Neonatal lidocaine toxicity

PURPOSE: To characterize clinical profile of pediatric local anesthetic (LA) systemic toxicity (LAST) and to identify determinants of life-threatening outcomes. METHODS: Spontaneous reports notified to the French Pharmacovigilance Network were retrieved and followed by a case-by-case review, according to the following criteria: LA as suspected drug, age < 18 years, adverse drug reactions related to nervous system, cardiac, respiratory, psychiatric or general disorders...

In utero drug exposure is a significant public health threat to the well-being and normal development of the neonate. Recently, testing of umbilical cord tissue (UCT) has been employed to measure illicit drug exposure, as drugs used by the mother during the third trimester may be retained in the UCT. Focus has also been given to potential adverse health effects among drug users, resulting from exposure to pharmacologically active adulterants and cutting agents in the street drug supply. The in utero effects of these substances have not been well studied in humans, nor has their presence been demonstrated as a means for assessing adverse health effects in the neonate...

A term newborn girl presented with apnoea and seizures at approximately 20 min of life following an uneventful vaginal delivery. She required admission to the Neonatal Intensive Care Unit following intubation and was commenced on conventional ventilation. Her mother had received a local lidocaine injection for an episiotomy prior to delivery. Initial investigations confirmed electrographic seizures for which she received an anticonvulsant with successful termination of seizure activity. Investigations for hypoxic injury, intracranial trauma, structural brain abnormalities, metabolic disorders and infection were unremarkable...

Toxic adulterants are drug or chemical agents used to add bulk volume to traditional drugs of abuse such as cocaine, and heroin. These cutting agents include levamisole, metamizole, noxiptillin, phenacetin, and xylazine as well as common legal drugs such as acetaminophen, caffeine, diphenhydramine, lidocaine, quinine, quetiapine, and tramadol. Because they possess pharmacological activity they result in exposure of the user, but also in the case of pregnant women, the developing fetus, to potential drug toxicity...

BACKGROUND AND PURPOSE: Voltage-gated sodium (NaV ) channels are expressed de novo in carcinomas where their activity promotes invasiveness. Breast and colon cancer cells express the neonatal splice variant of NaV 1.5 (nNaV 1.5) which has several amino acid substitutions in the domain I voltage-sensor compared to its adult counterpart (aNaV 1.5). This study aimed to determine whether nNaV 1.5 could be distinguished pharmacologically from aNaV 1.5. EXPERIMENTAL APPROACH: Cells expressing either nNaV 1...

AIMS: Lidocaine is used to treat neonatal seizures refractory to other anticonvulsants. It is effective, but also associated with cardiac toxicity. Previous studies have reported on the pharmacokinetics of lidocaine in preterm and term neonates and proposed a dosing regimen for effective and safe lidocaine use. The objective of this study was to evaluate the previously developed pharmacokinetic models and dosing regimen. As a secondary objective, lidocaine effectiveness and safety were assessed...

BACKGROUND: Epidural-related maternal fever (ERMF) is an adverse effect of epidural analgesia during labor and is associated with perinatal and neonatal morbidity. Local anesthetics have been proposed to trigger ERMF via sterile inflammation. Ropivacaine is currently the most frequently used epidural anesthetic and considered least toxic. This study investigates molecular effects of ropivacaine on human umbilical vein endothelial cells (HUVECs) as model system for endothelial cells and human placental trophoblasts (TBs), compares the effects to the putative anti-inflammatory lidocaine and investigates the partially alleviating impact of the anti-inflammatory corticosteroid dexamethasone...

Neonatal seizures are frequent in neonatal intensive care and the most common cause is perinatal asphyxia. Among other causes, toxin exposure is rare.We present a boy with an uneventful vaginal birth, who presented one hour after birth with apnea, hypotonia, mydriasis, tongue fasciculation, and tonic seizures. There was no hypoxic ischemic encephalopathy and brain imaging was normal. Toxicology screening revealed a toxic concentration of lidocaine in his blood. The intoxication was transplacental, as a cord blood sample confirmed the toxic level...

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...

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...

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...

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...

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...

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...

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...

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...

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)...

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...

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...

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...