazolam (0.3 mg/kg) was intravenouslyinjected into all dogs for pre-anaesthetic medication. After sedation, anaesthesia was induced with propofol (4 mg/kg, IV)and then the dogs were orotracheally intubated using cuffed endotracheal tubes. General anaesthesia was maintained byadministration of 2% isoflurane. The ventral abdomen was prepared aseptically for OHE following the general anaesthesia.All animals were operated on by the same surgeon. During surgery, sprayed bupivacaine 0.5% (4.4 mg/kg) with an equalvolume of saline in BP group, levobupivacaine 0.5% (4.4 mg/kg) with an equal volume of saline in LP were then appliedover the ovaries, uterine broad ligaments and cervix uteri. After removal of the uterine body, either LP or BP was sprayedto left and right, or cranial and caudal parts of the abdominal cavity...(AU)

Ultrasound-guided adductor canal block using levobupivacaine versus periarticular levobupivacaine infiltration after totalknee arthroplasty: a randomized clinical trial

ABSTRACT BACKGROUND: Both postoperative pain control and range of motion are important in total knee arthroplasty (TKA). However, in the literature, there is little comparison of peripheral nerve blocks and periarticular infiltration techniques using levobupivacaine. The aim of our study was to measure pain with visual analogue scale (VAS) and knee range of motion (ROM) between in patients undergoing adductor canal block (ACB) for TKA using levobupivacaine compared to periarticular levobupivacaine infiltration (PAI-L). DESIGN AND SETTING: Prospective randomized clinical trial in a university hospital. METHODS: Patients aged 40-85 years who underwent unilateral TKA were included; 39 were treated withperiarticular infiltration using 40 ml (0.125 mg) of levobupivacaine (PAI-L group); and 40 were treated with ACB using 20 ml of 0.25% levobupivacaine (ACB-L group). Postoperative pain scores at rest and during active physical therapy were assessed using a VAS, along with knee ROM in flexion and extension. In addition, 100-foot walking time results, total morphine consumption and time of first analgesia requirement were recorded postoperatively. RESULTS: VAS scores at rest and during active physical therapy and the total amount of morphine consumed were lower in the ACB-L group than in the PAI-L group (P < 0.05). In contrast, knee ROM in flexion and extension and 100-foot walking times were greater in the PAI-L group than in the ACB-L group (P < 0.05). CONCLUSION: ACB-L was superior to PAI-L regarding pain treatment after TKA; however, PAI-L was superior to ACB-L regarding postoperative ROM and walking ability. CLINICAL TRIAL REGISTRY: ACTRN-12618000438257.

Evaluation of intraperitoneal and incisional bupivacaine or levobupivacaine for postoperative analgesia in ovariohysterectomized dogs

Background: Ovariohysterectomy (OHE) is the most commonly performed elective surgical procedure in companionanimals. OHE offers benefits of control of population and decreased risk of potentially life-threatening diseases such asmammarian tumours and pyometra. Traditional OHE intervention causes inflammation and pain due to trauma duringorgan manipulation. The purpose of this study was to compare the effect of intraperitoneal and incisional administrationof bupivacaine (BP) or levobupivacaine (LP) on postoperative analgesia in dogs undergoing the OHE procedure.Materials, Methods & Results: A total of 24 mix-breed bitches aged between 1 - 3 years and weighed 19 - 20 kg wereused in this study. The animals were divided into three groups as control (n = 8), BP (n = 8) and LP group (n = 8). Theanimals were kept under surveillance at the hospitalisation unit of the animal hospital for one day before the elective OHE.The dogs were fasted for 12 h before the surgery, with adlib water consumption. Atropine sulphate 0.045 mg/kg was administered subcutaneously approximately 30 min before general anaesthesia. Midazolam (0.3 mg/kg) was intravenouslyinjected into all dogs for pre-anaesthetic medication. After sedation, anaesthesia was induced with propofol (4 mg/kg, IV)and then the dogs were orotracheally intubated using cuffed endotracheal tubes. General anaesthesia was maintained byadministration of 2% isoflurane. The ventral abdomen was prepared aseptically for OHE following the general anaesthesia.All animals were operated on by the same surgeon. During surgery, sprayed bupivacaine 0.5% (4.4 mg/kg) with an equalvolume of saline in BP group, levobupivacaine 0.5% (4.4 mg/kg) with an equal volume of saline in LP were then appliedover the ovaries, uterine broad ligaments and cervix uteri. After removal of the uterine body, either LP or BP was sprayedto left and right, or cranial and caudal parts of the abdominal cavity...

