ObjectiveRefractory convulsive Status Epilepticus (SE) which does not respond to first line drugs (benzodiazepines, phenytoin and phenobarbital) heralds an emergency condition in pediatric neurology which can cause irreparable brain damage. There is no consensus on the choice of drug treatment for refractory generalized  convulsive status epilepticus in children. Lidocaine is a valuable forgotten antiepileptic agent with favorable properties which include prompt responses, less alteration of consciousness, and fewer adverse effects such as respiratory depression.Materials & MethodsIn a retrospective study conducted to investigate clinical efficacy and safety of intravenous lidocaine in treating refractory generalized convulsive SE of children, the medical records of 13 patients admitted to the Shaheed Sadoughi Hospital of Yazd between 2003 and 2005 and treated with intravenous lidocaine, were reviewed.Results13 patients, 7 girls and 6 boys (average age 3 years, SD=2.7years) were treated with lidocaine. Neurodevelopmental delay was seen in 38.5 %, and in 46.2% of them EEG and neuroimaging abnormalities were observed.Seizures ceased in eight patients (61/5 %), without any undesirable side effects. Two patients had to be intubated because of non-responsiveness to lidocaine, and other treatments were begun .Mean duration of ICU stay was 4.77 days, SD=3days.ConclusionIt is recommended that lidocaine be used as a second-line, anticonvulsive drug in the treatment of status epilepticus, especially when faced with unavailability of appropriate respiratory care and intubation equipment.Key words:Status Epilepticus, Refractory Status Epilepticus, Generalized Convulsive Status Epilepticus, Intravenous Lidocaine

Fallah MD, R.

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47Iran J Child Neurology  Aug. 2007IV LIDOCAINE: A SECOND LINE DRUG THERAPY FORPEDIATRIC CONVULSIVE STATUS EPILEPTICUS?R. Fallah    MDAbstract:ObjectiveRefractory convulsive Status Epilepticus (SE) which does not respond to firstline drugs (benzodiazepines, phenytoin and phenobarbital) heralds anemergency condition in pediatric neurology which can cause irreparablebrain damage. There is no consensus on the choice of drug treatment forrefractory generalized convulsive status epilepticus in children. Lidocaineis a valuable forgotten antiepileptic agent with favorable properties whichinclude prompt responses, less alteration of consciousness, and fewer adverseeffects such as respiratory depression.Materials & MethodsIn a retrospective study conducted to  investigate clinical  efficacy and safetyof intravenous  lidocaine in treating refractory generalized  convulsive  SEof children, the medical records of  13 patients admitted to the ShaheedSadoughi Hospital of Yazd between 2003 and  2005 and treated  withintravenous lidocaine,  were reviewed.Results13 patients, 7 girls and 6 boys (average age 3 years, SD=2.7years) weretreated with lidocaine. Neurodevelopmental delay was seen in 38.5 %, andin 46.2% of them EEG and neuroimaging abnormalities   were observed.Seizures ceased in eight patients (61/5 %), without any undesirable sideeffects. Two patients had to be intubated because of non-responsiveness tolidocaine, and other treatments were begun .Mean duration of ICU staywas 4.77 days, SD=3days.ConclusionIt is recommended that lidocaine be used as a second-line, anticonvulsivedrug in the treatment of status epilepticus, especially when faced withunavailability of appropriate respiratory care and intubation equipment.Key words: Status Epilepticus, Refractory Status Epilepticus, GeneralizedConvulsive Status  Epilepticus,  Intravenous  Lidocaine.Assistant Professor of Pediatricneurology, Shaheed SadoughiUniversity of Medical SciencesCorresponding author:R. Fallah MDTel: +98 351 8224000 - 9Fax:  +98 351 8224100Email:FALLAH@ssu.ac.irRESEARCH ARTICLEIntroductionStatus epilepticus (SE), defined as a seizure that persists for a duration longenough, or is repeated frequently enough, to produce a fixed and enduring epilepticcondition lasting 30 minutes or longer, is a common neurologic medicalemergency(1), of which generalized convulsive SE is the most common anddangerous type. SE occurs more frequently in young children and elderly adults,although patients of all ages may experience prolonged seizures (2). It is estimatedIran J Child Neurology  Aug. 200748that this life-threatening condition occurs in 1.3% to 16%of all epileptic children and in some patients presents asthe initial seizure.