Procaine and mepivacaine have less toxicity in vitro than other clinically used local anesthetics

The neurotoxicity of local anesthetics can be demonstrated in vitro by the collapse of growth cones and neurites in cultured neurons. We compared the neurotoxicity of procaine, mepivacaine, ropivacaine, bupivacaine, lidocaine, tetracaine, and dibucaine by using cultured neurons from the freshwater snail Lymnaea stagnalis. A solution of local anesthetics was added to the culture dish to make final concentrations ranging from 1 x 10(-6) to 2 x 10(-2) M. Morphological changes in the growth cones and neurites were observed and graded 1 (moderate) or 2 (severe). The median concentrations yielding a score of 1 were 5 x 10(-4) M for procaine, 5 x 10(-4) M for mepivacaine, 2 x 10(-4) M for ropivacaine, 2 x 10(-4) M for bupivacaine, 1 x 10(-4) M for lidocaine, 5 x 10(-5) M for tetracaine, and 2 x 10(-5) M for dibucaine. Statistically significant differences (P < 0.05) were observed between mepivacaine and ropivacaine, bupivacaine and lidocaine, lidocaine and tetracaine, and tetracaine and dibucaine. The order of neurotoxicity was procaine = mepivacaine < ropivacaine = bupivacaine < lidocaine < tetracaine < dibucaine. Although lidocaine is more toxic than bupivacaine and ropivacaine, mepivacaine, which has a similar pharmacological effect to lidocaine, has the least-adverse effects on cone growth among clinically used local anesthetics. IMPLICATIONS: Systematic comparison was assessed morphologically in growth cones and neurites exposed to seven local anesthetics. The order of neurotoxicity was procaine = mepivacaine < ropivacaine = bupivacaine < lidocaine < tetracaine < dibucaine. Although lidocaine is more toxic than bupivacaine and ropivacaine, mepivacaine, which has a similar pharmacological effect to lidocaine, is the safest among clinically used local anesthetics.     

General anaesthesia combined with bilateral paravertebral blockade (T5-6) vs. general anaesthesia for laparoscopic cholecystectomy: a prospective, randomized clinical trial

BACKGROUND AND OBJECTIVE: The efficiency of bilateral paravertebral blockade combined with general anaesthesia (active) vs. general anaesthesia alone (control) in reducing postoperative pain following laparoscopic cholecystectomy was evaluated using a prospective randomized study design. METHODS: Patients were randomly assigned to either group. Nerve-stimulator guided paravertebral blockade at the T5-6 level was performed with a local anaesthetic mixture (0.30 mL kg(-1)). Twenty millilitres of the mixture contained lidocaine 2% 6 mL; lidocaine 2% 6 mL with epinephrine 1/200 000; bupivacaine 0.5% 5 mL; fentanyl 1 mL (50 microg mL(-1)) and clonidine 2 mL (150 microg mL(-1)). Postoperative pain and consumption of opioids were assessed during the first 72 h. RESULTS: Two-times 30 patients were analysed. Patient characteristics data, and pre- and peroperative variables were similar in both groups. Mean pain scores visual analogue scale were significantly less with active compared with control (P < 0.05) at 6h (1.56 +/- 1.58 vs. 4.78 +/- 1.67), at 12 h (1.52 +/- 1.58 vs. 3.81 +/- 1.63), at 24 h (1.16 +/- 1.34 vs. 2.71 +/- 1.50), at 36h (0.68 +/- 1.02 vs. 2.29 +/- 1.41), at 48h (0.60 +/- 1.04 vs. 1.61 +/- 1.33) and at 72 h (0.40 +/- 0.86 vs. 1.19 +/- 1.16). The number of patients consuming supplemental analgesics was significantly less (P < 0.05) with active compared with control, at 6 h (6 vs. 29), at 12 h (2 vs. 26), at 24 h (1 vs. 23) and at 36 h (2 vs. 15). More patients were free from nausea (P < 0.05) with active compared with control at 6 h (23 vs. 9) and at 12 h (29 vs. 19). CONCLUSION: When used as a complement to general anaesthesia, bilateral nerve-stimulator guided paravertebral blockade with lidocaine, bupivacaine, fentanyl and clonidine may improve postoperative pain relief.     

