HTX-011 reduced pain intensity and opioid consumption versus bupivacaine HCl in bunionectomy: phase III results from the randomized EPOCH 1 study.

BACKGROUND AND OBJECTIVES: There is a need for local anesthetics that provide consistent analgesia through 72 hours after surgery. This study evaluates the use of HTX-011 (bupivacaine and meloxicam in Biochronomerpolymer technology), an extended-release, dual-acting local anesthetic, in reducing both postoperative pain over 72 hours and postoperative opioid use when compared with bupivacaine hydrochloride (HCl) and saline placebo. Inclusion of low-dose meloxicam in HTX-011 is designed to reduce local inflammation caused by surgery, potentiating the analgesic effect of bupivacaine. Previously, significant synergy has been observed with bupivacaine and meloxicam with both given locally together. METHODS: EPOCH 1 was a randomized, double-blind, placebo-controlled and active-controlled phase III study in subjects undergoing a primary unilateral, distal, first metatarsal bunionectomy in which subjects received either a single intraoperative dose of HTX-011, immediate-release bupivacaine HCl or saline placebo. RESULTS: A total of 412 subjects were dosed. The results for the primary and all four key secondary endpoints were statistically significant in favor of HTX-011. HTX-011 demonstrated superior, sustained pain reduction through 72 hours, significantly reduced opioid consumption and resulted in significantly more opioid-free subjects compared with saline placebo and bupivacaine HCl. Safety was similar across groups with fewer opioid-related adverse events observed in the HTX-011 group. CONCLUSIONS: HTX-011 demonstrated significant reduction in postoperative pain through 72 hours with significant reduction in opioid consumption and a significant increase in the proportion of opioid-free subjects compared with saline placebo and the most widely used local anesthetic, bupivacaine HCl. TRIAL REGISTRATION NUMBER: NCT03295721

Local anaesthetic bupivacaine induced ovarian and prostate cancer apoptotic cell death and underlying mechanisms in vitro

Retrospective studies indicate that the use of regional anesthesia can reduce cancer recurrence after surgery which could be due to ranging from immune function preservation to direct molecular mechanisms. This study was to investigate the effects of bupivacaine on ovarian and prostate cancer cell biology and the underlying molecular mechanisms. Cell viability, proliferation and migration of ovarian carcinoma (SKOV-3) and prostate carcinoma (PC-3) were examined following treatment with bupivacaine. Cleaved caspase 3, 8 and 9, and GSK-3β, pGSK-3β(tyr216) and pGSK-3β(ser9) expression were assessed by immunofluorescence. FAS ligand neutralization, caspase and GSK-3 inhibitors and GSK-3β siRNA were applied to further explore underlying mechanisms. Clinically relevant concentrations of bupivacaine reduced cell viability and inhibited cellular proliferation and migration in both cell lines. Caspase 8 and 9 inhibition generated partial cell death reversal in SKOV-3, whilst only caspase 9 was effective in PC-3. Bupivacaine increased the phosphorylation of GSK-3β(Tyr216) in SKOV-3 but without measurable effect in PC3. GSK-3β inhibition and siRNA gene knockdown decreased bupivacaine induced cell death in SKOV-3 but not in PC3. Our data suggests that bupivacaine has direct ‘anti-cancer’ properties through the activation of intrinsic and extrinsic apoptotic pathways in ovarian cancer but only the intrinsic pathway in prostate cancer

Intraarticular Tramadol-Bupivacaine Combination Prolongs the Duration of Postoperative Analgesia After Outpatient Arthroscopic Knee Surgery

BACKGROUND: Intraarticular (IA) local anesthetics are often used for the management and prevention of pain after arthroscopic knee surgery. Recently, IA tramadol was also used for the management of these patients. However, the IA combination of local anesthetic and tramadol has not been evaluated in arthroscopic outpatients. Our primary aim in this study was to evaluate the analgesic effect of an IA combination of bupivacaine and tramadol when compared with each drug alone using visual analog scale (VAS) pain scores in patients undergoing day-care arthroscopic knee surgery. Additionally, we assessed analgesic demand. METHODS: Ninety ASA I/II patients undergoing arthroscopic partial meniscectomy, performed by a single surgeon under general anesthesia, were assigned in a randomized, double-blind manner into three groups: group B (n = 30) received 0.25% bupivacaine, group T (n = 30) received 100 mg tramadol, and group BT (n = 30) received 0.25% bupivacaine and 100 mg tramadol to a total volume of 20 mL by the IA route after surgery. Postoperative pain scores were measured on a VAS, at rest and on mobilization at 0.5, 1, 2, 4, 6, 8, 12, and 24 h. Duration of analgesia, the subsequent 24 h consumption of rescue analgesia, time to ambulation, and time to discharge were evaluated. In addition, the systemic side effects of the IA injected drugs were also assessed. RESULTS: The results showed significantly lower VAS pain scores in group BT (P << 0.1) when compared with groups T and B. Group BT had a later onset of postsurgical pain and longer time to first rescue analgesic than groups B and T. The 24 h consumption of analgesic was significantly less in group BT when compared with the other two groups (26.7% of the patients required rescue analgesia in group BT, whereas this number was 90% in group B and 86.7% in group T). In addition, time in hours to discharge and time to unassisted ambulation were significantly shorter in group BT when compared with groups T and B, and this was not associated with any detectable systemic effects. CONCLUSION: The IA admixture of tramadol 100 mg with bupivacaine 0.25% provides a pronounced prolongation of analgesia compared with either drug alone in patients undergoing day care arthroscopic knee surgery