(3) Correct management strategyinvolves prompt control of seizures and treatment of theunderlying etiology. The morbidity and mortality of status epilepticus aresignificant and directly dependent upon availability ofprompt and appropriate medical therapy; the sequelaeand neurocognitive deficits are particularly pronouncedand potentially fatal in children when the conditionprogresses beyond 30 to 60 minutes. Refractory statusepilepticus is defined as seizures that are ongoing, despitethe use of two first-line drugs, usually a benzodiazepineplus either phenytoin or phenobarbital, or seizures thatcontinue for more than 60-90 minutes in spite of adequatetreatment(4,5,6). All these patients must be managed ina pediatric ICU, with aggressive monitoring of theirhemodynamic and respiratory status. There is noconsensus on the choice of drug treatment for refractorygeneralized convulsive status epilepticus in children. Ifcessation of seizures cannot be achieved, other therapeuticstrategies may have to be used  such as  induction ofbarbituric coma with thiopental, general anesthesia usingpropofol(7), diazepam drip(8,9), buccal, nasal  orcontinuous  infusion  of midazolam(10,11,12)  andintravenous valproate(13,14) .Use of these modalities, however, may be associatedwith respiratory depression needing mechanical ventilationand hypotension requiring vasopressor support andinvasive hemodynamic monitoring.Lidocaine has many pharmacologic attributes such asantiarrhythmic, local anesthetic and antiepilepticproperties; 1 - 2 mg/kg intravenously, once or twice, andif necessary, followed by continuous infusion at 2 - 4mg/kg/hour is one of the second-line drugs in treatmentof  SE(15). The properties of this  drug effective in  SE treatment include prompt responses, less alteration ofconsciousness, and fewer adverse effects  such  as  lessrespiratory depression(16). The basic mechanisms oflidocaine as an antiepileptic are thought to be analogousto  its local  anesthetic action; it has a specific membranesealing or stabilizing effect on the CNS that restricts themovement of sodium and potassium across the membrane,thereby decreasing membrane excitability(17).Pascual et al suggested that lidocaine may be used as afirst–line drug, as a diazepam substitute, in patients inwhom respiratory or consciousness depression isundesirable and in those with no response to intravenousdiazepam. The absence of response to lidocaine   indicatesSE is resistant to treatment and  has poor prognosis(18).Aggarwal et al document lidocaine as a valuable drug,forgotten in the emergency department(19).Evidence of lidocaine efficacy has been demonstrated inmany clinical studies, most of which were case reportsor were performed on a limited number of patients(lessthan 10).The purpose of this retrospective study  was to  investigatethe clinical  efficacy and safety of  intravenous  lidocainein controlling refractory  generalized  convulsive  SE inchildren admitted to the Shaheed  Sadoughi Hospital ofYazd .Materials and MethodsIn  a retrospective study, medical  records  of allgeneralized  convulsive  status epilepticus of  childrentreated with intravenous lidocaine  between 2003 and2005   in Yazd  Shaheed Sadoughi Hospital reviewed.Inclusion criteria: No history of liver or kidneydysfunction- past or current-, no hypotension, cardiacarrhythmia  or block and electrolyte  abnormality; a firsttime occurrence of status epilepticus; BUN, Cr, sodium,potassium, total calcium, and glucose values withinnormal limits to exclude electrolyte abnormalities andhypoglycemia as causes of seizures; admission to theICU for aggressive cardiac monitoringLidocaine  was used as a second–line drug, because oflack of seizure-response to benzodiazepines plus eitherphenytoin or Phenobarbital.Lidocaine treatment   protocol:Initial dose of 1 mg/Kg was given intravenously at a rateof  25 mg/min. If no response occurred or seizuresrecurred, a second bolus dose of 1 mg/Kg was infused.If seizures did not  stop within  15 minutes following thesecond  dose, continuous  lidocaine  infusion  of 1mg/Kg/h  was  used  and  increased  for  1 mg/Kg/h every15 minutes until control of  seizures or maximum doseof 5 mg/Kg/h. If the drug was effective in control ofseizures, the same dose would be repeated for 12 hoursand then decreased 0.5 mg/kg/hour until cessation ofseizures, when the treatment would be consideredIV LIDOCAINE: A SECOND LINE DRUG THERAPY FOR PEDIATRIC ...49Iran J Child Neurology  Aug. 2007effective. ECG, blood