Concentrations Of Ropivacaine Research Articles

Pharmacokinetics of 400 mg ropivacaine after periarticular local infiltration analgesia for total knee arthroplasty

Although considered safe, no pharmacokinetic data of high dose, high volume local infiltration analgesia (LIA) with ropivacaine without the use of a surgical drain or intra-articular catheter have been described. The purpose of this study is to describe the maximum total and unbound ropivacaine concentrations (Cmax , Cu max ) and corresponding maximum times (Tmax , Tu max ) of a single-shot ropivacaine (200 ml 0.2%) and 0.75 mg epinephrine (1000 μg/ml) when used for LIA in patients for total knee arthroplasty. In this prospective cohort study, 20 patients were treated with LIA of the knee for primary total knee arthroplasty. Plasma samples were taken at 20, 40, 60, 90, 120, 240, 360 min and at 24 h after tourniquet release, in which total and unbound ropivacaine concentrations were determined. Results are given as median [IQR]. Highest ropivacaine concentration (Cmax ) was 1.06 μg/ml [0.34]; highest unbound ropivacaine concentration (Cu max ) was 0.09 μg/ml [0.05]. The corresponding time to reach the maximum concentration for total ropivacaine was 312 min [120] after tourniquet release, and for the unbound fraction 265 [110] min after tourniquet release. Although great inter-individual variability was found between the maximum ropivacaine concentrations, both maximum total and unbound serum concentrations of ropivacaine remained well below the assumed systemic toxic thresholds of 4.3 and 0.56 μg/ml.

Effects of Intraperitoneal Local Anaesthetics Bupivacaine and Ropivacaine versus Placebo on Postoperative Pain after Laparoscopic Cholecystectomy: A Randomised Double Blind Study.

Laparoscopic Cholecystectomy (LC) is the most frequently performed elective daycare surgery and provision of postoperative pain relief is of importance. After laparoscopic cholecystectomy shoulder and abdominal pain causes considerable distress. Visceral pain during coughing, respiration and mobilization increases morbidity, hospital stay and costs. To compare the analgesic efficacy of intraperitoneally instilled equipotent concentrations of bupivacaine and ropivacaine versus placebo in relieving postoperative pain after laparoscopic cholecystectomy when used as a part of multimodal analgesia. In this randomised, prospective, double blind, placebo controlled study, 90 ASA Class I or II patients were randomly divided into three groups of 30 each. Group S received intraperitoneal infiltration with 35 ml of 0.9% normal saline, Group B with 35 ml of 0.25% bupivacaine and Group R with 35 ml of 0.375% ropivacaine. All groups received standard general endotracheal anaesthesia and analgesia with IV paracetamol 15 mg/kg and diclofenac 1.5 mg/kg. Numerical Rating Scale (NRS) score of analgesia at rest and on cough/movement, duration of analgesia, haemodynamic parameters, need for a rescue analgesic (IV tramadol 1 mg/kg) was recorded and adverse effects of procedure and drugs if any were monitored. Data was analysed with SPSS statistical software version 21.0. One way ANOVA or the Kruskal-Wallis test was used to compare continuous data across all three groups as appropriate. Subsequent analysis of continuous data between two groups was achieved by Tukey's post hoc test. Significance was accepted as p<0.05. The mean NRS was <5 till only four hours in Group S, till eight hours in Group B and till 16 hours in Group R. The duration of analgesia was 13.47±1.38 hours in Group R, 7.93±1.44 hours in Group B and 4.47±0.86 hours in Group S. Intraperitoneal infiltration of LA significantly reduces pain intensity scores in the early postoperative period after LC surgery and helps in improving the postoperative recovery profile and outcome. This makes LC surgery more amenable to day care surgical setup. Ropivacaine (0.375%) is more efficacious, longer acting with a higher intensity of postoperative analgesia than bupivacaine (0.25%).

Comparative Efficacy of Minimal Concentration of Racemic Bupivacaine (0.0625%) with Fentanyl and Ropivacaine (0.1%) with Fentanyl for Epidural Labor Analgesia.

