Cardiac resuscitation after incremental overdosage with lidocaine, bupivacaine, levobupivacaine, and ropivacaine in anesthetized dogs

There is no information comparing the ability to reverse the cardiotoxic effects associated with incremental overdosage of bupivacaine (BUP) to levobupivacaine (LBUP), ropivacaine (ROP), or lidocaine (LIDO). Open-chest dogs were randomized to receive incremental escalating infusions of BUP, LBUP, ROP, and LIDO to the point of cardiovascular collapse (mean arterial pressure [MAP] < or = 45 mm Hg). Hypotension and arrhythmias were treated with epinephrine, open-chest massage, and advanced cardiac life support protocols, respectively. Outcomes were defined as the following: successful (stable rhythm and MAP > or = 55 mm Hg for 20 min), successful with continued therapy (stable rhythm and MAP <55 mm Hg after 20 min), or death. Continued therapy was required in 86% of LIDO dogs compared with only 10%-30% of the other dogs (P < 0.002). Mortality from BUP, LBUP, ROP, and LIDO was 50%, 30%, 10%, and 0%, respectively. Myocardial depression was primarily responsible for the profound hypotension, as the occurrence of lethal arrhythmias preceding resuscitation was not different among local anesthetics. Epinephrine-induced ventricular fibrillation occurred more frequently in BUP-intoxicated dogs than in dogs given LIDO or ROP (P < 0.05). The unbound plasma concentrations at collapse were larger for ROP, 19.8 microg/mL (10-39 microg/mL), compared with BUP, 5.7 microg/mL (3-11 microg/mL); whereas the concentrations of LBUP, 9.4 microg/mL (5-18 microg/mL) and BUP were not significantly different from each other. Implications: There were consistent differences among the local anesthetics, the sum of which suggests that larger doses and blood concentrations of ropivacaine (ROP) and lidocaine will be tolerated as compared with bupivacaine (BUP) and levobupivacaine (LBUP). Lidocaine intoxication results in myocardial depression from which resuscitation is consistently successful but will require continuing drug support. After BUP, LBUP, or ROP, resuscitation is not always successful, and the administration of epinephrine may lead to severe arrhythmias. The unbound plasma concentrations at collapse were larger for ROP compared with BUP, whereas the concentrations of LBUP and BUP were not significantly different from each other. Furthermore, larger plasma concentrations of ROP than BUP are present after resuscitation, suggesting a wider margin of safety when large volumes and large concentrations are used to establish upper or lower extremity nerve blocks for surgical anesthesia and during long-term infusions for pain management.     

Comparison of 0.5% intrathecal bupivacaine with 0.5% intrathecal ropivacaine in the treatment of refractory cancer and noncancer pain conditions: results from a prospective, crossover, double-blind, randomized study

BACKGROUND AND OBJECTIVES: Intrathecal (IT) administration of bupivacaine (BUP) for treatment of "refractory" pain has sometimes been associated with unacceptable side effects. This study was undertaken to determine if IT-ropivacaine (ROP) can reduce the rate and intensity of these side effects e.g., urinary retention, paresthesia, and particularly, paresis with gait impairment. A prospective, crossover, double-blind, randomized study. METHODS: Twenty-one patients were enrolled, 9 dropped out of the study, and data were analyzed from 12 patients. Patients were treated by insertion of IT tunneled nylon catheters, continuous infusion of 0.5% ROP followed by 0.5% BUP or 0.5% BUP followed by 0.5% ROP solutions from an external electronic pump. Each local anesthetic was infused for 7 days, and their order of infusion randomized. The comparative efficacy of the ROP and BUP IT infusions was assessed from the daily doses of IT ROP and IT BUP, oral and parenteral opioids, and daily scores of nonopioid analgetic and sedative drug consumption. Self-reported pain intensity (visual analogue scale [VAS] mean scores) and scores of Bromage relaxation, ambulation, nocturnal sleep pattern, rates of side-effects attributable to the IT drugs, the patients' assessment of the IT ROP v the IT BUP periods of the trial, and the comparative daily cost of IT ROP v IT BUP were recorded. RESULTS: The daily doses of the local anesthetics used were 23% higher for ROP than for BUP. Further, the daily cost was approximately equals 3 times higher for ROP than for BUP. No other significant differences between IT ROP and IT BUP were found. CONCLUSION: The results of this study do not support the hypothesis that IT infusion of 0.5% ROP has advantages over IT infusion of 0.5% BUP when administered for relief of "refractory" pain.     