Local anesthetics inhibit thromboxane A2 signaling in Xenopus oocytes and human k562 cells

Thromboxane A(2) (TXA(2)) has been proposed as a mediator of perioperative myocardial ischemia, vasoconstriction, and thrombosis. As these adverse events are minimized with epidural anesthesia, rather than general anesthesia, we hypothesized that local anesthetics would inhibit TXA(2)-receptor signaling. We used fluorometric determination of intracellular [Ca(2+)] in human K562 cells and 2-electrode voltage clamp measurements in Xenopus laevis oocytes expressing TXA(2) receptors. After 10-min incubation, lidocaine (IC(50): 1.02 +/- 0.2 x 10(-3) M), ropivacaine (IC(50): ropivacaine 6.3 +/- 0.9 x 10(-5) M), or bupivacaine (IC(50): 1.42 +/- 0.08 x 10(-7) M) inhibited TXA(2)-induced [Ca(2+)](i) in K562 cells. These data were confirmed in Xenopus oocytes recombinantly expressing TXA(2) receptors, with IC(50)s of bupivacaine 1.2 +/- 0.2 x 10(-5) M, R(+) ropivacaine 4.9 +/- 1.7 x 10(-4) M, S(-) ropivacaine 5.3 +/- 0.9 x 10(-5) M, and lidocaine 6.4 +/- 2.8 x 10(-4) M. Intracellular pathways activated by IP(3) and GTPgammaS were not significantly affected by the local anesthetics tested. QX314, a positively charged lidocaine analog, inhibited only if injected intracellularly (IC(50): 5.3 +/- 1.7 x 10(-4) M), indicating one local anesthetic target is most likely inside the cell. Benzocaine (largely uncharged) inhibited with an IC(50) of 8.7 +/- 1.8 x 10(-4) M. This suggests that some of the beneficial effects of regional anesthesia techniques might be due to direct interaction of local anesthetics with the functioning of membrane proteins.     

In children, the addition of epinephrine modifies the pharmacokinetics of ropivacaine injected caudally

PURPOSE: To describe the modification of the ropivacaine (R) pharmacokinetics produced by the addition of epinephrine (E). METHODS: After Institutional Review Board approval, 18 ASA I boys received a caudal block (1 mL x kg(-1)) with either plain 0.2% R (Group E-) or with 0.2% R containing E (5 microg x mL(-1); Group E+). Venous blood samples were taken at zero, 15, 30, 60, 90, 120, 180, 240, 420, 720, 1440 min after caudal injection. Total R concentration in plasma was determined by high pressure liquid chromatography. Maximal concentration (C(max)) and time to peak concentration (T(max)) were obtained from the data, terminal half-life (T(1/2z)), clearance (Cl) and volume of distribution (Vd) were estimated by a non-compartmental approach. Subsequently, in order to determine the absorption rate (Ka) and to reduce to number of blood samples, 25 other children, receiving plain R and another group of 25 receiving the E solution were studied using a population approach (NONMEM). A one compartment model with first order absorption was used. The effect of weight, age and E on Cl, Vd and Ka was estimated. RESULTS: C(max) was significantly lower in Group E+ (0.93 mg x L(-1) +/- 0.29 vs 0.61 mg x L(-1) +/- 0.28, P = 0.05) and T(max) occurred later (124 min +/- 53 vs 47 min +/- 16, P = 0.003). Weight was a significant covariate for Cl and Vd while E significantly slowed R Ka [Group I Ka 0.025 min(-1) [coefficient of variation (CV) 21%] vs 0.078 min(-1) (CV 25%) in Group II]. CONCLUSION: The addition of E significantly modifies the pharmacokinetics of R injected caudally.     

Plasma lidocaine concentrations during epidural blockade with isoflurane or halothane anesthesia.

Because isoflurane maintains hepatic blood flow at higher flows than halothane, we proposed that the elimination of lidocaine would be different between these two volatile anesthetics. The plasma lidocaine concentrations were determined in 14 female patients undergoing epidural blockade plus isoflurane anesthesia and compared with those obtained during halothane anesthesia for lower abdominal surgery. General anesthesia was maintained with isoflurane (0.46% +/- 0.04% [mean +/- SE] inspired, n = 7) or halothane (0.48% +/- 0.05% inspired, n = 7) and 67% nitrous oxide in oxygen. All patients received 2% lidocaine solution, 10 mL as a bolus dose and continuous administration at a rate of 10 mL/h, through the epidural catheter. The plasma lidocaine concentrations over 180 min after the epidural injection in patients receiving isoflurane were similar to those in patients receiving halothane. The results suggest that low inspired concentrations of isoflurane do not reduce plasma lidocaine concentrations in patients during epidural blockade, compared with halothane.     