The chondrotoxic and apoptotic effects of levobupivacaine and bupivacaine on the rabbit knee joint / Os efeitos condrotóxicos e apoptóticos de levobupivacaína e bupivacaína na articulação do joelho de coelhos

Abstract Background: A single dose injection or continuous infusion of local anesthetics into the joint space is considered to be a well-defined analgesia technique. The aim of this study was to investigate the chondrotoxic and apoptotic effects of single-dose intra-articular injection of levobupivacaine and bupivacaine on rabbit knee joint tissues. Materials and methods: The animals were allocated into two groups each containing 20 rabbits. 0.5% levobupivacaine (Group L) and 0.5% bupivacaine (Group B) were applied intra-articularly to the left posterior joints of rabbits. At the same time, normal saline was applied to the right posterior leg knee joints of rabbits in both groups and used as a control (Group S). At the end of the 7th and 28th days after the intraarticular injections, ten randomly chosen rabbits in each group were killed by applying intraperitoneal thiopental. Sections of cartilage tissue samples were stained for light microscopic examinations and the TUNEL method was used to investigate apoptotic cells. Results: As a result of immunofluorescence microscopic examination, the number of apoptotic cells in Group B at day 7 and day 28 were both significantly higher than Group L and S (p < 0.05). Also, the number of apoptotic cells in Group L at day 7 and day 28 were both significantly higher than Group S (p < 0.05). Conclusions: We found that bupivacaine is more chondrotoxic than other anesthetic agent and increases the number of apoptotic cells. These results indicated that bupivacaine caused high chondrotoxic damage and it led to more apoptotic activation than levobupivacaine.

Resumo Justificativa: Uma injeção em dose única ou infusão contínua de anestésicos locais no espaço articular é considerada uma técnica de analgesia bem definida. O objetivo deste estudo foi investigar os efeitos condrotóxicos e apoptóticos da injeção intra-articular com dose única de levobupivacaína e bupivacaína em tecidos articulares do joelho de coelho. Material e métodos: Os animais foram alocados em dois grupos, cada um contendo 20 coelhos. Levobupivacaína a 0,5% (Grupo L) e bupivacaína a 0,5% (Grupo B) foram aplicadas intra-articularmente nas articulações posteriores esquerdas de coelhos. Ao mesmo tempo, solução salina normal foi aplicada nas articulações do joelho da perna posterior direita de coelhos em ambos os grupos e usada como controle (Grupo S). Ao fim do 7° e 28° dias após as injeções intra-articulares, 10 coelhos escolhidos aleatoriamente em cada grupo foram mortos por aplicação de tiopental intraperitoneal. Seções de amostras de tecido cartilaginoso foram coradas para exames de microscopia de luz, e o método TUNEL foi usado para investigar células apoptóticas. Resultados: Como resultado do exame microscópico de imunofluorescência nos dias 7 e 28, o número de células apoptóticas no Grupo B foi significativamente maior que nos grupos L e S (p < 0,05). Além disso, o número de células apoptóticas nos dias 7 e 28 foi significativamente maior no Grupo L do que no Grupo S (p < 0,05). Conclusões: Demonstramos que a bupivacaína é mais condrotóxica do que o outro agente anestésico e aumenta o número de células apoptóticas. Esses resultados indicaram que a bupivacaína causou intensa lesão condrotóxica e levou a uma ativação apoptótica maior do que a levobupivacaína.

