Hemodynamic and cardiac electrophysiologic effects of lidocaine-bupivacaine mixture in anesthetized and ventilated piglets

BACKGROUND: The sensory blockade induced by a lidocaine-bupivacaine mixture combines the faster onset of lidocaine and the longer duration of bupivacaine. The current study compared the effects of large doses lidocaine (16 mg/kg), bupivacaine (4 mg/kg), and a mixture of 16 mg/kg lidocaine-4 mg/kg bupivacaine on hemodynamic and cardiac electrophysiologic parameters in anesthetized and ventilated piglets. METHODS: After carotid artery cannulation, a double micromanometer measured mean aortic pressure, left ventricular end diastolic pressure, and the first derivative of left ventricular pressure. Electrocardiogram recording and a bipolar electrode catheter measured RR, PQ, QRS, QT C, JT C, AH, and HV intervals. Lidocaine, bupivacaine, or the mixture was administered intravenously over 30 s, and studied parameters were measured throughout 30 min. RESULTS: Mean aortic pressure decreased in all groups ( P < 0.05). The first derivative of left ventricular pressure was decreased in all groups ( P < 0.001) but to a greater extent with the mixture compared with lidocaine ( P < 0.04). RR, QT C, and JT C intervals were similarly increased in all groups ( P < 0.05). In all groups, PQ, AH, HV, and QRS intervals were widened ( P < 0.001). The lengthening of PQ was greater with bupivacaine ( P < 0.02). The lengthening of AH was greater and delayed with bupivacaine compared with lidocaine ( P < 0.03). The lengthening of HV and the widening of QRS were greater and delayed with bupivacaine ( P < 0.01). The widening of QRS was greater with the mixture than with lidocaine ( P < 0.01). CONCLUSIONS: The alterations of ventricular conduction parameters are greater with 4 mg/kg bupivacaine than with a mixture of 16 mg/kg lidocaine-4 mg/kg bupivacaine, whereas the hemodynamic parameters are similarly altered.     

Succinylcholine does not worsen bupivacaine-induced cardiotoxicity in pentobarbital-anaesthetized dogs

The intravascular injection of a large dose of bupivacaine induces electrophysiological cardiac impairment, mainly by slowing ventricular conduction velocity, and haemodynamic depression, by a decrease in myocardial contractility. When cardiotoxicity occurs, succinylcholine rapidly stops convulsions. However, the possible interactions between bupivacaine and succinylcholine on cardiac electrophysiology and haemodynamic status have never been investigated. Thus, we used an experimental electrophysiological model involving closed-chest dogs. Three groups (n = 6) of pentobarbital-anaesthetized dogs were given 0.2 mg.kg-1 atropine iv. Dogs in Group 1 were given saline. The others received 4 mg.kg-1 bupivacaine iv over ten seconds. Dogs in Group 2 were then given saline and those in Group 3 were then given 2 mg.kg-1 succinylcholine iv from one to two minutes after the administration of bupivacaine. The following electrophysiological variables were measured: heart rate represented by RR interval (RR), PR, atria-His (AH), and His-ventricle (HV) intervals, QRS duration, and QT interval corrected for heart rate (QTc). The following haemodynamic variables were measured: mean aortic pressure (MAoP), the peak of the first derivative of left ventricular pressure (LV dP/dt max), and LV end diastolic pressure (LVEDP). Comparison between Groups 1 and 2 showed that bupivacaine induced more than 100% HV interval lengthening and QRS widening (P less than 0.01), prolonged QTc interval by more than 25% (P less than 0.01), and decreased LV dP/dt max by more than 50% (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

LEMAKALIM, A POTASSIUM CHANNEL AGONIST, REVERSES ELECTROPHYSIOLOGICAL IMPAIRMENTS INDUCED BY A LARGE DOSE OF BUPIVACAINE IN ANAESTHETIZED DOGS

