Fatal Lignocaine Poisoning: Report of Two Cases and Review of the Literature

Dawling, S.; Flanagan, R.J.; Widdop, B.

doi:10.1177/096032718900800512

Cited by 15 publications

(10 citation statements)

References 12 publications

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“…A blood concentration of 40 mg/L was reported in a 58-year-old man who died after oral ingestion of the drug [8]. An 18-month-old infant who died after ingestion of 2% viscous lidocaine had a blood concentration of 1.1 mg/mL [16] (Table 2).…”

Section: Discussionmentioning

confidence: 99%

“…Neurotoxic manifestations appear at lower concentrations than cardiotoxic symptoms which are correlated with plasma levels of lidocaine [8,23]. Severe systemic symptoms related to the central nervous system consist of respiratory depression, convulsion, and coma [1].…”

Section: Discussionmentioning

confidence: 99%

“…Various several accidental fatalities and suicides following intravenous injection of lidocaine have been reported [5][6][7][8][9][10][11][12] while, rare are the fatal cases realized after oral ingestion of lidocaine [8,[13][14][15][16].…”

Section: Introductionmentioning

confidence: 99%

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Suicide due to oral ingestion of lidocaine: a case report and review of the literature

Centini

Fiore

Riezzo

et al. 2007

Forensic Science International

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Suicide due to oral ingestion of lidocaine: a case report and review of the literature

Centini

Fiore

Riezzo

et al. 2007

Forensic Science International

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“…Lidocaine solution may also be swallowed before endoscopic procedures. There are several reports of toxicity from orally administered lidocaine, especially in paediatric patients (Hess & Walson 1988; Dawling et al 1989; Gonzalez del Ray et al 1994; Zuberi et al 2000). In the present study the C max of lidocaine after placebo ranged from approximately 50 to 220 ng/ml, and after fluvoxamine alone and together with erythromycin from 110 to 900 ng/ml.…”

Section: Discussionmentioning

confidence: 99%

Effect of Fluvoxamine and Erythromycin on the Pharmacokinetics of Oral Lidocaine

Isohanni

Neuvonen

Olkkola

2006

Basic Clin Pharma Tox

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Lidocaine is metabolized by cytochrome P450 3A4 (CYP3A4) and CYP1A2 enzymes, but inhibitors of CYP3A4 have had only a minor effect on its pharmacokinetics. We studied the effect of co-administration of fluvoxamine (CYP1A2 inhibitor) and erythromycin (CYP3A4 inhibitor) on the pharmacokinetics of lidocaine in a double-blind, randomized, three-way cross-over study. Eight healthy volunteers ingested daily either 100 mg fluvoxamine and placebo, 100 mg fluvoxamine and 1500 mg erythromycin, or their corresponding placebos (control) for five days. On day 6, 1 mg/kg lidocaine was administered orally. Plasma concentrations of lidocaine, monoethylglycinexylidide (MEGX) and 3-hydroxylidocaine (3-OH-lidocaine) were measured for 10 hr. During the fluvoxamine phase the area under the plasma concentration-time curve (AUC) and peak concentration (C max ) of oral lidocaine were 305% (PϽ0.001) and 220% (PϽ0.05) of the control values. During the combination of fluvoxamine and erythromycin, lidocaine AUC was 360% (PϽ0.001) and C max 250% (PϽ0.05) of those during placebo. Fluvoxamine alone had no statistically significant effect on the half-life of lidocaine (t 1/2 ), but during the combination phase t 1/2 (3.8 hr) was significantly longer than during the placebo phase (2.4 hr; PϽ0.01). Fluvoxamine alone and in the combination with erythromycin decreased MEGX peak concentrations by approximately 50% (PϽ0.001) and 30% (PϽ0.01), respectively. We conclude that inhibition of CYP1A2 by fluvoxamine considerably reduces the presystemic metabolism of oral lidocaine and may increase the risk of lidocaine toxicity if lidocaine is ingested. The concomitant use of both fluvoxamine and a CYP3A4 inhibitor like erythromycin may further increase plasma lidocaine concentrations.Lidocaine is an amide-type local anaesthetic widely used for infiltration anaesthesia. It can be applied also to mucous membranes of the oral cavity and ingested after spraying it into the upper respiratory and gastrointestinal tract. Lidocaine is extensively metabolised and only traces are excreted unchanged in urine (Tucker & Mather 1979).Both cytochrome P450 (CYP) 3A4 and 1A2 isoenzymes can be important in the metabolism of lidocaine. The tissue distribution of CYP3A4 and 1A2 is different: CYP3A4 is extensively expressed in the gastrointestinal wall and liver whereas CYP1A2 is mainly located in the liver (Shimada et al. 1994;Kivistö et al. 1996). Accordingly, the relative role of CYP3A4 and 1A2 in lidocaine metabolism can depend on the route of its administration.It has been shown previously that fluvoxamine, a potent inhibitor of CYP1A2 (Brøsen et al. 1993;Rasmussen et al. 1995), considerably decreases the elimination of intravenous lidocaine (Orlando et al. 2004;Olkkola et al. 2005), whereas the strong inhibitors of CYP3A4 erythromycin and itraconazole have only a minor effect (Isohanni et al. 1998). The concomitant inhibition of CYP1A2 and CYP3A4 has affected the pharmacokinetics of intravenous lidocaine

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“…The patients received a constant rate intravenous infusion of 100 mg lidocaine hydrochoride over 15 minutes. Blood samples for determination of lidocaine were collected at 0, 5,10,15,20,25,30,45,60,75,90,105,120,135,150,165,180, and 195 minutes after the start of the infusion, and the plasma concentrations of lidocaine were determined by HPLC.…”

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confidence: 99%

Tinnitus suppression by intravenous lidocaine in relation to its plasma concentration

Hartigh

Hilders

Schoemaker

et al. 1993

Clin Pharmacol Ther

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In a double-blind controlled trial in nine patients with tinnitus we measured the lidocaine plasma concentrations during and after intravenous administration of lidocaine or placebo and scored the level of tinnitus on a visual analog scale. No patient showed any effect during the placebo infusion. Administration of lidocaine resulted in total suppression or suppression to a non-annoying level of tinnitus in five patients, slight suppression but still annoying tinnitus in two patients, and worsening tinnitus in one patient. No effect of lidocaine was observed in one patient. Most relief was obtained at plasma concentrations between 1.5 and 2.5 micrograms/ml. In this concentration range a significant (p < 0.05) effect of lidocaine on tinnitus was observed. However, notable side effects were observed at plasma concentrations greater than 2.0 micrograms/ml. The effect persisted until plasma levels of about 0.5 microgram/ml were reached. A large variability in the effects existed because of variations in lidocaine kinetics and because of the presumed psychologic components of tinnitus.

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Fatal Lignocaine Poisoning: Report of Two Cases and Review of the Literature

Cited by 15 publications

References 12 publications

Suicide due to oral ingestion of lidocaine: a case report and review of the literature

Suicide due to oral ingestion of lidocaine: a case report and review of the literature

Effect of Fluvoxamine and Erythromycin on the Pharmacokinetics of Oral Lidocaine

Tinnitus suppression by intravenous lidocaine in relation to its plasma concentration

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