Ultrasound-guided transversus abdominis plane block in patients undergoing laparoscopic cholecystectomy: comparison of efficacy of bupivacaine and levobupivacaine on postoperative pain control / Bloqueio do plano abdominal transverso guiado por ultrassom em pacientes submetidos à colecistectomia laparoscópica: comparação da eficácia de bupivacaína e levobupivacaína no controle da dor pós-operatória

Abstract Background and objective The use of transversus abdominis plane block with different local anesthetics is considered as a part of multimodal analgesia regimen in laparoscopic cholecystectomy patients. However no studies have been published comparing bupivacaine and levobupivacaine for transversus abdominis plane block. We aimed to compare bupivacaine and levobupivacaine in ultrasound-guided transversus abdominis plane block in patients undergoing laparoscopic cholecystectomy. Methods Fifty patients (ASA I/II), undergoing laparoscopic cholecystectomy were randomly allocated into two groups. Following anesthesia induction, ultrasound-guided bilateral transversus abdominis plane block was performed with 30 mL of bupivacaine 0.25% in Group B (n = 25) and 30 mL of levobupivacaine 0.25% in Group L (n = 25) for each side. The level of pain was evaluated using 10 cm visual analog scale (VAS) at rest and during coughing 1, 5, 15, 30 min and 1, 2, 4, 6, 12 and 24 h after the operation. When visual analogue scale > 3, the patients received IV tenoxicam 20 mg. If visual analogue scale remained >3, they received IV. tramadol 1 mg.kg−1. In case of inadequate analgesia, a rescue analgesic was given. The analgesic requirement, time to first analgesic requirement was recorded. Results Visual analogue scale levels showed no difference except first and fifth minutes postoperatively where VAS was higher in Group L (p < 0.05). Analgesic requirement was similar in both groups. Time to first analgesic requirement was shorter in Group L (4.35 ± 6.92 min vs. 34.91 ± 86.26 min, p = 0.013). Conclusions Bupivacaine and levobupivacaine showed similar efficacy at TAP block in patients undergoing laparoscopic cholecystectomy.

Resumo Justificativa e objetivo O uso do bloqueio do plano transverso abdominal com diferentes anestésicos locais é considerado como parte do regime de analgesia multimodal em pacientes submetidos à colecistectomia laparoscópica. No entanto, nenhum estudo comparando bupivacaína e levobupivacaína para bloqueio do plano transverso abdominal foi publicado. Nosso objetivo foi comparar bupivacaína e levobupivacaína em bloqueio do plano transverso abdominal guiado por ultrassom em pacientes submetidos à colecistectomia laparoscópica. Métodos Cinquenta pacientes (ASA I/II), submetidos à colecistectomia laparoscópica foram alocados aleatoriamente em dois grupos. Após a indução da anestesia, o bloqueio do plano transverso abdominal bilateral guiado por ultrassom foi realizado com 30 mL de bupivacaína a 0,25% no Grupo B (n = 25) e 30 mL de levobupivacaína a 0,25% no Grupo L (n = 25) para cada lado. O nível de dor foi avaliado usando a escala visual analógica de 10 cm em repouso e durante a tosse em 1, 5, 15, 30 minutos e em 1, 2, 4, 6, 12 e 24 horas após a operação. Quando a escala visual analógica > 3, os pacientes receberam 10 mg de tenoxicam por via intravenosa (IV). Se a escala visual analógica permanecesse > 3, os pacientes recebiam tramadol IV (1 mg.kg−1). Em caso de analgesia inadequada, um analgésico de resgate foi administrado. A necessidade de analgésico e o tempo até a primeira solicitação de analgésico foram registrados. Resultados Os escores da escala visual analógica não mostraram diferença, exceto no primeiro e quinto minutos de pós-operatório, onde a escala visual analógica foi maior no Grupo L (p < 0,05). A necessidade de analgésico foi semelhante em ambos os grupos. O tempo até a primeira solicitação de analgésico foi menor no Grupo L (4,35 ± 6,92 min vs. 34,91 ± 86,26 min, p = 0,013). Conclusões Bupivacaína e levobupivacaína apresentaram eficácia similar no bloqueio TAP em pacientes submetidos à colecistectomia laparoscópica.

[The chondrotoxic and apoptotic effects of levobupivacaine and bupivacaine on the rabbit knee joint]. / Os efeitos condrotóxicos e apoptóticos de levobupivacaína e bupivacaína na articulação do joelho de coelhos.

