Concentrations Of Ropivacaine Research Articles

A Randomized Controlled Study of 0.5% Bupivacaine, 0.5% Ropivacaine and 0.75% Ropivacaine for Supraclavicular Brachial Plexus Block.

For any surgery in the upper extremity that does not involve the shoulder, a supraclavicular block is preferred, as it is a safe procedure associated with rapid onset and reliable anaesthesia. Although ropivacaine has been extensively studied for epidural anaesthesia, very few reports exist on its use in supraclavicular brachial plexus block. This study was conducted to investigate and compare the effectiveness of supraclavicular brachial plexus anaesthesia with two different concentrations of ropivacaine (0.5% and 0.75%) and to compare them with the standard 0.5% bupivacaine. Ninety patients of age 18 to 60 years belonging to American Society of Anaesthesiologists (ASA) status 1 or 2, admitted to Pondicherry Institute of Medical Sciences were chosen for the study and were divided into three groups. Group A received 30 ml of 0.5% bupivacaine, group B received 30 ml of 0.5% ropivacaine and group C received 30 ml of 0.75% ropivacaine into the supraclavicular region, by a nerve-stimulator technique. Onset time of each of the drug was recorded both for the sensory and motor block. Duration of sensory and motor block was recorded along with peri-operative haemodynamic monitoring. The onset of complete sensory and motor block observed with both ropivacaine groups and bupivacaine was similar (16.85±6.67 min in group A, 17.79±5.03 min in group B and 18.48±6.14 in group C, p>0.05); onset of motor block (21.45±4.45 min in group A, 22.23±4.05 min in group B and 22.33±5.17 in group C, p < 0.05). The duration of sensory block with 0.5% bupivacaine was 11.58 hours, with 0.5% ropivacaine was 9.02 hours with 0.75% ropivacaine was 8.87 hours (p<0.001). The duration of motor block with 0.5% bupivacaine was 12.94 hours, with 0.5% ropivacaine was 8.29 hours with 0.75% ropivacaine was 7.89 hours (p<0.001). Multiple comparison test with Bonferroni correction showed there was statistically significant difference in mean duration of sensory block between Group A (0.5% bupivacaine) and Group B (0.5% ropivacaine) and also between Group A (0.5% bupivacaine) and Group C (0.75% ropivacaine). However, there were no statistically significant difference in mean duration of sensory block between Group B (0.5% ropivacaine) and Group C (0.75% ropivacaine). The preoperative, intra operative and postoperative heart rate, systolic & diastolic blood pressure and oxygen saturation were comparable among the three study groups (p>0.05). No side effects were recorded in the study. The onset of sensory and motor block was similar in all the three groups. However, when compared to bupivacaine group, recovery of motor functions was faster in both the ropivacaine groups. Patients in all the 3 groups did not experience any adverse effects.

Abstracts and Highlight Papers of the 35th Annual European Society of Regional Anaesthesia & Pain Therapy (ESRA) Congress 2016.

Background and Aims: 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) and corresponding times to maximum concentration (Tmax) of a single shot ropivacaine (200ml 0.2%) and 0.75 mg epinephrine (1000μg mL-1) when used for LIA. Methods: In this prospective cohort study twenty 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 minutes and at 24 hours after tourniquet release, in which total and unbound ropivacaine concentrations were determined. Results: Results are given as mean (SD); median (range). Maximum total ropivacaine concentration was 1.06 (0.36); 1.00 (0.61 - 2.26) μg mL-1, corresponding Tmax was 311 (227); 240 (40-1440) minutes after tourniquet release (Figure 1). The highest measured unbound ropivacaine concentration was 0.13 μg mL-1. Conclusions: Maximumtotal and unbound serum concentrations of ropivacaine remained well below the assumed toxic thresholds of 4.3 and 0.56 μg mL-1, respectively, for systemic toxicity. (Figure Presented).

