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Biomedical subjects

A S Manolis

Publications and source records attributed to A S Manolis.

At least 19 recordsLinked to original sources

Limited clinical utility of endomyocardial biopsy in patients presenting with ventricular tachycardia without apparent structural heart disease.

To determine the cardiac pathology underlying ventricular tachyarrhythmias, endomyocardial biopsy was performed in 14 patients, 10 men and 4 women, with a mean age of 40 years (range 17-63) and no apparent structural heart disease, presenting with high-density symptomatic nonsustained ventricular tachycardia (VT) (n = 4), sustained VT (n = 6), and ventricular fibrillation (n = 4). The absence of coronary or valvular heart disease was documented by cardiac catheterization. The mean left ventricular ejection fraction was 56 +/- 10%. Noninvasive assessment of the ventricular arrhythmia was made in all patients with Holter monitoring and/or exercise testing, while invasive evaluation with programmed electrical stimulation was performed in 13 patients. Biopsy findings included subendocardial and interstitial fibrosis in 7 patients, and monocytes containing periodic acid Schiff (PAS) positive vacuoles in 1 patient; biopsy was normal in 6 patients. There was no relationship between the presence or absence of pathologic abnormalities on biopsy and left ventricular ejection fraction, presenting or induced arrhythmias, or prognosis. Pathologic evidence supporting a specific treatable diagnosis was not present in any biopsy. Drugs to suppress spontaneous (3 patients) or induced (8 patients) VT were instituted, while 2 patients were not treated. In 1 patient who was resuscitated from out-of-hospital cardiac arrest an automatic defibrillator was implanted. In 24.6 months of mean follow-up there was 1 nonfatal arrhythmia recurrence, 1 noncardiac death, and 1 sudden death in a patient with fibrosis on biopsy, an ejection fraction of 45%, and both inducible and spontaneous sustained VT suppressed with an antiarrhythmic agent.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Cost-effectiveness of the implantable cardioverter-defibrillator: effect of improved battery life and comparison with amiodarone therapy.

The implantable cardioverter-defibrillator (ICD) greatly reduces the incidence of sudden cardiac death among patients with recurrent sustained ventricular tachycardia and fibrillation who do not respond to conventional antiarrhythmic therapy. A cost-effectiveness analysis was performed, comparing the ICD, amiodarone and conventional agents. Actual variable costs of hospitalization and follow-up care were used for 21 ICD- and 43 amiodarone-treated patients. Life expectancy and total variable costs were predicted with use of a Markov decision analytic model. Clinical event rates and probabilities were based on published reports or expert opinion. Life expectancy with an ICD (6.1 years) was 50% greater than that associated with treatment with amiodarone (3.9 years) and 2.5 times that associated with conventional treatment (2.5 years). Assuming replacement every 24 months, ICD lifetime treatment costs (in 1989 dollars) for a 55-year old patient are expected to be $89,600 compared with $24,800 for amiodarone and $16,100 for conventional therapy, yielding a marginal cost/effectiveness ratio for ICD versus amiodarone therapy of 1f429,200/year of life saved, which is comparable to that of other accepted medical treatments. If technologic improvements extend average battery life to 36 months, the marginal cost/effectiveness ratio would be $21,800/year of life saved, and at 96 months it would be $13,800/year of life saved. Patient age at implantation did not significantly affect these results. If quality of life on amiodarone therapy is 30% lower than that with the ICD, the marginal cost/effectiveness ratio decreases by 35%. If the quality of life for patients receiving drugs is 40% lower than that of patients treated with an ICD, use of the defibrillator becomes the dominant strategy.

Amiodarone

Electrophysiological and electropharmacological studies in pre-excitation syndromes: results with propafenone therapy and isoproterenol infusion testing.

