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Background: Recommendations regarding the technical aspects of nerve stimulator-assisted nerve localization are conflicting. The objectives of this study were to determine whether the placement of the cutaneous electrode affects nerve stimulation and to determine the duration and intensity of an electrical stimulus that allows nerve stimulation with minimal discomfort., Methods: Ten healthy volunteers underwent an interscalene and a femoral nerve block. After obtaining a clearly visible motor response of the biceps (interscalene) and quadriceps (femoral) muscles at the minimal current (0.1 ms, 2 Hz), the position of the cutaneous electrode was varied. Next, the duration of the stimulating current was set at 0.05, 0.1, 0.3, 0.5, or 1.0 ms, in random order. Intensity of the motor response and discomfort on stimulation were recorded., Results: The minimal current at which a visible motor response was obtained was 0.32 +/- 0.1 mA (0.23-0.38 mA) for the inter-scalene block and 0.29 +/- 0.1 mA (0.15-0.4 mA) for the femoral block. Changing the position of the return electrodes did not result in any change in the grade of the motor response or in the current required to maintain it. Currents of longer duration caused discomfort and more forceful contraction at a lower current intensity as compared with currents of shorter duration (P < 0.01). When the current was adjusted to maintain the same visible motor response, there was no significant discomfort among studied current durations., Conclusion: Site of placement of the cutaneous electrode is not important when constant current nerve stimulators are used during nerve localization in regional anesthesia. There is an inverse relation between the current required to obtain a visible motor response and current duration. Selecting a current duration between 0.05 and 1.0 ms to specifically stimulate sensory or motor components of a mixed nerve does not seem to be important in clinical practice.

Background: Levobupivacaine, the single levorotatory isomer of bupivacaine, is now available for clinical use. This study was undertaken to determine whether pregnancy affects the systemic toxicity of levobupivacaine and to compare the systemic toxicity of levobupivacaine with that of bupivacaine and ropivacaine., Methods: Chronically prepared nonpregnant and pregnant sheep were randomized to receive an intravenous infusion of 0.52% levobupivacaine, 0.52% bupivacaine, or 0.50% ropivacaine at a constant rate of 0.1 ml x kg(-1) x min(-1) until circulatory collapse. The investigators were blinded to the identity of the local anesthetic. Physiologic parameters, including cardiac rhythm, were monitored throughout the study. Arterial blood samples were obtained before infusion and at the onset of toxic manifestations. These were analyzed for total and free serum drug concentrations as well as arterial blood pH and gas tensions., Results: The doses of all three drugs required to produce convulsions were lower in pregnant than nonpregnant animals. However, as the infusion continued, there were no significant differences between pregnant and nonpregnant ewes in the dose of drug required to produce more advanced manifestations of toxicity: hypotension, apnea, and circulatory collapse. The mean cumulative dose and serum concentration at each toxic manifestation was lowest for bupivacaine, intermediate for levobupivacaine, and highest for ropivacaine in both pregnant and nonpregnant animals. For all three local anesthetics, there were no significant differences between pregnant and nonpregnant ewes in total and free serum drug concentrations, except that at circulatory collapse, these were higher in pregnant animals., Conclusions: Pregnancy increases the risk of convulsions but not of more advanced manifestations of local anesthetic toxicity. The risk of toxicity is greatest with bupivacaine and least with ropivacaine. However, in actual clinical practice, the risk of systemic toxicity may also be affected by the relative potency and effectiveness of these drugs.

Background: The purposes of this study were to assess the effects of levobupivacaine on uterine blood flow and fetal well-being and to compare its placental transfer with that of bupivacaine and ropivacaine., Methods: After a control period, pregnant ewes that were fitted with instruments for long-term monitoring were randomized to receive a two-step intravenous infusion of levobupivacaine, bupivacaine, or ropivacaine, in a blinded manner, for 1 h. Maternal and fetal hemodynamics were monitored during the study. Arterial blood samples were drawn at 30 and 60 min of infusion from the mother and fetus to determine the acid-base status (60 min only) and serum drug concentrations. The fetal brain, heart, liver, lungs, adrenal glands, and kidneys were obtained to measure tissue drug levels., Results: Maternal blood pressure, central venous and intraamniotic pressures, acid-base status and uterine blood flow were unaffected by any drug infusion. In contrast to the other two local anesthetics, the infusion of bupivacaine was associated with a small but significant decrease in the ewe's heart rate. At the end of the study, the heart rate in the bupivacaine-treated animals was significantly less than in the animals treated with the other two drugs. All fetuses were in good condition at the start of study, and none of the local anesthetics affected fetal well-being. No significant differences were found among the three drugs in the maternal serum, fetal serum, fetal tissue concentrations, and tissue:serum concentration ratios., Conclusions: Levobupivacaine was similar to bupivacaine and ropivacaine in causing no important hemodynamic changes in the pregnant ewe and fetus. There were no significant differences in the fetal serum and tissue levels of the drugs.