Does local anesthetic stereoselectivity or structure predict myocardial depression in anesthetized canines?

BACKGROUND AND OBJECTIVES: It is unclear whether the susceptibility to myocardial depression from an accidental intravascular local anesthetic (LA) administration is associated with LA stereoselectivity or structure. By using direct left ventricular pressure monitoring and echocardiographic indices of contractile function in anesthetized, ventilated dogs, we compared the cardiac depressant effects of bupivacaine, ropivacaine, levobupivacaine, and lidocaine. METHODS: Open-chest dogs were randomized to receive escalating incremental infusions of the 4 local anesthetics until cardiovascular collapse. We assumed a concentration relationship for potency of 4:1 for lidocaine/bupivacaine, ropivacaine, and levobupivacaine. RESULTS: All LAs produced concentration-dependent increases in left ventricular end diastolic pressure (LVEDP) and decreases in dP/dtmax, ejection fraction % (EF), fractional shortening (%) (FS), and cardiac output (CO). When comparing the long-acting agents, the effect was least for ropivacaine. The effective concentration estimates for ropivacaine that produced 35% reductions in dP/dtmax and FS were 4.0 micro g/mL (95% confidence intervals [CI(95)]: 3.1 to 5.2 micro g/mL) and 3.0 micro g/mL (CI (95): 2.1 to 4.2 micro g/mL), respectively. The concentrations of levobupivacaine that produced these same end points of contractile dysfunction were significantly less: 2.4 micro g/mL (CI(95): 1.9 to 3.1 micro g/mL) and 1.3 micro g/mL (CI(95): 0.9 to 1.8 micro g/mL), respectively, and these were not different from bupivacaine. As expected, the concentrations of lidocaine that produced 35% reductions in dP/dtmax and FS were significantly greater than the longer acting agents; 8.0 micro g/mL (CI(95): 5.7 to 11.0 micro g/mL) and 5.5 micro g/mL (CI(95): 3.5 to 8.7 micro g/mL), respectively. CONCLUSIONS: This study suggests that smaller molecular size and possibly a piperidine-free structure as opposed to stereoselectivity may be the more important factor in reducing the risk of LA-induced myocardial depression.     

Ventricular irritability associated with the use of naloxone hydrochloride. Two case reports and laboratory assessment of the effect of the drug on cardiac excitability

Two instances of ventricular tachycardia and fibrillation have followed the injection of naloxone hydrochloride (Narcan) that had been given to reverse the effects of morphine following cardiac surgical procedures. Injection of the drug into 5 dogs that had received morphine was associated with ventricular extrasystoles in 2 animals, although no increase in ventricular excitability could be demonstrated as measured by either strength/interval curves or ventricular diastolic threshold. Naloxone hydrochloride should be used with caution in patients with cardiac irritability.     

Effects of CNS site-directed carotid arterial infusions of bupivacaine,levobupivacaine, and ropivacaine in sheep