BACKGROUND: A single dose injection or continuous infusion of local anesthetics into the joint space is considered to be a well-defined analgesia technique. The aim of this study was to investigate the chondrotoxic and apoptotic effects of single-dose intra-articular injection of levobupivacaine and bupivacaine on rabbit knee joint tissues. MATERIALS AND METHODS: The animals were allocated into two groups each containing 20 rabbits. 0.5% levobupivacaine (Group L) and 0.5% bupivacaine (Group B) were applied intra-articularly to the left posterior joints of rabbits. At the same time, normal saline was applied to the right posterior leg knee joints of rabbits in both groups and used as a control (Group S). At the end of the 7th and 28th days after the intraarticular injections, ten randomly chosen rabbits in each group were killed by applying intraperitoneal thiopental. Sections of cartilage tissue samples were stained for light microscopic examinations and the TUNEL method was used to investigate apoptotic cells. RESULTS: As a result of immunofluorescence microscopic examination, the number of apoptotic cells in Group B at day 7 and day 28 were both significantly higher than Group L and S (p<0.05). Also, the number of apoptotic cells in Group L at day 7 and day 28 were both significantly higher than Group S (p<0.05). CONCLUSIONS: We found that bupivacaine is more chondrotoxic than other anesthetic agent and increases the number of apoptotic cells. These results indicated that bupivacaine caused high chondrotoxic damage and it led to more apoptotic activation than levobupivacaine.

Effects of local anesthetics on wound healing / Efeitos dos anestésicos locais na cicatrização de feridas

Abstract Introduction Local anesthetic infiltration is used widely for post-operative analgesia in many situations. However the effects of local anesthetics on wound healing are not demonstrated clearly. This study planned to evaluate the effects of lidocaine, prilocaine, bupivacaine and levobupivacaine on wound healing, primarily on wound tensile strength and on collagen ultrastructure. Methods This study was conducted on male Sprague Dawley rats. On days 0, 8th, 15th, and 21st, all animals were weighed and received a preincisional subcutaneous infiltration of 3 mL of a solution according the group. Control saline (C), lidocaine (L) 7 mg.kg-1, prilocaine (P) 2 mg.kg-1, bupivacaine (B) 2 mg.kg-1 and levobupivacaine (LVB) 2.5 mg.kg-1. The infiltrations were done at the back region 1.5 cm where incision would be performed at the upper, middle and lower part along the midline, under general anesthesia. Wound tensile strengths were measured after 0.7 cm × 2 cm of cutaneous and subcutaneous tissue samples were obtained vertical to incision from infiltrated regions. Tissue samples were also obtained for electron microscopic examination. Evaluations were on the 8th, 15th and 21st days after infiltration. Results There was no difference between groups in the weights of the rats at the 0th, 8th, 15th and 21st days. The collagen maturation was no statistically different between groups at the 8th and 15th days. The maturation scores of the B and L groups at the 21st day was significantly lower than the Group C (1.40, 1.64 and 3.56; respectively). The wound tensile strength was no statistically different between groups at the 8th and 15th days but at the 21st day the Groups B and LVB had significantly lower value than Group C (5.42, 5.54 and 6.75; respectively). Conclusion Lidocaine and prilocaine do not affect wound healing and, bupivacaine and levobupivacaine affect negatively especially at the late period.

Resumo Introdução A infiltração de anestésico local é amplamente usada para analgesia pós-operatória em muitas situações. No entanto, os efeitos dos anestésicos locais na cicatrização de feridas não foram demonstrados claramente. Neste estudo planejamos avaliar os efeitos de lidocaína, prilocaína, bupivacaína e levobupivacaína sobre a cicatrização de feridas, principalmente sobre a força tênsil da ferida e a ultraestrutura do colágeno. Métodos Este estudo foi feito em ratos machos da linhagem Sprague Dawley. Nos dias 0, 8, 15 e 21, todos os animais foram pesados e receberam uma infiltração subcutânea pré-incisional de 3 mL de uma solução, de acordo com a designação dos grupos: Grupo C recebeu salina (controle); Grupo L recebeu lidocaína (7 mg.kg-1); Grupo P recebeu prilocaína (2 mg.kg-1); Grupo B recebeu bupivacaína (2 mg.kg-1); Grupo LVB recebeu levobupivacaína (2,5 mg.kg-1). As infiltrações foram feitas na região posterior a 1,5 cm de onde a incisão seria feita na parte superior, média e inferior ao longo da linha média, sob anestesia geral. A força tênsil da ferida foi medida após amostras de 0,7 × 2 cm de tecido cutâneo e subcutâneo serem obtidas das regiões infiltradas, verticalmente à incisão. Amostras de tecido também foram obtidas para exame microscópico eletrônico. As avaliações foram feitas nos dias 8, 15 e 21 após a infiltração. Resultados Não houve diferença entre os grupos em relação ao peso dos ratos nos dias 0, 8, 15 e 21. A maturação do colágeno não foi estatisticamente diferente entre os grupos nos dias 8 e 15. Os escores de maturação dos grupos B e L no dia 21 foram significativamente inferiores aos do Grupo C (1,40, 1,64 e 3,56, respectivamente). A força tênsil da ferida não foi estatisticamente diferente entre os grupos nos dias 8 e 15, mas no dia 21 os grupos B e LVB apresentaram valores significativamente menores que o Grupo C (5,42, 5,54 e 6,75, respectivamente). Conclusão Lidocaína e prilocaína não afetam a cicatrização de feridas, enquanto bupivacaína e levobupivacaína afetam negativamente, especialmente no período tardio.

