Addition of bicarbonate to plain bupivacaine does not significantly alter the onset or duration of plexus anesthesia.

BACKGROUND AND OBJECTIVES: In an effort to elucidate further the effect of alkalinization of bupivacaine on its anesthetic effect, a study was undertaken using alkalinized and non-alkalinized bupivacaine for lumbar plexus block and comparing the results with those obtained previously with brachial plexus block. METHODS: Thirty consenting adult patients about to undergo lower extremity surgery under regional anesthesia were selected for the study. All of the patients received an inguinal paravascular lumbar plexus block ("3-in-1 block"), along with a sciatic block to allow the anticipated surgery to be carried out. The patients were divided into two groups, one receiving plain "alkalinized" 0.5% bupivacaine; the other receiving plain "non-alkalinized" 0.5% bupivacaine. After each lumbar plexus block, the onset and duration of analgesia and anesthesia of the nerves derived from the lumbar plexus were determined by an independent investigator who was unaware of which solution had been administered. RESULTS: There was no statistically significant difference between the two groups with respect to the onset or duration of anesthesia and analgesia. CONCLUSIONS: The data obtained in the present study indicate that alkalinization of non-epinephrine-containing bupivacaine does not reduce the latency or increase the duration of analgesia or anesthesia after lumbar plexus block. Since most of the studies that do show such an effect of alkalinization were carried out using epinephrine-containing bupivacaine, it is postulated that in those studies alkalinization contributed to the decrease in latency and increase in duration, not so much by providing an increased amount of local anesthetic in the free base form, but by reactivating epinephrine's vasoconstrictor activity, which is inactivated by a low pH.

Cardiac electrophysiologic effects of articaine compared with bupivacaine and lidocaine.

Articaine is a local anesthetic structurally different from lidocaine and bupivacaine in that it contains a thiophene ring. We compared its cardiodepressant effects with those of lidocaine and bupivacaine in a randomized, blinded study using the isolated rabbit heart preparation. The hearts were removed quickly from thiamylal anesthetized/killed animals. The right septal wall was placed in a warm, aerated, Tyrode's solution-perfused chamber. The effects of the three local anesthetics on action potentials from the Purkinje fiber (PF) and ventricular muscle (VM) tissues were determined. Bupivacaine (17.4 microM) and articaine (141 microM) depressed action potential overshoot, amplitude, and maximal rate of depolarization (Vmax) by similar amounts. Bupivacaine's effects persisted significantly longer than articaine and lidocaine (P < 0.05). Rate-dependent decreases in steady-state (SS) Vmax were obtained with all three drugs. At their highest concentrations, bupivacaine (17 microM) and lidocaine (85 microM) produced decreases in SS Vmax from the first Vmax response. However, articaine (141 microM) increased SS Vmax at 1 and 2 Hz and only decreased SS Vmax at 3 Hz. During superfusion of a "bolus concentration" of the local anesthetics, bupivacaine blocked PF-VM conduction significantly longer than either articaine or lidocaine (P < 0.001). Articaine, at ten times its observed clinical blood concentration was significantly less cardiodepressant in these in vitro experiments than bupivacaine at five times its observed clinical blood concentration.

Effect of progesterone on the cardiac electrophysiologic alterations produced by ropivacaine and bupivacaine.

Bupivacaine-induced cardiotoxicity is enhanced in pregnant laboratory animals and in progesterone-pretreated isolated cardiac tissues. Ropivacaine is a new local anesthetic chemically related to bupivacaine. Although clinically equipotent with bupivacaine, ropivacaine is less cardiodepressant. Progesterone levels are elevated during pregnancy, and exogenously increasing progesterone levels in rabbits has increased bupivacaine's depressive effects on excitability. In neural tissues, bupivacaine's increased onset of block and depression of compound action potentials in tissues from progesterone-treated animals was similar to its effect in nerves from pregnant animals. This study determined whether exogenously increased progesterone levels can increase myocardial sensitivity to ropivacaine. Female ovariectomized rabbits were pretreated with progesterone for 4 days. After killing, the hearts were removed and Purkinje fibers (PFs) and ventricular muscle (VM) action potential parameters recorded. Tissues from animals receiving either progesterone or placebo were exposed to either ropivacaine or bupivacaine at concentrations ranging from 3.5 to 18.7 microM. Preparations were routinely paced at 2 Hz except where rate-dependent effects on the maximal rate of depolarization of phase zero (Vmax) were determined. Progesterone increased depression of myocardial Vmax only to bupivacaine (P less than 0.05). Ropivacaine was generally 3-5 times less potent in depressing cardiac electrophysiologic parameters. Bupivacaine demonstrated rate-dependent depression of Vmax that at higher frequencies was greater than ropivacaine's effects (P less than 0.05). Ropivacaine is less cardiodepressant than bupivacaine in this isolated PF-VM preparation. Exogenously increasing progesterone levels in vivo does not increase ropivacaine's depression of myocardial Vmax in isolated PF-VM tissues as it does to bupivacaine.(ABSTRACT TRUNCATED AT 250 WORDS)

Chronotropic and inotropic effects of ropivacaine, bupivacaine, and lidocaine in the spontaneously beating and electrically paced isolated, perfused rabbit heart.

BACKGROUND AND OBJECTIVES: The purpose of this study was to compare the inotropic and chronotropic effects of ropivacaine, bupivacaine, and lidocaine in an isolated, spontaneously beating rabbit heart preparation. The ability to electrically pace the heart in the presence of local anesthetic also was examined. METHODS: Hearts were perfused with Krebs-Henseleit solution, then exposed to ropivacaine or bupivacaine at 1, 6, or 13 micrograms/ml or lidocaine at 6, 20, or 40 micrograms/ml (n = 6, each concentration). Left ventricular pressure, left ventricular dP/dt (rate of change derivation from analog waveform of the left ventricular pressure wave), pulmonary artery flow, oxygen consumption, and electrocardiogram were monitored throughout the studies. Drug exposure was for 30 minutes or until a 75% decrease in left ventricular pressure occurred. RESULTS: All preparations were exposed to 1 microgram/ml bupivacaine or ropivacaine and 6 micrograms/ml lidocaine for the full 30 minutes. At the intermediate concentrations, only one of six bupivacaine preparations (6 micrograms/ml) survived the full 30-minute exposure period, compared to six of six preparations for both ropivacaine (6 micrograms/ml) and lidocaine (20 micrograms/ml; p less than 0.05). Similar results were found with exposure to the highest concentrations of these local anesthetics. No electrocardiogram changes were observed with any of the three lidocaine concentrations or with the lowest ropivacaine and bupivacaine concentration. At the intermediate concentration, atrioventricular conduction changes were seen with bupivacaine in five of six preparations, compared to one of six ropivacaine preparations (p less than 0.05). With the high concentration, ventricular tachycardia occurred in four of six bupivacaine preparations, compared to zero of six with ropivacaine (p less than 0.05). In general, left ventricular systolic pressure, dP/dt, heart rate, and oxygen consumption were reduced during exposure to all concentrations of the three local anesthetics. The most profound effects (greater than 75% reduction) were seen with 13 micrograms/ml bupivacaine. All local anesthetics caused an increase in the voltage required to pace the hearts via the atria. With 6 micrograms/ml bupivacaine and 13 micrograms/ml ropivacaine, 50% of the preparations could not be paced via the atria; and with 13 micrograms/ml bupivacaine, none of the preparations could be paced via the atria. The depressant effects of 6 micrograms/ml bupivacaine approximated those seen with 13 micrograms/ml ropivacaine. The reductions in oxygen consumption and pulmonary artery flow were not significantly different between treatment groups. CONCLUSION: The results of this study indicate that bupivacaine is more cardiodepressant and arrhythmogenic than either ropivacaine or lidocaine.

Effects of progesterone on the cardiac electrophysiologic action of bupivacaine and lidocaine.

Pregnancy is accompanied by an increased cardiac and neural sensitivity to some local anesthetic agents such as bupivacaine. The current study was initiated to investigate the relationship between increased progesterone concentrations and the electrophysiologic effects of bupivacaine, and lidocaine in isolated Purkinje fiber (PF)-ventricular muscle (VM) preparations. Twenty-four oophorectomized female white rabbits were killed after receiving 30 mg.kg-1.day-1 of progesterone intramuscularly or peanut oil alone for 4 days. PF and VM action potentials were recorded using standard electrophysiologic procedures. Plasma progesterone concentrations were 5 +/- 2.9 ng/ml in control animals compared to 59.8 +/- 11.0 ng/ml in progesterone-treated animals (P less than 0.05). Bupivacaine (3.5-17.4 microM) depressed the maximal rate of depolarization (Vmax) of PF to a significantly greater extent in tissues from progesterone-treated animals as compared to control animals. For example, at 3.5 microM bupivacaine decreased PF Vmax 52% in progesterone-treated tissues compared to 32% in controls (P less than 0.05); the Vmax of VM was also depressed to a greater extent in tissues from progesterone-treated animals (P less than 0.001). Lidocaine did not demonstrate an enhanced depressant effect in tissues from progesterone-treated animals. These results indicate that progesterone selectively increases the cardiac membrane depressant effects of bupivacaine but not lidocaine. This may contribute to the enhanced toxicity of bupivacaine in pregnant animals.

Effect of ropivacaine and bupivacaine on uterine blood flow in pregnant ewes.

The effects of ropivacaine, a new amide local anesthetic, on uterine blood flow and fetal well-being were compared with those of bupivacaine in 10 chronically instrumented pregnant ewes. In random sequence, animals received two intravenous infusions of each drug. The low infusion rate regimens were chosen to result in clinically relevant maternal plasma concentrations of local anesthetics, whereas the more rapid rates of infusions were given to assess the safety of higher maternal drug concentrations. An epinephrine infusion was given to demonstrate the appropriateness of the animal model for the measurement of uterine blood flow. Maternal and fetal heart rates, arterial blood pressure, and the ewe's central venous pressure, intraamniotic pressure, and uterine blood flow were recorded continuously. Arterial blood samples were taken from mother and fetus at frequent intervals to determine acid-base status and local anesthetic concentrations. A total of 39 studies were performed. None of the infusions of either local anesthetic resulted in a significant decrease in uterine blood flow or deterioration in fetal condition. The mean maternal plasma concentrations at the end of infusions were as follows: ropivacaine low dose, 1.60 +/- 0.35 micrograms/mL; bupivacaine low dose, 1.55 +/- 0.15 micrograms/mL; ropivacaine high dose, 2.50 +/- 0.37 micrograms/mL; and bupivacaine high dose, 1.83 +/- 0.19 micrograms/mL. Epinephrine infusion resulted in a 25% decrease in uterine blood flow without adverse fetal effects. We conclude that neither ropivacaine nor bupivacaine, as administered in this study, led to any ill effects on uterine artery blood flow or fetal well-being.

The effects of epinephrine on the anesthetic and hemodynamic properties of ropivacaine and bupivacaine after epidural administration in the dog.

