Epilepsiu, 33(5):913-916, 1992 Raven Press, Ltd., New York 0 International League Against Epilepsy
Lidocaine in Refractory Status Epilepticus: Confirmation of Efficacy with Continuous EEG Monitoring Christopher M. De Giorgio, Karen Altman, Elizabeth Hamilton-Byrd, and Adrian L. Rabinowicz Department of Neurology, USC School of Medicine, Los Angeles, California, U.S.A.
Summary: Lidocaine was efficacious in 2 patients with refractory status epilepticus (RSE) unresponsive to severa1 antiepileptic drugs (AEDs), including high-dose barbiturates. We confirmed the efficacy of lidocaine with,
for the first time in adults, continuous EEG monitoring. Lidocaine, when properly used, may be a treatment option in RSE. Key Words: Lidocaine-Status epilepticusAnticonvulsants-Electroencephalography.
Status epilepticus (SE) is a medical emergency, with mortality rates of 10-12% (Delgado-Escueta et al., 1982). Prolonged or refractory SE causes significant brain injury and neuronal loss (De Giorgio et al., 1992) and is highly lethal; mortality may be as high as 77% (Treiman et al., 1984; Rashkin et al., 1987). Refractory SE (RSE) may evolve into nonconvulsive SE (NCSE) defined as confusion, stupor, or coma with continuous EEG epileptiform activity (Bauer et al., 1982; Treiman et al., 1984; Guberman et al., 1986; Fagan and Lee, 1990). NCSE is the final common pathway for RSE in humans and animals (Treiman et al., 1984, 1990). The drugs of choice for RSE or NCSE are not well defined. Delgado-Escueta et al. (1982) recommended a management protocol including lidocaine or paraldehyde if sequential infusion of diazepam, phenytoin (PHT), and phenobarbital (PB) are ineffective. Uthman and Wilder (1989) also consider lidocaine a valuable drug in RSE. Leppik (1986, 1990) recommends against lidocaine use for SE, echoing concerns about lidocaine’s potential to be a proconvulsant. Pentobarbital coma has been recommended in RSE, despite pentobarbital’s potential for serious toxicity, including severe hypotension (frequently requiring pressors), prolonged coma, and the need for prolonged intensive care (Orlowski et al., 1984; Rashkin et al., 1987; Lowenstein et al., 1988). We could find no reports in the English literature confirming, with continuous EEG monitoring, the
efficacy of lidocaine in RSE. We report the safety and efficacy of lidocaine in two patients with RSE. Patient 1 A 23-year-old, 75-kg man with chronic epilepsy was admitted to the emergency room (ER). Six weeks before, he had run out of PHT, and 3 days before admission, his family noted multiple prolonged periods of unresponsiveness, left hemibody clonic movements, eye deviation to the left, and urinary incontinence. He was unresponsive to verbal stimuli at the time of admission. Two milligrams of intravenous (i.v.) lorazepam was administered in the ER with no effect. Multiple, discrete, bilateral occipital onset electrographic seizures characterized by rhythmic fast activity followed by generalized high-frequency bisynchronous spike and wave discharges were noted. Despite infusion of 4 mg i.v. lorazepam, EEG and clinical seizure activity continued. PHT was initiated at a rate of 50 mg/min i.v., but only 700 mg could be infused (9 mg/kg) because of hypotension. The patient was intubated, administered 10 mg diazepam i.v. push, and loaded with 1,300 mg i.v. phenobarbital (PB) at a rate of 100 mg/min, and 4 mg i.v. lorazepam; clinical seizure activity persisted. Pentobarbital coma was induced with an initial bolus of 5 mg/kg (375 mg) i.v. push followed first by a continuous i.v. infusion of 75 mg/h (1 mg/kg/h) and then by 150 mg/h (2 mg/kg/ h). A repeat EEG demonstrated continuous ictal activity, and pentobarbital was increased to 188 mg/h (2.5 mg/kg/h). Moderate hypotension occurred. Continuous EEG monitoring was initiated and showed a continuous generalized spike and slow wave ictal pattern. Administration of 8 mg
Received June 1991; revision accepted February 1992. Address reprint requests to Dr. C. M. De Giorgio at Department of Neurology, USC School of Medicine, 2025 Zonal Ave., Los Angeles, CA 90033, U.S.A.