Pharmacokinetics of levobupivacaine with epinephrine in transversus abdominis plane block for postoperative analgesia after Caesarean section.

BACKGROUND: Transversus abdominis plane block is increasingly used for post-Caesarean section analgesia. Cases of toxicity and the limited pharmacokinetic information during pregnancy motivated this study. The objective of the study was to characterise and compare the pharmacokinetics of levobupivacaine with epinephrine in tranversus abdominis plane block, in post-Caesarean section patients and healthy volunteers. METHODS: After approval by the Ethics Committee, we collected data from 12 healthy parturients after elective Caesarean section (Study 1) and data from 11 healthy male volunteers from a previous study (Study 2). Transversus abdominus plane block was performed under ultrasound guidance. The following injectates were used: levobupivacaine 0.25%, 20 ml with epinephrine 5 µg ml-1 (Study 1) per side; 20 ml of the same solution (unilateral block) (study 2). The plasma venous concentration of levobupivacaine was measured serially for 90 min. Pharmacokinetic parameters (volume of distribution, clearance, and absorption half-life) were estimated using a non-linear mixed effects model (NONMEM). Simulation in 1000 patients estimated the maximum concentration and the time to reach it after bilateral transversus abdominis plane block. RESULTS: Venous concentrations were below toxic levels (2.62 mg L-1). Levobupivacaine volume of distribution after Caesarean section was higher than in healthy volunteers [172 L (70 kg)-1 (95% confidence interval: 137-207) vs 94.3 L (70 kg)-1 (95% CI: 62-128); P<0.01]. Clearance and absorption half-life were similar. The simulation showed that maximum levobupivacaine concentration is lower and occurs later in postpartum patients (P<0.01). Postoperative analgesia was effective. CONCLUSIONS: Postpartum women reached relatively low plasma concentrations of levobupivacaine after transversus abdominal plane block given a volume of distribution 80% higher than volunteers, which could confer a greater margin of safety. CLINICAL TRIAL REGISTRATION: NCT02852720.

[Effects of local anesthetics on wound healing]. / Efeitos dos anestésicos locais na cicatrização de feridas.

INTRODUCTION: Local anesthetic infiltration is used widely for post-operative analgesia in many situations. However the effects of local anesthetics on wound healing are not demonstrated clearly. This study planned to evaluate the effects of lidocaine, prilocaine, bupivacaine and levobupivacaine on wound healing, primarily on wound tensile strength and on collagen ultrastructure. METHODS: This study was conducted on male Sprague Dawley rats. On days 0, 8th, 15th, and 21st, all animals were weighed and received a preincisional subcutaneous infiltration of 3mL of a solution according the group. Control saline (C), lidocaine (L) 7mg.kg-1, prilocaine (P) 2mg.kg-1, bupivacaine (B) 2mg.kg-1 and levobupivacaine (LVB) 2.5mg.kg-1. The infiltrations were done at the back region 1.5cm where incision would be performed at the upper, middle and lower part along the midline, under general anesthesia. Wound tensile strengths were measured after 0.7cm×2cm of cutaneous and subcutaneous tissue samples were obtained vertical to incision from infiltrated regions. Tissue samples were also obtained for electron microscopic examination. Evaluations were on the 8th, 15th and 21st days after infiltration. RESULTS: There was no difference between groups in the weights of the rats at the 0th, 8th, 15th and 21st days. The collagen maturation was no statistically different between groups at the 8th and 15th days. The maturation scores of the B and L groups at the 21st day was significantly lower than the Group C (1.40, 1.64 and 3.56; respectively). The wound tensile strength was no statistically different between groups at the 8th and 15th days but at the 21st day the Groups B and LVB had significantly lower value than Group C (5.42, 5.54 and 6.75; respectively). CONCLUSION: Lidocaine and prilocaine do not affect wound healing and, bupivacaine and levobupivacaine affect negatively especially at the late period.