Background and Aims:This study aims to compare the minimum effective concentration of local anesthetic (LA) bupivacaine and ropivacaine with highly lipid soluble opioids fentanyl for providing optimal labor epidural analgesia.Settings and Design:The objective of this study was to evaluate the efficacy of racemic bupivacaine 0.0625% and 0.1% of ropivacaine both mixed with 2 μg/ml of fentanyl for epidural labor analgesia in parturients with spontaneous labor and normal fetal heart rate tracing.Methodology:Sixty parturients requesting for labor analgesia were divided into two groups. Group B (n = 30) received racemic bupivacaine (0.0625%) and fentanyl 2 μg/ml of 10 ml and Group R (n = 30) received ropivacaine (0.1%) and fentanyl 2 μg/ml. In both groups, the drug was given in 5 ml fractionated doses at 5 min interval. Parturients not experiencing analgesia within 15 min of initial bolus were supplemented with additional 5 ml of the same concentration of the solution. Epidural analgesia was maintained by timed top ups at the end of 90 min with the dosage equal to the initial dose of the drug. Duration of labor analgesia, motor block, visual analog scale, maternal hemodynamic parameters, mode of delivery, and maternal satisfaction was assessed.Statistical Analysis:Data were analyzed with odds variance, unpaired t-test, and Chi-square tests. P < 0.05 was considered statistically significant.Results:In our study, results indicate that both drugs were equally effective clinically. Maternal demographic characteristics were comparable. There were no statistically significant differences in visual analog pain score, highest sensory block, maternal satisfaction, mode of delivery, total dose of LAs during labor and motor block at delivery between the groups.Conclusions:In our study, both the drugs produced equivalent analgesia for labor at low concentration when used with highly lipid soluble opioid such as fentanyl.

Optimal Dose of Epidural Dexmedetomidine Added to Ropivacaine for Epidural Labor Analgesia: A Pilot Study.

Background Dexmedetomidine combined with local anesthetics can decrease the concentration of epidural ropivacaine. However, the optimal dose of epidural dexmedetomidine combined with ropivacaine for labor analgesia is still uncertain. This study investigated the effect of adding different dose of epidural dexmedetomidine to ropivacaine during epidural labor analgesia. Methods One hundred women were randomly assigned to one of the four groups (Groups A, B, C, and D received 0.25, 0.5, 0.75, and 1 μg/ml of dexmedetomidine plus 0.1% ropivacaine, resp.). The onset of epidural anesthesia and stages of labor were studied, and pain was assessed using a visual analogue scale (VAS). Hemodynamic parameters and fetal heart rate were monitored. Apgar scores and umbilical artery pH were recorded. The side effects, if any, were recorded also. Results The addition of 0.25, 0.5, and 0.75 μg/ml of dexmedetomidine to 0.1% ropivacaine provided safe and effective analgesia, but 1 μg/ml of dexmedetomidine resulted in increasing incidence of motor block. The hemodynamic parameters were similar between groups (P > 0.05). Side effects in Group D were significantly higher than those in the other three groups (P < 0.05). Conclusions When dexmedetomidine is combined with 0.1% ropivacaine, the optimal concentration of dexmedetomidine is 0.5 μg/ml for epidural labor analgesia (this trial is registered with ChiCTR-OPC-16008548).

Comparison of Three Different Concentrations 0.2%, 0.5%, and 0.75% Epidural Ropivacaine for Postoperative Analgesia in Lower Limb Orthopedic Surgery.

Introduction:Ropivacaine has been studied previously and holds promise as an agent that offers a safe, efficacious, and better recovery profile than other conventional agents such as bupivacaine. The aim of the present study was to compare the safety and efficacy of equal volume of different concentration of ropivacaine for epidural analgesia in patients undergoing major lower limb orthopedic surgery.Subjects and Methods:One hundred and fifty adult patients were randomized into three groups to receive single dose of equal volume of ropivacaine through epidural route in concentrations of 0.2%, 0.5%, and 0.75%, respectively. All the groups received equal dose of ropivacaine of same concentration for subarachnoid block using combined spinal-epidural technique.Results:Modified Bromage Scale and Numeric rating scale was used to assess motor block and analgesia. Data analysis was done using WINDOW SPSS Student Version 17 ANOVA test. Student's t-test was performed for comparison between two groups, and qualitative data were analyzed by applying Chi-square test.Conclusion:0.5% and 0.75% ropivacaine were sufficient and effective for intrathecal subarachnoid block as well as for postoperative analgesia with epidural use. Shorter duration of motor blockade and analgesia was seen with ropivacaine 0.2%.