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lorazepam had only slight EEG effect. An i.v. bolus of lidocaine 75 mg (1 mg/kg) was administered and repeated in 20 min, followed by a continuous i.v. infusion of 1 mg/min followed by 2 mglmin. The EEG response to treatment is shown in Fig. 1 . Lidocaine successfully eliminated all ictal EEG activity, and the patient gradually awakened. Followup EEGs showed progressive background normalization. Clinical and electrical S E did not recur. Patient 2 A 37-year-old, 80-kg man with a recurrent left temporal astrocytoma and left temporal onset secondarily generalized seizures was admitted for Pneumocystis pneumonia and intubated for respiratory failure. The patient was successfully extubated but continuous right-sided clonic jerking and clonic eye deviation to the right developed acutely; he was unresponsive to verbal and painful stimulus. Lorazepam i.v. stopped clinical seizure activity, but the patient remained unresponsive. Continuous EEG monitoring showed a continuous left hemispheric sharp and slow wave pattern consistent with EEG SE. PB 1,700 mg was infused i.v. (21 mg/kg), but a continuous ictal pattern persisted. Lidocaine as an 80-mg i.v. bolus ( 1 mg/kg) was administered, followed by a continuous i.v. infusion at a rate of 1 mg/min. The EEG SE was terminated within 54 min after the i.v. lidocaine infusion was started. Figure 2 shows the EEG response to treatment.
DISCUSSION Lidocaine, a local anesthetic, anticonvulsant, and antiarrhythmic agent, was introduced in 1948. It primarily blocks sodium channels, thereby decreasing membrane excitability (Stone and Javid, 1988). Lidocaine effectively blocks seizures induced by ouabain (a sodium/potassium pump antagonist), and is effective against glutamate-induced seizures but is ineffective against penicillin and pentylenetetrazol seizures (Stone and Javid, 1988). Overall, lidocaine has an anticonvulsant spectrum of activity similar to phenytoin, and blocks sodium-dependent epileptiform spike activity (Stone and Javid, 1988). Lidocaine i.v. is rapidly distributed, with a distribution half-life (tY2) of 8-17 min; elimination t?h is 1-8 h (Lindsay, 1989; Goodman Gilman et al., 1990). Effective antiarrhythmic concentrations are achieved with a bolus of 1-1.5 mg/kg, followed by half the dose in 5 min (Goodman Gilman et al., 1990). Infusion rates of 1 - 4 mg/min result in plasma levels of 1-5 pg/ml (Goodman Gilman et al., 1990). CNS toxicity, including confusion, stupor, respiratory arrest, or seizures, occur at levels >5 pg/ml, Epilepsiu, Vol. 33, N o . 5 , 1992
usually in chronic heart failure, severe hepatic disease, or shock; in the elderly, lower infusion rates are necessary (Lindsay, 1989; Goodman Gilman et al., 1990). Seizures secondary to lidocaine have been reported, but the actual risk is low (Buckman et al., 1980; Forrenge et al., 1986). Buckman et al. (1990), in a prospective study correlating blood levels with toxicity, reported lidocaine-induced seizures in 1 of 50 patients, an alcoholic patient with lidocaine levels of 9.3 pg/ml. CNS toxicity (confusion, drowsiness, tremulousness, tinnitus, and psychosis) was reported in 26 patients at levels >2.9 pg/ml. These symptoms occurred in all patients with levels >5.9 pg/ml. Rodman et al. (1984), in another large study comparing computer-assisted infusion with conventional therapy, reported no seizures in 156 patients. In addition to heart and liver disease, neuromuscular blockade may also increase the risk for toxicity. Simon et al. (1984) reported that neuromuscular blockade results in partitioning of lidocaine into the CNS, resulting in potentially toxic CNS levels, significantly higher than plasma levels would indicate. To our knowledge, there are no reports of additional seizures or of prolongation or recurrence of SE when lidocaine was administered as an anticonvulsant Many short literature reports document the efficacy of lidocaine in SE (Bernhard et al., 1955; Taverner and Bain, 1958; Lemmen et al., 1978; Morris, 1979; Browne, 1983; Pascual et al., 1988). Bernhard et al. (1955) first reported the efficacy of lidocaine for SE. Taverner and Bain (1958) reported the only prospective blinded study of lidocaine for SE that clearly showed efficacy when lidocaine was compared with saline in 3 patients. Lidocaine or saline was infused after a seizure, and the interval to the next seizure was measured, with lidocaine clearly prolonging the time to the next seizure. By 1979, lidocaine was recognized as a “neglected anticonvulsant” (Morris, 1979). Browne (1983) reviewed 148 reported cases of SE treated with lidocaine and concluded that lidocaine is effective in SE and may control SE when diazepam, PHT, PB, and paraldehyde fail. He noted that the antiepileptic effect is rapid (20-30 s) and short-lived, which may necessitate a continuous infusion. A prospective study by Pascual et al. (1988) confirms this conclusion. We believe that ours is the first report of lidocaine efficacy in RSE, documented by continuous EEG monitoring, which is essential in documenting success of treatment in SE and in diagnosing nonconvulsive SE. NCSE subsequent to generalized convulsive SE is an increasingly recognized phenomenon (Treiman et al., 1984, 1987, 1990;
C . M . DE GIORGIO ET AL.