pressure, and oxygen saturationwere continuously monitored to detect any cardiovascularcomplications. Serum lidocaine concentration was notmeasured. Lidocaine was not administered to patientswith known or suspected cardiac diseases.If seizures did not cease with maximum dose of druginfusion drip, it was regarded as being ineffective andunsuccessful, and hence was discontinued, and abenzodiazepines or pentobarbital drip was introduced.Data were gathered from the medical records of thepediatric ICU. All information on variables such as age,sex, neuroimaging and EEG findings, concomitant fever,neurodevelopmental delay, adverse effects (hypotension,arrhythmia, respiratory depression needing intubationand mechanical ventilation, acidosis, hypothermia,hypoxia), seizure control and length of stay in the ICUwere carefully recorded. The data were analyzed usingSPSS 13   statistical software. P values< 0.05 wereconsidered statistically significant. Written informedconsent was obtained from subject's parents.ResultsIn this retrospective study conducted to determine theefficacy and safety of intravenous lidocaine in treatingseizures caused by refractory generalized convulsivestatus epilepticus, the ages of  children ranged from onemonth to 9 years( mean age 3 years and SD=2.7 years).Clinical and Para clinical characteristics of patients arepresented in Table 1.In eight  of 13 patients( 61/5 %), lidocaine  was  effective in controlling seizure; in three patients, seizures  stoppedwith the initial dose of  1 mg/Kg  and in another threewith  second bolus dose of 1 mg/Kg;  in one this waswith infusion  of 1 mg/Kg/h and in  another with  2mg/Kg/h .Etiology of SE and response to treatment of patients areshowed in Table 2. No undesirable side effects(paraclinical or clinical) were observed in patients.Two patients had to be intubated because of non-responsiveness to lidocaine; they were treated with otherdrugs. Duration of stay in the ICU ranged between 1 to11 days (mean 4.77, SD=3.03).IV LIDOCAINE: A SECOND LINE DRUG THERAPY FOR PEDIATRIC ...SE:Status EpilepticusIran J Child Neurology  Aug. 200750DiscussionThe purpose of this retrospective study was to investigateintravenous lidocaine efficacy and safety in refractoryconvulsive SE of children. According to the results ofthe study the drug was effective in   61.5 % of patients.Other similar studies have shown a response rate rangingfrom 35.8 to 100% (15,16,20,21,22).  One possibleexplanation for this discrepancy is the small number ofour patients. Further studies need to be carried to confirmthe efficacy of intravenous lidocaine in treating refractorystatus epilepticus.The results of this study  indicate  that  intubation andmechanical ventilation  were  not needed in lidocaineuse, which is in agreement with recommendations ofother studies that recommend use of lidocaine  in themanagement of SE of patients in whom respiratorydepression is undesirable  (18) or management ofrespiratory depression is not possible. Considering thefact that no alteration of consciousness and respirationoccurred, the lidocaine treatment was cost-effective sincecessation of seizures without side effects shortened theduration of ICU stay. Our results which show nooccurrence of undesirable effects are in agreement withthose of other studies(16,20,23,24).Walker and Slovis recommended lidocaine beforebarbiturate coma in SE treatment, which agrees withobservations of the current study(25).The initial bolus doses of lidocaine were effective in sixof eight   patients in whom SE was controlled, indicatingthat lidocaine is a rapid acting anticonvulsant, useful inthe short term management of SE. One limitation of this study was lack of video-EEGmonitoring and hence our inability to identify/recognizeelectrographic seizures cessation.We conclude that lidocaine, based on its prompteffectiveness and low risk of side effects, can be used asa second-line, anti-convulsive drug in status epilepticus,especially for patients with chronic respiratory diseaseor in those having severe disability and respiratoryimpairement .References1. Mitchell WG. Status epilepticus and acute serial seizures in   children. 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IV LIDOCAINE: A SECOND LINE DRUG THERAPY FOR PEDIATRIC CONVULSIVE STATUS EPILEPTICUS?

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IV LIDOCAINE: A SECOND LINE DRUG THERAPY FOR PEDIATRIC CONVULSIVE STATUS EPILEPTICUS?

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