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Neonatal lidocaine toxicity

Lisa V Doan, Olga Eydlin, Boris Piskoun, Richard P Kline, Esperanza Recio-Pinto, Andrew D Rosenberg, Thomas J J Blanck, Fang Xu
BACKGROUND: Neuraxial local anesthetics may have neurological complications thought to be due to neurotoxicity. A primary site of action of local anesthetics is the dorsal root ganglia (DRG) neuron. Physiologic differences have been noted between young and adult DRG neurons; hence, the authors examined whether there were any differences in lidocaine-induced changes in calcium and lidocaine toxicity in neonatal and adult rat DRG neurons. METHODS: DRG neurons were cultured from postnatal day 7 (P7) and adult rats...
January 2014: Anesthesiology
Halima Maulidi, Carol McNair, Neil Seller, Joel Kirsh, Timothy J Bradley, Steven C Greenway, Chris Tomlinson
Infants in NICUs undergo a variety of painful procedures. The management of pain has become an integral part of newborn infant care with the use of both systemic and topical agents to provide analgesia and anesthesia for procedural pain. Tetracaine and prilocaine-lidocaine are the 2 topical anesthetics most frequently used. Tetracaine belongs to an ester group of local anesthetics available as a topical 4% gel (Ametop, Smith and Nephew, Canada). The major side effects reported when using topical anesthetics are cutaneous reactions...
December 2012: Pediatrics
Aruna T Nathan, Maryam Naim, Lisa M Montenegro, Victoria L Vetter
Long QT syndrome is characterized by electrocardiographic appearance of long QT intervals and propensity to polymorphic ventricular tachycardia. Aggressive anticipatory clinical management is required for a good outcome, especially in the symptomatic neonate. We present a neonate with a compound mutation with refractory ventricular tachycardia that necessitated multimodal pharmacotherapy with lidocaine, esmolol, and amiodarone along with ventricular pacing. Despite normal serum lidocaine levels, complex pharmacokinetic interactions resulted in presumed neurotoxicity due to lidocaine...
February 2012: Anesthesia and Analgesia
Sufang Yang, Matthew S Abrahams, Patricia D Hurn, Marjorie R Grafe, Jeffrey R Kirsch
BACKGROUND: Peripheral nerve blocks with local anesthetics (LAs) are commonly performed to provide surgical anesthesia or postoperative analgesia. Nerve injury resulting in persistent numbness or weakness is a potentially serious complication. Local anesthetics have previously been shown to damage neuronal and Schwann cells via several mechanisms. We sought to test the hypothesis that LAs are toxic to Schwann cells and that the degree of toxicity is directly related to the concentration of LA and duration of exposure...
September 2011: Regional Anesthesia and Pain Medicine
Marcel P H van den Broek, Alwin D R Huitema, Johan G C van Hasselt, Floris Groenendaal, Mona C Toet, Toine C G Egberts, Linda S de Vries, Catharine M A Rademaker
BACKGROUND AND OBJECTIVE: The application of lidocaine (lignocaine) as an anticonvulsant in neonates originated more than 40 years ago in Scandinavia. Lidocaine has been shown to be an effective anticonvulsant for the treatment of neonatal seizures that persist in spite of first-line anticonvulsant therapy. However, lidocaine toxicity, mainly in the form of cardiac arrhythmias, can be life threatening. Therapeutic drug monitoring can be useful to prevent toxicity. In a previous study, a dosing regimen was developed for term neonates, but it was not evaluated for preterm neonates...
July 2011: Clinical Pharmacokinetics
Massoud Rezvani, Yaron Finkelstein, Zul Verjee, Craig Railton, Gideon Koren
We report a case of neonatal seizures after lidocaine administration for circumcision. A 3-month-old male infant received an overdose as evidenced by toxic lidocaine levels and developed generalized seizures shortly after. Back extrapolation of the serum lidocaine concentration to time zero was used to determine the administered dose. The Naranjo scale was used to determine causation; probable causation was defined. Particular care must be taken to administer an appropriate dose of local anesthetics in infants to avoid life-threatening seizures...