Effect of dexmedetomidine on the medium effective concentration of ropivacaine for thoracic paravertebral block in aged patients

Objective To investigate effect of dexmedetomidine(Dex) on the medium effective concentration(EC50) of ropivacaine for ultrasound-guided thoracic paravertebral block. Methods Sixty ASA Ⅱor Ⅲ patients, aged 65-79 y, scheduled for lobectomy under video-assisted thoracoscopic surgery, requiring ultrasound-guided thoracic paravertebral block, were randomly assigned into 2 groups(n=30): control group(group C) and Dex group(group D). Paravertebral block was performed by using only ropivacaine in group C. In group D the mixture of ropivacaine and 0.75 μg/kg Dex was injected for the block. The initial concentration of ropivacaine was 0.5% and the ratio between the two successive concentrations was 1.2. If the block was effective, the next patient received a lower dose of ropivacaine, or if ineffective, a higher dose was given to the next patient. The EC50 and 95% confidence interval (CI) of ropivacaine were determined by using probit regression method. Results The EC50 of ropivacaine was 0.42% and 95%CI was 0.40%-0.45% in group C, The EC50 of ropivacaine was 0.35% and 95% CI was 0.32%-0.37% in group D. Conclusions The combined use of Dex can decrease the EC50 of ropivacaine for ultrasound-guided thoracic paravertebral block. Key words: Elderly; Dexmedetomidine; Paravertebral block

Ropivacaine, Interleukin-6 and Tumor Necrosis Factor Alpha Plasma Levels during Intermittent Epidural and Continuous Wound Infusion of Ropivacaine for Analgesia after Hysterectomy or Myomectomy: An Observational Study

Background/Aims: The concentration-time profile of the long-acting local anesthetic ropivacaine after epidural (EP) administration at fixed time intervals or continuous subcutaneous (SC) infusion has not been fully evaluated. The objective of this work was to determine total plasma concentrations of ropivacaine and changes in cytokine interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) levels during EP and SC. Methods: In this prospective randomized controlled trial, 18 patients undergoing abdominal hysterectomy or myomectomy were randomly selected to receive ropivacaine either every 6 h via an EP catheter or by continuous wound infusion along the skin incision, after a bolus dose, for 48 h. Total plasma ropivacaine concentrations were measured before the bolus and 2, 4, 8, 24, 48, and 50 h after the bolus using high-performance liquid chromatography-UV and IL-6 and TNF-α levels were measured at 0, 8 and 24 h with ELISA and analyzed statistically. Results: During EP, mean ± SD ropivacaine concentrations were relatively stable up to 50 h postoperatively, that is, 239 ± 89 ng/ml, while during SC, initial concentrations between 2 and 8 h were comparatively lower (101.5 ± 42.9 ng/ml) than 24-50 h concentrations (437.1 ± 206 ng/ml). An increase in IL-6 levels was noted between 0 and 24 h during EP and SC, but TNF-α levels increased slightly, between 0 and 24 h, only during EP. Conclusion: Ropivacaine plasma concentrations with both EP and SC were found to be safe throughout the administration time interval. IL-6 levels increased during the same time interval, while TNF levels varied only slightly.

Local anaesthetic toxicity after bilateral thoracic paravertebral block in patients undergoing coronary artery bypass surgery.

We conducted a small pilot observational study of the effects of bilateral thoracic paravertebral block (BTPB) as an adjunct to perioperative analgesia in coronary artery bypass surgery patients. The initial ropivacaine dose prior to induction of general anaesthesia was 3 mg/kg, which was followed at the end of the surgery by infusion of ropivacaine 0.25% 0.1 ml/kg/hour on each side (e.g. total 35 mg/hour for a 70 kg person). The BTPB did not eliminate the need for supplemental opioids after CABG in the eight patients studied. Moreover, in spite of boluses that were within the manufacturer's recommendation for epidural and major nerve blocks, and an infusion rate that was only slightly higher than what appeared to be safe for epidural infusion, potentially toxic total plasma ropivacaine concentrations were common. We also could not exclude the possibility that the high ropivacaine concentrations were contributing to postoperative mental state changes in the postoperative period. Also, one patient developed local anaesthetic toxicity after the bilateral paravertebral dose. As a result, the study was terminated early after four days. The question of whether paravertebral block confers benefits in cardiac surgery remains unanswered. However, we believe that the bolus dosage and the injection rate we used for BTPB were both too high, and caution other clinicians against the use of these doses. Future studies on the use of BTPB in cardiac surgery patients should include reduced ropivacaine doses injected over longer periods.

Effect of Intralipid® on the Dose of Ropivacaine or Levobupivacaine Tolerated by Volunteers: A Clinical and Pharmacokinetic Study.

