Novel insights on the encapsulation mechanism of PLGA terminal groups on ropivacaine.

Currently, the influences of free terminal groups (hydroxyl, carboxyl and ester) of PLGA on encapsulating active pharmaceutical ingredient are relatively ambiguous even though PLGA types were defined as critical quality attributes in vast majority of design of experiment process. In this study, emulsion method combined with premix membrane emulsification technique has been used to encapsulate ropivacaine (RVC), a small molecule local anesthetic in clinical. Based on the narrow particle size distribution, the influences and mechanisms of the terminal groups on properties of ropivacaine loaded microspheres have been investigated in detail. It was found that microspheres prepared by PLGA with hydroxyl or ester groups exhibited lower encapsulation efficiency but faster in vitro release rate than that of carboxyl groups. In the meanwhile, on microcosmic level analysis by quartz crystal microbalance with dissipation, atomic force microscope and confocal laser scanning microscopy, we attributed this distinction to the specific interaction between ropivacaine and different terminal groups. Subsequently, the reaction activation centers were verified by density functional simulation calculation and frontier molecular orbital theory at molecular level. Additionally, pharmacokinetics and pharmacodynamic research of infiltration anesthesia model were performed to compare sustained release ability, duration and intensity of the anesthetic effect in vivo. Finally, potential safety and toxicity were evaluated by the biochemical analysis. This study not only provides a novel mechanism of drug encapsulation process but also potential flexible selections in terms of various anesthesia indications in clinical.

Increase in early wound leakage in total knee arthroplasty with local infiltrative analgesia (LIA) that includes epinephrine: a retrospective cohort study.

Background and purpose - After introducing a new local infiltration anesthesia (LIA) protocol with addition of 30 mL ropivacaine 2% and 1 mg epinephrine, we noted an increase in early wound leakage. As wound leakage is associated with prosthetic joint infection, our department aims to minimize postoperative wound leakage. This study evaluates the incidence of early wound leakage and postoperative pain after knee arthroplasty (KA) following adjustment of the LIA protocol with addition of 30 cc ropivacaine 2% and 1 mg epinephrine. Patients and methods - In this retrospective medical dossier study all patients (n = 502) undergoing a primary total or unicondylar knee arthroplasty between January 1, 2018 and July 1, 2019 were included. Patients received an LIA protocol containing 120 mL 2 mg/mL ropivacaine (ROPI- group; n = 256). After October 30, patients received an LIA protocol containing 150 mL 2 mg/mL ropivacaine with 1 mg epinephrine in the first 100 mL (ROPI + group; n = 246). The primary outcome measure was early wound leakage (< 72 hours postoperatively), defined as wound fluid leaking past the barrier of the wound dressing. Secondary outcome measure, 10-point numeric rating scale (NRS) pain (< 72 hours postoperatively) was also assessed. Data was evaluated using logistic regression. Results - The incidence of wound leakage was higher in the ROPI + group: 24% versus 17% in the ROPI- group (p = 0.06). After adjusting for the differences between surgeons the relative risk of this increase was 1.4 (1.0-2.0). The ROPI + and ROPI- group were similar regarding postoperative pain assessment. Interpretation - Adjustment of the LIA protocol with 30 mL 2% ropivacaine and 1 mg epinephrine led to an increase in early wound leakage in knee arthroplasty but no difference in pain scores.

Multimodal analgesia with ropivacaine wound infiltration and intravenous flurbiprofen axetil provides enhanced analgesic effects after radical thyroidectomy: a randomized controlled trial.