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Fagan and Lee, 1990). Several EEG patterns have been reported to be associated with NCSE (Fagan and Lee, 1990; Treiman et al., 1990). These patterns are remarkably similar to those reported in our 2 patients (patient 1, Fagan and Lee, 1990, Fig. 2; patient 2, Treiman et.al., 1990, Fig. 3A). The resolution of these two ictal patterns confirms the efficacy of lidocaine. We believe that the relative risks of lidocaine may be less than those of pentobarbital and recommend a prospective comparison of pentobarbital and lidocaine in RSE. Our results support the recommendation by Delgado-Escueta et al. (1982) that lidocaine may be used as an alternative drug for SE after diazepam, PHT, and PB have failed. Note: We remind readers that SE is not a U.S. FDAapproved indication for lidocaine.
Acknowledgment: A.L.R. received support from the Garnier Trust for Epilepsy Research.
REFERENCES Bauer G, Aichner F , Mayr U. Nonconvulsive status epilepticus following generalized tonic-clonic seizures. Eur Neurol 1982; 21:411-9. Bernhard GC, Bohm E, Hojeberg S. A new treatment of status epilepticus, intravenous injections of a local anesthetic (lidocaine). Arch Neurol Psychiatry 1955;74:208-14. Browne TR. Paraldehyde, chlormethiorale, and lidocaine for treatment of status epilepticus. In: Delgado-Escueta AV, Wasterlain CG, Treiman DM, Porter RJ, eds. Status epilepficus. Mechanisms of brain damage and treatment. Raven Press: New York, 1983:509-17. (Advances in neurology; vol. 34.) Buckman K, Claiborne K, deGuzman M, Walberg CB, Haywood J. Lidocaine efficacy and toxicity assessed by a new rapid method. Clin Pharmacol Ther 1980;28:177-81. De Giorgio CM, Tomiyasu U , Gott PS, Treiman DM. Hippocampal pyramidal cell loss in human status epilepticus. Epilepsia 1992;33:23-7. Delgado-Escueta AV, Wasterlain C, Treiman DM, Porter RJ. Current concepts in neurology: management of status epilepticus. N Engl J Med 1982;306:133740. Fagan KJ, Lee SI. Prolonged confusion following convulsions due to generalized nonconvulsive status epilepticus. Neurology 1990;40: 1689-94. Forrenge E, Covinsky JO, Multen C. A seizure induced by concurrent lidocaine-tocainamide therapy. Is it just a case of additive toxicity? Drug Intel1 Clin Pharmacol 1986;20:5&9. Goodman Gilman A, Rall TW, Niej AJ, Taylor P. In: The pharmacological basis of therapeutics, 8th ed. New York: 1990:320, 861. Guberman A, Cantu-Reyna G, Stuss D, Broughton R. Nonconvulsive generalized status epilepticus-clinical features, neuropsychological testing, and long-term follow-up. Neurology 1986;36:1284-91. Lemmen LJ, Klassen M, Duiser B. Intravenous lidocaine in the treatment of convulsions. J A M A 1978;239:2025. Leppik I . Status epilepticus. Neurol Clin 1986;4:63343. Leppik I . Status epilepticus: the next decade. Neurology 1990; 4O(suppl 2):&9. Lindsay BD. Cardiac arrhythmias. In: Dunagon WC, Ridner ML, eds. Manual of medical therapeutics, 26th ed. Boston: Little Brown, 1989:159. Epilepsia, Vol. 33, No. 5 , 1992