Ropivacaine is a new local anesthetic that is chemically related to mepivacaine and bupivacaine. Previous laboratory studies have demonstrated that ropivacaine possesses an anesthetic profile similar to that of bupivacaine and has less arrhythmogenic potential. The current study was initiated to compare the hemodynamic and anesthetic effects of epidurally administered 0.75% bupivacaine and 1% ropivacaine, with and without epinephrine (1:200,000), in the dog. Two groups of six dogs were randomly assigned to the ropivacaine or bupivacaine treatment groups. Administration of 0.75% bupivacaine and 1% ropivacaine with and without epinephrine was randomized. Volumes of 3 ml of each solution were injected in a blinded manner via an indwelling lumbar epidural catheter with 48 hours between injections. No statistically significant difference existed between the four treatment groups with regard to onset and duration of sensory or motor block. Hemodynamic changes were, for the most part, not different between drugs. Significant decreases were seen in mean arterial blood pressure and cardiac output in all test groups. No difference in the degree of cardiovascular depression was observed. The addition of epinephrine did not alter onset or duration of sensory or motor block in this animal model. Epinephrine reduced the average anesthetic blood concentration observed in both treatment groups at the various time intervals, but not the time to achieve the mean maximum blood level. No residual adverse effects were observed in any animal.

Treatment of acute systemic toxicity after the rapid intravenous injection of ropivacaine and bupivacaine in the conscious dog.

Two groups of six beagle dogs received rapid intravenous (IV) injections of ropivacaine or bupivacaine on two occasions in a blinded random fashion. Initially, a dose sufficient to cause convulsions (CD) was given followed by twice the CD (2 x CD), which was administered 48 h later. The CD of bupivacaine (4.3 mg/kg) and ropivacaine (4.9 mg/kg) caused significant (P less than 0.05) increases in heart rate and mean arterial blood pressure. There was no difference between drug groups. Seizures were abolished by 10 mg/kg of intravenous thiamylal. Endotracheal intubation and controlled respiration with O2-enriched air with no other treatment resulted in rapid and complete recovery in all dogs. All dogs receiving 2 x CD of bupivacaine (8.6 mg/kg) or ropivacaine (9.8 mg/kg) were initially treated with thiamylal and mechanical ventilation. Two dogs in the bupivacaine group developed hypotension, respiratory arrest, ventricular tachycardia, and ventricular fibrillation, which were resistant to closed chest cardiac massage, treatment with epinephrine, bretylium, and atropine, and direct current cardioversion. The four remaining dogs in the infusion group were successfully resuscitated. All of the animals in the ropivacaine-treated group survived the administration of the 2 x CD dose. Mild hypotension developed in one dog and was treated with intravenous epinephrine (0.75 mg). This resulted in nodal tachycardia, which was abolished after treatment with bretylium. Another dog had two 1-s bursts of premature ventricular contractions requiring no treatment. The rapid treatment of convulsions and cardiovascular toxicity resulted in a decreased number of deaths in both groups when compared with dogs from a previously published study in which no therapy was instituted. Thus, early aggressive treatment of central nervous system and cardiovascular system toxicity is capable of reducing the incidence of mortality associated with the rapid intravenous administration of excessive doses of local anesthetics.

Systemic toxicity of ropivacaine during ovine pregnancy.

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.

Acute progesterone treatment has no effect on bupivacaine-induced conduction blockade in the isolated rabbit vagus nerve.

Pregnancy decreases anesthetic requirements during regional anesthesia. Using an in vitro animal model, this study attempts to elucidate the mechanism of hormonal effects on nerve conduction in desheathed rabbit vagus nerve. The acute effects of progesterone administration on neural blockade induced by bupivacaine were investigated in terms of changes in compound action potentials of A, B, and C fibers. No change in baseline compound action potential was found after 30 min of perfusion of the nerve with progesterone. Exposure of the nerve to progesterone before exposure to bupivacaine did not significantly increase the degree of conduction blockade produced by bupivacaine, and a radioactive assay demonstrated that progesterone was taken up acutely by neural tissue over a 45-min measurement period. These results indicate that although progesterone was taken up in significant amounts by neural tissue, an acute exposure does not increase the sensitivity of the nerves to bupivacaine. Hence, the increased sensitivity of nerves to local anesthetics seen with pregnancy or with chronic progesterone treatment requires some period of time to occur. The mechanism is therefore unlikely to be a direct effect of progesterone on the cell membrane but may involve hormonal effects on protein synthesis.

Pregnancy does not alter lidocaine toxicity.