BACKGROUND: Previous preclinical safety studies in ewes have found intravenous levobupivacaine and ropivacaine to be less potent toward causing central nervous system (CNS) and cardiac toxicity than bupivacaine. Analogous cardiotoxicity has been demonstrated directly in various cardiac preparations ex vivo. Moreover, drug-related arrhythmogenicity has been demonstrated from direct CNS injection of local anesthetic agents in vivo, suggesting CNS-related cardiotoxicity. This study investigated whether CNS site-directed blood-borne drug administration (with minimal systemic recirculation) would demonstrate drug-related cardiotoxicity. METHODS: Direct CNS effects and indirect cardiotoxic sequelae were determined after bilateral carotid arterial infusions of levobupivacaine, bupivacaine, or ropivacaine in ewes. After pilot studies to validate the procedures, equimolar doses (24-96 micromol, approximately 7.5-30 mg) were infused over 3 min using a crossover design. Behavioral CNS signs, quantitative electroencephalographic (EEG), cardiovascular, and electrocardiographic effects were recorded. Drug blood concentrations in superior sagittal sinus and aorta were measured serially. RESULTS: Blood drug concentrations in the superior sagittal sinus were 5-10 times those concurrently in the aorta, confirming highly selective CNS delivery with minimal systemic recirculation. Dose-dependent CNS excitatory behavior and EEG changes, with increased mean arterial blood pressure, heart rate, cardiac output, and myocardial contractility, were found, consistent with sympathetic nervous system stimulation. The overall rank order of potency for these effects was ropivacaine < levobupivacaine < bupivacaine. Nonfatal cardiac arrhythmias were observed, but the type or frequency did not differ between drugs. CONCLUSIONS: Although CNS site-selective drug delivery produced quantitative differences between bupivacaine, levobupivacaine, and ropivacaine in some CNS effects and cardiac sequelae, no differences were found in their arrhythmogenic potential.     

Comparison of resuscitation of sheep and dogs after bupivacaine-induced cardiovascular collapse

This study evaluated interspecies sensitivity and ability to resuscitate pentobarbital anesthetized sheep and dogs after cardiovascular toxic doses of bupivacaine. Every minute, 3 mg/kg of bupivacaine was injected into the right atrium over the course of 10 sec until cardiovascular collapse occurred. While the bupivacaine was given, the animals were made apneic for 90 sec and then ventilated with 100% oxygen. After the bupivacaine administration, cardiovascular collapse occurred in the form of electromechanical dissociation progressing to asystole in dogs, whereas in sheep the predominant rhythm was ventricular fibrillation leading to asystole. Resuscitation was performed using open chest heart massage, bretylium for treatment of ventricular tachycardia and fibrillation, and epinephrine with atropine for treatment of electromechanical dissociation or asystole. The initial dose of bupivacaine used to cause cardiovascular collapse was 3.5 +/- 1.2 mg/kg in sheep and 24.6 +/- 8.5 mg/kg in dogs (P less than 0.01). All sheep and dogs were resuscitated from the first cardiovascular collapse. The resuscitation time was 2.1 +/- 1.0 min in dogs and 36.9 +/- 15.4 min in sheep (P less than 0.01). All dogs could be resuscitated after two additional cardiovascular collapses induced by bupivacaine, but no sheep could be resuscitated after a second cardiovascular collapse. Concentrations of bupivacaine in cardiac tissue and serum levels of bupivacaine after the last resuscitation attempt were significantly greater in the dogs than in the sheep. We conclude that sheep are more sensitive to bupivacaine than dogs, but that even sheep can be resuscitated after cardiovascular collapse produced by bupivacaine.     

Comparison of the effects of racemic bupivacaine, levobupivacaine, and ropivacaine on ventricular conduction, refractoriness, and wavelength: an epicardial mapping study