[Ultrasound-guided transversus abdominis plane block in patients undergoing laparoscopic cholecystectomy: comparison of efficacy of bupivacaine and levobupivacaine on postoperative pain control]. / Bloqueio do plano abdominal transverso guiado por ultrassom em pacientes submetidos à colecistectomia laparoscópica: comparação da eficácia de bupivacaína e levobupivacaína no controle da dor pós­operatória.

BACKGROUND AND OBJECTIVE: The use of transversus abdominis plane block with different local anesthetics is considered as a part of multimodal analgesia regimen in laparoscopic cholecystectomy patients. However no studies have been published comparing bupivacaine and levobupivacaine for transversus abdominis plane block. We aimed to compare bupivacaine and levobupivacaine in ultrasound-guided transversus abdominis plane block in patients undergoing laparoscopic cholecystectomy. METHODS: Fifty patients (ASA I/II), undergoing laparoscopic cholecystectomy were randomly allocated into two groups. Following anesthesia induction, ultrasound-guided bilateral transversus abdominis plane block was performed with 30mL of bupivacaine 0.25% in Group B (n=25) and 30mL of levobupivacaine 0.25% in Group L (n=25) for each side. The level of pain was evaluated using 10cm visual analog scale (VAS) at rest and during coughing 1, 5, 15, 30min and 1, 2, 4, 6, 12 and 24h after the operation. When visual analogue scale>3, the patients received IV tenoxicam 20mg. If visual analogue scale remained >3, they received IV. tramadol 1mg.kg-1. In case of inadequate analgesia, a rescue analgesic was given. The analgesic requirement, time to first analgesic requirement was recorded. RESULTS: Visual analogue scale levels showed no difference except first and fifth minutes postoperatively where VAS was higher in Group L (p<0.05). Analgesic requirement was similar in both groups. Time to first analgesic requirement was shorter in Group L (4.35±6.92min vs. 34.91±86.26min, p=0.013). CONCLUSIONS: Bupivacaine and levobupivacaine showed similar efficacy at TAP block in patients undergoing laparoscopic cholecystectomy.

Levobupivacaine Thermogel for Long-acting Analgesia.

The adequate management of analgesia, by pharmacological methods or not, is a great challenge. Local anesthetics are used for pain relief, mainly by parenteral, intramuscular, catheter, and other routes of administration. The use of in situ forming systems becomes an alternative for the control of pain. The present research investigates development of thermogels containing poloxamer and levobupivacaine. All formulations were prepared by the cold method; the compatibilities of the excipients were evaluated by DSC, rheology and viscosities, transition temperature, syringeability, release kinetics, and permeation. The compatibility of the tested excipients with the drug was initially observed; all formulations had a viscosity increase at 37°C. Different delivery rates were observed in both the release and permeation studies. The developed systems maintained the in vitro release of the drug for a long period, likely decreasing side effects in vivo and avoiding the need for supplementary analgesia by other routes.

The effect of intra-articular levobupivacaine on shoulder cartilage at different doses - experimental study / O efeito de levobupivacaína intra-articular na cartilagem do ombro em doses diferentes-estudo experimental