2007: Paediatric Drugs
Mirte M Malingré, Linda G M Van Rooij, Carin M A Rademaker, Mona C Toet, Tessa F F T Ververs, Charlotte van Kesteren, Linda S de Vries
INTRODUCTION: Lidocaine is an effective drug for the treatment of neonatal convulsions not responding to traditional anticonvulsant therapy. However, one of the side-effects is a risk of cardiac arrhythmias. The aim of this study was to develop an optimal dosing strategy with minimal risk of cardiac arrhythmias. MATERIALS AND METHODS: As a first step, we studied 20 neonates during routine treatment of neonatal seizures with lidocaine. All were given a loading dose of 2 mg/kg in 10 min, followed by the continuous infusion of 6 mg/kg per hour for 12 h, 4 mg/kg per hour for 12 h and finally 2 mg/kg per hour for 12 h...
September 2006: European Journal of Pediatrics
Lisa O'Brien, Anna Taddio, Dorothy A Lyszkiewicz, Gideon Koren
A topical formulation of the ester-type local anesthetic amethocaine (tetracaine) [Ametop ] is currently available for reducing pain from cutaneous procedures such as venipuncture. The Ametop mark preparation contains 40 mg of amethocaine base (4% w/w) and produces anesthesia within 30-45 minutes of application; duration of action ranges from 4 to 6 hours. Clinical studies have demonstrated the superiority of the 4% amethocaine preparation over placebo in pediatric populations for indications such as intravenous cannulation, vaccination, and venipuncture...
2005: Paediatric Drugs
Jean-Xavier Mazoit, Bernard J Dalens
Amide local anaesthetics used for regional anaesthesia in paediatric patients are potent sodium channel blockers with marked stereospecificity, which consistently influences their action, especially their toxic action on the heart. At toxic concentrations, they induce severe arrhythmias with the potential for cardiac arrest. These agents are all bound to serum proteins, mainly to alpha(1)-acid glycoprotein (AAG), but also to human serum albumin. Protein binding ranges from 65% (lidocaine) to more than 95% (bupivacaine, ropivacaine)...
2004: Clinical Pharmacokinetics
Joel B Gunter
Regional anesthesia has become a routine part of the practice of anesthesiology in infants and children. Local anesthetic toxicity is extremely rare in infants and children; however, seizures, dysrhythmias, cardiovascular collapse, and transient neuropathic symptoms have been reported. Infants and children may be at increased risk from local anesthetics compared with adults. Larger volumes of local anesthetics are used for epidural anesthesia in infants and children than in adults. Metabolism and elimination of local anesthetics can be delayed in neonates, who also have decreased plasma concentrations of alpha(1)-acid glycoprotein, leading to increased concentrations of unbound bupivacaine...
2002: Paediatric Drugs
A Taddio
Circumcision is the most common surgical procedure performed in the neonatal period in North America. If untreated, the pain of circumcision causes both short and long term changes in infant behaviours. The most widely studied pharmacological intervention for pain management during circumcision is dorsal penile nerve block (DPNB) by injected lidocaine (lignocaine). Randomised controlled trials have demonstrated its efficacy; infants premedicated with lidocaine have significantly smaller changes in physiological and pain-related behaviours compared with infants who are not given analgesics...
2001: Paediatric Drugs
E Tanaka
Very few studies have been carried out looking at how the effects of drugs and their toxicity in humans change during their lifespan (developing and ageing). The purpose of this study is to review the literature on the changes in probe-drug metabolism, classified by cytochrome P450 (P450 or CYP) at five stages in life: neonates < 4 weeks, infants < 12 months, children < 19 years, young/mature adults 20-64 years, and elderly adults > 65 years. The main probe drugs include caffeine and theophylline, whose metabolism is catalysed by CYP1A2, tolbutamide, phenytoin and ibuprofen, catalysed by CYP2C9, amitriptyline and nortriptyline, catalysed by CYP2C19, acetaminophen, catalysed by CYP2E1 and lidocaine, midazolam and terfenadine, catalysed by 3A3/4...
August 1998: Journal of Clinical Pharmacy and Therapeutics
L M Resar, M A Helfaer
OBJECTIVE: We report recurrent seizures in a neonate after intravenous lidocaine administration at the recommended dose for intubation and supplementation of general anesthesia. STUDY DESIGN: Further evaluation of this case included determination of serum lidocaine level, serum electrolyte levels, and arterial blood gas values; cerebral spinal fluid analysis; an electroencephalogram; head ultrasonography; brain stem auditory evoked response testing; and a complete developmental evaluation...