Rapid intravenous administration of lipid emulsion has become the standard treatment of severe local anesthetic systemic toxicity. This experiment in volunteers aimed at determining the effect of Intralipid® administration on the time to neurologic symptoms. Ropivacaine or levobupivacaine was infused intravenously in 16 volunteers (8 mg/min up to 120 mg) with 120 ml Intralipid® 20% (Fresenius, Paris France) or placebo infused at T + 2 min). Each subject received all four treatments in a crossover manner. The infusion was stopped after the intended dose had been administered or on occurrence of incipient neurologic signs of toxicity. The primary outcome was time-to-event. In addition, blood ropivacaine and levobupivacaine concentrations were measured. The dose infused was not different whether volunteers received placebo (81.7 ± 22.3 vs. 80.8 ± 31.7 mg, ropivacaine vs. levobupivacaine) or Intralipid® (75.7 ± 29.1 vs. 69.4 ± 26.2 mg, ropivacaine vs. levobupivacaine), P = 0.755, Intralipid® versus placebo groups. Plasma concentrations were best modeled with an additional volume of distribution associated with Intralipid®. Simulations suggested that decreased peak concentrations would be seen if Intralipid® was given during a period of increasing concentrations after extravascular administration. At modestly toxic doses of ropivacaine or levobupivacaine, we were unable to find any effect of the infusion of Intralipid® on the time to early signs of neurologic toxicity in volunteers. Peak concentration was decreased by 26 to 30% in the subjects receiving Intralipid®. Simulations showed that Intralipid® might prevent the rapid increase of local anesthetic concentration after extravascular administration.

Dexamethasone and Clonidine, but not Epinephrine, Prolong Duration of Ropivacaine Brachial Plexus Blocks, Cross-Sectional Analysis in Outpatient Surgery Setting.

The primary aim of this study is to determine the effect of adding dexamethasone, clonidine or both with and without epinephrine to ropivacaine and bupivacaine brachial plexus blocks. Observational study of prospectively collected data. Single academic outpatient surgery center. We evaluated 5,515 patient entries who received brachial plexus block (BPB). Multiple, rescue, unsuccessful, and distal nerve blocks of the upper extremity were excluded. The duration was calculated from the time the block was performed until the resolution of the block by patient report. Block durations were compared using Analysis of Variance. After exclusions, 3,706 nerve blocks were analyzed. The median concentration of ropivacaine used was 0.5%. Both clonidine and dexamethasone significantly increased block duration by 1.1 and 3.0 hours, respectively. Combining clonidine and dexamethasone with ropivacaine increased block duration by 6.2 hours (p<0.001) when compared to ropivacaine alone. Dexamethasone and Clonidine increased block duration by 5.2 hours (p<0.001) when compared to clonidine alone and by 3.2 hours (p<0.001) compared to dexamethasone alone. The addition of epinephrine to any of the adjuvants made no statistically significant difference to the duration of action except when it was added to dexamethasone. For brachial plexus blocks, epinephrine did not affect the duration of analgesia when added to ropivacaine. Epinephrine did not enhance the observed increase of block duration induced by clonidine or the combination of clonidine and dexamethasone. The most block duration enhancement was observed when combination of clonidine and dexamethasone were added to ropivacaine.

Assessment of the analgesic potency of ropivacaine 0.2% versus ropivacaine 0.5% in transversus abdominis plane block after cesarean delivery

BackgroundTransversus abdominis plane (TAP) block provides sensory block from T6 to L1. It is one of the most widely used regional analgesic techniques and important component of multimodal approach for postoperative analgesia in multiple lower abdominal surgeries.ObjectiveTo compare between the analgesic potency of ropivacaine 0.2% and ropivacaine 0.5% when used in transversus abdominis plane (TAP) block for post operative analgesia after cesarean delivery.Patients and methodsFifty parturients with American society of Anesthesiologists Physical Status I or II aged between 25 and 35 years undergoing cesarean delivery with general anesthesia were included in this prospective, randomized, double blind study. They were randomly divided into 2 groups according to the concentration of ropivacaine used in TAP block. The 1st group received bilateral 20 ml of 0.2% ropivacaine while the 2nd received the same volume of 0.5% ropivacaine at the end of the surgery. Intensity of postoperative pain at rest and during movement, time to 1st analgesic request, total dose of tramadol used, time to 1st mobilization from bed, parturients satisfaction of pain management, and complications of TAP block were recorded.ResultsVisual Analogue Scale (VAS) at rest and during movement, time to 1st analgesic request, total dose of tramadol, time to 1st mobilization from bed, patients satisfaction of pain management were comparable between the two groups.ConclusionRopivacaine 0.2% when used in TAP block provided postoperative analgesia similar to ropivacaine 0.5% in TAP block after cesarean delivery.