Effective concentration of Ropivacaine for post-operative pain relief in Total knee replacement surgeries using ultra sound guided continuous femoral block – A randomized double blinded study

Introduction: Postoperative pain in total knee replacement surgeries is severe and needs intense analgesia. Of various analgesic techniques available, continuous femoral nerve block is safe and associated with minimal side effects. Objectives: To compare the analgesic effect of various concentrations of ropivacaine using continuous femoral nerve block for post-operative pain relief in total knee replacement surgeries. Methods: 120 patients posted for elective total knee replacement (TKR) surgeries under American Society of Anesthesiologists (ASA) physical classification I or II, under spinal anaesthesia, were randomly allocated into four groups of 30 each. Group 1, 2, 3 and 4 received ropivacaine 0.12%, 0.16%, 0.20% and 0.25% respectively at 10 mL per hour infusion, by ultrasound-guided continuous femoral nerve block. Pain relief was assessed by visual analogue scale (VAS). Analgesic requirement in the post-operative period and hemodynamic changes compared between four groups. Results: There was no statistical difference in change in hemodynamics over time between all four groups. Analgesic requirement was significantly less and VAS score was significantly low in group 3 and group 4. Conclusion: In this study, the minimum effective concentration of ropivacaine when used for pain relief in continuous femoral block in total knee replacement surgeries is found to be 0.20%. Keywords: Analgesia; Knee replacement; Nerve block; Ropivacaine; Ultrasound

Optimum Concentration of Caudal Ropivacaine & Clonidine - A Satisfactory Analgesic Solution for Paediatric Infraumbilical Surgery Pain.

Ropivacaine is amide local anaesthetic pure S(-)enantiomer of bupivacaine. Its duration of analgesia is similar to that of Bupivacaine (in equivalent doses) but the motor block is slower in onset, less intense, shorter in duration for a given level of sensory block with lesser cardiac side effects but addition of an adjuvant like clonidine which is an imidazoline derivative has been studied for its sedative, anxiolytic and analgesic properties. This study was aimed to show the optimum concentrations of Ropivacaine and Clonidine to maximize analgesia without side effects by evaluating its safety and efficacy. Sixty children aged 2-10 years of ASA grade 1, scheduled to undergo infraumbilical surgeries were randomly allocated to Group A & Group B of 30 each. Group A received 0.2% Ropivacaine with normal saline and Group B received 0.2% Ropivacaine and preservative free Clonidine 1μg/kg, the total volume of solution being 1ml/kg haemodynamic changes were monitored intraoperatively and haemodynamic parameters along with motor blockade, pain score and sedation score were assessed postoperatively. Done with unpaired student t and Mann-Whitney test. The groups were comparable regarding demographic characterstics. The mean duration of analgesia was prolonged in group B (12+2.22 hours) than in group A (6.53+1.16 hours) with p-value <0.001 leading to less rescue analgesia in former group. None of the children in the groups had a pain score of ≥ 4 at the end of 2 hours. A 6.6% and 60% of group A children had score of ≥ 4 at the end of 4(th) & 6(th) hour respectively. None in Group B had a score of ≥ 4. At the end of 8(th) hour, only 6.6% of the children in Group B had a pain score of ≥ 4 whereas it was 33.33% in Group A which is statistically significant. No bradycardia or hypotension and no significant sedation. Combination of Ropivacaine and Clonidine in the concentration used (0.2% ropivacaine and 1μg/kg of clonidine) can be optimal for postoperative analgesia in paediatric population.

Epinephrine Affects Pharmacokinetics of Ropivacaine Infiltrated Into Palate.

Pulpal anesthesia success rates for ropivacaine following maxillary infiltration anesthesia seem to be low. We investigated the hypothesis that the addition of epinephrine would affect the pharmacokinetics of ropivacaine by retaining ropivacaine in the mucosa of the injected area through the time-dependent distribution of ropivacaine in the rat maxilla and serum following maxillary infiltration anesthesia using (3)H-labeled ropivacaine. We then examined the vasoactivity of ropivacaine with or without epinephrine on local peripheral blood flow. The addition of epinephrine to ropivacaine increased ropivacaine concentrations in the palatal mucosa and adjacent maxilla by more than 3 times that of plain ropivacaine at 20 minutes. By observing the autoradiogram of (3)H-ropivacaine, plain ropivacaine in the maxilla was remarkably reduced 20 minutes after injection. However, it was definitely retained in the palatal mucosa, hard palate, adjacent maxilla, and maxillary nerve after the administration with epinephrine. Ropivacaine with epinephrine significantly decreased labial blood flow. This study suggests that 10 μg/mL epinephrine added to 0.5% ropivacaine could improve anesthetic efficacy and duration for maxillary infiltration anesthesia over plain ropivacaine.