Background: Ropivacaine is a new amide local anesthetic, having therapeutic properties similar to those of bupivacaine but with a wider margin of safety. Bupivacaine is probably the most commonly used drug in obstetric epidural analgesia, even though laboratory studies have suggested that pregnancy increases the cardiotoxicity of bupivacaine but not of other local anesthetics. The current study was designed to reevaluate, in a random and blinded fashion, the systemic toxicity of bupivacaine and ropivacaine in nonpregnant and pregnant sheep., Methods: Chronically prepared nonpregnant and pregnant ewes were randomized to receive an intravenous infusion of ropivacaine or bupivacaine at a constant rate of 0.5 mg.kg-1.min-1 until circulatory collapse. The investigators were blinded to the identity of local anesthetic. Heart rate, arterial blood pressure, and cardiac rhythm were monitored throughout the study. Arterial blood samples were obtained before infusion and at the onset of toxic manifestations, which appeared in the following sequence: convulsions, hypotension, apnea, and circulatory collapse. Serum drug concentrations and protein binding were determined. Blood pH and gas tensions were measured., Results: There were no significant differences between non-pregnant and pregnant animals in the doses or serum concentrations of either drug required to elicit toxic manifestations. In nonpregnant animals, similar doses and serum concentrations of ropivacaine and bupivacaine were associated with the onset of convulsions and circulatory collapse. In pregnant ewes, greater doses of ropivacaine as compared to bupivacaine were required to produce convulsions (7.5 +/- 0.5 vs. 5.0 +/- 0.6 mg.kg-1) and circulatory collapse (12.9 +/- 0.8 vs. 8.5 +/- 1.2 mg.kg-1). The corresponding serum concentrations of ropivacaine were similar to those of bupivacaine. Pregnancy did not affect the serum protein binding of either drug. The proportion of animals manifesting a malignant ventricular arrhythmia as the terminal event was similar among all groups., Conclusions: The systemic toxicity of ropivacaine or bupivacaine is not enhanced by gestation in sheep. This is in contrast to an earlier study in which the cardiotoxicity of bupivacaine was enhanced during ovine pregnancy. Greater doses of ropivacaine, as compared to bupivacaine, are needed to produce toxic manifestations in pregnant animals.

Ropivacaine is a new amide local anesthetic structurally related to bupivacaine and mepivacaine. Its potency and duration of action are similar to those of bupivacaine but its therapeutic index may be greater. Since pregnancy enhances the cardiotoxicity of bupivacaine, the current study was devised to compare the toxicity of ropivacaine in chronically instrumented nonpregnant and pregnant ewes during continuous intravenous infusion of the drug at the rate of 0.5 mg.kg-1.min-1. In all animals, symptoms of local anesthetic toxicity occurred in the usual order--convulsions, hypotension, apnea, and circulatory collapse. There were no significant differences between the two groups of animals in the doses and plasma concentrations of ropivacaine associated with each toxic manifestations. For example, circulatory collapse occurred at a mean dose of 11.3 +/- 1.1 mg.kg-1 in nonpregnant and 12.4 +/- 0.9 mg.kg-1 in pregnant animals, with corresponding plasma concentrations of 7.3 +/- 0.3 and 9.6 +/- 2.1 micrograms.ml-1 (P = not significant). Protein binding of ropivacaine in the concentration range associated with toxic manifestations was similar in sera obtained from nonpregnant and pregnant ewes. In conclusion, ovine pregnancy does not enhance the systemic toxicity of ropivacaine, possibly because of an absence of gestation-related increase in the availability of free drug.

The effects of lidocaine on the fetal circulatory responses to asphyxia were evaluated in chronically instrumented pregnant sheep. Twenty-six preparations were studied. Animals were assigned to one of three groups. The animals in group I (N = 10) did not have umbilical cord occluders placed. Lidocaine at 0.1 mg X kg-1 X min-1 was infused to the mother for 180 min. The animals in group II (N = 11) had an umbilical cord occluder, which was inflated to induce fetal asphyxia (PaO2 15 mmHg) for 90 min. Occlusion was then maintained for an additional 180 min while lidocaine at 0.1 mg X kg-1 X min-1 was infused. The animals in group III (N = 5) also had an umbilical cord occluder inflated for 90 min. While occlusion was maintained for an additional 180 min, saline was infused, in place of lidocaine. The infusion rate of lidocaine of 0.1 mg X kg-1 X min-1 over 180 min resulted in a steady-state arterial lidocaine blood concentration in the mother of approximately 2.15 micrograms/ml. Fetal circulatory responses to asphyxia were evaluated before and after maternal infusion of lidocaine or normal saline. Measurements included heart rate, blood pressure, arterial pH, and blood gases. Cardiac output and organ blood flow were determined using the radio-labelled microsphere technique. In general, arterial and tissue lidocaine concentrations in asphyxiated fetuses were higher than those in the nonasphyxiated ones, the differences being significant in the brain, heart, liver, and adrenal glands.(ABSTRACT TRUNCATED AT 250 WORDS)