Pre- and intraoperative epidural ropivacaine have no early preemptive analgesic effect in major gynecological tumour surgery

PURPOSE: Thoracic epidural analgesia (TEA) is an established technique for postoperative pain relief after major abdominal surgery. However it is still under discussion whether pre-incisional TEA can reduce postoperative pain perception or postoperative analgesic consumption. METHODS: The present prospective, randomized, double-blind study was performed to investigate the effects of intra- and postoperative TEA vs only postoperative TEA using ropivacaine 0.375% in 30 women scheduled for major abdominal tumour surgery. Prior to induction of general anesthesia patients received an epidural bolus of 10 mL saline in Group I (GI) and 10 mL ropivacaine 0.375% in Group II (GII) followed by an infusion of 6 mL x hr(-1) of the respective solution during surgery. Postoperatively all patients received an epidural infusion of 6 mL x hr(-1) ropivacaine 0.375% during 24 hr followed by patient controlled epidural analgesia for the next 72 hr. Operative data, dynamic pain scores, consumption of local anesthetics and standardized supplemental analgesics were analyzed. RESULTS: No difference was seen between groups with respect to the amount of required postoperative local anesthetics and supplemental analgesics, pain scores and side effects during the first 96 hr following surgery except a reduction of intraoperative sufentanil consumption (GI: 143.2 +/- 52.6 vs GII: 73.3 +/- 32.6 microg, P < 0.001). CONCLUSION: Intraoperative TEA with ropivacaine 0.375% did not significantly reduce the amount of analgesics required after major abdominal gynecological tumour surgery.     

Comparative systemic toxicity of convulsant and supraconvulsant doses of intravenous ropivacaine, bupivacaine, and lidocaine in the conscious dog

This study evaluated the systemic toxicity, arrhythmogenicity, and mode of death of convulsant and supraconvulsant doses of lidocaine, bupivacaine, and ropivacaine. Experiments in awake dogs were designed to mimic the clinical situation of an accidental intravenous (IV) injection of local anesthetics. On the first experimental day, lidocaine (8 mg.kg-1.min-1), bupivacaine (2 mg.kg-1.min-1), and ropivacaine (2 mg.kg-1.min-1) were infused intravenously until seizures occurred (n = 6 for each group). The average dose and arterial plasma concentration at seizure onset was 20.8 +/- 4.0 mg/kg and 47.2 +/- 5.4 micrograms/mL for lidocaine, 4.31 +/- 0.36 mg/kg and 18.0 +/- 2.7 micrograms/mL for bupivacaine, and 4.88 +/- 0.47 mg/kg and 11.4 +/- 0.9 micrograms/mL for ropivacaine. The margin of safety between the convulsive and lethal doses was determined by administering two times the convulsive dose 24 h later. Two dogs given lidocaine died because of progressive hypotension, respiratory arrest, and finally cardiovascular collapse with an average peak plasma concentration (Cmax) of 469 micrograms/mL. No ventricular arrhythmias were observed in this group. Ventricular arrhythmias occurred in five of six dogs receiving bupivacaine. Four animals died because of hypotension, respiratory arrest, and cardiovascular collapse. One additional animal died because of ventricular fibrillation. The Cmax for bupivacaine was 70.1 +/- 14.6 micrograms/mL in nonsurvivors. In the ropivacaine group one animal died because of hypotension, respiratory arrest, and cardiovascular collapse (Cmax = 72.4 micrograms/mL). A surviving dog had transient premature ventricular contractions. Twenty-four hours later three times the convulsive dose was administered to the survivors.(ABSTRACT TRUNCATED AT 250 WORDS)     

Airway anesthesia alone does not explain attenuation of histamine-induced bronchospasm by local anesthetics: a comparison of lidocaine, ropivacaine, and dyclonine