To study the electrophysiological effects of oral propafenone on accessory pathways and determine the potential for catecholamine-mediated reversal of these effects, comprehensive electrophysiology studies (EPS) were conducted in 11 patients with manifest (n = 9) or concealed (n = 2) pre-excitation syndrome. EPS were performed at baseline (in the drug-free state), after oral propafenone loading, and with isoproterenol infusion during propafenone therapy. The study group included 10 men and 1 woman with a mean age of 39 +/- 13 years, who presented with symptoms of palpitations (n = 6), presyncope (n = 3) and syncope (n = 2). The clinical arrhythmia was atrioventricular reciprocating tachycardia (n = 6), atrial flutter/fibrillation (n = 3), or both (n = 2). During the baseline EPS the accessory pathway location was identified as left (n = 6) or septal (n = 5). The mean anterograde effective refractory period was 265 +/- 42 ms, the shortest pre-excited RR interval 259 +/- 20 ms and the retrograde refractory period 258 +/- 39 ms. Orthodromic atrioventricular reciprocating tachycardia was induced in 10 patients (mean cycle length = 324 +/- 31 ms). Antidromic reciprocating tachycardia was induced in one patient (cycle length = 340 ms). In all the 11 patients EPS were repeated after 4 days of oral propafenone loading (668 +/- 226 mg daily) when drug steady state was expected to have been achieved. One additional patient had baseline EPS but developed clinical arrhythmia recurrences after propafenone loading and thus he was excluded from the study; follow-up EPS were conducted on procainamide.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists

Effect of successful coronary angioplasty on the signal-averaged electrocardiogram.

The effect of successful coronary artery angioplasty on the signal-averaged electrocardiogram (SAECG) was examined in 50 patients (41 men, 9 women, aged 55 +/- 8 years) with stable (26 patients) or unstable angina (24 patients) and good overall left ventricular function (ejection fraction = 55% +/- 8%). The SAECG was recorded before and within 24-48 hours after the angioplasty and was filtered at 40-250 Hz, with 250 beats averaged. The noise level averaged 0.57 +/- 0.15 microV before and 0.56 +/- 0.17 microV after the procedure. There was no overall significant difference between pre- and postangioplasty SAECGs. Subgroup analysis showed that 14 patients had a significant increase of the root mean square voltage of the last 40 msec of the filtered QRS that was independent of noise level changes, previous myocardial infarction, stable or unstable angina status, positive or negative baseline SAECG, or vessel being dilated. Eleven patients (22%) had late potentials at baseline, of whom four (36%) lost them after angioplasty, while one patient developed them after the procedure, all due to root mean square voltage changes. Thus, successful angioplasty exerted no significant overall effect on the SAECG, suggesting that the substrate of late potentials was not grossly altered by the procedure in our patients. However, there appear to be some patients, constituting approximately one third of this study population, who derive a favorable influence on the SAECG from angioplasty, a subgroup that needs to be further defined in future studies.

Angina Pectoris

Electrophysiologic and electrocardiographic effects, efficacy and safety of encainide in malignant ventricular arrhythmias associated with coronary artery disease.

The electrophysiologic and electrocardiographic effects, efficacy and safety of encainide were evaluated in 48 patients with coronary artery disease undergoing programmed stimulation for ventricular tachyarrhythmias. The study group included 41 men and 7 women, aged 64 +/- 8 years (mean +/- standard deviation), who had presented with nonsustained ventricular tachycardia (VT) (4 patients), sustained VT (32), ventricular fibrillation (8) or unexplained syncope (4). The left ventricular ejection fraction averaged 34 +/- 13%. The arrhythmias induced at the baseline, drug-free electrophysiologic study included nonsustained VT in 8 patients, sustained VT in 35 and ventricular fibrillation in 5. All patients had failed greater than or equal to 1 class IA and a combination of class IA and IB agents (mean 2.2 +/- 1.1 drugs) before encainide. Oral encainide was given in a mean daily dose of 80 +/- 11 mg for greater than or equal to 3 days before repeat programmed stimulation. Encainide was discontinued before follow-up electrophysiologic testing in 5 patients due to spontaneous development of new sustained VT. Of the 43 patients undergoing electropharmacologic testing with encainide, 5 had no inducible arrhythmia. In 9 patients VT was inducible by fewer extrastimuli, in 2 patients a previously stable VT required cardioversion, whereas in 28 patients VT remained inducible by the same number of or more extrastimuli. Thus, encainide prevented the induction of VT or ventricular fibrillation in 5 of 48 patients (10%), while it had a possible proarrhythmic effect in 15 patients (31%). Of the 5 patients without inducible VT administered long-term encainide therapy, 1 returned within 4 weeks of hospital discharge with VT recurrence.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

Syncope: current diagnostic evaluation and management.