BACKGROUND: The study was designed to compare the effects of equimolar concentrations of racemic bupivacaine, levobupivacaine, and ropivacaine on ventricular conduction, anisotropy, duration and homogeneity of refractoriness, and wavelengths, and to provide a potency ratio for effects on conduction velocity. METHODS: Isolated frozen rabbit hearts (which leave a thin layer of surviving epicardial muscle) were treated with 0.1, 1, and 10 mum racemic bupivacaine, levobupivacaine, or ropivacaine. Left ventricular longitudinal and transverse conduction velocities, anisotropic ratio, minimum pacing cycle length, use dependency, duration and dispersion of ventricular effective refractory period, and wavelengths were studied. A high-resolution mapping system was used for data acquisition. In addition to two-way analysis of variance for repeated measures, data for conduction velocities were fitted simultaneously using a nonlinear mixed-effect modeling program to allow intergroup comparison. RESULTS: Each agent induced a concentration- and use-dependent slowing of conduction velocities, with no change of the anisotropic ratio. The use-dependent effect of levobupivacaine is similar to that of racemic bupivacaine concerning longitudinal conduction velocity. Fitting of conduction velocities provided a racemic bupivacaine to levobupivacaine and to ropivacaine ratio of 1:1.38 for concentration effect at 1,000-ms pacing cycle length, and 1:0.74 for use-dependent effect at 600-ms pacing cycle length. Racemic bupivacaine and levobupivacaine prolonged the ventricular effective refractory period, whereas ropivacaine did not. No dispersion in ventricular effective refractory period values occurred. All three agents induced significant decreases in wavelengths. This effect was not different among groups. CONCLUSIONS: Differences among racemic bupivacaine, levobupivacaine, and ropivacaine at equimolar concentrations are mainly caused by the use-dependent effects on conduction velocities and the concentration-dependent effects on ventricular effective refractory period. Therefore, one must take into account the corresponding pacing rates when comparing the potency ratios of local anesthetics.     

Thoracic epidural anaesthesia decreases the incidence of ventricular arrhythmias during acute myocardial ischaemia in the anaesthetized rat

The aim of the present investigation was to study the effect of high thoracic epidural anaesthesia (TEA) on the incidence of ventricular arrhythmias after ligation of the left coronary artery in chloralose-anaesthetized rats. Forty animals were randomly assigned to receive either 40-50 microliter of bupivacaine (5 mg/ml) or saline in implanted thoracic epidural catheters. TEA decreased mean arterial pressure (MAP) from 118 +/- 5 mmHg to 72 +/- 4 mmHg and heart rate (HR) from 450 +/- 9 to 387 +/- 8 beats/min, while epidural saline did not affect MAP and HR. In both groups coronary artery ligation induced a transient decrease in MAP within the first 5-10 min after ligation. In the control group HR increased, during the 30-min post-ligation period, from 453 +/- 9 to 474 +/- 10 beats/min (P less than 0.05) while no significant change was seen in the TEA group. In both groups the mortality rate was 10%. In the TEA group 30% and in the control group 0% had normal sinus rhythm during the recording period (P less than 0.001). The incidence of ventricular fibrillation and/or tachycardia was significantly lower (P less than 0.05) in the TEA group (20%) compared to the control group (53%). The incidence of ventricular extrasystoles did not differ between the two groups. We conclude that TEA-induced blockade of sympathetic afferents and efferents may offer protection against malignant ventricular arrhythmias in the early phase of acute myocardial infarction.     

The effect of bupivacaine on myocardial tissue hypoxia and acidosis during ventricular fibrillation

Previously we observed that during bupivacaine-induced circulatory collapse, myocardial tissue pH declined more slowly than expected. Here we evaluated the effect of bupivacaine on myocardial acidosis induced by ventricular fibrillation. Sixteen dogs were anesthetized with 1.5% end-tidal isoflurane, the chest was opened, and a probe that measured oxygen pressure (PmO(2)), carbon dioxide pressure, pH, and temperature was inserted into myocardial tissue. After baseline measures, each dog received either 10 mg/kg bupivacaine (n = 8) or a sham saline treatment (n = 8). Three minutes later ventricular fibrillation was initiated electrically, and the rate of change in PmO(2) and pH during ventricular fibrillation was measured. Baseline physiological measures were similar in the two groups of dogs. During ventricular fibrillation there was a rapid decrease in PmO(2), and the rate of decrease was not different between sham- and bupivacaine-treated dogs. Tissue pH decreased during ventricular fibrillation, and the rate of decrease was 4 times faster in sham- compared with bupivacaine-treated dogs (P < 0.05). These results show that bupivacaine attenuated myocardial tissue acidosis during ventricular fibrillation. This potentially beneficial effect may be a result of bupivacaine's ability to inhibit myocardial lactate and carbon dioxide production. This suggests a potential clinical application of bupivacaine for myocardial preservation. IMPLICATIONS: In this animal study pretreatment with bupivacaine attenuated the progression of myocardial acidosis during ventricular fibrillation. The dogs regained normal hemodynamic variables after lipid infusion. The findings suggest such that bupivacaine may protect the heart against ischemic acidosis.     