BACKGROUND: Lidocaine inhalation attenuates histamine-induced bronchospasm while evoking airway anesthesia. Because this occurs at plasma concentrations much lower than those required for intravenous lidocaine to attenuate bronchial reactivity, this effect is likely related to topical airway anesthesia and presumably independent of the specific local anesthetic used. Therefore, the authors tested the effect of dyclonine, lidocaine, and ropivacaine inhalation on histamine-induced bronchospasm in 15 volunteers with bronchial hyperreactivity. METHODS: Bronchial hyperreactivity was verified by an inhalational histamine challenge. Histamine challenge was repeated after inhalation of dyclonine, lidocaine, ropivacaine, or placebo on 4 different days in a randomized, double-blind fashion. Lung function, bronchial hyperreactivity to histamine, duration of local anesthesia, and lidocaine and ropivacaine plasma concentrations were measured. Statistical analyses were performed with the Friedman and Wilcoxon rank tests. Data are presented as mean +/- SD. RESULTS: The inhaled histamine concentration necessary for a 20% decrease of forced expiratory volume in 1 s (PC20) was 7.0 +/- 5.0 mg/ml at the screening evaluation. Lidocaine and ropivacaine inhalation increased PC20 significantly to 16.1 +/- 12.9 and 16.5 +/- 13.6 mg/ml (P = 0.007), whereas inhalation of dyclonine and saline did not (9.1 +/- 8.4 and 6.1 +/- 5.0 mg/ml, P = 0.7268). Furthermore, in contrast to saline and lidocaine, inhalation of both ropivacaine and dyclonine significantly decreased forced expiratory volume in 1 s from baseline (P = 0.0016 and 0.0018, respectively). The longest lasting and most intense anesthesia developed after dyclonine inhalation (48 +/- 13 vs. 28 +/- 8 [lidocaine] and 25 +/- 4 min [ropivacaine]). CONCLUSION: Both lidocaine and the new amide local anesthetic ropivacaine significantly attenuate histamine-induced bronchospasm. In contrast, dyclonine, despite its longer lasting and more intense local anesthesia, does not alter histamine-evoked bronchoconstriction and irritates the airways. Thus, airway anesthesia alone does not necessarily attenuate bronchial hyperreactivity. Other properties of inhaled local anesthetics may be responsible for attenuation of bronchial hyperreactivity.     

Central nervous system side effects are less important afteriv regional anesthesia with ropivacaine 0.2% compared to lidocaine 0.5% in volunteers

PURPOSE: Following release of a double tourniquet for intravenous regional anesthesia (IVRA), ropivacaine was shown to have a longer duration of action and less central nervous system (CNS) side effects than lidocaine. This study examines the correlation of CNS side effects to plasma levels of lidocaine 0.5% and ropivacaine 0.2% when injected intravenously for IVRA. METHODS: In a double-blind, cross-over study, ten volunteers received IVRA with 40 mL ropivacaine 0.2% or lidocaine 0.5% at least four days apart. Both cuffs of a double-cuff tourniquet remained inflated until they could no longer be tolerated. The incidence, duration and intensity of CNS side effects were recorded at three, ten, and 30 min after tourniquet release and correlated with simultaneous venous blood samples. RESULTS: There was a lower incidence of CNS side effects with ropivacaine (6/10 volunteers) when compared to lidocaine (10/10 volunteers). There was also less duration of these side effects (mean +/- SD, 5.1 +/- 5.2 min vs 11.7 +/- 6.7 min). Measured total plasma levels were highest at ten minutes with ropivacaine 0.2% (1.2 +/- 0.3 microg.mL(-1)) and at three minutes with lidocaine 0.5% (1.7 +/- 0.6 microg.mL(-1)). Peak CNS symptoms correlated with measured venous plasma levels for lidocaine, but occurred earlier with ropivacaine. CONCLUSIONS: We observed a lower incidence of CNS side effects with ropivacaine as compared to lidocaine. Although ropivacaine's greater lipid solubility should, theoretically, lead to more CNS side effects, this was, likely, offset by slower release from tissues and lesser percentage of unbound (free) drug.     

A prospective study comparing the analgesic efficacy of levobupivacaine, ropivacaine and bupivacaine in pediatric patients undergoing caudal blockade

BACKGROUND: The aim of our study was to compare postoperative analgesic efficacy, analgesic duration and motor blockade of levobupivacaine, ropivacaine and bupivacaine administered caudally in equal concentrations to children undergoing elective minor surgery. METHODS: In the study, 182 children, aged 1-7 years, undergoing either inguinal hernia repair or orchidopexy, were randomly allocated to one of the three groups. They received via a caudal extradural either 1 ml x kg(-1) levobupivacaine 0.2% (Group L) or 1 ml x kg(-1) ropivacaine 0.2% (Group R) or 1 ml x kg(-1) bupivacaine 0.2% (Group B). RESULTS: No statistically significant difference was noted in age, weight, duration of the operation or level of the caudal block between the groups. The onset of analgesia was significantly later after levobupivacaine. Postoperative pain scoring evaluated with Children's and Infant's Postoperative Pain Scale observational scale showed no statistical difference between groups. Median postoperative analgesia was 5.75 h (SEMed: +/- 0.65) in Group L, 5.7 h (SEMed: +/- 0.8) in Group R and 5.35 h (SEMed: +/- 1.3) in Group B the difference being statistically nonsignificant. CONCLUSIONS: The degree of motor block was significantly less after ropivacaine and levobupivacaine during the first 2 h postoperatively.     