OBJECTIVE: To provide a comprehensive review of the causes, current diagnostic evaluation, and treatment of syncope. DATA IDENTIFICATION: New data and knowledge in this evolving field were critically analyzed by doing a MEDLINE search on syncope supplemented by selective review of English language literature citations in the Index Medicus before 1980. STUDY SELECTION: We reviewed approximately 200 published articles on syncope and closely related topics as well as using our own clinical experience. We selected articles if they addressed the pathophysiology of syncope, classification and causes, differential diagnosis, noninvasive and invasive evaluation, and current therapy. RESULTS OF DATA SYNTHESIS: Syncope is a common clinical problem, occurring in 30% to 50% of the adult population. The prognosis for syncope depends on its cause. Cardiac syncope has the worst prognosis and therefore mandates thorough evaluation and prompt treatment. Diagnostic evaluation is made difficult by the transient nature of the episodes and the many causes. Noninvasive testing reveals the cause of syncope in approximately 50% of cases. More extensive evaluation, including invasive electrophysiologic studies, has assumed a larger role in defining the cause of syncope in selected patients with structural heart disease in whom a noninvasive evaluation has been nondiagnostic. Recently tilt-table studies have been proposed as a clinically useful noninvasive test for vagally mediated syncope. CONCLUSIONS: A rational stepwise diagnostic and therapeutic approach to patients with syncope can be developed by initially doing a careful history and physical examination followed by a noninvasive evaluation and selective use of additional, more specialized or invasive tests. Future research should focus on defining the validity and utility of current diagnostic testing in syncope and on exploring further the pathophysiology of patients with recurrent, unexplained syncope.

Cardiovascular Diseases

Value of programmed ventricular stimulation in the evaluation and management of patients with nonsustained ventricular tachycardia associated with coronary artery disease.

Programmed ventricular stimulation with up to 3 extrastimuli at the right ventricular apex was performed in 52 patients with spontaneous nonsustained ventricular tachycardia (VT) associated with coronary artery disease. There were 44 men and 8 women, aged 66 +/- 9 years (range 45 to 86). The mean left ventricular ejection fraction was 41 +/- 14%. Nonsustained VT was asymptomatic in 10 patients (19%), while the arrhythmia was detected during evaluation of palpitations in 5 patients (10%), presyncope in 11 (21%) and syncope in 26 patients (50%). All patients were tested in the drug-free state and were classified as having no inducible arrhythmia (31 patients, group I), or an inducible arrhythmia (21 patients, group II). The age, gender, type of heart disease, symptoms and left ventricular ejection fraction were similar in both groups. Group I patients had a higher overall incidence of syncope. Group I patients received no therapy, while group II patients received antiarrhythmic therapy guided by electropharmacologic testing. At 21 +/- 17 months there was no sustained VT in either group. There were 3 deaths in group I patients, including 1 sudden, 1 nonsudden cardiac and 1 noncardiac death. In group II patients 6 deaths occurred including 4 nonsudden cardiac and 2 noncardiac deaths. In patients with nonsustained VT and coronary artery disease undergoing programmed ventricular stimulation, the incidence of significant arrhythmic events is low in those without therapy with no inducible arrhythmia, and in those with an inducible arrhythmia with therapy guided by electrophysiologic testing.

Anti-Arrhythmia Agents

Randomized double-blind study of intravenous tocainide versus lidocaine for suppression of ventricular arrhythmias after cardiac surgery.