SENSORY REGRESSION TIME FROM SUBARACHNOID BLOCK WITH HYPERBARIC 0.75% BUPIVACAINE IN THE OBESE PATIENT

The purpose of this study was to determine if obese patients have a different sensory regression time from subarachnoid block than non-obese patients using hyperbaric 0.75% bupivacaine. A quasi-experimental design was used. Twenty patients were separated into two groups; one group was classified as obese, and the other group was classified as non-obese. The data consisting of age, height, weight, sex, and surgical procedure were recorded preoperatively. All the patients received hyperbaric 0.75% bupivacaine via subarachnoid puncture. The levels of spinal anesthesia were recorded at the highest level achieved. The injection time was also recorded. When the surgery was completed, the patient was transferred to the recovery room and levels of sensory blockade were checked by pin-prick with an 18-gauge needle every 10 minutes until complete recovery from the spinal anesthesia had been achieved. The hypothesis, there will be no difference in sensory regression time from SAB with hyperbaric 0.75% bupivacaine between obese and non-obese patients, failed to be rejected. No statistically significant difference, using linear regression analysis, was found in mean regression time between groups (obese versus non-obese)

Intraperitoneal aerosolization of bupivacaine is a safe and effective method in controlling postoperative pain in laparoscopic Roux-en-Y gastric bypass.

INTRODUCTION: Obesity is a worldwide problem and has grown in severity in the last few decades making bariatric surgery and, in particular, laparoscopic banding and Roux-en-Y gastric bypass efficacious and cost-effective procedures. The laparoscopic approach has been shown to offer significant healthcare benefits, of particular interests are reports of decreased postoperative pain resulting in a shorter hospital stay and an earlier return to normal activity. However, many patients still experience significant pain, including shoulder tip pain, that require strong analgesia including opiates during their early recovery period. The aims of this study were to establish the safe use of the aerosolization technique in bariatric surgery and to investigate the possible benefits in reducing postoperative pain. METHODS: In this study, fifty patients undergoing laparoscopic gastric bypass were recruited and divided into two groups; control (n = 25) and therapeutic (n = 25). The control group received intraperitoneal aerosolization of 10 mL of 0.9% normal saline while the therapeutic group received 10 mL of 0.5% bupivacaine. All the patients had standard preoperative, intraoperative, and postoperative care. Pain scores were carried out by the nursing staff in recovery and 6 h, 12 h and 24 h postoperatively using a standard 0-10 pain scoring scale. In addition, opiate consumption via patient-controlled analgesia (PCA) was recorded. RESULTS: Aerosolized bupivacaine reduced postoperative pain in comparison to normal saline (p < 0.05). However, PCA usage showed no statistically significant change from the control group. CONCLUSION: The aims of this study were achieved and we were able to establish the safe use of the aerosolization technique in bariatric surgery and its benefits in reducing postoperative pain

Fast glycorrhachia and cerebrospinal fluid protein as predictors of sensory block in anesthesia with subarachnoid Ropivacaine

BACKGROUND: Identify if glycorrhachia and cerebrospinal fluid protein could influence the time of sensory block to T10, the duration and the metameric block's level, after a standard dose of Ropivacaine. METHODS: 80 patients, ASA I - III undergoing to transurethral prostate resection with spinal anesthesia in a prospected open study were recruited. A 0.2 ml liquor's sample was taken; glycorrhachia, by glycemic stix and CSF protein, by urinary stix, were got, before Ropivacaine 0.5% 15 mg injection (0.10 - 0.15 mlsec). After anti-trendelemburg, with 30 ° tilting for 15 min, the onset of sensory block to T10, the maximum metameric level to 15' and the time of sensory block were reported. The data collection were analyzed using the software language R. RESULTS: A significant correlation liquor specific weigh preoperative glycemia (0.749), liquoral specific weigh glycorrhachia (rho = 0.751; R2 = 0.564; P 0.05) and specific weigh CSF protein (rho = 0.684; R2 = 0.468; P 0.05) were reported. Inverse relation CSF weightsensory block level (rho -0.789, P 0.05, R2 0.621) was evidenced. Inverse relation onset time to T10 glycorrhachia (84%) and cephalic block glycorrhachia (76%) were found. Inverse correlation onset time to T 10 CSF protein and cephalic block proteinorrachia was respectively 84% and 67%. A rho of 0.712 with R2 of 51% BMI onset to T10 and rho of 0.681 with R2 of 51% BMI maximum cephalic block with P 0.05 were reported. CONCLUSIONS: The predictability of a iso-hypobaric local anesthetic could reduce the risk of procedure failure and adverse events by further cephalic spread