Continuous wound infiltration with 0.2% ropivacaine versus a single intercostal nerve block with 0.75% ropivacaine for postoperative pain management after reconstructive surgery for microtia

In reconstructive surgery for microtia during childhood, costal cartilage is used for pinna formation. Postoperative pain in the region from which the costal cartilage is taken is severe, which delays recovery after surgery. We evaluated prospectively whether continuous wound infiltration (CWI) of a local anesthetic (LA) reduces pain and enables rapid recovery compared with a single intercostal nerve block (ICNB). Forty-eight patients were randomly divided into two groups. In Group I, a single ICNB with 10ml of 0.75% ropivacaine was performed at the end of surgery. In Group C, a catheter was inserted into the space between the abdominal external oblique muscle and the rectus abdominis muscle. Then, a 0.4-ml/kg bolus of 0.2% ropivacaine was administered, followed by continuous infusion at 2-4ml/h for 48h. Postoperative pain intensity evaluated using the Face Scale, dose of supplemental analgesics, and time until mobilization were evaluated. In Group C, the plasma concentrations of ropivacaine were analyzed. The pain intensity at rest was significantly lower in Group C than in Group I, but the values during coughing were comparable. The number of patients receiving a supplemental analgesic and the median number of doses were significantly larger in Group I than in Group C (P=0.029, P=0.0007, respectively). The plasma concentrations of ropivacaine were within the safe range over 48h. The times until mobilization were comparable. CWI of 0.2% ropivacaine is a better and safe technique for postoperative pain management after costal cartilage graft harvest in children.

The efficacy of simultaneous bilateral axillary brachial plexus block under the guidance of neurostimulator or ultrasound: a prospective study.

This study was designed to investigate the risk of local anesthetic toxicity and efficacy of simultaneous bilateral axillary brachial plexus block performed under the guidance of ultrasound or a neurostimulator. One hundred and twenty patients who were anesthetized with bilateral axillary plexus block simultaneously between February 2012 and March 2014 were enrolled in the study. The patients were anesthetized under the guidance of a neurostimulator (group N, n=60) or ultrasound (group U, n=60). The block performance time, procedure-related pain, adverse events, total and free plasma concentrations of ropivacaine, and other data were recorded. The comparison was analyzed statistically. The block performance time, and onset of the sensory and motor block, of group N was longer than that of group U (p<0.001). The procedure-related pain of group N was more serious than that of group U (p<0.05). The patient satisfaction rate of group U was higher than that of group N (p<0.05). The total plasma concentrations of ropivacaine in group N were comparable to those of group U, except for the value at 50min after injection (p<0.05). The free plasma concentrations of ropivacaine of group N at 5min were significantly higher than that of group U (p<0.001). No apparent serious adverse events were observed perioperatively in both groups. Simultaneous bilateral axillary brachial plexus block guided by neurostimulator or ultrasound in bilateral distal upper extremity surgery seems to have a low risk of local anesthetic toxicity and to be effective. The ultrasound-guided block is superior in terms of providing the same degree of anesthesia with shorter duration, less pain, and faster onset of sensory and motor blockades, which is important in clinical practice.

Evaluation of the clinical effect of ropivacaine on caesarean operation

Objective To explore the toxic effect and application safety of ropivacaine after transversus abdominis plane block for caesarean section. Methods Sixty cases puerperas who were suffered with transversus abdominis plane block for caesarean section in the People’s Hospital of Yan’an were retrospectively analyzed.Blood sample was collected after TAP block at different times and at the same time asked if they had neurotoxicity.The collected blood was measured for the concentration of ropivacaine.The ages, weight, height, BMI and total doses of ropivacaine were compared, and the mean total peak ropivacaine concentrations and the mean time to the maximum concentration in symptomatic and asymptomatic puerperas were compared to assess the reasonable threshold for clinical in symptomatic puerperas and suitable ropivacaine concentration. Results The BMI and total doses of ropivacaine of symptomatic group was (70.30±7.90) kg, (225.80±17.60) mg, significantly higher than the asymptomatic group((62.60±12.40) kg, (189.00±22.40) mg), the differences were significant(t=4.613, 7.143, P<0.05). The mean total peak ropivacaine concentrations in symptomatic group was increased compared with asymptomatic group((2.82±0.55) mg/L vs. (1.33±0.47) mg/L, t=0.779, P<0.05), and the mean time to the maximum concentration in symptomatic group was decreased compared with asymptomatic group((26.80±5.40) min vs. (39.20±6.30) min, t=4.158, P<0.05). Conclusion There is a certain neurotoxicity when applying ropivacaine after transversus abdominis plane block for caesarean section.Ropivacaine concentration 2.2 kg/ml as a reasonable threshold for clinical toxicity in puerperas undergoing TAP block, and 2.5 mg/L ropivacaine is fit for puerperal on lean body mass, and further reduction may be required as puerperal weight increases. Key words: Caesarean; Ropivacaine; Transversus abdominis plane

A Novel Proliposomal Ropivacaine Oil: Pharmacokinetic-Pharmacodynamic Studies After Subcutaneous Administration in Pigs.