To compare the therapeutic efficacy and safety of intravenous tocainide with that of intravenous lidocaine in patients with ventricular arrhythmias after cardiac surgery, 25 patients were randomized to either agent in a double-blind manner. Tocainide was given in 16 patients as a 250 mg bolus followed by a loading infusion of 500 mg over 15 minutes and a maintenance infusion of 33.3 mg/min. Lidocaine was administered in 9 patients as a 100 mg bolus followed by a loading infusion of 60 mg over 15 minutes and a maintenance infusion of 1.4 mg/min. Therapy was continued for 24 hours in initially responding patients. With analysis of 24-h taped electrocardiograms it was found that single premature ventricular complexes (PVCs) were suppressed by tocainide by more than 80% in 94% of patients and by lidocaine in 75% of patients (p = NS). Couplets and ventricular tachycardia events were eliminated in all patients by either drug. Multiform PVCs were abolished in 94% of the patients after tocainide and in 75% after lidocaine (p = NS). Average overall success over the 24 hours with more than 80% suppression of single PVCs and simultaneous elimination of higher forms of arrhythmia was 71% with tocainide and 59% with lidocaine (p = NS). Adverse effects were negligible, with only one patient in the lidocaine group developing diaphoresis without necessitating termination of therapy. Treatment rapidly produced and then maintained blood levels of 4-10 mg/l for tocainide and 1-4 mg/l for lidocaine. We conclude that intravenous tocainide is well tolerated and has comparable efficacy to lidocaine in the acute therapy of postcardiac surgery ventricular arrhythmias.

Adult

Mexiletine: pharmacology and therapeutic use.

Mexiletine is a Class IB antiarrhythmic which has basic and clinical electrophysiologic properties similar to lidocaine. Like other Class I antiarrhythmic agents, mexiletine blocks the rapid inward sodium current responsible for phase 0 of the action potential. It has been noted in the clinical electrophysiology laboratory to have minimal effect on sinus node function and AV nodal and His-Purkinje system conduction. Pharmacokinetic studies have shown that oral absorption is rapid with bioavailability of 80-90%. Mexiletine is predominantly metabolized by the liver with elimination half-life of 9 to 12 hours. The antiarrhythmic effects of the primary drug's metabolites remain to be defined. Hemodynamic studies have shown mexiletine to have a lesser negative inotropic effect than procainamide or disopyramide. Although mexiletine as a single agent successfully suppresses 60 to 80% of spontaneous ventricular arrhythmias, it has lower efficacy in suppression of induced ventricular arrhythmias. Multiple studies have shown that as monotherapy mexiletine is effective in preventing the induction of ventricular tachycardia in approximately 20% of patients. When used in combination with a Class IA antiarrhythmic drug for suppression of induced ventricular arrhythmias, multiple investigators have reported greater efficacy. Neurological side effects (tremor, dizziness, memory loss) occur in approximately 10% of patients while gastrointestinal side effects (nausea, anorexia, gastric irritation) occur in up to 40% of patients. Proarrhythmia or other serious toxicity from the drug is uncommon.

Anti-Arrhythmia Agents

Apical hypertrophic cardiomyopathy presenting with sustained monomorphic ventricular tachycardia and electrocardiographic changes simulating coronary artery disease and left ventricular aneurysm.

A 52-year-old male presented with sustained monomorphic ventricular tachycardia as the initial manifestation of apical hypertrophic cardiomyopathy. The electrocardiogram during normal sinus rhythm showed a pattern of an old anterior wall myocardial infarction with aneurysm formation. Cardiac catheterization documented angiographically normal coronary arteries. Apical hypertrophic cardiomyopathy was documented at cardiac catheterization and by echocardiogram and Doppler studies. Monomorphic ventricular tachycardia was reproducibly initiated and terminated during electrophysiological studies and antiarrhythmic drugs failed to control the tachycardia. At the time of implantation of a cardioverter defibrillator, left ventricular apical biopsy revealed pathologic findings characteristic of hypertrophic cardiomyopathy.

Cardiomyopathy, Hypertrophic

Automatic implantable cardioverter defibrillator. Current status.

The automatic implantable cardioverter defibrillator was conceived by Mirowski as an implantable device for detection and termination of ventricular fibrillation. Since the initial human implant of the defibrillator in 1980, there has been a dramatic expansion of the clinical experience with more than 5000 implants. The technology of the device, which is now capable of sensing and terminating both ventricular tachycardia and fibrillation, has evolved rapidly. Although still not an ideal antiarrhythmic device, it has already had a major impact on arrhythmic mortality with a marked reduction in the sudden death rates in a high-risk patient population.

Arrhythmias, Cardiac

Reversal of electrophysiologic effects of flecainide on the accessory pathway by isoproterenol in the Wolff-Parkinson-White syndrome.