Lowenstein DH, Aminoff MJ, Simon RP. Barbiturate anesthesia in the treatment of refractory status epilepticus. Neurology 1988;38:395-400. Morris HH. Lidocaine: a neglected anticonvulsant? South Med J 1979;72:1564-5. Orlowski JP, Erenberg G, Lueders H, Cruse RP. Hypothermia and barbiturate coma for refractory status epilepticus. Crit Care Med 1984;12:367-372. Pascual J, Sedano MJ, Polo JM, Berciano J . Intravenous lidocaine for status epilepticus. Epilepsia 1988;29:584-9. Rashkin MC, Youngs C, Penovich P. Pentobarbital treatment of refractory status epilepticus. Neurology 1987;37:50&3. Rodman JH, Jelliffe RW, Kolb E , et al. Clinical studies with computer-assisted initial lidocaine therapy. Arch Intern Med 1984;144:703-9. Simon RP, Benowitz NL, Culala S. Motor paralysis increases brain uptake of lidocaine during status epilepticus. Neurology 1984;34:384-7. Stone WE, Javid MJ. Anticonvulsive and convulsive effects of lidocaine: comparison with those of phenytoin, and implications for mechanism of action concepts. Neurol Res 1988;lO: 161-8. Taverner D, Bain WA. Intravenous lidocaine as an anticonvulsant. In status epilepticus and serial epilepsy. Lancet 1958; 2:1145-7. Treiman DM, De Giorgio CM, Salusbury SM, Wickboldt CL. Subtle generalized convulsive status epilepticus. Epilepsiu 1984;25:653. Treiman DM, Walton N Y , Wickboldt C , De Giorgio CM. Predictable sequence of EEG changes during generalized convulsive status epilepticus in man and three experimental models of status epilepticus in the rat. Neurology 1987;37(suppl 1):244. Treiman DM, Walton NY, Kendrick C. A progressive sequence of electroencephalographic changes during generalized convulsive status epilepticus. Epilepsy Res 1990;5:4940. Uthman BM, Wilder BJ. Emergency management of seizures: an overview. Epilepsia 1989;30(suppl 2):S33-7.
RESUME L a llidocaine s’est revtlee efficace chez 2 patients presentant un Ctat de ma1 Cpileptique refractaire, qui n’avait pas rCpondu a plusieurs medicaments antikpileptiques, y compris a des doses ClevCes de barbituriques. Les auteurs confirment, pour la premiere fois chez l’adulte, sous monitorage EEG continu, I’efficacitk de la lidocaine. Lorsqu’elle est utilisee de faGon adaptee, la lidocaine peut representer une option therapeutique dans l’ktat de ma1 epileptique rebelle. (P. Genton, Marseille)
RESUMEN La lidocaina ha sido eficaz en 2 pacientes con status epilCptico refractario al tratamiento con varias medicaciones antiepilkpticas incluyendo dosis altas de barbituricos. Los autores confirman, por primera vez en adultos, la eficacia de la lidocaina administrada durante una monitorizacion continua con EEG. L a lidocaina cuando se usa de mod0 apropiado puede ser el tratamiento opcional en el status epiltptico refractario. (A. Portera-SBnchez, Madrid)
ZUSAMMENFASSUNG Lidocain war bei 2 Patienten mit therapieresistentem Status epileptikus wirksam, der nicht auf verschiedene Antiepileptika und hohe Dosen Barbiturat ansprachen. Zum erstenmal bestatigen wir fur das Erwachsenenalter die Wirksamkeit von Lidocain durch kontinuierliches EEG-Monitoring. Bei richtiger Anwendung stellt Lidocain eine Behandlungsmoglichkeit des therapieresistenten Status Epileptikus dar. (C. G. Lipinski, HeidelberglNeckargemiind)
Lidocaine in Refractory Status Epilepticus: Confirmation of Efficacy with Continuous EEG Monitoring Christopher M. De Giorgio, Karen Altman, Elizabeth Hamilton-Byrd, and Adrian L. Rabinowicz Department of Neurology, USC School of Medicine, Los Angeles, California, U.S.A.