Liposomal local anesthetics are limited by a short liposomal shelf-life, even when under refrigeration. We describe a novel proliposomal ropivacaine that produces liposomes in situ, only after exposure to aqueous media. In vitro: Nanoparticles were assessed (particle size distribution analyzer, cryo-transmission electron microscopy) at baseline and after exposure to saline/plasma. In porcine wound healing study (n = 12), healing was assessed by photography, clinical assessment, and histology. Pharmacodynamics: Seventeen young piglets were randomly assigned to plain 0.5% ropivacaine (n = 5), proliposomal 4% ropivacaine (n = 6), or sham (n = 6). Tactile threshold was assessed using von Frey filaments applied to the surgical wound; the nonoperated skin was used as a control. Tactile threshold over time was determined using area under the curve (AUC) and assessed by 1-way analysis of variance. 8 young piglets were randomly assigned to plain 0.5% (25 mg, n = 4) or proliposomal 4% (200 mg, n = 4) ropivacaine. Plasma ropivacaine was assessed by high-performance liquid chromatography at baseline and at intervals over 36 hours. Paired ropivacaine concentration (from wound exudate and plasma) was obtained at 96 hours. Data were analyzed using noncompartmental and compartmental models. In vitro: On exposure to saline and plasma, the study drug was transformed from a homogenous oil to an emulsion containing liposomes of approximately 1.4-μm diameter; this effect was dilution dependent and stable over time. All wounds healed well; no effect of drug group was observed. Pharmacodynamics: Plain and proliposomal ropivacaine provided sensory anesthesia for approximately 6 and 30 hours, respectively. There was an approximately 7-fold increase in the AUC of anesthesia for proliposomal ropivacaine compared with plain ropivacaine (mean difference, 1010; 95% confidence interval [CI], 625-1396 g·h/mm; P < 0.0001). There was no difference in Cmax (2.31 ± 0.74 vs 2.32 ± 0.46 mg/L), despite an approximately 8-fold difference in dose. However, proliposomal ropivacaine was associated with a marked prolongation of Tmax (6.50 ± 6.35 vs 0.5 ± 0.0 hours), terminal half-life (16.07 ± 5.38 vs 3.46 ± 0.88 hours; P = 0.0036), and ropivacaine-time AUC (47.72 ± 7.16 vs 6.36 ± 2.07 h·mg/L; P < 0.0001), when compared with plain ropivacaine. The proliposomal formulation provided an approximately 250-fold higher ropivacaine concentration in the surgical wound (mean difference, 3783 ng/mL; 95% CI, 1708-5858; P = 0.001) and an approximately 25-fold higher wound:plasma ropivacaine concentration ratio (mean difference, 126; 95% CI 38-213; P = 0.011). Proliposomal ropivacaine exerted prolonged anesthesia with delayed elimination, typical for liposomal drugs. The advantage of this novel proliposomal ropivacaine is its ease of preparation and its extended shelf-stability (>2 years) at room temperature.

Proliposomal Ropivacaine Oil: Pharmacokinetic and Pharmacodynamic Data After Subcutaneous Administration in Volunteers.