Patient-controlled epidural analgesia reduces analgesic requirements compared to continuous epidural infusion after major abdominal surgery

PURPOSE: To compare the quality of pain relief and incidence of side effects between 24-hr postoperative continuous epidural infusion (CEI) and subsequent patient-controlled epidural analgesia (PCEA) with different analgesics after major abdominal surgery. METHODS: Twenty-eight women undergoing extended gynecological tumour surgery received postoperative CEI with 0.15 mL x kg(-1) x hr(-1) 0.2% ropivacaine (R: n = 14) or 0.125% bupivacaine plus 0.5 micro g x mL(-1) sufentanil (BS: n = 14) during 24 postoperative hours. Twenty-four hours later, postoperative pain management was switched to PCEA without background infusion and 5 mL single bolus application of R or BS every 20 min at most. Visual analogue scales (VAS; 1-100 mm) were assessed by patients at rest and on coughing after 24 hr of CEI and PCEA. Side effects, doses of local anesthetics and opioids were recorded and plasma concentrations of total and unbound ropivacaine and bupivacaine were measured. RESULTS: Patients required lower doses of each respective analgesic medication with PCEA (R: 108 +/- 30 mL; BS: 110 +/- 28 mL) than with CEI (R: 234 +/- 40; BS: 260 +/- 45; P < 0.01). Ropivacaine plasma concentrations were lower 24 hr after PCEA when compared with CEI (P < 0.01). No patient after PCEA but two after CEI (n = 4; NS) presented motor block. PCEA with R provided better postoperative pain relief than CEI (37 +/- 32 vs 59+/-27, P < 0.05). No difference in parenteral opioid rescue medication between CEI and PCEA was seen. CONCLUSION: PCEA in comparison to preceding CEI provides equivalent analgesia with lower local anesthetic doses and plasma levels, and without motor blocking side effects, irrespective of the applied drug regimen.     

The P-glycoprotein inhibitor quinidine decreases the threshold for bupivacaine-induced, but not lidocaine-induced, convulsions in rats

PURPOSE: To examine whether inhibition of P-glycoprotein (P-gp) activity by quinidine affects the central nervous system toxicity of lidocaine and racemic bupivacaine (bupivacaine). METHODS: Forty male Sprague-Dawley rats were randomly divided into four groups (n = 10). Fifteen minutes following administration of 15 mg x kg(-1) of quinidine (QL and QB groups) or saline (L and B groups), lidocaine (L and QL groups, 4 mg x kg(-1) x min(-1)) or bupivacaine (B and QB groups, 1 mg x kg(-1) x min(-1)) was infused until convulsions occurred. Concentrations of lidocaine and its primary metabolite, monoethylglycinexylidide (MEGX) and bupivacaine in plasma and in the brain at the onset of convulsions were measured by high-performance liquid chromatography. RESULTS: There were no differences in the dose of lidocaine required to induce convulsions between the L and QL groups. There were no differences in the concentrations of total (L = 17.2 +/- 3.5, QL = 16.6 +/- 2.6 micro g x mL(-1)) or unbound lidocaine (L = 7.8 +/- 2.5, QL = 7.3 +/- 2.3 micro g x mL(-1)), total (L = 1.2 +/- 0.5, QL = 1.3 +/- 0.7 micro g x mL(-1)) or unbound MEGX (L = 0.9 +/- 0.5, QL = 0.8 +/- 0.4 micro g x mL(-1)) in plasma, total lidocaine or MEGX in the brain at the onset of convulsions between the L and QL groups. The dose of bupivacaine required to induce convulsions was comparable in the B and QB groups. At the onset of convulsions, plasma concentrations of both total (B = 4.9 +/- 1.1, QB = 4.0 +/- 0.6 micro g x mL(-1), P = 0.03) and unbound bupivacaine (B = 1.4 +/- 0.6, QB = 0.9 +/- 0.2 micro g x mL(-1), P = 0.02) were significantly lower in the QB group than in the B group. There were no differences in concentration of total bupivacaine in the brain between the B and QB groups. CONCLUSION: These results suggest that quinidine inhibited P-gp activity, resulting in increased brain/plasma concentration ratio of bupivacaine, but not of lidocaine, and decreased the threshold of plasma concentration for bupivacaine-induced convulsions.     