To determine the reversibility of the effects of flecainide on accessory pathways, electrophysiologic studies were performed in the drug-free control state, after flecainide loading and with isoproterenol infusion during flecainide treatment in 12 patients with symptomatic preexcitation syndrome. After the baseline drug-free evaluation, oral flecainide was given in dosages of 50 to 200 mg twice daily (mean daily dose 282 +/- 75) for at least 4 days before the repeat electrophysiologic study. Isoproterenol infusion was given in dosages of 1 to 4 micrograms/min to increase the heart rate at rest by 50%. Anterograde block in the accessory pathway was observed in 3 patients with flecainide therapy, whereas in the other patients the anterograde refractory period increased from 243 +/- 20 to 315 +/- 23 ms (p less than 0.05). The shortest preexcited RR interval during atrial fibrillation lengthened from 234 +/- 27 ms before flecainide to 313 +/- 38 ms (p less than 0.05). Retrograde block occurred in 2 patients after flecainide, whereas the retrograde refractory period of the accessory pathway increased from 247 +/- 26 to 337 +/- 45 ms in the other patients. Orthodromic atrioventricular reciprocating tachycardia, inducible in 10 patients before therapy, became noninducible in 3 patients. Its rate was significantly slowed in the other 7 patients (from 346 +/- 50 to 471 +/- 81 ms). In 2 patients the tachycardia was nonsustained during flecainide treatment. Atrial fibrillation, inducible in all patients at baseline, was rendered nonsustained and more difficult to induce in 7 patients with flecainide. When isoproterenol was infused during flecainide treatment, complete anterograde (3 patients) or retrograde block (2 patients) persisted in the accessory pathway.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Prognostic value of early electrophysiologic studies for ventricular tachycardia recurrence in patients with coronary artery disease treated with amiodarone.

Amiodarone was used in 86 patients with ventricular tachycardia (VT) (67 patients) or ventricular fibrillation (19 patients) secondary to coronary artery disease. The mean +/- standard deviation left ventricular ejection fraction was 30 +/- 12% (range 8 to 65%). Prior trials with 4 +/- 1.2 alternate antiarrhythmic agents had been unsuccessful. Amiodarone was loaded at dosages of 1,200 to 1,800 mg/day, with maintenance dosages of 400 to 600 mg/day. Drug efficacy was evaluated by programmed stimulation at 10 to 14 days in 68 patients. In 38 patients sustained VT or ventricular fibrillation was inducible (group I), whereas 30 patients (group II) had either no inducible VT (8) or had nonsustained VT induced (22). Holter monitoring was used to assess drug efficacy in 18 patients (group III). All patients were evaluated at 3- to 6-month intervals with Holter monitors for efficacy and a standard protocol for toxicity. During a long-term follow-up of 18 +/- 16 months, sudden death occurred in 5 patients and nonfatal arrhythmia recurrences were detected in 16. The actuarial probability of freedom from fatal and nonfatal arrhythmia recurrences at 24 months was 0.52 for group I, 0.97 for group II and 0.68 for group III. The mode of induction, rate change or hemodynamic tolerance of the induced ventricular tachycardia did not predict arrhythmia recurrence. Among the clinical variables analyzed, only an ejection fraction of less than or equal to 30% was identified as a significant predictor of arrhythmia recurrence. Nonsudden cardiac death occurred in 21 patients, including 19 from heart failure and 2 from myocardial infarction. Noncardiac death occurred in 7 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

External cardiac programmed stimulation for noninvasive termination of sustained supraventricular and ventricular tachycardia.

To examine the feasibility of using a noninvasive temporary pacemaker for termination of well-tolerated supraventricular (SVT) and ventricular tachycardia (VT), a standard external demand pacemaker was modified to allow stimulation with single or multiple extrastimuli and overdrive pacing. To evaluate the efficacy, safety and tolerance of external cardiac programmed stimulation, a standard arrhythmia termination protocol was used in 223 tachycardias in 22 patients. The technique of external cardiac programmed stimulation was used in 209 episodes of SVT in 13 patients. It terminated 95% of the episodes with success in 19 of 20 episodes of atrioventricular nodal reentrant tachycardia and 179 of 189 episodes of atrioventricular reciprocating tachycardia. Of 198 episodes of SVT terminated by the technique 168 (85%) were terminated by a single extrastimulus and 28 (14%) by double extrastimuli. Only 2 episodes of SVT required overdrive pacing for termination. External cardiac programmed stimulation did not result in atrial fibrillation or arrhythmia acceleration. Of 14 episodes of sustained monomorphic VT 5 were terminated by external cardiac programmed stimulation. One tachycardia was terminated by a single extrastimulus, 1 by double extrastimuli and 3 by overdrive pacing. Arrhythmia acceleration occurred once and was terminated by endocardial pacing. On 27 separate occasions patient evaluation of maximal discomfort included 4 ratings of mild, 10 of moderate, 11 of severe and 2 of intolerable discomfort. External cardiac programmed stimulation is effective and safe in patients with well-tolerated sustained supraventricular or ventricular arrhythmias.