Slow-release liposomal formulations of local anesthetics prolong plasma redistribution and reduce peak plasma drug concentration, allowing safer administration of larger doses and further prolonging sensory effects. However, their clinical applicability is limited by expensive manufacture and liposomal leakage. Previously, we described the simple preparation of a novel proliposomal ropivacaine oil that produces multilamellar liposomal vesicles on exposure to aqueous media and that has a shelf-life of >2 years at room temperature. In this study, we present both pharmacodynamic and pharmacokinetic data in healthy volunteers after subcutaneous injection of this novel proliposomal preparation of ropivacaine. In the pharmacodynamic phase of this study, 15 volunteers received 3 separate subcutaneous injections of 2.5 mL containing 1 of the following drugs: proliposomal 4% ropivacaine, plain 0.5% ropivacaine, and the ropivacaine-free proliposomal vehicle. Drugs were administered into the lower back, and their location was randomized and blinded; a separate area was used as an uninjected, open control. Experimental sensory assessment was made at repeated intervals over 72 hours using both pinprick sensation and experimental heat pain tolerance (assessed using quantitative sensory testing). In a separate pharmacokinetic phase of this study, 9 volunteers received subcutaneous injections of 2.5 mL of either proliposomal 4% ropivacaine (n = 6) or plain 0.5% ropivacaine (n = 3); these participants had plasma ropivacaine concentrations assessed at repeated intervals over 72 hours. The mean ± SE duration of pinprick anesthesia after proliposomal and plain ropivacaine administration lasted 28.8 ± 6.0 and 15.9 ± 3.5 hours, respectively (mean difference, 16.8 hours; 95% confidence interval, 10.0-23.7; P = 0.001). For experimental heat pain, the anesthesia duration was approximately 36 and 12 hours, respectively, with mean ± SE area under the curve of the normalized heat pain tolerance over time 55.0 ± 28.8 Δ°C·min for proliposomal ropivacaine and 9.6 ± 26.0 Δ°C·min for plain ropivacaine (mean difference, 64.6 Δ°C·min; 95% confidence interval, 10.2-119.0; P = 0.036). In the pharmacokinetic study, there was no significant difference in peak plasma concentration in the proliposomal ropivacaine group (164 ± 43 ng/mL compared with 100 ± 41 ng/mL in the plain ropivacaine group; P = 0.07) despite an 8-fold increase in ropivacaine dose in the proliposomal group. The 99% upper prediction limit for peak plasma concentrations (351 ng/mL proliposomal; 279 ng/mL plain) was well below the putative toxic plasma concentration for both groups. The mean ± SE terminal half-life and area under the curve for proliposomal ropivacaine versus plain ropivacaine were 13.8 ± 3.6 hours vs 5.9 ± 2.3 hours (P = 0.011) and 5090 ± 1476 h·ng/mL vs 593 ± 168 h·ng/mL (P = 0.0014), respectively. The prolonged pharmacodynamic effect of proliposomal ropivacaine, together with its delayed elimination and prolonged redistribution to plasma, is compatible to depot-related slow-release and similar to the performance of other liposomal local anesthetics. The advantage of the proliposomal oil is its ease of preparation and its extended shelf-stability at room temperature.

Effect of Local Anesthetic Concentration (0.2% vs 0.1% Ropivacaine) on Pulmonary Function, and Analgesia After Ultrasound-Guided Interscalene Brachial Plexus Block: A Randomized Controlled Study.

This study aims to assess diaphragmatic excursion and measure pulmonary functions as measures of the degree to which the phrenic nerve is blocked after ISB with two different concentrations of ropivacaine: 0.2% and 0.1%. Randomized, double-blinded study. Ambulatory surgical facility. Fifty patients undergoing shoulder arthroscopy for rotator cuff repair. Patients were randomized to receive ultrasound-guided ISB with 20 mL of either 0.2% or 0.1% ropivacaine. Diaphragmatic excursion was measured using M-mode ultrasound. Pulmonary functions were assessed by portable spirometer. Additional outcome data included oxygen saturation in post-anesthesia care unit (PACU), pain scores, quality of recovery scores (QOR), and opioid consumption over 72 hour period after surgery. Forced vital capacity (FVC) was significantly reduced 30 minutes after block placement and in PACU in the 0.2% group when compared with the 0.1% group (P = 0.04, P = 0.03, respectively). Forced expiratory volume (FEV1) was also significantly decreased in the 0.2% group in PACU when compared with the 0.1% group (P = 0.04). There were no significant differences in pain scores, length of stay, and total opioid consumption in PACU. Patients who received 0.2% ropivacaine had a longer block duration (18 vs 11.9 hours, P = 0.04) and used less opioid in the 72 hours after surgery (55 mg vs 102 mg codeine equivalents, P = 0.02), when they were compared to their counterparts who received 0.1% for their block. 0.1% ropivacaine may impair pulmonary function less than 0.2% ropivacaine. The clinical significance of these differences needs to be further studied.

The minimum effective concentration (MEC90 ) of ropivacaine for ultrasound-guided supraclavicular brachial plexus block.

The aim of this study was to determine the minimum effective concentration of ropivacaine for ultrasound-guided supraclavicular brachial plexus block. Fifty-one patients undergoing arm surgery received double-injection ultrasound-guided supraclavicular block using ropivacaine 40 ml. The concentration of ropivacaine administered to each patient started at 0.225% and then depended on the response of the previous one, based on a biased coin design up-and-down sequential method. In case of failure, the ropivacaine concentration was increased by 0.025% w/v in the next subject. In the case of a successful block, the next patient was randomised to the same concentration or a concentration 0.025% w/v less. Success was defined as complete sensory blockade of the brachial plexus 30 min after the block together with pain-free surgery. The minimum effective ropivacaine concentration in 90% of subjects was 0.257% w/v (95% CI 0.241-0.280%).