Epinephrine increases the extracellular lidocaine concentration in the brain: a possible mechanism for increased central nervous system toxicity

BACKGROUND: Local anesthetics exert central nervous system (CNS) toxicity by inhibiting intracerebral neuronal activity, while epinephrine augments the CNS toxicity of intravenously administered local anesthetics. Viewed together, increases of extracellular concentrations of local anesthetics in the brain may be directly associated with increased CNS toxicity. The authors examined the hypothesis that epinephrine enhances the CNS toxicity of lidocaine by increasing the extracellular concentration in the brain. METHODS: An awake, spontaneously breathing rat model was used. Twenty male Sprague-Dawley rats received an intravenous infusion of lidocaine (3 mg x kg x min; group C) or lidocaine with epinephrine (3 mg x kg x min and 2 microg x kg x min, respectively; group E) for 10 min (n = 10 in each group). Effects of epinephrine on the convulsive dose and concentrations of total (protein-bound and unbound) and unbound lidocaine in plasma were examined. Concentrations of extracellular lidocaine in the cerebral nucleus accumbens were quantitatively determined by a microdialysis method. RESULTS: The convulsive dose of lidocaine was significantly lower in group E than in group C (22.4 +/- 5.5 vs. 27.9 +/- 3.1 mg/kg, respectively; P < 0.05). Overall concentrations and area under the plasma concentration-versus-time curve of unbound lidocaine in group E were significantly higher than those in group C. Concentrations of extracellular lidocaine in the nucleus accumbens in group E were comparable to those of unbound fraction in plasma and were also significantly higher than those in group C. CONCLUSIONS: Concomitant administration of epinephrine significantly enhanced the CNS toxicity of intravenously administered lidocaine. Increased extracellular concentration in the brain would be related to this mechanism.     

Sufentanil modifies the antibacterial activity of bupivacaine and ropivacaine

PURPOSE: The purpose of our study was to investigate the effect on the growth of Escherichia coli (E. coli), Staphylococcus aureus (S. aureus), and Enterococcus faecalis (E. faecalis) of bupivacaine at a final concentration of 0.77 mg.mL(-1), ropivacaine at 1.2 mg.mL(-1), and sufentanil at 0.38 and 0.5 microg.mL(-1) (alone or in combination with bupivacaine and ropivacaine). METHODS: The strains were diluted to approximately 3 x 10(4) cfu.mL(-1) in Mueller-Hinton broth. The anesthetics (0.5 mL) were incubated with the bacterial suspensions (0.5 mL) for 24 hr at 37 degrees C. RESULTS: Bupivacaine inhibited the growth of E. coli (59 +/- 0.8%; P < 0.05) and S. aureus (22 +/- 3.6%; P < 0.05). Ropivacaine also inhibited the growth of E. coli (41 +/- 1.2%; P < 0.05) and S. aureus (25.5 +/- 4.1%; P < 0.05). Both anesthetics were ineffective against E. faecalis. Sufentanil only inhibited S. aureus (13.8 +/- 3.1%; P < 0.05) at a concentration of 0.5 microg.mL(-1). Sufentanil modified the antibacterial activity of bupivacaine and ropivacaine. It increased the inhibitory effect of bupivacaine on E. faecalis and S. aureus by 10 +/- 2.1% (P < 0.05) and on E. coli by 7% (P < 0.05). Sufentanil did not increase the inhibitory effect of ropivacaine on the growth of S. aureus. On the other hand, sufentanil reduced the inhibitory effect of ropivacaine on E. coli by 11% (P < 0.05). CONCLUSION: Both bupivacaine and ropivacaine alone or combined with sufentanil inhibited the growth of E. coli and S. aureus. E. faecalis was partially sensitive to a bupivacaine + sufentanil mixture. Sufentanil had a partial synergistic effect on bupivacaine and a partial antagonistic effect on ropivacaine's antibacterial activity.     

Epidural anesthesia with lidocaine reduces propofol injection pain

PURPOSE: To determine whether epidural lidocaine reduces the severity of propofol injection pain compared with iv lidocaine. METHODS: A prospective, randomized double-blind clinical study was conducted in 120 female patients scheduled for elective gynecological laparotomy. A lumbar epidural catheter and an iv catheter placed in the cephalic vein of the non-dominant hand were used in all patients. Patients of the control group (Group C) were given epidural normal saline followed by iv normal saline then iv propofol. Patients of Group E were given epidural 2% lidocaine (0.08 mL.cm(-1)) followed by iv normal saline and then propofol. Patients of Group V were given epidural normal saline followed by iv 2% lidocaine (0.05 mL.kg(-1)) then propofol. Pain was scored as no pain=0, minimal pain=1, moderate pain=2, severe pain=3. RESULTS: The pain scores, in group E; 1 (0-2) and group V; 2 (0-2), were significantly lower than in group C; 2 (1-3); median (25th-75th percentile) (P <0.001). There was no difference in pain score between groups E and V The plasma lidocaine concentration 15 min after epidural lidocaine was 2.74 +/- 0.54 microg.ml(-1), compared with 1.54 +/- 0.31 microg.mL(-1) at three minutes after iv lidocaine. CONCLUSION: Epidural and iv lidocaine equally reduced the severity of propofol injection pain despite higher lidocaine plasma concentrations in epidurally administered lidocaine.     