Pregnant sheep are more vulnerable to the toxic effects of bupivacaine, a potent local anesthetic, than are nonpregnant sheep. In contrast, ovine pregnancy does not enhance the toxicity of mepivacaine, a drug with properties similar to lidocaine. We studied the central nervous and cardiovascular toxicity of lidocaine in pregnant sheep receiving a continuous intravenous drug infusion at the rate of 2 mg/kg/min and compared our results with data previously obtained in nonpregnant ewes. In all animals, toxic manifestations occurred in the following sequence: convulsions, hypotension, respiratory arrest, and circulatory collapse. The doses of lidocaine required to produce these symptoms in pregnant and nonpregnant ewes were similar. Convulsions occurred at 5.9 +/- 0.6 mg/kg (mean +/- SE) in the pregnant ewe and 5.8 +/- 1.8 mg/kg in the nonpregnant ewe, whereas circulatory collapse occurred at 40.7 +/- 2.6 and 36.7 +/- 3.3 mg/kg in the pregnant and nonpregnant animals, respectively. Lidocaine plasma concentrations associated with the onset of convulsions in both pregnant and nonpregnant ewes were almost identical (12.1 +/- 0.7 and 11.7 +/- 2.0 micrograms/ml, respectively). At circulatory collapse, these concentrations were 35.1 +/- 3.2 and 41.2 +/- 6.7 micrograms/ml, respectively. It appears that pregnancy does not enhance the toxic effects of lidocaine. These findings are similar to those for mepivacaine but not for bupivacaine, and may be related in part to differences in the way pregnancy affects serum protein binding of these drugs.

Pharmacokinetics of ropivacaine in nonpregnant and pregnant ewes.

The pharmacokinetics of ropivacaine were studied in chronically instrumented nonpregnant and pregnant ewes. On the day of study, the urinary bladder was catheterized. Ropivacaine (2.5 or 3.0 mg/kg) was administered by intravenous infusion over 2 or 4 min. Serial samples of arterial blood and urine were collected over 5 h, and drug concentrations were determined using a gas chromatographic technique. Total clearance of ropivacaine was lower in the pregnant animals (21.6 +/- 4.5 mL.min-1.kg-1) compared with the nonpregnant animals (45.1 +/- 6.7 mL.min-1.kg-1). There was a tendency toward a decrease in the volume of distribution during the terminal exponential phase of drug elimination of 2.03 +/- 0.36 L/kg in the pregnant and 4.32 +/- 1.03 L/kg in the nonpregnant sheep. Thus the difference in the elimination half-life was only minimal: 74.7 +/- 10.7 min in the pregnant and 64.4 +/- 7.4 min in the nonpregnant animals. It is concluded that ovine pregnancy is accompanied by changes in the pharmacokinetics of ropivacaine. Inadvertent intravenous injections of similar drug doses to pregnant and nonpregnant women might result in higher plasma concentrations of ropivacaine in the former. However, the rate of decline in plasma levels of the drug would be similar in both.

Cardiac electrophysiologic properties of bupivacaine and lidocaine compared with those of ropivacaine, a new amide local anesthetic.