THE COSTS OF REGIONAL ANESTHESIA WITH THE USE OF LEVOBUPIVACAINE, RACEMIC BUPIVACAINE AND ROPIVACAINE

Background and Objective . Currently in clinical practice are widely used local anesthetics, including racemic bupivacaine, levo isomer of its levobupivacaine and structurally similar to bupivacaine levo isomer ropivacaine. The aim of this work was to assess the cost of anesthesia levobupivacaine, bupivacaine and ropivacaine. Material and methods . In accordance with the results of comparative clinical trials and expert evaluation analysis was conducted in two ways: under the assumption of equal clinical effectiveness of levobupivacaine and bupivacaine and a higher efficiency of levobupivacaine compared with ropivacaine (assumed in various clinical situations with an equal volume of solution used ropivacaine in concentrations of 0.5% may be replaced without reducing clinical efficacy of levobupivacaine in a concentration of 0.5%, ropivacaine in a concentration of 0.75% – levobupivacaine in a concentration of 0.5 and 0.75% (in equal proportions); ropivacaine at a concentration of 1% – levobupivacaine at a concentration of 0.75%. The ropivacaine dose equivalent to 1 mg of levobupivacaine, made when calculating the average of 1.20 mg), and under the assumption of equal clinical effectiveness compare local anesthetics. The analysis was carried out for medicines containing 10 ml of solution per ampoule on the basis of registered prices of bupivacaine and ropivacaine. The cost of levobupivacaine was calculated based on expected rates of registration in the case of inclusion in the Essential Drugs List (0,5% R-R amp. 10 ml №10 – 947,74 RUB; 0.75% of p-p amp. 10 ml №10 – 1421,60 RUB). Results . Subject to the adopted scenario 1 assumptions levobupivacaine allows you to reduce costs 29.6-56.9 per cent compared with bupivacaine and ropivacaine. Taking into account the consumption of local anesthetics in 2016 (according to IMS Health), the replacement of bupivacaine and ropivacaine by levobupivacaine will allow you to reduce costs on average by 38.0%. Projected savings when replacing bupivacaine and ropivacaine in concentrations of 0.5-1.0% in ampoules of 10 ml will be 69,305 million RUB/year, taking into account the accepted assumptions. Under the assumption of equal effectiveness bupivacaine, ropivacaine and levobupivacaine (scenario 2), the replacement of bupivacaine and ropivacaine on levobupivacaine will reduce costs by an average of 29.6%. Given the amount of consumption savings will be 34,012 million RUB/year. Conclusion. Replacement of bupivacaine and ropivacaine in concentrations of 0.5-1.0% in vials of 10 ml levobupivacaine at a concentration of 0.5-0.75% will allow taking into account assumptions significantly reduce budget costs without reducing the effectiveness of treatment. Reducing the burden on the budget could be achieved under the assumption of equal efficacy of drugs and replacement of bupivacaine and ropivacaine by levobupivacaine in the same concentration.

Efficacy and Safety of a Lidocaine and Ropivacaine Mixture for Scalp Nerve Block and Local Infiltration Anesthesia in Patients Undergoing Awake Craniotomy.

Mixtures of various local anesthetics, such as lidocaine and ropivacaine, have been widely used. However, their efficacy and safety for scalp nerve blocks and local infiltration during awake craniotomy have not been fully elucidated. We prospectively investigated 53 patients who underwent awake craniotomy. Scalp block was performed for the blockade of the supraorbital, supratrochlear, zygomaticotemporal, auriculotemporal, greater occipital, and lesser occipital nerves with a mixture containing equal volumes of 2% lidocaine and 0.75% ropivacaine, including 5 μg/mL of epinephrine. Infiltration anesthesia was applied at the site of skin incision using the same mixture. The study outcomes included changes in heart rate and blood pressure after head pinning and skin incision, and incidence of severe pain on emergence from anesthesia. Total doses and plasma concentrations of lidocaine and ropivacaine were measured at different time points after performing the block. The heart rate and blood pressure after head pinning were marginally, but significantly, increased when compared with baseline values. There were no significant differences in heart rate and blood pressure before and after the skin incision. Nineteen percent of the patients (10/53) complained of incisional pain at emergence from anesthesia. The highest observed blood concentrations of lidocaine and ropivacaine were 1.9±0.9 and 1.1±0.4 μg/mL, respectively. No acute anesthetic toxicity symptom was observed. Scalp block with a mixture of lidocaine and ropivacaine seems to provide effective and safe anesthetic management in patients undergoing awake craniotomy.