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.     

Tolerability of large-dose intravenous levobupivacaine in sheep

In preclinical pharmacological studies of levobupivacaine (S-bupivacaine), we determined its tolerability, cardiovascular actions, and pharmacokinetics, and we estimated its margin of safety compared with bupivacaine in conscious sheep. Levobupivacaine HCl. H(2)O was infused IV for 3 min into 10 previously instrumented ewes (approximately 50 kg). On subsequent days, the doses were increased by 50 mg from 200 or 250 mg until fatality occurred. All doses produced convulsions, QRS widening, and cardiac arrhythmias. With incremental doses, 4 of 4 animals survived 200 mg, 7 of 10 survived 250 mg, 3 of 7 survived 300 mg, but 0 of 3 survived 350 mg. Death resulted from sudden onset ventricular fibrillation (n = 3, within 2-3 min), electromechanical dissociation-pump failure (n = 5, within 4-5 min), or ventricular tachycardia-induced cardiac insufficiency (n = 2, >10 min). The estimated fatal dose (mean +/- SD) was 277 +/- 51 mg for levobupivacaine (compared with 156 +/- 31 mg found previously for bupivacaine). Pharmacokinetic analysis indicated initial and total distribution volumes = 4.5 (+/-1.6) and 97 (+/-22) L, total clearance = 1.7 (+/-0.4) L/min, and slow half life = 70 (+/-29) min; these values did not differ from those found previously with smaller doses. Heart and brain tissue levobupivacaine concentrations were approximately 3 times those in arterial blood. The doses of levobupivacaine survived were larger than found previously for bupivacaine, indicating its greater margin of safety. IMPLICATIONS: Levobupivacaine produced fatal cardiac toxicity at doses significantly greater than those found in previous studies with bupivacaine. As the two drugs have similar potency for producing clinical nerve blocks, the data imply that levobupivacaine should provide a safer alternative to bupivacaine in practice.     

Systemic toxicity and resuscitation in bupivacaine-, levobupivacaine-, or ropivacaine-infused rats

We compared the systemic toxicity of bupivacaine, levobupivacaine, and ropivacaine in anesthetized rats. We also compared the ability to resuscitate rats after lethal doses of these local anesthetics. Bupivacaine, levobupivacaine, or ropivacaine was infused at a rate of 2 mg. kg(-1). min(-1) while electrocardiogram, electroencephalogram, and arterial pressure were continuously monitored. When asystole was recorded, drug infusion was stopped and a resuscitation sequence was begun. Epinephrine 0.01 mg/kg was administered at 1-min intervals while external cardiac compressions were applied. Resuscitation was considered successful when a systolic arterial pressure > or =100 mm Hg was achieved within 5 min. The cumulative doses of levobupivacaine and ropivacaine that produced seizures were similar and were larger than those of bupivacaine. The cumulative doses of levobupivacaine that produced dysrhythmias and asystole were smaller than the corresponding doses of ropivacaine, but they were larger than those of bupivacaine. The number of successful resuscitations did not differ among groups. However, a smaller dose of epinephrine was required in the Ropivacaine group than in the other groups. We conclude that the systemic toxicity of levobupivacaine is intermediate between that of ropivacaine and bupivacaine when administered at the same rate and that ropivacaine-induced cardiac arrest appears to be more susceptible to treatment than that induced by bupivacaine or levobupivacaine.     