We have examined the ability of lemakalim to correct bupivacaine-inducedcardiac electrophysiological impairment in an experimental electrophysiologicalmodel in closed-chest dogs. Two groups (n = 6) of pentobarbitone-anaesthetizeddogs were given atropine 0.2mg kg^–1 i.v., and bupivacaine4 mg kg^–1 i.v. over 10 s. Group 2 received also lemakalim0.03 mg kg^–1 i.v. Bupivacaine induced bradycardia, prolongedPR and His-ventricle (HV) intervals, QRS duration, QTc and JTcintervals, decreased left ventricular (LV) dP/dt max and increasedLV end-diastolic pressure. Lemakalim reversed bupivacaine-inducedPR, HV, ORS, QTc and JTc prolongation, and did not worsen bupivacaine-inducedbradycardia and haemo dynamic depression. We conclude that lemakalimcan antagonize the main deleterious electrophysiological effectsinduced by a large dose of bupivacaine in anaesthetized dogs.(Br. J. Anaesth. 1993; 71: 534–539)     

The comparative electrophysiologic and hemodynamic effects of a large dose of ropivacaine and bupivacaine in anesthetized and ventilated piglets.

Ropivacaine is less potent and less toxic than bupivacaine. We administered these two local anesthetics in a cardiac electrophysiologic model of sodium thiopental-anesthetized and ventilated piglets. After assessing the stability of the model, bupivacaine (4 mg/kg) and ropivacaine (6 mg/kg) were given IV in two groups (n = 7) of piglets. No alteration in biological variables was reported throughout the study. Bupivacaine and ropivacaine similarly decreased mean aortic pressure from 99 +/- 22 to 49 +/- 31 mm Hg and from 87 +/- 17 to 58 +/- 28 mm Hg, respectively, and decreased the peak of the first derivative of left ventricular pressure from 1979 +/- 95 to 689 +/- 482 mm Hg/s and from 1963 +/- 92 to 744 +/- 403 mm Hg/s, respectively. Left ventricular end-diastolic pressure was similarly increased from 6 +/- 5 to 9 +/- 5 mm Hg and from 6 +/- 4 to 12 +/- 4 mm Hg, respectively. Bupivacaine and ropivacaine similarly lengthened the cardiac cycle length (R-R; from 479 +/- 139 to 706 +/- 228 ms and from 451 +/- 87 to 666 +/- 194 ms, respectively), atria His (from 71 +/- 15 to 113 +/- 53 ms and from 64 +/- 6 to 86 +/- 10 ms, respectively), and QTc (QTc = QT x R-R(-0.5), Bazett formula; from 380 +/- 71 to 502 +/- 86 ms and from 361 +/- 33 to 440 +/- 56 ms, respectively) intervals. Bupivacaine altered to a greater extent the PQ (the onset of the P wave to the Q wave of the QRS complex) (from 97 +/- 20 to 211 +/- 60 ms versus from 91 +/- 8 to 145 +/- 38 ms, P < 0.05), QRS (from 58 +/- 3 to 149 +/- 34 ms versus from 60 +/- 5 to 101 +/- 17 ms, P < 0.05), and His ventricle interval (from 25 +/- 4 to 105 +/- 30 ms vs from 25 +/- 4 to 60 +/- 30 ms, P < 0.05) than ropivacaine. A 6 mg/kg ropivacaine dose induced similar hemodynamic alterations as 4 mg/kg bupivacaine. However, bupivacaine altered the variables of ventricular conduction (QRS and His ventricle) to a greater extent. IMPLICATIONS: A 6 mg/kg ropivacaine dose induced similar hemodynamic alterations as 4 mg/kg bupivacaine. However, bupivacaine altered the variables of ventricular conduction (QRS and His ventricle) to a greater extent.     

Reversal of electrophysiologic and hemodynamic effects induced by high dose of bupivacaine by the combination of clonidine and dobutamine in anesthetized dogs.