Ropivacaine is a new amino-amide local anesthetic whose anesthetic profile appears similar to that of bupivacaine. Moreover, in intact animals ropivacaine was reportedly less arrhythmogenic than bupivacaine. These experiments evaluated the cardiac transmembrane electrophysiologic effects of ropivacaine compared with those of lidocaine and bupivacaine in an isolated rabbit Purkinje fiberventricular muscle preparation. Only bupivacaine (3-5 micrograms/ml, 0.92-1.5 x 10(-5) m) significantly decreased Purkinje fiber maximum diastolic potential. Action potential amplitude and maximal rate of depolarization (Vmax) were significantly decreased by all agents in the following order: bupivacaine, ropivacaine, lidocaine. High concentrations of bupivacaine and ropivacaine caused premature depolarizations during phase 3 in some preparations. In addition, bupivacaine altered the action potential configuration by producing "notching" not seen with either ropivacaine or lidocaine. This may reflect effects caused by changes in Ca2+, K+, or electrotonic effects. Ropivacaine and bupivacaine (30 micrograms/ml, 9.2 x 10(-5) m) and lidocaine (100 micrograms/ml, 3.74 x 10(-4) m) caused Purkinje fiber inexcitability and Purkinje fiber-ventricular muscle conduction block. However, the duration of PF inexcitability following exposure to ropivacaine and lidocaine was significantly shorter than in bupivacaine-treated preparation. Duration of PF-VM conduction block also tended to be shorter for ropivacaine than bupivacaine, but significantly longer than lidocaine. In general, ropivacaine is less potent than bupivacaine but more potent than lidocaine in terms of its depressant effect on cardiac excitation and conduction.

A new local anesthetic, ropivacaine. Its epidural effects in humans.

The current study was initiated to evaluate the epidural anesthetic properties of 0.5%, 0.75%, and 1.0% ropivacaine, a new local anesthetic agent structurally similar to bupivacaine. Fifteen patients scheduled for lower limb orthopedic surgery were enrolled in the study. As the concentration of ropivacaine increased from 0.5% to 1.0%, the time to onset of sensory anesthesia decreased from 6.4 +/- 1.7 (SD) min to 2.4 +/- 0.6 min and the maximum level of sensory anesthesia increased from T6 to T1. These changes were not statistically significant. Time to regression of anesthesia to T12 increased from 255 +/- 73 min with the 0.5% solution to 356 +/- 75 min with 1.0% ropivacaine (P less than 0.05). The degree of motor blockade using the Bromage scale varied with the concentration. When the 0.5% concentration was used, only one patient (20%) had greater than 1+ motor blockade. However, all of the patients receiving the 0.75% or 1.0% solution had at least 2+ motor blockade. Sensory anesthesia was adequate for surgery in 14 of the 15 patients. The mean peak plasma concentration of ropivacaine (Cmax) increased from 0.65 +/- 0.15 micrograms/mL with the 100-mg dose to 1.30 +/- 0.43 microgram/mL with the 200-mg dose. No adverse effects were noted in any patient in the study. These initial studies in humans suggest that ropivacaine provides satisfactory sensory anesthesia with minimal motor blockade at a concentration of 0.5%. An increase in concentration resulted in a more profound motor blockade. The Cmax of ropivacaine in this study was below levels associated with toxicity in animal studies.

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)

Adverse effects of maternally administered lidocaine on the asphyxiated preterm fetal lamb.

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.

Comparison of bupivacaine- and ropivacaine-induced conduction blockade in the isolated rabbit vagus nerve.

Ropivacaine (LEA-103) is a new amino-amide local anesthetic agent the chemical structure and anesthetic properties of which are similar to bupivacaine. Preliminary studies in animals indicate that the CNS toxicities of ropivacaine and bupivacaine are similar, but that ropivacaine may have less arrhythmogenic effects than bupivacaine. The current study arrhythmogenic effects than bupivacaine. The current study was designed to compare the in vitro potency, onset and recovery from block of ropivacaine and bupivacaine using an isolated rabbit vagus nerve model. The effect of varying concentrations of ropivacaine and bupivacaine on the compound action potential of A and C nerve fibers was assessed to determine whether motor and sensory fibers have different sensitivities to the two agents. The results showed that the depressant effect of bupivacaine was 16% greater than that of ropivacaine on motor fibers, but only 3% greater on sensory fibers. An analysis of variance indicated that this was a statistically significant difference (P = 0.028). Thus, at the concentrations tested, ropivacaine appears to produce relatively less blockade of motor fibers than does bupivacaine but with similar sensory blockade. The onset of this difference became significant as early as five minutes after the drug exposure was begun. No significant differences in recovery times were observed.

Does pregnancy alter the systemic toxicity of local anesthetics?

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.