Adult

Clinical experience in seventy-seven patients with the automatic implantable cardioverter defibrillator.

Seventy-seven patients with drug-refractory sustained ventricular tachycardia (VT) (28 patients) or ventricular fibrillation (VF) (49 patients) underwent implantation of an automatic cardioverter defibrillator (AICD). The 67 men and 10 women, with a mean age of 60 +/- 12 years (range 18 to 79), had coronary artery disease (60 patients), idiopathic cardiomyopathy (eight patients), mitral valve prolapse (four patients), hypertensive heart disease (one patient), Ebstein's anomaly (one patient), long QT syndrome (one patient), and primary electrical disease (two patients). The mean left ventricular ejection fraction was 35 +/- 16% (range 10% to 75%). Sustained VT/VF was induced in 64 patients (83%) at baseline electrophysiologic testing. A mean of 4.1 +/- 1.3 antiarrhythmic drugs failed to control the arrhythmia. Associated surgery at AICD implantation included coronary artery bypass in 19 patients, coronary bypass with aneurysmectomy in six patients, and aneurysmectomy alone in one patient. Five patients had only prophylactic patches implanted during aneurysmectomy or coronary bypass and the AICD device was subsequently implanted under local anesthesia to prevent arrhythmia recurrence or to control persistently inducible VT. Operative mortality was 2.6% with two deaths from intractable VF. Fifty-two patients (69%) continued receiving antiarrhythmic drugs to suppress spontaneous VT. During a mean follow-up of 15 +/- 13 months (range 1 to 63), six patients died: two suddenly due to probable pulse generator failure (greater than 2 years old), one of acute myocardial infarction, two of heart failure, and one of respiratory failure.(ABSTRACT TRUNCATED AT 250 WORDS)

Actuarial Analysis

Therapeutic serum lidocaine and metabolite concentrations in patients undergoing electrophysiologic study after discontinuation of intravenous lidocaine infusion.

Serum concentrations of lidocaine and its metabolites monoethylglycinexylidide (MEGX) and glycinexylidide (GX) were measured in seven patients after discontinuation of intravenous lidocaine necessary for control of spontaneous arrhythmias prior to electrophysiologic study. Standard loading doses of lidocaine were given intravenously followed by 2 mg/min infusions for 79.5 +/- 6.5 hours. Electrophysiologic studies all started more than 5 half-lives or 7.5 hours after discontinuation of intravenous lidocaine. Local anesthesia with subcutaneous lidocaine (mean 162 +/- 96 mg) was administered in six patients. Plasma concentrations of lidocaine and its metabolites were determined at the termination of the infusion, 2 and 4 hours afterwards, at the start of the electrophysiologic study prior to local anesthesia, and at the end of the study. Levels were also determined at 12 and 24 hours after discontinuation of the infusion. Mean plasma concentrations of lidocaine, MEGX, and GX at the start of the study were 1.02, 0.86, and 0.62 micrograms/ml, respectively. These had increased to 2.78, 0.92, and 0.68 by the end of the electrophysiologic study. One patient with coronary artery disease and prior out-of-hospital ventricular fibrillation had a therapeutic lidocaine level and no inducible arrhythmia at the time of the initial study. At a subsequent electrophysiologic study, no lidocaine or metabolites were detected in the serum and ventricular fibrillation was induced. Thus using the reported half-life of 90 minutes and discontinuing lidocaine 5 half-lives prior to electrophysiologic evaluation does not ensure lack of electrophysiologic effects of the parent compound or its metabolites. Lidocaine given for local anesthesia further increases lidocaine and metabolite levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged