Clinical Pharmacokinetics of Lignocaine

Abstract

Lignocaine is widely used as a local anaesthetic and antiarrhythmic drug. It is commonly administered to patients with acute myocardial infarction as prophylaxis for ventricular fibrillation, although its efficacy in preventing primary ventricular fibrillation is still debated. Toxicity, sometimes with serious clinical consequence, is not uncommom and is usually related to overdosage. Blood lignocaine concentrations correlate roughly with antiarrhythmic and toxic effects and might be useful as an end point for monitoring prophylactic therapy. Administration of lignocaine as a local anaesthetic may result in blood lignocaine concentration in the antiarrhythmic or even toxic ranges. Expected peak levels for various routes of local anaesthesia are tabulated so that 'safe' total doses can be calculated. Intramuscular injection of high doses results in sustained therapeutic levels but is often associated with early minor toxicity. Lignocaine is eliminated primarily by hepatic metabolism, which appears to be limited by liver perfusion. Active metabolites may contribute to therapeutic and/or toxic effects. Disease states such as cardiac failure or drugs that alter hepatic blood flow may significantly affect lignocaine clearance. Pharmacokinetic studies in man show wide variability in drug disposition between patients, even when cardiac and hepatic status is considered, making specific dosing recommendations a problem. With intravenous injection, multicompartment kinetics is observed, with an initial rapid decline phase and initial decline in antiarrhythmic activity due to redistribution. With constant infusion, steady state concentrations of lignocaine are seen after 3 to 4 hours in normal subjects and after 8 to 10 hours in patients with myocardial infarction without circulatory insufficiency. In patients with cardiac failure, blood lignocaine concentration may continue to rise for 24 to 48 hours. In the presence of cardiac failure, decreased volumes of distribution and clearance require reduction in loading and maintenance doses. Lignocaine clearance is reduced in patients with liver disease and appears to be a sensitive index of liver dysfunction. A dosing algorithm for treatment of patients with myocardial infarction is presented.

The effect of intravenous lidocaine on laryngeal and respiratory reflex responses in anaesthetised children*

“…No adverse reactions were observed when a lidocaine bolus of 2 mg.kg ) in this study is unlikely to cause side effects in anaesthetised patients [18]. A lidocaine dose-response relationship was observed in a study by Yukioka et al [9], who reported complete suppression of cough when Anaesthesia 2013, 68, 13-20 Erb et al | Intravenous lidocaine and respiratory reflex responses plasma levels were above 3 lg.ml )1 when tracheal intubation was attempted in adults.…”

Which is Safer to Avoid an Increase in ICP After Endotracheal Suctioning in Severe Head Injury: Intravenous or Endotracheal Lidocaine?

“…There are conflicting views in studies regarding maximum safe doses of local anesthetic drugs [30][31][32][33]. There was direct correlation between pharmacological effect of lidocaine [30,31] and blood concentration of lidocaine in arterial plasma at which symptoms of local anesthetic toxicity were evident ranging from 2.0 to 6.0 μg/mL [34]. Therefore, we suggest that ETL can be used as safely as IVL, as long as plasma levels of lidocaine are outside the range of toxicities.…”

“…For ETL dosage in our study we used 1 mg/kg of lidocaine while Groeben et al [25] used 5 mg/kg and had a lidocaine plasma concentration of 1.5 ± 0.14 μg/mL, that suggests that the level of lidocaine in our patients' plasma was lower than 1.5 μg/mL. There are conflicting views in studies regarding maximum safe doses of local anesthetic drugs [30][31][32][33]. There was direct correlation between pharmacological effect of lidocaine [30,31] and blood concentration of lidocaine in arterial plasma at which symptoms of local anesthetic toxicity were evident ranging from 2.0 to 6.0 μg/mL [34].…”

A Population Pharmacokinetic Model of Epidural Lidocaine in Geriatric Patients: Effects of Low-Dose Dopamine

“…When taken orally, lidocaine has a high hepatic extraction ratio (4) with a fast, liver-dependent first-pass elimination (25). Given intravenously, a bolus lidocaine injection has been described by a two-compartment pharmacokinetic model with a fast distribution phase (half-life 8 min), and slower elimination phase (half-life, 100 min) (31).…”