Postoperative pain management in children: Guidance from the pain committee of the European Society for Paediatric Anaesthesiology (ESPA Pain Management Ladder Initiative)

The main remit of the European Society for Paediatric Anaesthesiology (ESPA) Pain Committee is to improve the quality of pain management in children. The ESPA Pain Management Ladder is a clinical practice advisory based upon expert consensus to help to ensure a basic standard of perioperative pain management for all children. Further steps are suggested to improve pain management once a basic standard has been achieved. The guidance is grouped by the type of surgical procedure and layered to suggest basic, intermediate, and advanced pain management methods. The committee members are aware that there are marked differences in financial and personal resources in different institutions and countries and also considerable variations in the availability of analgesic drugs across Europe. We recommend that the guidance should be used as a framework to guide best practice

Effects of Diet-Induced Obesity on Extracellular Matrix Remodeling During Skeletal Muscle Regeneration

THE EFFECT OF DIET-INDUCED OBESITY ON EXTRACELLULAR MATRIX REMODELING DURING SKELETAL MUSCLE REGENERATION Michelle A. Tedrowe, Lemuel A. Brown, Richard A. Perry Jr., Megan E. Rosa, Jacob L. Brown, David E. Lee, Nicholas P. Greene, Tyrone A. Washington. University of Arkansas, Fayetteville, Arkansas Skeletal muscle has the ability to regenerate from damage; however, recent studies have reported a negative effect of obesity on skeletal muscle regenerative capacity. The extracellular matrix (ECM) contributes to skeletal muscle structure acting as a scaffold for skeletal muscle. Additionally, skeletal muscle serves as a reservoir for proteins and growth factors that promote regeneration. Optimal skeletal muscle regeneration includes inflammation, ECM remodeling, and myofiber growth. Disruption to any of these processes can negatively affect skeletal muscle regeneration. PURPOSE: The purpose of this study was to determine how diet-induced obesity (DIO) affects ECM remodeling during skeletal muscle regeneration. METHODS: Fifty-six male C57BL/6J mice were randomly assigned to two groups; lean diet (10% fat) and high fat diet (HFD) (60% fat). Within those two groups, mice were randomly assigned to either a PBS (uninjured) group or a bupivacaine (injured) group. Bupivacaine is a myotoxin which induces injury to skeletal muscle. Both groups received injections into the tibialis anterior (TA). Three or 28 days post-bupivacaine injection, the TAs were extracted and PCR reaction was done to quantify ECM-related gene expression (i.e. Collagen-I, Collagen-III, Fibronectin, TGF-β, MMP-2, MMP-9, and TIMP-I). RESULTS: There was no difference in Collagen III:I gene expression 3 days post-injection in the lean group (p\u3e0.05). However, there was a 3 fold increase (p0.05). Three and 28 days post injection there was a main effect of injury to increase MMP-2 gene expression (pCONCLUSION: Obesity altered ECM composition during skeletal muscle regeneration. This could negatively impact the ability of obese muscle to recovery form injury. These findings suggest that an altered composition could lead to a change in exercise prescription for this specific population. This work was supported by a grant from the American Biosciences Institute and a Student Undergraduate Research Fellowship Grant

The challenge of evaluating pain and a pre-incisional local anesthetic block.

Background. Our objective was to test the effectiveness of a local anesthetic line block administered before surgery in reducing postoperative pain scores in dogs undergoing ovariohysterectomy (OVHX). Methods. This study is a prospective, randomized, blinded, clinical trial involving 59 healthy female dogs. An algometric pressure-measuring device was used to determine nociceptive threshold, and compared to three subjective pain scales. Group L/B received a line block of lidocaine (4 mg/kg) and bupivacaine (1 mg/kg) subcutaneously in the area of the incision site and saline subcutaneously as premedication; group L/BM (positive control) received a similar block and morphine (0.5 mg/kg) subcutaneously for premedication; and group SS (negative control) received a saline line block and saline premedication. Criteria for rescue analgesia were defined before the study. Dogs were assessed prior to surgery, at extubation (time 0) and at 2, 4, 6, 8 and 24 h post-recovery. The data were analyzed with one-way ANOVA, and a Split Plot Repeated Measures ANOVA with one grouping factor and one repeat factor (time). P &lt; 0.05 was considered statistically significant. Results. Approximately 33% of dogs required rescue analgesia at some point during the study, with no significant difference between groups. There was no significant difference between treatment groups with any assessment method. Conclusions. As there were no statistically significant differences between positive and negative controls, the outcome of this technique cannot be proven