Buprenorphine, Clonidine, Dexamethasone, and Ropivacaine for Interscalene Nerve Blockade: A Prospective, Randomized, Blinded, Ropivacaine Dose-Response Study.

This study investigated interscalene block for shoulder arthroplasty with various ropivacaine concentrations in the presence of clonidine, dexamethasone, and buprenorphine. The goal was prolonged analgesia with minimal motor blockade. Prospective, double-blind, randomized controlled trial. University-affiliated orthopedic hospital. Patients (20/group) received acetaminophen, ketorolac, pregabalin, opioids, and "Control"; interscalene block, 0.375% ropivacaine, intravenous additives (buprenorphine, clonidine, dexamethasone); "High Dose"; 0.375% ropivacaine, perineural additives; "Medium Dose"; 0.2% ropivacaine, perineural additives; and "Low Dose"; 0.1% ropivacaine, perineural additives. Pain with movement at 24 hours was 4.9 ± 2.5 (mean ± standard deviation [SD]) (Control), 4.5 ± 3.0 (High Dose), 3.4 ± 1.8 (Medium Dose), 4.2 ± 2.4 (Low Dose). The difference between Medium Dose and Control was -1.5 (95% CI: -2.9, -0.1) (P = 0.040). Median time until need for opioids was 16.1 hours (Control) vs 23.7 hours (High Dose); hazard ratio 0.37 [95% CI: 0.17, 0.79]. High Dose had less pain with movement the morning after surgery, vs Control; 2.9 ± 2.5 vs 4.9 ± 2.7; P = 0.027. Pain with movement in the Post-Anesthesia Care Unit was higher in Low Dose, vs Control; 0.9 ± 1.4 vs 0 ± 0, P = 0.009. Low Dose had superior hand strength in the Post-Anesthesia Care Unit (mean ± SD of pre-operative strength: 44.0 ± 20.3%) compared to Control (27.5 ± 24.5%) (P = 0.031). For maximum pain reduction, combining perineural additives with ropivacaine 0.375% or 0.2% is suggested. To minimize motor blockade, perineural additives can be combined with ropivacaine, 0.1%.

Plasma concentrations of ropivacaine following ultrasound-guided or nerve-stimulator-guided femoral nerve block: A prospective randomised study

ObjectiveOur aim was to establish a plasma concentration curve for ropivacaine following femoral nerve blockade and to ascertain whether the resulting plasma concentrations differ significantly depending on whether neurostimulation (NS) or ultrasound (US) guidance was used. MethodsSixteen male and female subjects aged 18 to 80 who were scheduled to undergo unilateral total knee replacement or anterior cruciate ligament reconstruction under general or spinal anaesthesia, and for whom a femoral nerve block was indicated for postoperative analgesia, were enrolled in this prospective, randomised study. Patients were randomised to undergo either US or NS-guidance femoral nerve blocks. All blocks were performed with 20mL of 5mg/mL ropivacaine. Blood samples were drawn before the nerve block and 20, 30, 40, 50, 60, 70, and 80minutes after the block. Plasma levels of ropivacaine were analysed by high performance liquid chromatography (HPLC). ResultsAll blocks were successful and no patient showed signs or symptoms of local anaesthetic toxicity. The plasma concentration of ropivacaine peaked at 30minutes in both arms. There was no significant difference in peak levels between US and NS-guidance (0.325±0.186 versus 0.356±0.106μg/mL). Cmax and tmax were very similar between groups (0.364±0.177 versus 0.344±0.127μg/mL, 33.75±15.06 versus 31.25±13.56min for US and NS, respectively). ConclusionPlasma concentrations of ropivacaine peak around 30minutes after a femoral nerve block regardless of the technique used. No significant difference was found between US- and NS-guidance.

Cardiac arrest after thoracic paravertebral block with ropivacaine in a 6-year-old child

We encountered cardiac arrest induced by 0.375 % ropivacaine 7 ml administered via a catheter for continuous thoracic paravertebral block (TPVB) in a 6-year-old female who underwent pacemaker implantation for sick sinus syndrome (SSS). She was successfully resuscitated with adrenaline and lipid emulsion. Plasma concentration of ropivacaine was 5.2 μg/ml, suggesting intravascular administration of ropivacaine. Inadvertent intravascular administration is a crucial complication of TPVB.

Comparison of different concentrations of ropivacaine combined with sufentanyl in labor analgesia

Objective To explore the effect and value of sufentanyl combined with different concentrations of ropivacaine in labor analgesia. Methods 120 analgesia childbirth pregnant women were divided into 3 groups(group A 0.5g/L, group B 1.0g/L, group C 2.0g/L) by random number table method, 40 cases in each group, they were given sufentanyl combined with different concentrations of ropivacaine in labor analgesia.The labor analgesia effect of three groups of pregnant women was recorded. Results The postpartum 2 h blood loss and total labor time of group A were (147.55±25.39)mL and (727.54±56.38)min, which of group B were (131.03±18.73)mL, (573.53±40.09)min, which of group C were (120.03±14.84)mL, (493.82±34.51)min, there were statistically significant differences among the three groups(F=3.342 7, 7.551 7, all P 0.05). Conclusion Using 1.5g/L ropivacaine combined with sufentanyl in labor analgesia is remarkable, high safety, neonatal and maternal prognosis is good, and therefore should be preferred to 1.5g/L ropivacaine combined with sufentanyl in labor analgesia. Key words: Labor pain; Analgesia, obstetrical; Fentanyl; Ropivacaine

Clinically relevant concentrations of lidocaine and ropivacaine inhibit TNFα-induced invasion of lung adenocarcinoma cells in vitro by blocking the activation of Akt and focal adhesion kinase

Matrix-metalloproteinases (MMP) and cancer cell invasion are crucial for solid tumour metastasis. Important signalling events triggered by inflammatory cytokines, such as tumour necrosis factor α (TNFα), include Src-kinase-dependent activation of Akt and focal adhesion kinase (FAK) and phosphorylation of caveolin-1. Based on previous studies where we demonstrated amide-type local anaesthetics block TNFα-induced Src activation in malignant cells, we hypothesized that local anaesthetics might also inhibit the activation and/or phosphorylation of Akt, FAK and caveolin-1, thus attenuating MMP release and invasion of malignant cells. NCI-H838 lung adenocarcinoma cells were incubated with ropivacaine or lidocaine (1 nM-100 µM) in absence/presence of TNFα (20 ng ml(-1)) for 20 min or 4 h, respectively. Activation/phosphorylation of Akt, FAK and caveolin-1 were evaluated by Western blot, and MMP-9 secretion was determined by enzyme-linked immunosorbent assay. Tumour cell migration (electrical wound-healing assay) and invasion were also assessed. Ropivacaine (1 nM-100 μM) and lidocaine (1-100 µM) significantly reduced TNFα-induced activation/phosphorylation of Akt, FAK and caveolin-1 in NCI-H838 cells. MMP-9 secretion triggered by TNFα was significantly attenuated by both lidocaine and ropivacaine (half-maximal inhibitory concentration [IC50]=3.29×10(-6) M for lidocaine; IC50=1.52×10(-10) M for ropivacaine). The TNFα-induced increase in invasion was completely blocked by both lidocaine (10 µM) and ropivacaine (1 µM). At clinically relevant concentrations both ropivacaine and lidocaine blocked tumour cell invasion and MMP-9 secretion by attenuating Src-dependent inflammatory signalling events. Although determined entirely in vitro, these findings provide significant insight into the potential mechanism by which local anaesthetics might diminish metastasis.

Efficacy of ropivacaine by the concentration of 0.25%, 0.5%, and 0.75% on surgical performance, postoperative analgesia, and patient's satisfaction in inguinal hernioplasty: a randomized controlled trial.

BackgroundThe purpose of this study was to evaluate the use of different concentrations of ropivacaine in ultrasound-guided regional anesthesia with regard to postoperative analgesic and patient’s satisfaction in elderly patients undergoing inguinal hernioplasty in the People’s Republic of China.MethodsA total of 60 patients (>75 years of age) who scheduled inguinal hernioplasty at the Shenzhen People’s Hospital from December 2013 to March 2015 were randomly assigned to three groups: 0.25% ropivacaine (n=20), 0.5% ropivacaine (n=20), and 0.75% ropivacaine (n=20). Ultrasound-guided regional anesthesia was performed before every surgery. Non-invasive blood pressure and heart rate were recorded before the operation, during the first 5 minutes of the surgical procedure, and 5 minutes after the operation of the patients, and compared between the groups. Incidence of adverse reactions, postoperative Visual Analog Scale score, and analgesic effect were also recorded and analyzed.ResultsThe surgical procedure and anesthesia was performed successfully in all patients. Patients with high-dose ropivacaine (0.5% and 0.75%) in ultrasound-guided regional anesthesia exhibited lower arterial pressure and lower heart rate during the operation when compared to low-dose group. The interquartile range of Visual Analog Scale scores in both group C (0.75% ropivacaine) and group B (0.5% ropivacaine) were significantly lower (P<0.05) than in group A (0.25% ropivacaine). Accordingly, the interquartile range of satisfactory scores in both group C (0.75% ropivacaine) and group B (0.5% ropivacaine) were significantly higher (P<0.05) than in group A (0.25% ropivacaine). More cases in high-dose groups reported abnormal skin sensation; however, it did not negatively affect the satisfaction level of patients.ConclusionThe use of ultrasound-guided regional anesthesia with ropivacaine as an anesthetic in inguinal hernia repair for elderly patients is safe and effective, and ropivacaine is optimally effective at the concentration of 0.5% with least side effects.

Effects of different doses of dexmedetomidine on median effective concentration of ropivacaine for brachial plexus block

Objective To determine the optimum dose of dexmedetomidine administered locally through evaluating the effects of different doses of dexmedetomidine on the median effective concentration(EC50)of ropivacaine for brachial plexus block. Methods American Society of Anesthesiologists physical status Ⅰ or Ⅱ patients of both sexes, aged 19-50 yr, weighing 50-80 kg, scheduled for elective ulna and radius fracture open reduction and internal fixation, requiring ultrasound-guided axillary brachial plexus block, were randomly assigned into 4 groups using a random number table: control group(group C)and dexmedetomidine 0.4, 0.6 and 0.8 μg/kg groups(D1, D2 and D3 groups). Axillary brachial plexus block was performed only with ropivacaine in group C. In D1-3 groups, axillary brachial plexus block was performed with the mixture of ropivacaine and dexmedetomidine 0.4, 0.6 and 0.8 μg/kg, respectively.The effective block was defined as complete loss of pain sensation in the areas innervated by the brachial plexus.The volume of local anesthetics was 40 ml.The concentration of ropivacaine was determined by up-and-down technique.The initial concentration was 0.4% and the ratio between the two successive concentrations was 1.0.If the block was effective, the next patient received a lower dose of ropivacaine; or conversely if ineffective, a higher dose was given in the next patient.At least 7 independent crossover pairs were observed in each group.The EC50 of ropivacaine was the mean of the concentration of ropivacaine of each crossover pair.The occurrence of brachial plexus block-related adverse events, adverse cardiovascular events and over-sedation was recorded. Results In C, D1, D2 and D3 groups, 20, 22, 24 and 19 patients were enrolled, respectively.Compared with group C, the EC50 of ropivacaine was significantly decreased in D2 and D3 groups, and no significant change in the EC50 of ropivacaine was found in group D1.No patients developed adverse events in group D1.The incidence of bradycardia was 17%, but it was transient in group D2.In group D3, the incidence of bradycardia and hypotension was 58% and 32%, respectively, and they required special treatment, and the incidence of over-sedation was 10%. Conclusion The optimum dose of dexmedetomidine is 0.6 μg/kg when mixed with ropivacaine for brachial plexus block. Key words: Dexmedetomidine; Amides; Brachial plexus; Nerve block; Dose-response relation, drug

The viability of chondrocytes after an in vivo injection of local anaesthetic and/or corticosteroid: a laboratory study using a rat model.

This in vivo controlled laboratory study was performed to evaluate various intra-articular clinical injection regimes that might be less toxic than some in vitro studies suggest. We hypothesised that low-concentration, preservative-free, pH-balanced agents would be less toxic than high-concentration non-pH-balanced agents with preservatives, and that injections of individual agents are less toxic than combined injections. The left knees of 12- to 13-week-old Sprague-Dawley rats were injected once with eight different single agents, including low and high concentrations of ropivacaine and triamcinolone, alone and in combination, as well as negative and positive controls. The rats were killed at one week or five months, and live-dead staining was performed to quantify the death of chondrocytes. All injections except pH-balanced 0.2% ropivacaine combined with preservative-free 1 mg/ml triamcinolone acetonide resulted in statistically significant decreases in chondrocyte viability, compared with control knees, after one week and five months (p < 0.001). After one week there was no significant difference in viability between 0.2% and 0.5% ropivacaine; however, 4 mg/ml triamcinolone resulted in a lower viability than 1 mg/ml triamcinolone. Although many agents commonly injected into joints are chondrotoxic, in this in vivo study diluting preservative-free 10 mg/ml triamcinolone 1:9 in 0.2% pH-balanced ropivacaine resulted in low toxicity.

Population pharmacokinetic model of free and total ropivacaine after transversus abdominis plane nerve block in patients undergoing liver resection.

The aim of this study was to develop a pharmacokinetic model in order to characterize the free and total ropivacaine concentrations after transversus abdominis plane block in a population of patients undergoing liver resection surgery. In particular, we evaluated the impact of the size of liver resection on ropivacaine pharmacokinetics. This work is based on a single-centre, double-blinded, randomized, placebo-controlled study. Among the 39 patients included, 19 patients were randomized to the ropivacaine group. The free and total ropivacaine concentrations were measured in nine or 10 blood samples per patient. A pharmacokinetic model was built using a nonlinear mixed-effect modelling approach. The free ropivacaine concentrations remained under the previously published toxic threshold. A one-compartment model, including protein binding site with a first-order absorption, best described the data. The protein binding site concentration was considered as a latent variable. Bodyweight, the number of resected liver segments and postoperative fibrinogen evolution were, respectively, included in the calculation of the volume of distribution, clearance and binding site production rate. The resection of three or more liver segments was associated with a 53% decrease in the free ropivacaine clearance. Although large liver resections were associated with lower free ropivacaine clearance, the ropivacaine pharmacokinetic profile remained within the safe range after this type of surgery.

Effect of dexmedetomidine administered locally on median effective concentration of ropivacaine for paravertebralnerve block

Objective To evaluate the effect of dexmedetomidine administered locally on the median effective concentration (EC50) of ropivacaine for paravertebral nerve block (PVNB) . Methods Forty-eight ASA physical status Ⅰ or Ⅱ female patients, aged 20-64 yr, with body mass index<24 kg/m2, scheduled for elective unilateral segmental mastectomy under PVNB, were randomly divided into 2 groups (n=24 each) using a random number table: ropivacaine group (group R) and ropivacaine mixed with dexmedetomidine group (group RD) . PVNB was performed at T4 on the operated side guided by ultrasound and nerve stimulator.Ropivacaine 20 ml and a mixture of ropivacaine and 20 μg dexmedetomidine 20 ml were injected locally in group R and group RD, respectively.The concentration of ropivacaine was determined by up-and-down sequential allocation.The initial ropivacaine concentration was set at 0.35%, and the ratio between the two successive concentrations was 1.2.The EC50 and 95% confidence interval of ropivacaine were calculated using Dixon-Massey method. Results The EC50 (95% confidence interval) of ropivacaine was 0.27% (0.23%-0.30%) and 0.22% (0.18%-0.25%) in group R and group RD, respectively.Compared with group R, the EC50 of ropivacaine was significantly decreased by 19% in group RD. Conclusion Small dose of dexmedetomidine administered locally can significantly enhance the efficacy of PVNB with ropivacaine. Key words: Dexmedetomidine; Amides; Never block; Dose-response relationship, drug

