Effect of Lidocaine on Ventricular Arrhythmias in Patients with Coronary Heart Disease

Gianelly, Ralph E.; Groeben, J. O. von der; Spivack, Alfred P.; Harrison, Donald C.

doi:10.1056/nejm196712072772301

Cited by 374 publications

(91 citation statements)

References 5 publications

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“…Lignocaine plasma concentrations above 6,g/ml are thought likely to result in toxicity reactions (Gianelly, Van der Groeben, Spivak & Harrison, 1967). More recent reports (Strong & Atkinson, 1972;Strong, Parker & Atkinson, 1973;Blumer et al, 1973;Halkin et al, 1975) have suggested the possible role of MEGX in the development of adverse reactions to lignocaine.…”

Section: Discussionmentioning

confidence: 99%

Lignocaine kinetics in cardiac patients and aged subjects.

Nation¹,

Triggs²,

Selig³

1977

Brit J Clinical Pharma

158

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1 The pharmacokinetics following long term intravenous infusion of lignocaine to cardiac patients have been examined. 2 Plasma levels and half‐lives of lignocaine and monoethylglycinexylidide (MEGX) showed wide inter‐patient variability. 3 Toxicity reactions to therapy were associated with elevated lignocaine and/or MEGX plasma levels. 4 In a separate study the effect of age on the pharmacokinetics of lignocaine was examined using bolus doses (50 mg) of the drug to young and aged subjects. 5 Elderly subjects had significantly longer half‐lives for lignocaine compared to younger individuals although no change in plasma clearance occurred. 6 The drug appeared to distribute differently in the aged as reflected by significantly increased apparent volumes of distribution. 7 The 24 h urinary recovery of the major metabolite (total 4‐hydroxyxylidine) showed a significant reduction in the elderly when compared to the young. 8 The clinical significance of these studies with respect to lignocaine therapy has been discussed.

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Section: Discussionmentioning

confidence: 99%

Lignocaine kinetics in cardiac patients and aged subjects.

Nation¹,

Triggs²,

Selig³

1977

Brit J Clinical Pharma

158

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“…Similarly, Bromage z states that from his resuits, the rate of absorption from the trachea was not predictable. Gianelly et al 8 concluded that the concentration of lidocaine in the blood following intravenous administration was directly related to the dose given. They also concluded that an effective safe blood level of 2 to 5/zg/ml is obtained by an intravenous bolus of 1 to 2 mg/kg, and that maior side effects may occur with blood levels of 9/zg/ ml.…”

Section: Discussionmentioning

confidence: 99%

Plasma lidocaine concentrations following topical aerosol application to the trachea and bronchi

Pelton

Daly

Cooper

et al. 1970

Can. Anaesth. Soc. J.

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Tins STUDY evolved from two recent developments at the Hospital for Sick Children, Toronto. The first was the avoidance of explosive anaesthetic agents for routine clinical practice. The second was the introduction into clinical use of a new endotracheal aerosol with a metering system which could deliver accurate doses of lidocaine. 1Previously, 4 per cent lidocaine was administered to the glottic and tracheal regions from a Macintosh spray. With this method, toxic blood levels could readily be reached in small infants from rapid absorption or from overdose. Foldes et aI. 2 investigated the acute toxicity of lldocahae following intravenous infusion. Objective signs of toxicity developed after an average dose of 6.4 mg/kg with a corresponding serum concentration of 5.29 -+-0.55 ftg/ml.Using 4 per cent lidocaine, Bromage et al? showed that the rate of absorption from the larynx and trachea varied. Following a dose of 3.5 to 10.5 mg/kg, peak blood concentrations occurred in 5 to 25 minutes. Bromage observed no toxic signs, although serum concentration did reach 10 ftg/ml in one case. He stated that statistically there is one chance in 20 that the concentration will reach 10 /zg/ml when a dose of 6 mg/kg is given jntratracheally. Therefore, he recommended that the dosage should be below this amount. METHODS

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“…23 As was the case in our study, it was shown in cardiac patients that the therapeutic and toxic effects of lidocaine are dose-dependent. 24 We found that side effects are rare (14%) if only patients with impaired liver function (Child B and C) are tested with the low-dose MEG-X test (Table 3). The inverse relationship between liver function and incidence of reported side effects was unexpected.…”

Section: Pharmacokinetic Parametersmentioning

confidence: 88%

The low-dose monoethylglycinexylidide test: Assessment of liver function with fewer side effects

et al. 1997

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tients with chronic active hepatitis and cirrhosis. [4][5][6][7] Other The hepatic metabolism of lidocaine (1 mg/kg intravestudies have speculated that the test could replace histology nously) to its metabolite monoethylglycinexylidide for the diagnosis of cirrhosis. [8][9][10] However, in addition to the (MEG-X) is the basis of the standard MEG-X test. To retest's diagnostic value, its side effects must be considered. duce the lidocaine-induced side effects, we evaluated the The majority of authors have reported a low preva-MEG-X formation after 0.5 and 1 mg/kg lidocaine intravelence. 3,4,8,10,11 Only one study reported side effects in almost nously in subjects with normal (n Å 5) and severely imall tested individuals. 9 Surprisingly, the symptoms following paired liver function (n Å 7) (study I). From this study, lidocaine injection were not related to the degree of hepatic a low-dose test (MEG-X concentration 30 minutes after histological changes or to the Child class. 9 Because of these 50 mg lidocaine intravenously [MEG-X 30min ] normalized contradictory findings, the safety of the MEG-X test has been to standard MEG-X test results) was developed. Sensory questioned, and further studies were recommended. 12,13 Most side effects from this low dose and from the standard lidocaine-induced side effects are dose-dependent. In con-MEG-X test were compared in a double-blind, randomtrast, lidocaine clearance and the MEG-X formation rate are ized, cross-over study (study II) comprising 15 individudose-independent. 14 To date, it has not been evaluated als with normal liver function and 45 patients with cirwhether this first-order kinetic model holds true for patients rhosis (15 Child A, 15 Child B, and 15 Child C). In study I, with advanced cirrhosis. If this were the case, it should be MEG-X formation rate was dose-independent in patients possible to reduce side effects by extrapolating MEG-X values with severely impaired liver function. In study II, norobtained with lower lidocaine doses to standard MEG-X test malized MEG-X test results (ranging from°4 to 120 mg/ results. Therefore, we studied (study I) the dose-dependent L) were virtually identical to the standard test results pharmacokinetics of lidocaine in patients with severely im-(mean difference: 01.9 mg/L; 95% confidence interval paired liver function. In a second double-blind randomized [CI]: 05.3; 1.5 mg/L). Fewer individuals experienced side controlled study (study II), we assessed the sensory quality effects (30% vs. 53%) with the low-dose test (P Å .0013).and intensity of patients' side effects with the aim of finding In a multivariate analysis, the Child-Pugh score was intheir relationship to lidocaine dosage and liver function. and 0.5 mg/kg body weight to individuals with normal (n Å 5) and severely impaired liver function (n Å 7). To compare the low-dose versus the standard MEG-X test (study II: double-blind, randomized, Lidocaine is metabolized to its principal metabolite, monocross-over design), we injected 1 mg/kg body weight lidocaine and 50 ...

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Effect of Lidocaine on Ventricular Arrhythmias in Patients with Coronary Heart Disease

Cited by 374 publications

References 5 publications

Lignocaine kinetics in cardiac patients and aged subjects.

Lignocaine kinetics in cardiac patients and aged subjects.

Plasma lidocaine concentrations following topical aerosol application to the trachea and bronchi

The low-dose monoethylglycinexylidide test: Assessment of liver function with fewer side effects

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