May 1998: Journal of Perinatology: Official Journal of the California Perinatal Association
A B Acharya, P C Bustani, J D Phillips, N A Taub, R M Beattie
AIM: To assess the safety and efficacy of EMLA cream (eutectic mixture of local anaesthetics) used to induce surface anaesthesia for venepuncture in healthy preterm infants. METHODS: Nineteen infants, median gestational age 31 weeks (range 26-33 weeks) were assessed in a randomised, double blind, placebo controlled, cross-over trial. Changes in physiological variables (heart rate, blood pressure, oxygen saturation) and behavioural responses (neonatal facial coding system score, crying time) before and after venepuncture with EMLA cream were compared with those obtained with a placebo cream to assess efficacy...
March 1998: Archives of Disease in Childhood. Fetal and Neonatal Edition
I A Walker, C M Slovis
Intravenous lidocaine has the potential to control seizures. This article reviews the available evidence related to lidocaine's efficacy and clarifies its potential role in the management of status epilepticus (SE). Although there are no large, double-blind, placebo-controlled studies of lidocaine's efficacy in SE, numerous case reports and case series support its use. Most of the reported cases involve patients who were refractory to multiple antiseizure medications. Additional support for lidocaine's efficacy in SE comes from the pediatric literature, where lidocaine has been very effective in controlling SE in neonates who have not responded to barbiturates...
September 1997: Academic Emergency Medicine: Official Journal of the Society for Academic Emergency Medicine
S C Russell, E Doyle
Since its introduction, eutectic lidocaine-prilocaine cream ('EMLA')1 has been found to be an effective topical anaesthetic agent, with a high degree of efficacy, particularly for venepuncture and venous cannulation, and an impressive tolerability profile. Reports of adverse effects are remarkable for their rarity. The only problems that are likely to be encountered are oral ingestion of the cream (which may lead to anaesthesia of the oropharynx and possible toxicity secondary to rapid absorption of local anaesthetic from oral mucous membranes) and methaemoglobinaemia following repeated applications in neonates and infants...
April 1997: Drug Safety: An International Journal of Medical Toxicology and Drug Experience
R M Law, S Halpern, R F Martins, H Reich, V Innanen, A Ohlsson
A statistically significant (p = 0.049) increase in methemoglobin (MetHb), which did not exceed normal values, was noted 8 h after application of 1 g of EMLA (Eutectic Mixture of Local Anesthetics) to the foreskin of 10 normal newborns to reduce pain associated with circumcision. The highest MetHb concentration observed was 3 g/l (toxic > 50 g/l). No infant showed clinical signs of methemoglobinemia. We conclude that EMLA is safe to use as a local anesthetic in term neonates.
1996: Biology of the Neonate
M Palot, H Visseaux, C Botmans
The placental transfer of local anaesthetics (LA) depends on maternal, placental and fetal factors. The assessment of effects of LA and epidural anaesthesia (EA) on the fetus is based on the monitoring of fetal heart rate (FHR) and the measurement of the fetal pH. Apgar score and neurobehavioral tests allow an evaluation of the neonatal effects of the drugs used. Direct effects of LA: a diminution of variability of FHR was observed shortly after the beginning of an EA using lidocaine but there was no modification of FHR after EA using bupivacaine or lidocaine with epinephrine...
1995: Cahiers D'anesthésiologie
T Mizuki, H Kobayashi, Y Nakashima, A Kuroiwa, F Izumi
Some physiological functions of the heart are modulated through cardiac beta-adrenoceptors. In acute myocardial infarction, ventricular arrhythmias occur frequently and class I antiarrhythmic drugs such as lidocaine are often administered continuously over long period. The aim of this study was to investigate the effects of long-term treatment with lidocaine on cardiac beta-adrenoceptors. Ventricular cardiocytes from 2-day-old Wistar rat were cultured in the presence or absence of lidocaine, and beta-adrenoceptors of the membrane fraction of the cells were measured with a binding assay using [125I]-iodocyanopindolol ([125I]CYP) as a radioligand...
February 1994: Naunyn-Schmiedeberg's Archives of Pharmacology
J Hamza
The placental transfer of local anaesthetics (LA) depends on maternal factors (LA dosage, degree of protein binding, blood pH), placental factors (surface of placental exchange, placenta thickness) and fetal factors (maternal-fetal gradient of pH, fetal hepatic metabolism of the LA, redistribution of the cardiac output in case of fetal hypoxia). The assessment of effects of LA and epidural anaesthesia (EA) on the fetus is based on the monitoring of the fetal heart rate and the measurement of the fetal pH allowing to rapidly detect an acute fetal distress...
1994: Cahiers D'anesthésiologie
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