The toxicity of mepivacaine in chronically instrumented nonpregnant and pregnant sheep was evaluated, and compared with data from previous studies of the toxicity of other local anesthetics. Thirteen preparations were studied, seven nonpregnant (NP) and six pregnant (P). Mepivacaine 2 mg.kg-1.min-1 was infused at a constant rate into the femoral vein until toxic manifestations occurred, in the following sequence: convulsions, hypotension, respiratory arrest, and circulatory collapse. The doses and plasma concentrations of mepivacaine necessary to produce toxic symptoms were similar in NP and P animals, whereas, in a previous study, pregnancy enhanced the cardiotoxicity of bupivacaine. No malignant ventricular arrhythmias were observed throughout the study. Protein binding of mepivacaine was also determined in sera from nonpregnant and pregnant ewes and compared with that for bupivacaine. Serum protein binding of mepivacaine was not reduced in pregnancy at the drug concentrations associated with toxic symptoms; at circulatory collapse, it was approximately 22% in NP and P. In contrast, the proportion of bound bupivacaine was 73% in NP and 51% in P, a significant difference. These protein binding data suggest that, although lethal concentrations of bupivacaine, determined in the previous study, were higher in NP than in P animals, concentrations of free drug were similar. Thus, the difference between the two drugs may be related to gestational increases in the availability of free drug in the case of bupivacaine.

Lidocaine was infused at a constant rate of 0.1 mg.kg-1.min-1 for 180 min into 12 chronically prepared pregnant sheep while asphyxia, induced by partial umbilical cord occlusion, was maintained in the premature fetus (80% of gestation). In five similar preparations saline instead of lidocaine was infused into the mother for 180 min. Maternal and fetal arterial blood pressure, heart rate, pHa, PaCO2, and PaO2 were monitored, and fetal cardiac output and the distribution of blood flow to fetal organs were measured, using labeled microspheres, before and after asphyxia and again after maternal infusion of lidocaine or saline. Maternal and fetal arterial blood and maternal urine were obtained at intervals for determination of lidocaine concentrations and urinary drug clearance. At the end of infusion, these animals were killed and tissues dissected for determination of lidocaine concentrations and organ blood flow. Maternal and fetal lidocaine plasma concentrations at steady state were 2.32 +/- 0.12 and 1.23 +/- 0.17 microgram/ml, respectively, similar to those seen during human epidural anesthesia. Asphyxia resulted in a significant drop in fetal heart rate and increased blood flow to the brain, heart, and adrenals. Asphyxia and saline did not produce additional deterioration of the fetus, but asphyxia and lidocaine led to a significant increase in PaCO2 and decreases in pHa, mean arterial pressure, and blood flows to the brain, heart, and adrenals. It is concluded that the immature fetus loses its cardiovascular adaptation to asphyxia when exposed to clinically acceptable plasma concentrations of lidocaine obtained transplacentally from the mother.

The pharmacokinetics and pharmacodynamics of lidocaine were studied in nine chronically prepared pregnant ewes and their fetuses at a mean ( +/- SE) gestation of 119 +/- 1.0 days, and the results were compared to the data previously published for ten animals at 138 +/- 1.2 days of gestation (term 148 days). Lidocaine was infused intravenously to the mother at a constant rate of 0.1 mg.kg-1.min-1 over a period of 180 min, in order to reach a steady-state maternal plasma lidocaine concentration of approximately 2 micrograms/ml. Maternal and fetal blood samples and maternal urine were collected at intervals throughout the infusion for determination of pH, blood gases, and lidocaine concentrations. Maternal and fetal heart rate, blood pressure, and intraamniotic pressure were continuously recorded. Fetal cardiac output and organ blood flow were determined before and at the end of lidocaine infusion using radionuclide-labeled microspheres. Lidocaine tissue concentrations were determined in several maternal and fetal organs excised at the end of infusion. In both groups, the steady-state plasma concentrations of lidocaine were similar; namely, 2.3 +/- 0.17 and 2.1 +/- 0.21 micrograms/ml in preterm and term ewes, respectively. There were also no significant differences in steady-state plasma drug concentrations in preterm and term fetuses (1.3 +/- 0.11 and 1.2 +/- 0.15 micrograms/ml). The mean fetal maternal concentration ratios (F/M) were the same; namely, 0.6. Maternal urinary excretion of lidocaine correlated with urine pH, being greater in the more acid urine. Tissue uptake of drug tended to be higher in the preterm than term mothers, but only significantly so in the brain and adrenals.(ABSTRACT TRUNCATED AT 250 WORDS)