A Comparison of Differences Between the Systemic Pharmacokinetics of Levobupivacaine and Ropivacaine During Continuous Epidural Infusion

BACKGROUND:Epidural infusion of levobupivacaine and ropivacaine provides adequate postoperative pain management by minimizing side effects related to IV opioids and improving patient outcome. The safety profile of different drugs can be better estimated by comparing their pharmacokinetic profiles than by considering their objective side effects. Because levobupivacaine and ropivacaine have different pharmacokinetic properties, our aim was to investigate whether there is a difference in the pharmacokinetic variability of the 2 drugs in a homogeneous population undergoing continuous epidural infusion. This double-blind, multicenter, randomized, controlled trial study was designed to compare the pharmacokinetics of continuous thoracic epidural infusion of levobupivacaine 0.125% or ropivacaine 0.2% for postoperative pain management in adult patients who had undergone major abdominal, urological, or gynecological surgery. This study is focused on the evaluation of the coefficient of variation (CV) to assess the equivalence in the systemic exposure and interindividual variability between levobupivacaine and ropivacaine and, therefore, the possible differences in the predictability of the plasmatic concentrations of the 2 drugs during thoracic epidural infusion.METHODS:One hundred eighty-one adults undergoing major abdominal surgery were enrolled in the study. Patients were randomized to receive an epidural infusion of levobupivacaine 0.125% + sufentanil 0.75 μg/mL or of ropivacaine 0.2% + sufentanil 0.75 μg/mL at 5 mL/h for 48 hours. The primary end point of this study was to analyze the variability of plasma concentration of levobupivacaine and ropivacaine via an area under the curve within a range of 15% of the CV during 48 hours of continuous epidural infusion. The CV shows how the concentration values of local anesthetics are scattered around the median concentration value, thus indicating the extent to which plasma concentration is predictable during infusion. Secondary end points were to assess the pharmacologic profile of the local anesthetics used in the study, including an analysis of mean peak plasma concentrations, and also to assess plasma clearance, side effects, pain intensity (measured with a verbal numeric ranging score, i.e., static Numeric Rating Scale [NRS] and dynamic NRS]), and the need for rescue doses.RESULTS:The comparison between the 2 CVs showed no statistical difference: the difference between area under the curve was within the range of 15%. The CV was 0.54 for levobupivacaine and 0.51 for ropivacaine (P = 0.725). The plasma concentrations of ropivacaine approached the Cmax significantly faster than those of levobupivacaine. Clearance of ropivacaine decreases with increasing patient age. There were no significant differences in NRS, dynamic NRS scores, the number of rescue doses, or in side effects between groups.CONCLUSIONS:Considering the CV, the interindividual variability of plasma concentration for levobupivacaine and ropivacaine is equivalent after thoracic epidural infusion in adults. We found a reduction in clearance of ropivacaine depending on patient age, but this finding could be the result of some limitations of our study. The steady-state concentration was not reached during the 48-hour infusion and the behavior of plasma concentrations of ropivacaine and levobupivacaine during continuous infusions lasting more than 48 hours remains to be investigated, because they could reach toxic levels. Finally, no differences in the clinical efficacy or in the incidence of adverse effects between groups were found for either local anesthetic.

Strength and sensation after epidural ropivacaine in men and women.

We injected 15ml epidural ropivacaine in 30 men and 30 women to determine the median dose required to impair a straight-leg raise. We started at a concentration of 0.425%, increasing the concentration by 0.025% after an ineffective injection and decreasing the concentration by 0.025% after an effective injection. The median (95% CI) concentration of ropivacaine that prevented straight-leg raise within 30min of injection was 0.43% (0.41-0.45%) in men and 0.40% (0.39-0.41%) in women, p=0.001. There were no differences in dermatome levels for loss of pinprick and cold sensation between men and women.