Combination of hyperbaric lidocaine and ropivacaine in spinal anaesthesia for day surgery

BACKGROUND AND OBJECTIVE: Motor function recovers rapidly but the extended duration of sensory block after spinal anaesthesia with hyperbaric ropivacaine may delay patients' ambulation after surgery. We tested whether compensating a reduction of the ropivacaine dose with a small dose of lidocaine would be adequate for surgery and shorten recovery from spinal anaesthesia. METHODS: Fifty-six consecutive outpatients, who were scheduled for lower extremity surgery under spinal anaesthesia, were randomized into two groups to receive either a hyperbaric solution of lidocaine 20 mg and ropivacaine 5 mg (Group LR) or hyperbaric ropivacaine 10 mg (Group R). Sensory block was tested with pinprick and motor block on the Bromage scale at 5-min intervals until 30 min, then at 15-min intervals until 90 min, and thereafter at 30-min intervals until full bilateral recovery. Blinded interviews were performed on the first and seventh postoperative day. RESULTS: The groups did not differ significantly regarding success of sensory block reaching T10 dermatome on the operative side, 24 (86%) in Group LR and 23 (82%) in Group R, median (range) onset time 5 (5-20) vs. 10 (5-25) min or median duration of T10 sensory block 68 (5-115) vs. 50 (20-115) min, respectively. Two patients in each group required general anaesthesia. Recovery did not differ between the groups, median time of full motor recovery was 75 min in both groups, sensory recovery of S2 2.5 h vs. 2.8 h, first voluntary micturition 4.2 (2.2-6.1) vs. 4.5 (2.4-6.6) h in the LR vs. R Group, respectively. Transient neurological symptoms did not appear. CONCLUSION: It is concluded that spinal anaesthesia with hyperbaric lidocaine 20 mg+ropivacaine 5 mg and hyperbaric ropivacaine 10 mg was quite similar regarding frequency, onset, duration of T10 dermatome sensory block and recovery. The patients would have been ready for discharge after voluntary micturition, 4.2-4.5 h from the subarachnoid injection of local anaesthetics.     

Effects of bupivacaine, levobupivacaine and ropivacaine on myocardial relaxation

PURPOSE: Ropivacaine and levobupivacaine were developed to reduce the risk of occasional toxicity reported with bupivacaine. While the effects of long-acting local anesthetics (LAAs) on myocardial contractility (inotropy) are well described, their effects on relaxation (lusitropy) remain largely unknown. The present study aimed to compare the effects of LAAs on rat myocardium. METHODS: Left ventricular papillary muscles of male Wistar rats were used to compare the inotropic and lusitropic responses of increasing concentrations of LAAs (10(-8) to 10(-3) M) under isometric and isotonic conditions. Data are mean % (SD) of baseline value. RESULTS: Long-acting local anesthetics induced a significant impairment of relaxation in isotonic and isometric conditions. As compared to ropivacaine, bupivacaine and levobupivacaine induced greater negative lusitropic effects in isotony [at 10(-3) M, maximum unloaded shortening velocity ((max)Vr) = 27 +/- 11 vs 13 +/- 6 and 8 +/- 5%] and isometry (at 10(-3) M, time-to-half-relaxation: 106 +/- 10 vs 127 +/- 17 and 133 +/- 17%). When the comparison was made with equipotent concentrations, the negative lusitropic effects induced with levobupivacaine were significantly greater than those of bupivacaine and ropivacaine in isometric and isotonic conditions (at 10(-3) M, (max)Vr = 7 +/- 4 vs 13 +/- 6 and 17 +/- 4 %). As previously described, LAAs also induced concentration-dependent negative inotropic effects that were greater for levobupivacaine compared to equivalent or equipotent concentrations of bupivacaine and ropivacaine. CONCLUSIONS: Long-acting local anesthetics induce marked negative inotropic and lusitropic effects. Among LAAs, levobupivacaine exerts the greater depressant effects. Impairment of calcium handling and sarcoplasmic reticulum could explain the differential responses to local anesthetics.     