The ability of clonidine and dobutamine to correct bupivacaine-induced cardiac electrophysiologic and hemodynamic impairment was evaluated in an experimental electrophysiologic model on closed-chest dogs. Five groups (n = 6) of pentobarbital-anesthetized dogs were given atropine (0.2 mg/kg IV). Group 1 was given a saline solution; all other dogs were given bupivacaine (4 mg/kg IV) over a 10-s period. Group 2 was given only bupivacaine. Group 3 was given clonidine (0.01 mg/kg IV) over a 1-min period. Group 4 was given a dobutamine infusion at 5 micrograms.kg-1.min-1. Group 5 was given the combination of clonidine and dobutamine. Bupivacaine induced bradycardia, prolonged atrioventricular conduction time (PR interval), atrioventricular node conduction time (AH interval), His-Purkinje conduction time (HV interval), and QRS duration. Bupivacaine decreased left ventricular (LV) dP/dt max and increased LV end-diastolic pressure (LVEDP). Clonidine improved QRS duration and HV interval but enhanced AH interval, bradycardia, and hemodynamic depression induced by bupivacaine. Dobutamine infusion improved LV dP/dt max but did not modify bupivacaine-induced ventricular electrophysiologic impairment. The combination of clonidine and dobutamine corrected not only the electrophysiologic impairment induced by bupivacaine but also the hemodynamic depression. As the HV interval and the QRS duration could be correlated with ventricular conduction velocities, we conclude that (a) clonidine reversed the slowing of ventricular conduction velocities induced by bupivacaine, and (b) the combination of clonidine and dobutamine was able to correct the cardiac disturbances induced by bupivacaine in anesthetized dogs.     

Differential depressant and electrophysiologic cardiotoxicity of local anesthetics: an experimental study with special reference to lidocaine and bupivacaine

In 15 pigs lidocaine and bupivacaine were injected into the left anterior descending (LAD) coronary artery to investigate the cardiotoxic effects of these drugs. Anesthesia was maintained by a continuous intravenous pentobarbital infusion and ventilation was controlled. Aortic, pulmonary arterial, right atrial, and left ventricular pressures, a standard 12 lead ECG, cardiac output, and great cardiac venous blood flow were recorded. The local anesthetics were administered at body temperature over approximately 10 sec in a random, crossover fashion at the following equipotent anesthetic doses: bupivacaine, 0.25, 0.5, 1, 2, and 4 mg; lidocaine, 1, 2, 4, 8, and 16 mg. The hemodynamic effects were short-lived, peaking about 5 sec after drug infusion. At the highest dose, both drugs decreased left ventricular dP/dT by 28% (P less than 0.001) and aortic blood pressure by 12% (lidocaine) and 8% (bupivacaine) (P less than 0.001 and P less than 0.01). Heart rate, cardiac output, and coronary venous blood flow did not change. Thus, the cardiodepressant ratio between the two drugs was comparable with their local anesthetic the two drugs was comparable with their local anesthetic potency ratio (bupivacaine/lidocaine, 4:1). Seven animals died in ventricular fibrillation within 1 min after 4 mg bupivacaine dose. All animals given 16 mg lidocaine survived. Ventricular fibrillation was preceded by progressive widening of the QRS complexes recorded over the area perfused by the LAD. The ECG changes after 16 mg lidocaine were of the same magnitude as those recorded after 1 mg bupivacaine. In five of the surviving animals 32 and 64 mg lidocaine were injected intracoronarily after termination of the crossover study.(ABSTRACT TRUNCATED AT 250 WORDS)     

Adverse events associated with intravenous regional anesthesia (Bier block): a systematic review of complications

Study ObjectiveTo characterize the complications reported with intravenous regional anesthesia (IVRA).DesignLiterature search.SettingUniversity-affiliated hospital.MeasurementsA search was done in the American National Library of Medicine's PUBMED, EMBASE (1980-2007, wk 11), and Medline (from 1950) in March 2007. All complications associated with IVRA were reviewed.Main ResultsThe lowest dose of local anesthetic associated with a seizure was 1.4 mg/kg for lidocaine; 4 mg/kg for prilocaine, and 1.3 mg/kg for bupivacaine. Cardiac arrests and deaths were reported with lidocaine and bupivacaine only. The lowest dose associated with a cardiac arrest was 2.5 mg/kg for lidocaine and 1.6 mg/kg for bupivacaine. Local anesthetic toxicity occurring during tourniquet inflation has been reported, with tourniquet pressure exceeding initial systolic arterial blood pressure by 150 mmHg. Seizures occurring after tourniquet deflation have been reported with a tourniquet time as long as 60 minutes. Ten cases of compartment syndrome are reported.ConclusionSeizures have been reported with lidocaine at its lowest effective dose (1.5 mg/kg).     