EFFECT OF PROPRANOLOL ON CATECHOLAMINE-INDUCED ARRHYTHMIAS DURING NITROUS OXIDE-HALOTHANE ANAESTHESIA IN THE DOG

In dogs under nitrous oxide-halothane anaesthesia, ventriculararrhythmias were produced by intravenous injection of adrenalineand noradrenaline 2–3 µg/kg or isoprenaline 1µg/kg,and completely prevented by propranolol 0.3 mg/kg. Adrenalineor noradrenaline (20–30 µg/kg) produced slow rateventricular extrasystoles and ventricular bigeminy, withoutincrease in the rate of sinus rhythm. Doses of 100 to 150 µg/kgproduced ventricular tachycardia in all and ventricular fibrillationin some experiments. Increase in sinus rate always precededventricular tachycardia. Isoprenaline 10 µ/kg producedventricular tachycardia preceded by an increase in sinus rate.Very large doses (50 µg/kg) produced a greater increasein sinus rate, and later ventricular tachycardia and even ventricularfibrillation resulted in all the experiments. Dosages of catecholamineswhich did not produce any increase in the rate of sinus rhythmnever produced ventricular tachycardia or fibrillation.     

Minimum local analgesic doses of ropivacaine, levobupivacaine, and bupivacaine for intrathecal labor analgesia

BACKGROUND: Doses for intrathecal opioid-local anesthetic mixtures have been arbitrarily chosen. The aim of this study was to compare the analgesic efficacies of intrathecal ropivacaine, levobupivacaine, and bupivacaine for labor analgesia and to determine the analgesic potency ratios for these three drugs. For this purpose, the authors used the up-down sequential allocation model, which estimates the minimum local analgesic dose for intrathecal local anesthetic. METHODS: Ninety-seven nulliparous term parturients in spontaneous labor, requesting combined spinal-epidural analgesia, were randomly allocated to one of three groups to receive 0.25% spinal ropivacaine, levobupivacaine, or bupivacaine. The initial dose of the local anesthetic drug was chosen to be 2.5 mg, and the testing interval was set at 0.25 mg. The subsequent doses were determined by the response of the previous parturient. Efficacy was accepted if the visual analog pain score decreased to 10 mm or less on a 100-mm scale within 30 min. The minimum local analgesic dose was calculated using the method of Dixon and Massey. RESULTS: The intrathecal minimum local analgesic dose was 3.64 mg (95% confidence interval, 3.33-3.96 mg) for ropivacaine, 2.94 (2.73-3.16) mg for levobupivacaine, and 2.37 (2.17-2.58) mg for bupivacaine. The relative analgesic potency ratios were 0.65 (0.56-0.76) for ropivacaine:bupivacaine, 0.80 (0.70-0.92) for ropivacaine:levobupivacaine, and 0.81 (0.69-0.94) for levobupivacaine:bupivacaine. There were significant trends (P levobupivacaine > ropivacaine.     

Comparison of the Effects of Racemic Bupivacaine, Levobupivacaine, and Ropivacaine on Ventricular Conduction, Refractoriness, and Wavelength: An Epicardial Mapping Study

Background: The study was designed to compare the effects of equimolar concentrations of racemic bupivacaine, levobupivacaine, and ropivacaine on ventricular conduction, anisotropy, duration and homogeneity of refractoriness, and wavelengths, and to provide a potency ratio for effects on conduction velocity.

Methods: Isolated frozen rabbit hearts (which leave a thin layer of surviving epicardial muscle) were treated with 0.1, 1, and 10 [mu]m racemic bupivacaine, levobupivacaine, or ropivacaine. Left ventricular longitudinal and transverse conduction velocities, anisotropic ratio, minimum pacing cycle length, use dependency, duration and dispersion of ventricular effective refractory period, and wavelengths were studied. A high-resolution mapping system was used for data acquisition. In addition to two-way analysis of variance for repeated measures, data for conduction velocities were fitted simultaneously using a nonlinear mixed-effect modeling program to allow intergroup comparison.