Effectiveness of local anaesthesia techniques in patients undergoing transrectal ultrasound-guided prostate biopsy: A prospective randomized study

AIM: This study was designed to compare the effectiveness of intrarectal lidocaine gel versus periprostatic lidocaine injection during transrectal ultrasound (TRUS)-guided prostate biopsy. METHODS: Ninety men undergoing transrectal prostate biopsy from July through December 2004 were randomized into three groups of 30 patients each. Before the biopsy, patients in Group 1 received 20 mL of 2% lidocaine gel intrarectally; patients in Group 2 received 5 mL (2.5 mL per side) of 2% lidocaine solution injected near the junction of the seminal vesicle with the base of the prostate (along the neurovascular bundles), and patients in Group 3 (control group) received 5 mL (2.5 mL per side) of normal saline injected along the neurovascular bundles. Pain level after the biopsy was assessed using a 10-point linear visual analog scale (VAS). Results were statistically compared by the Wilcoxon Rank Sum test. RESULTS: Patients in Group 2 had significantly lower VAS scores than those in Group 3 (3.6 +/- 2.1 vs 5.8 +/- 1.9, P < 0.0001), but those in Group 1 did not (5.5 +/- 2.7 vs 5.8 +/- 1.9, P = 0.67). Gross hematuria, rectal bleeding, and hemospermia occurred in 36 (40.0%), 6 (7%) and 5 (6%) patients. One patient had temporary vasovagal syncope. No patient reported febrile urinary tract infection or urinary retention. CONCLUSIONS: Periprostatic injection of local anaesthetic is a safe technique that significantly reduces pain during prostate biopsy, whereas intrarectal lidocaine injection did not reduce pain. This safe, simple technique should be applied in men undergoing TRUS-guided prostate biopsy to limit patient discomfort.     

Airway Anesthesia Alone Does Not Explain Attenuation of Histamine-induced Bronchospasm by Local Anesthetics: A Comparison of Lidocaine, Ropivacaine, and Dyclonine

Background: Lidocaine inhalation attenuates histamine-induced bronchospasm while evoking airway anesthesia. Because this occurs at plasma concentrations much lower than those required for intravenous lidocaine to attenuate bronchial reactivity, this effect is likely related to topical airway anesthesia and presumably independent of the specific local anesthetic used. Therefore, the authors tested the effect of dyclonine, lidocaine, and ropivacaine inhalation on histamine-induced bronchospasm in 15 volunteers with bronchial hyperreactivity.

Methods: Bronchial hyperreactivity was verified by an inhalational histamine challenge. Histamine challenge was repeated after inhalation of dyclonine, lidocaine, ropivacaine, or placebo on 4 different days in a randomized, double-blind fashion. Lung function, bronchial hyperreactivity to histamine, duration of local anesthesia, and lidocaine and ropivacaine plasma concentrations were measured. Statistical analyses were performed with the Friedman and Wilcoxon rank tests. Data are presented as mean +/- SD.

Results: The inhaled histamine concentration necessary for a 20% decrease of forced expiratory volume in 1 s (PC20) was 7.0 +/- 5.0 mg/ml at the screening evaluation. Lidocaine and ropivacaine inhalation increased PC20 significantly to 16.1 +/- 12.9 and 16.5 +/- 13.6 mg/ml (P = 0.007), whereas inhalation of dyclonine and saline did not (9.1 +/- 8.4 and 6.1 +/- 5.0 mg/ml, P = 0.7268). Furthermore, in contrast to saline and lidocaine, inhalation of both ropivacaine and dyclonine significantly decreased forced expiratory volume in 1 s from baseline (P = 0.0016 and 0.0018, respectively). The longest lasting and most intense anesthesia developed after dyclonine inhalation (48 +/- 13 vs. 28 +/- 8 [lidocaine] and 25 +/- 4 min [ropivacaine]).     

The pharmacokinetics of ropivacaine after four different techniques of brachial plexus blockade

Arterial plasma concentrations of ropivacaine were measured after brachial plexus blockade using four different approaches: lateral interscalene (Winnie), posterior interscalene (Pippa), axillary and vertical infraclavicular. Four groups of 10 patients were given a single 3.75 mg.kg(-1) injection of ropivacaine 7.5 mgxml(-1). The pharmacokinetics of ropivacaine were evaluated for 1 h after local anaesthetic injection. The supraclavicular techniques (lateral and posterior) were associated with earlier and higher peak plasma concentrations of local anaesthetic than the infraclavicular techniques (axillary and vertical infraclavicular): mean (SD) values = 3.30 (0.65) microgxml(-1) vs 2.55 (0.62) microgxml(-1) (p = 0.001) in 13.4 (6.9) min vs 25.0 (10.8) min (p = 0.0002). More ropivacaine is taken up by the systemic circulation in the first hour after the supraclavicular approaches; the mean (SD) area under the concentration-time curve was larger: 2.63 (0.51) microgxml(-1).h vs 2.10 (0.49) microgxml(-1).h (p = 0.002). These results show that the technique used for brachial plexus blockade significantly influences the systemic uptake of ropivacaine.