Amide local anesthetic alterations of effective refractory period temporal dispersion: relationship to ventricular arrhythmias

The hemodynamic and electrophysiologic effects of bupivacaine, etidocaine, mepivacaine, and lidocaine were investigated in 32 pentobarbital-anesthetized adult mongrel dogs. Following equipotent dosing, all four agents produced similar hemodynamic effects: decrease in stroke volume and cardiac output, heart rate slowing, increase in systemic vascular resistance, and increases in pulmonary arterial pressure (PAP) and pulmonary capillary wedge pressure (PCWP). The effects of the various agents on the ECG were different. Compared with the control period, mepivacaine and lidocaine produced slight increases and etidocaine and bupivacaine much greater increases in: the area under the curve of the T-wave; lengthening of the QTU interval; and enhancement of the "slow wave" or U-wave following the T-wave. The effects of the various agents on effective refractory period (ERP) temporal dispersion were dramatically different. The ERP temporal dispersion increased to 48.3 +/- 36.0 ms following mepivacaine, 37.4 +/- 10.1 ms following lidocaine, 97.1 +/- 36.2 ms following bupivacaine, and 92.5 +/- 30.5 ms following etidocaine. Six of seven bupivacaine, six of seven etidocaine, two of eight mepivacaine, and none of eight lidocaine animals sustained a polymorphic, undulating ventricular tachycardia similar to Torsades de Pointes following burst ventricular pacing. The results of this study suggest that bupivacaine, etidocaine, and occasionally mepivacaine can result in a Torsades de Pointes-like syndrome following intravenous administration. The magnitude of ERP temporal dispersion differences between the various agents appears to explain their differential arrhythmogenicity.     

Comparative CNS toxicity of lidocaine, etidocaine, bupivacaine, and tetracaine in awake dogs following rapid intravenous administration

The comparative central nervous system (CNS) toxicity of serially administered intravenous doses of lidocaine, bupivacaine, etidocaine, and tetracaine was investigated in awake dogs. The mean cumulative dose required for convulsive activity was 4.0 mg/kg tetracaine, 5.0 mg/kg bupivacaine, 8.0 mg/kg etidocaine, and 22.0 mg/kg lidocaine. The cumulative convulsive dose of lidocaine was significantly greater than that of the other three agents (P less than 0.01). A comparison of the in vivo anesthetic potency and the acute CNS toxicity of these various agents suggests little difference in the therapeutic ratio between less potent anesthetics such as lidocaine and more potent drugs, i.e., tetracaine, bupivacaine, and etidocaine. The relative CNS toxicity of the different agents as determined in awake dogs in this study was compared with their relative cardiovascular toxicity previously evaluated in a series of ventilated dogs anesthetized with pentobarbital. The dose of lidocaine, etidocaine, tetracaine, and bupivacaine required to produce irreversible cardiovascular depression was 3.5-6.7 times greater than that which produced convulsions. These results suggest that the CNS is the primary target organ for the toxic effects of both highly lipid-soluble and highly protein-bound local anesthetics (i.e., bupivacaine, etidocaine, and tetracaine) and less lipid-soluble and less protein-bound drugs (i.e., lidocaine) following rapid intravenous administration.     

Bupivacaine cardiovascular toxicity: comparison of treatment with bretylium and lidocaine

Using anesthetized dogs, this study compared treatment with lidocaine or bretylium for bupivacaine-induced cardiovascular toxicity. Pentobarbital-anesthetized and -ventilated dogs (n = 10) were given a bolus dose of bupivacaine, 4 mg/kg, and a constant infusion of 0.2 mg X kg-1 X min-1 to produce steady-state serum levels of 7.1 +/- 1.8 microgram/ml of bupivacaine. Using burst ventricular pacing, the ventricular tachycardia threshold was determined, along with hemodynamic and electrophysiologic parameters. The animals were then treated with bretylium, 20 mg/kg (n = 5), or lidocaine, 2 mg/kg, followed by a continuous infusion of lidocaine, 0.1 mg X kg-1 X min-1 (n = 5). Bupivacaine-induced alterations in cardiac output, stroke volume, heart rate, and systemic vascular resistance were corrected by bretylium but not lidocaine. Bupivacaine caused a significant lowering of the ventricular tachycardia threshold, which was consistently raised by bretylium, while lidocaine was either ineffective or caused a further lowering of the threshold. Bupivacaine caused a significant increase in the Q-TU interval and resulted in an undulating polymorphic ventricular tachycardia, similar to that seen in Torsades de Pointes.     