Abstract Background and objectives: In this study it was aimed to examine the histological and morphometric effects on cartilage structure of intra-articular application of levobupivacaine to the shoulder joint. Methods: In twenty New Zealand adult male rabbits, 35 shoulders were used for the study and prepared in 5 groups of 7. These groups were defined as Groups L1, L2, L3 and L4 which were right shoulders administered with 0.25% and 0.5% levobupivacaine, Group C which were left shoulders as the control group and Groups S1 and S2 which were left shoulders administered with 0.9% saline. On the 2nd and 15th days the animals were killed, the glenohumeral joints were evaluated macroscopically then cartilage samples were taken. These samples were evaluated with Mankin score, and histomorphometrically by measuring the thickness of the cartilage between the superficial cartilage layer and the tidemark and the thickness of calcified cartilage between the tidemark and the subchondral bone. Results: Macroscopically, on the 15th day the joint fluid was seen to have reduced in all the groups. After microscopic evaluation, the highest Mankin score (mean: 3.14 ± 2.1/14) was in the L4 group (15th day 0.5% levobupivacaine) and was found to be statistically significant (p < 0.05). No statistically significant difference was determined between the other groups. Conclusions: Histologically, as the highest Mankin score was in the L4 group, this indicates that in a single intra-articular injection of levobupivacaine a low concentration should be selected. Level of evidence: Level 5, animal study.

Resumo Justificativa e objetivo: Neste estudo o objetivo foi examinar os efeitos histológicos e morfométricos sobre a estrutura da cartilagem da aplicação intra-articular de levobupivacaína em articulação do ombro. Métodos: Trinta e cinco ombros de 20 coelhos New Zealand, machos e adultos, foram usados para o estudo e divididos em cinco grupos de sete. Os grupos foram definidos como L1, L2, L3 e L4, consistiram em ombros direitos nos quais levobupivacaína a 0,25% e 0,5% foi administrada; o Grupo C, que consistiu em ombros esquerdos, foi o grupo controle; os grupos S1 e S2, que consistiram em ombros esquerdos, receberam solução salina a 0,9%. Os animais foram sacrificados no segundo e no 15º dia; as articulações glenoumerais foram avaliadas macroscopicamente e, em seguida, amostras de cartilagem foram coletadas. As amostras foram avaliadas com o escore de Mankin e histomorfometricamente. Mediu-se a espessura da cartilagem entre a camada superficial e a "linha de maré" (tidemark) e a espessura da cartilagem calcificada entre a tidemark e o osso subcondral. Resultados: Macroscopicamente, observou-se no 15º dia que o líquido articular havia reduzido em todos os grupos. Após a avaliação microscópica, o maior escore de Mankin (média: 3,14 ± 2,1/14) foi observado no grupo L4 (15º dia levobupivacaína a 0,5%), considerado estatisticamente significativo (p < 0,05). Nenhuma diferença estatisticamente significativa foi determinada entre os outros grupos. Conclusões: Histologicamente, como o maior escore de Mankin foi observado no Grupo L4, isso indica que em uma única injeção intra-articular de levobupivacaína uma concentração baixa deve ser selecionada. Nível de evidência: Nível 5, estudo em animais.

The effect of intra-articular levobupivacaine on shoulder cartilage at different doses-experimental study.

BACKGROUND AND OBJECTIVES: In this study it was aimed to examine the histological and morphometric effects on cartilage structure of intra-articular application of levobupivacaine to the shoulder joint. METHODS: In twenty New Zealand adult male rabbits, 35 shoulders were used for the study and prepared in 5 groups of 7. These groups were defined as Groups L1, L2, L3 and L4 which were right shoulders administered with 0.25% and 0.5% levobupivacaine, Group C which were left shoulders as the control group and Groups S1 and S2 which were left shoulders administered with 0.9% saline. On the 2nd and 15th days the animals were killed, the glenohumeral joints were evaluated macroscopically then cartilage samples were taken. These samples were evaluated with Mankin score, and histomorphometrically by measuring the thickness of the cartilage between the superficial cartilage layer and the tidemark and the thickness of calcified cartilage between the tidemark and the subchondral bone. RESULTS: Macroscopically, on the 15th day the joint fluid was seen to have reduced in all the groups. After microscopic evaluation, the highest Mankin score (mean: 3.14±2.1/14) was in the L4 group (15th day 0.5% levobupivacaine) and was found to be statistically significant (p<0.05). No statistically significant difference was determined between the other groups. CONCLUSIONS: Histologically, as the highest Mankin score was in the L4 group, this indicates that in a single intra-articular injection of levobupivacaine a low concentration should be selected. LEVEL OF EVIDENCE: Level 5, animal study.