BACKGROUND: Thyroidectomy is a common procedure that causes mild trauma. Nevertheless, postoperative pain remains a major challenge in patient care. Multimodal analgesia comprising a combination of analgesics and analgesic techniques has become increasingly popular for the control of postoperative pain. The present study tested the hypothesis that multimodal analgesia with combined ropivacaine wound infiltration and intravenous flurbiprofen axetil after radical thyroidectomy provided better analgesia than a single dosage of tramadol. METHODS: This randomized controlled trial was conducted in a tertiary hospital. Forty-four patients (age, 18-75 years; American Society of Anesthesiologists status I or II; BMI < 32 kg/m2) scheduled for radical thyroidectomy were randomly assigned to a multimodal analgesia group (Group M) or a control group (Group C) by random numbers assignments, and 40 patients completed the study. All participants and the nurse in charge of follow-up observations were blinded to group assignment. Anesthesia was induced with sufentanil, propofol, and cisatracurium. After tracheal intubation, Group M received pre-incision wound infiltration with 5 ml of 0.5% ropivacaine mixed with epinephrine at 1:200,000 (5 µg/ml); Group C received no wound infiltration. Anesthesia was maintained with target-controlled infusion of propofol, remifentanil, sevoflurane, and intermittent cisatracurium. Twenty minutes before the end of surgery, Group M received 100 mg flurbiprofen axetil while Group C received 100 mg tramadol. Postoperative pain was evaluated with the numerical rating scale (NRS) pain score. Remifentanil consumption, heart rate, and noninvasive blood pressure were recorded intraoperatively. Adverse events were documented. The primary outcome was analgesic effect according to NRS scores. RESULTS: NRS scores at rest were significantly lower in Group M than in Group C before discharge from the postoperative anesthetic care unit (P = 0.003) and at 2 (P = 0.008), 4 (P = 0.020), and 8 h (P = 0.016) postoperatively. Group M also had significantly lower NRS scores during coughing/swallowing at 5 min after extubation (P = 0.017), before discharge from the postoperative anesthetic care unit (P = 0.001), and at 2 (P = 0.002) and 4 h (P = 0.013) postoperatively. Compared with Group C, NRS scores were significantly lower throughout the first 24 h postoperatively in Group M at rest (P = 0.008) and during coughing/swallowing (P = 0.003). No serious adverse events were observed in either group. CONCLUSION: Multimodal analgesia with ropivacaine wound infiltration and intravenous flurbiprofen axetil provided better analgesia than tramadol after radical thyroidectomy. TRIAL REGISTRATION: Chinese Clinical Trial Registry (registration number # ChiCTR1800020290 ; date of registration: 22/12/2018).

Brachial plexus block of the posterior and the lateral cord using ropivacaine 7.5 mg/mL.

BACKGROUND: We recently showed that the novel combination of a superficial cervical plexus block, a suprascapular nerve block, and the lateral sagittal infraclavicular brachial plexus block (LSIB) provides an alternative anaesthetic method for arthroscopic shoulder surgery. In this study, we hypothesised that the LSIB dose for this shoulder block could be significantly reduced by injecting only towards the shoulder relevant posterior and lateral cords. Our aim was to determine the minimum effective volume in 50% of the patients (MEV50 ) and to estimate the MEV95, when using ropivacaine 7.5 mg/mL to block these cords. METHODS: Twenty-three adult patients scheduled for hand surgery participated in the study. Considering the artery as a clock face with 12 o'clock ventral, the designated volume was injected immediately outside the arterial wall and between 8 and 9 o´clock. The in-plane technique was used. Block success was assessed 30 minutes after withdrawal of the needle. Successful posterior cord block was defined as anaesthesia or analgesia of the axillary nerve. Successful lateral cord block was defined as either anaesthesia or analgesia, or >50% motor block of the musculocutaneous nerve. MEV50 was determined by the staircase up-and-down method. Logistic regression and probit transformation were applied to estimate MEV95 . RESULTS: MEV50 and MEV95 were 7.8 mL [95% confidence interval (CI), 7.3-8.4] and 9.0 mL (95% CI, 7.8-10.3), respectively. CONCLUSION: For single-deposit infraclavicular posterior and lateral cord block, the MEV95 of ropivacaine 7.5 mg/mL was estimated to 9.0 mL.

Myotoxicity of local anesthetics is equivalent in individuals with and without predisposition to malignant hyperthermia.

PURPOSE: Malignant hyperthermia (MH) is an inherited muscle disorder caused by abnormal elevations of intracellular calcium (Ca2+) in skeletal muscle. There are several reports of myotoxicity caused by local anesthetics, and the increased intracellular Ca2+ is considered to be an important cause. However, there is insufficient evidence regarding myotoxicity in MH-susceptible individuals when large doses of local anesthetics are administered. This study investigated the effect of MH predisposition on myotoxicity. METHODS: Human skeletal muscle samples were obtained from 22 individuals to determine susceptibility to MH, and were evaluated according to whether their Ca2+-induced Ca2+ release (CICR) rates were accelerated or not. This study was performed using surplus muscle that remained after the CICR rate test. We calculated the 50% effective concentration (EC50) values of three local anesthetics, namely lidocaine, levobupivacaine, and ropivacaine using the ratiometric dye Fura-2 AM. Significance was tested using the unpaired t test. RESULTS: In the accelerated and unaccelerated groups, respectively, the mean ± SD of the EC50 values were 1.52 ± 0.72 and 1.75 ± 0.37 mM for lidocaine (p = 0.42), 0.72 ± 0.36 and 0.79 ± 0.46 mM for levobupivacaine (p = 0.68), and 1.21 ± 0.35 and 1.62 ± 0.57 mM for ropivacaine (p = 0.06). These values were similar in individuals with and without MH predisposition. CONCLUSION: The myotoxicity of local anesthetics was equivalent in individuals with and without predisposition to MH.