Comparative cardiovascular effects of verapamil, nifedipine, and diltiazem during halothane anesthesia in swine

Controversy persists about the cardiac toxicity of bupivacaine if accidentally administered intravenously during regional anesthesia. Using awake, unanesthetized sheep, we evaluated the cardiac effects of low and high equivalent doses of lidocaine and bupivacaine given intravenously over 10 s. All animals convulsed within 30 s of injections. Although both drugs significantly increased heart rate and systemic and pulmonary arterial blood pressure for up to 10 min, cardiac output was affected variably. The magnitude of hemodynamic changes that each drug produced did not differ significantly from each other at either dose level. However, of the sheep receiving intravenous lidocaine, none developed arrhythmias other than mild sinus tachycardia and minimal ST-T wave changes (which occurred in 25% of the animals). After intravenous bupivacaine injection, all sheep had transient changes on the EKG and/or arrhythmias (e.g., supraventricular tachycardia; atrioventricular condition blocks; ventricular tachycardia; multiform premature ventricular contractions; wide QRS complexes; ST-T wave changes; and in one animal, fatal ventricular fibrillation). Normal sinus rhythm usually returned within 8-10 min. Arterial blood gas and acid-base values stayed within the normal range during the studies, and serum potassium did not change significantly from control. In conclusion, in conscious adult sheep, equivalent doses of lidocaine or bupivacaine produced similar central nervous system (CNS) toxicity when rapidly injected intravenously. In the absence of marked hypoxia, respiratory or metabolic acidosis, hyperkalemia, or hypotension, serious cardiac arrhythmias occurred after bupivacaine but not lidocaine.     

The effect of magnesium sulfate administration on cerebral and cardiac toxicity of bupivacaine in dogs

The effect of acutely elevated serum magnesium on the CNS and cardiac toxicity of bupivacaine was studied. Anesthesia was induced in mongrel dogs with thiopental, 25 mg/kg, and ventilation was controlled. Sedation was maintained with fentanyl (25 micrograms/kg bolus and 5 micrograms.kg-1h-1) and pancuronium (0.15 mg/kg bolus and 0.05 mg.kg-1h-1) provided paralysis. Two hours after the thiopental bolus, all animals received an intravenous (iv) infusion of bupivacaine (1 mg.kg-1 min-1). The control group (5 animals) received bupivacaine only. The Mg++ group (5 animals) received MgSO4 140 mg/kg iv and 80 mg.kg-1 h-1 15 min prior to beginning the bupivacaine infusion. Lead II ECG, cardiac hemodynamics, and two-channel EEG were continuously monitored. Serum magnesium concentrations in the Mg++ group rose from 0.67 mM (1.3 mEq/L) to 2.42 mM (4.8 mEq/L). The bupivacaine infusion caused PR and QRS interval prolongation in both groups, but QRS widening was greater in the control group. QT interval corrected for heart rate (QTIc) lengthened only in the control group. A depression of left ventricular stroke work index (LVSWI) occurred to an equal extent in both groups. The seizure dose of bupivacaine was not different between the two groups: 12.9 +/- 2.3 (SEM) mg/kg in the control group and 13.9 +/- 2.5 mg/kg in the Mg++ group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cardiac dysrhythmias induced by infusion of local anesthetics into the lateral cerebral ventricle of cats

The hypothesis that neurogenically mediated cardiac arrhythmias can be induced by the intracerebroventrical (ICV) infusion of local anesthetic solutions was tested in 11 chronically prepared, unmedicated cats. Test substances were bupivacaine (0.1%), lidocaine (0.4%), procaine (0.4 or 0.8%), or saline (pH 5.8). Cats received one or more of the test substances with two or more days between infusions. Four cats were also given bupivacaine intravenously at 1.1 and 1.4 mg/kg to help determine whether ECG changes after ICV injection of local anesthetic were due to direct cardiac action after systemic absorption. Total dose was 3.8-7.8 X the largest ICV dose (0.7 mg). No ventricular arrhythmias were observed after the ICV infusion of saline or with intravenous doses of bupivacaine as large as 1.4 mg/kg. Only one of six cats given lidocaine ICV developed sustained, severe ventricular arrhythmias. Five of seven cats given ICV procaine developed ventricular arrhythmias. All ten cats given ICV bupivacaine developed ventricular arrhythmias. It is concluded that local anesthetics can produce neurogenically mediated ventricular arrhythmias in cats and that, of the three local anesthetics tested, bupivacaine is the most potent and effective and lidocaine is the least potent and effective.     