Effects of ropivacaine, bupivacaine and sufentanil in colon and pancreatic cancer cells in vitro

The perioperative period is supposed to be a vulnerable period for cancer progression. Results of clinical studies indicate that the use of regional anesthesia can influence and improve oncological outcome of cancer patients. Uncontrolled cell proliferation and resistance to apoptotic cell death are important characteristics of solid tumors. The aim of this study was to investigate the effects of the clinically used local anesthetics ropivacaine or bupivacaine and the opioid analgesic sufentanil on cell proliferation, cell cycle distribution and apoptosis of colon (HT 29 and SW 480) and pancreatic (PaTu 8988t and PANC 1) cancer cell lines in vitro.Cell proliferation was measured by Cell Proliferation ELISA BrdU Assay. Apoptosis was analyzed by annexin V staining and cell cycle distribution was detected by flow cytometry.Ropivacaine, bupivacaine and sufentanil did not change apoptosis rate and cell cycle distribution in clinically concentration. Only high concentrations of ropivacaine or bupivacaine revealed antiproliferative potency.Protective effects of epidural anesthesia observed in clinical studies seem not to be based on direct effects of these drugs on cancer cells.

Effects of ropivacaine combined with morphine at 0.15 and 0.2 mg kg(-1) in bitches undergoing epidural anesthesia.

To investigate cardiorespiratory effects and serum concentration of ropivacaine combined with morphine at different doses. Sixteen healthy adult female dogs weighting 9.8 ± 4.1 kg were included in the study. Twenty minutes after being premedicated with acepromazine and midazolam, the animals were randomly assigned to receive an epidural injection according to each group: RM0.15 = ropivacaine + morphine (0.15 mg kg(-1)) and RM0.2 = ropivacaine + morphine (0.2 mg kg(-1)). Variables recorded consisted of: heart rate and cardiac rhythm, respiratory rate, oxyhemoglobin saturation, inspired oxygen fraction, end-tidal carbon dioxide tension, systolic, mean and diastolic arterial pressures, serum cortisol, plasma ropivacaine and morphine. SAP, MAP and DAP were significantly increased at TPR in RM0.15 but returned to normal values at the end of the procedure. Arterial pH was decreased in T30 and TESu in both groups and also returned to acceptable ranges at TR. Both PaO2 and PaCO2 were increased along the duration period of the epidural blockade (T30 and TESu) and returned to acceptable values at TR. Serum cortisol was lower at TB, T30 and TR when compared to TESu. The procedures were performed safely and minimal changes in cardiovascular and respiratory variables.

Ropivacaine plasma levels following high-dose local infiltration analgesia for total knee arthroplasty.

We measured total and free plasma concentrations of ropivacaine following high-volume, high-dose local infiltration analgesia in 28 patients aged 65 years or over undergoing unilateral total knee arthroplasty. Patients received infiltration of ropivacaine 400 mg followed by infusion at 20 mg.h(-1) through an intra-articular catheter. Total and free plasma levels of ropivacaine were measured at specified time intervals during a 24-h period after tourniquet release. Patients were monitored for symptoms and signs of local anaesthetic toxicity. Total levels of plasma ropivacaine varied from 0.147 to 3.093 μg.ml(-1) (mean (SD) 1.105 (0.518) μg.ml(-1) ). Free levels of plasma ropivaca-ine varied from 0.001 to 0.104 μg.ml(-1) (mean (SD) 0.037 (0.020) μg.ml(-1) ). Six samples had total plasma ropivacaine levels greater the toxic threshold of 2.2 μg.ml(-1) . No samples reached the toxic threshold for free venous ropivacaine concentration. We conclude that the use of high-dose ropivacaine infiltration and catheter infusion for total knee arthroplasty in an elderly population does not result in free plasma ropivacaine levels previously associated with toxicity but that raised total plasma levels may be observed.