Results: Each agent induced a concentration- and use-dependent slowing of conduction velocities, with no change of the anisotropic ratio. The use-dependent effect of levobupivacaine is similar to that of racemic bupivacaine concerning longitudinal conduction velocity. Fitting of conduction velocities provided a racemic bupivacaine to levobupivacaine and to ropivacaine ratio of 1:1.38 for concentration effect at 1,000-ms pacing cycle length, and 1:0.74 for use-dependent effect at 600-ms pacing cycle length. Racemic bupivacaine and levobupivacaine prolonged the ventricular effective refractory period, whereas ropivacaine did not. No dispersion in ventricular effective refractory period values occurred. All three agents induced significant decreases in wavelengths. This effect was not different among groups.     

Surgery of ventricular tachycardia and ventricular fibrillation in patients with coronary artery disease and LV-aneurysms

In 26 patients with left ventricular aneurysm and ventricular tachycardia and/or ventricular fibrillation following myocardial infarction, coronary angiography, left ventriculography and electrophysiologic examination were performed preoperatively. Surgery in all cases consisted of aneurysmectomy and mapping-guided endocardial resection of the area found to be the arrhythmogenic center. Four patients died peroperatively or during the postoperative hospital stay. The 22 survivors were followed up for 3-48 (mean 22) months postoperatively. There were no late deaths. Repeated electrophysiologic studies were performed in 18 of the survivors. Freedom from ventricular tachycardia and fibrillation was achieved in 21 patients, 17 after surgery alone and four after combined surgical and medical treatment. The remaining patient still has ventricular tachycardia despite combined treatment.     

Differences in cardiac toxicity among ropivacaine,levobupivacaine, bupivacaine,and lidocaine

Local-anesthetic (LA) cardiotoxicity remains a vexing issue in clinical practice. Growing demand for integration of regional and general anesthesia with acute pain management mandates that the contemporary anesthesiologist be knowledgeable about LA capabilities and toxicity. Although various LA agents are available for clinical use, they often must meet the requirements for both acute, intraoperative regional anesthesia and subacute, postoperative regional anesthesia. Usually, the long-acting LAs (historically, bupivacaine) fulfill these needs. However, when large volumes of concentrated LA are needed to shorten latency and increase duration, systemic toxicity may become an issue. For this reason, the newer, long-acting, amide LAs, ropivacaine and levobupivacaine, were developed; both are touted to have less cardiotoxic potential than bupivacaine. This report reviews normal impulse conduction and cardiac contraction, as well as the basic physiology and pharmacology of LA-induced cardiotoxicity. In addition, safety concerns with the long-acting LAs, current laboratory data on cardiac toxicity from these agents, and the implications of the data for clinical practice are reviewed. Copyright © 2001 by W.B. Saunders Company     

Determination of the full dose-response relation of intrathecal bupivacaine, levobupivacaine, and ropivacaine, combined with sufentanil, for labor analgesia

BACKGROUND: Ropivacaine and levobupivacaine are local anesthetics that produce less motor block and greater sensory-motor separation when compared with equal milligram doses of bupivacaine. Although minimum local analgesic concentration studies suggested that they are less potent than bupivacaine, full dose-response studies have not been performed. The current trial describes the dose-response relation of levobupivacaine, ropivacaine, and bupivacaine, combined with sufentanil, when used for intrathecal labor analgesia. METHODS: Four hundred fifty term parturients in active labor were included in this double-blind, randomized trial. Combined spinal-epidural anesthesia was performed, and ropivacaine, levobupivacaine, or bupivacaine was intrathecally administered in a dose of 1.0, 1.5, 2.0, 2.5, 3.0, or 3.5 mg, always combined with 1.5 microg sufentanil. Patients were considered responders to spinal analgesia if the visual analog scale score for pain was less than 25 mm within 15 min and the visual analog scale score remained less than 25 mm for 45 min. Patient demographics, obstetric data, maternal side effects, and fetal and neonatal well-being were noted. Group-specific dose-response curves were constructed using a probit regression model. RESULTS: The ED95 of bupivacaine was 3.3 mg (95% confidence interval, 2.9-4.1). The ED95s of ropivacaine and levobupivacaine were 4.8 mg (95% confidence interval, 4.0-6.7) and 5.0 mg (95% confidence interval, 4.1-7.0), respectively. Racemic bupivacaine was significantly more potent than ropivacaine (P=0.0027) and levobupivacaine (P=0.0006). Ropivacaine and levobupivacaine were of similar potency (P=0.91). CONCLUSIONS: This full dose-response study suggests that ropivacaine and levobupivacaine are of similar potency, whereas bupivacaine is more potent than both other drugs.     