Focus on mobilisation after lower abdominal surgery. A double-blind randomised comparison of epidural bupivacaine with morphine vs. lidocaine with morphine for postoperative analgesia

BACKGROUND: Epidural infusion of morphine, usually with bupivacaine, for postoperative pain relief has proved to be safe and effective. Lidocaine with its short duration of action and low toxicity may be an alternative to bupivacaine. The clinical importance of the choice of local anaesthetic drug on mobilisation after lower abdominal surgery has not been studied previously. METHODS: A total of 52 patients was randomised to epidural infusion of morphine (1.6-4.4 micrograms.kg-1.h-1) with either lidocaine (0.44-0.98 mg.kg-1.h-1) or bupivacaine (0.10-0.28 mg.kg-1.h-1) in a double-blind fashion. The time to mobilisation, degree of pain relief, blood pressure, respiration and motor function were recorded at regular intervals postoperatively for 40 h. Serum concentrations of lidocaine, its main metabolite monoethylglycinexylidide (MEGX) and bupivacaine were measured at 3, 15 and 40 h. RESULTS: There were no significant differences in the clinical characteristics between the two patient groups. There were no significant differences in the time from the end of surgery to the time the patients were able to stand without support (bupivacaine: median 24 h (interquartile range (IQR): 22-31), lidocaine: median 28 h (IQR 23-40), P = 0.15) or were able to walk without support (bupivacaine: median 46 h (IQR 28-62), lidocaine: median 48 h (IQR 35-54), P = 0.78). No significant differences between the groups were recorded with respect to pain relief, blood pressure, respiration, sedation score and motor function. The plasma concentration of lidocaine and bupivacaine increased significantly during the treatment period (P < 0.01 for both drugs), but not the concentration of MEGX. The highest venous lidocaine concentration was 17.5 mumol/l and the highest bupivacaine concentration was 18.8 mumol/l. There was a significant correlation between the concentration of both lidocaine and bupivacaine and the concentration of alpha 1-acid glycoprotein (AAG) (lidocaine: r = 0.77, P < 0.001, bupivacaine: r = 0.60, P < 0.001), suggesting that the free fraction of the drugs did not increase. No patients showed serious signs of toxicity. The epidural infusion rates remained stable in both groups during the study period. CONCLUSION: There were no clinically or statistically significant differences in the postoperative course after lower abdominal surgery in patients who received an epidural infusion of morphine combined with bupivacaine as compared to patients who received morphine with lidocaine. Further clinical studies to establish the place of lidocaine in postoperative epidural analgesia should be performed.     

Maternal, fetal and placental distribution of lidocaine-epinephrine and bupivacaine after epidural administration for cesarean section

Bupivacaine and lidocaine are both lipophilic drugs, bupivacaine being more lipophilic and protein-bound. Our earlier studies, using human placenta perfused in vitro, showed that increased placental binding of bupivacaine restricts fetal transfer compared to the higher fetal transfer of lidocaine. However, placental tissue concentrations of local anesthetics have not been determined in the clinical context. Term parturients were randomized to receive either 2% lidocaine-epinephrine (n = 10) or 0.5% bupivacaine (n = 10) through a lumbar epidural catheter for elective cesarean section. Total drug concentrations of lidocaine and bupivacaine in maternal and umbilical plasma and placental tissue were determined. There was a higher incidence of maternal hypotension in the lidocaine-epinephrine group than in the bupivacaine group ( vs , P < 0.05). At delivery, fetal/maternal ratios for total concentrations of lidocaine and bupivacaine were similar (0.49 vs 0.42). The mean placental tissue/maternal plasma concentration ratio of lidocaine was higher than that of bupivacaine (1.45 vs 1.01, P < 0.05). The mean amount of the drug retained in the placenta per unit of dose (mg/kg) was also higher in the lidocaine-epinephrine group, although this difference did not reach statistical significance (0.46 mg/unit dose vs 0.40 mg/unit dose). Values for area under the concentration-time curves per unit of dose were similar. In conclusion, maternal plasma concentrations, fetal/maternal concentration ratios and placental tissue binding of lidocaine resembled those of bupivacaine after epidural administration. These findings are probably explainable by the effect of maternal hypotension on the distribution of lidocaine.     

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)     

The influence of midazolam on the plasma concentrations of bupivacaine and lidocaine after caudal injection of a mixture of the local anesthetics in children

Twenty children undergoing surgery received a caudal block using 1 ml per kg of a mixture of 50% lidocaine (1%) and 50% bupivacaine (0.25%). They were randomly allocated to two groups, one of which received midazolam 0.4 mg/kg rectally as premedication. Midazolam administration resulted in a significantly lower AUC value for lidocaine but did not influence the plasma concentrations of bupivacaine.     

Effects of intravenous administration of local anesthetics on the renal sympathetic nerve activity during nitrous oxide and nitrous oxide-halothane anesthesia in the cat

The effects of subseizure doses of lidocaine and bupivacaine administered intravenously (i.v.) on mean arterial pressure (MAP), heart rate (HR) and renal sympathetic nerve activity (RSNA) were studied in cats anesthetized with nitrous oxide (N2O)-O2 and N2O-O2-halothane (1%). In cats anesthetized with N2O-O2, MAP decreased briefly (P less than 0.01) and then returned to the initial level within a minute after the i.v. injection of lidocaine (5 mg/kg, 10 mg/kg). RSNA increased at first and then decreased slightly. In cats with denervated baroreceptors, the change in RSNA after lidocaine 5 mg/kg i.v. was similar to that in cats with intact baroreceptors. In contrast, MAP, HR and RSNA decreased significantly (P less than 0.01) after i.v. injection of lidocaine during N2O-O2-halothane anesthesia. The effects of bupivacaine on RSNA were similar to those of lidocaine. It is concluded that cardiovascular depression following intravenous local anesthetics during N2O-O2-halothane anesthesia may be caused by both a decreased sympathetic activity and a direct depressant effect on the myocardium.     

Effect of Bupivacaine on the Isolated Rabbit Heart: Developmental Aspect on Ventricular Conduction and Contractility

Background: Newborns and infants seem to be at greater risk of bupivacaine cardiotoxicity than adults do. Few experiments have studied the effects of local anesthetics on myocardium associated with developmental changes, and their conclusions are conflicting. The authors compared the effects of bupivacaine on an isolated heart preparation in newborn and adult rabbits.

Methods: The authors used a constant-flow, nonrecirculating Langendorff preparation paced atrially. Adult and newborn rabbit hearts were exposed to step-increasing concentrations of bupivacaine. For each concentration, heart rate was modified with pacing from 180 to 360 beats/min by increments of 30 beats/min. QRS complex duration (index of ventricular conduction) and the first derivative of left ventricular pressure (index of contractility) were measured. The two groups were compared using an Emax model.

Results: In newborn and adult rabbits, QRS complex duration increased with increasing bupivacaine concentration. No difference was observed between neonatal and adult hearts. Contractility decreased with increasing bupivacaine concentration. Newborn rabbits were approximately three times more sensitive than adult rabbits to the effects of bupivacaine. However, the concentration leading to 50% decrease in the first derivative of left ventricular pressure was much higher than the concentration leading to half maximum increase in QRS complex duration.     

Isoproterenol corrects the effects of bupivacaine on the electrophysiologic properties of the isolated rabbit heart

The purpose of this study was to test the hypothesis that isoproterenol could reverse bupivacaine toxicity. In eight isolated rabbit hearts an electrophysiologic evaluation was performed then repeated during infusion of bupivacaine (1 microgram/mL) alone and bupivacaine plus isoproterenol (1-2 micrograms/mL). Bupivacaine alone increased electrocardiographic intervals (P wave, QRS complex, PR, AV, and QTc interval) and refractory periods of the myocardium and atrioventricular junction as well as the Wenckebach cycle and pacing thresholds. The addition of isoproterenol corrected partially or completely all bupivacaine-induced abnormalities, and decreased sinus cycle length, suggesting a potential therapeutic value in the treatment of bupivacaine intoxication.