Postoperative cardiac arrhythmias (author's transl)]

13 male patients suffering from arteriosclerotic heart disease and/or arterial hypertension were monitored continuously before and after vascular surgical procedures using an arrhythmia computer. Heart rate, paroxysmal supraventricular tachycardias, ventricular extrasystoles, ventricular tachycardias, ventricular fibrillation and prematurity index (QnQe/QTn) were recorded numerically. Ventricular arrhythmias were detected as follows preoperatively in 12 patients, after operation in all patients, paired ventricular extrasystoles or episodes of ventricular tachycardia were found in 5 cases before and in 7 after operation, ventricular fibrillation in one case. The incidence of ventricular dysrhythmias increased significantly (p less than 0.05) early after operation, as did the heart rate during the observed postoperative period (p less than 0.001). The prematurity index dropped below 1.0 during the two days following operation. This differed significantly from the preoperative value (p less than 0.05). The incidence of ventricular extrasystoles was related to postoperative myocardial infarction and heart failure (p less than 0.01), which occurred in 6 cases, with a lethal outcome in three. Only occasionally controlled by trained staff in a normal surgical ward the "Servomed Dysrhythmiemonitor" yielded reliable numerical results during the main part of the monitored period. In two cases it led to immediate detection and rapid institution of treatment of severe tachyar rhythmias.     

Determination of the Full Dose-Response Relation of Intrathecal Bupivacaine, Levobupivacaine, and Ropivacaine, Combined with Sufentanil, for Labor Analgesia

Background: Ropivacaine and levobupivacaine are local anesthetics that produce less motor block and greater sensory-motor separation when compared with equal milligram doses of bupivacaine. Although minimum local analgesic concentration studies suggested that they are less potent than bupivacaine, full dose-response studies have not been performed. The current trial describes the dose-response relation of levobupivacaine, ropivacaine, and bupivacaine, combined with sufentanil, when used for intrathecal labor analgesia.

Methods: Four hundred fifty term parturients in active labor were included in this double-blind, randomized trial. Combined spinal-epidural anesthesia was performed, and ropivacaine, levobupivacaine, or bupivacaine was intrathecally administered in a dose of 1.0, 1.5, 2.0, 2.5, 3.0, or 3.5 mg, always combined with 1.5 [mu]g sufentanil. Patients were considered responders to spinal analgesia if the visual analog scale score for pain was less than 25 mm within 15 min and the visual analog scale score remained less than 25 mm for 45 min. Patient demographics, obstetric data, maternal side effects, and fetal and neonatal well-being were noted. Group-specific dose-response curves were constructed using a probit regression model.

Results: The ED95 of bupivacaine was 3.3 mg (95% confidence interval, 2.9-4.1). The ED95s of ropivacaine and levobupivacaine were 4.8 mg (95% confidence interval, 4.0-6.7) and 5.0 mg (95% confidence interval, 4.1-7.0), respectively. Racemic bupivacaine was significantly more potent than ropivacaine (P = 0.0027) and levobupivacaine (P = 0.0006). Ropivacaine and levobupivacaine were of similar potency (P = 0.91).