Summary: Lidocaine was efficacious in 2 patients with refractory status epilepticus (RSE) unresponsive to severa1 antiepileptic drugs (AEDs), including high-dose barbiturates. We confirmed the efficacy of lidocaine with,
for the first time in adults, continuous EEG monitoring. Lidocaine, when properly used, may be a treatment option in RSE. Key Words: Lidocaine-Status epilepticusAnticonvulsants-Electroencephalography.
Status epilepticus (SE) is a medical emergency, with mortality rates of 10-12% (Delgado-Escueta et al., 1982). Prolonged or refractory SE causes significant brain injury and neuronal loss (De Giorgio et al., 1992) and is highly lethal; mortality may be as high as 77% (Treiman et al., 1984; Rashkin et al., 1987). Refractory SE (RSE) may evolve into nonconvulsive SE (NCSE) defined as confusion, stupor, or coma with continuous EEG epileptiform activity (Bauer et al., 1982; Treiman et al., 1984; Guberman et al., 1986; Fagan and Lee, 1990). NCSE is the final common pathway for RSE in humans and animals (Treiman et al., 1984, 1990). The drugs of choice for RSE or NCSE are not well defined. Delgado-Escueta et al. (1982) recommended a management protocol including lidocaine or paraldehyde if sequential infusion of diazepam, phenytoin (PHT), and phenobarbital (PB) are ineffective. Uthman and Wilder (1989) also consider lidocaine a valuable drug in RSE. Leppik (1986, 1990) recommends against lidocaine use for SE, echoing concerns about lidocaine’s potential to be a proconvulsant. Pentobarbital coma has been recommended in RSE, despite pentobarbital’s potential for serious toxicity, including severe hypotension (frequently requiring pressors), prolonged coma, and the need for prolonged intensive care (Orlowski et al., 1984; Rashkin et al., 1987; Lowenstein et al., 1988). We could find no reports in the English literature confirming, with continuous EEG monitoring, the
efficacy of lidocaine in RSE. We report the safety and efficacy of lidocaine in two patients with RSE. Patient 1 A 23-year-old, 75-kg man with chronic epilepsy was admitted to the emergency room (ER). Six weeks before, he had run out of PHT, and 3 days before admission, his family noted multiple prolonged periods of unresponsiveness, left hemibody clonic movements, eye deviation to the left, and urinary incontinence. He was unresponsive to verbal stimuli at the time of admission. Two milligrams of intravenous (i.v.) lorazepam was administered in the ER with no effect. Multiple, discrete, bilateral occipital onset electrographic seizures characterized by rhythmic fast activity followed by generalized high-frequency bisynchronous spike and wave discharges were noted. Despite infusion of 4 mg i.v. lorazepam, EEG and clinical seizure activity continued. PHT was initiated at a rate of 50 mg/min i.v., but only 700 mg could be infused (9 mg/kg) because of hypotension. The patient was intubated, administered 10 mg diazepam i.v. push, and loaded with 1,300 mg i.v. phenobarbital (PB) at a rate of 100 mg/min, and 4 mg i.v. lorazepam; clinical seizure activity persisted. Pentobarbital coma was induced with an initial bolus of 5 mg/kg (375 mg) i.v. push followed first by a continuous i.v. infusion of 75 mg/h (1 mg/kg/h) and then by 150 mg/h (2 mg/kg/ h). A repeat EEG demonstrated continuous ictal activity, and pentobarbital was increased to 188 mg/h (2.5 mg/kg/h). Moderate hypotension occurred. Continuous EEG monitoring was initiated and showed a continuous generalized spike and slow wave ictal pattern. Administration of 8 mg
Received June 1991; revision accepted February 1992. Address reprint requests to Dr. C. M. De Giorgio at Department of Neurology, USC School of Medicine, 2025 Zonal Ave., Los Angeles, CA 90033, U.S.A.
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lorazepam had only slight EEG effect. An i.v. bolus of lidocaine 75 mg (1 mg/kg) was administered and repeated in 20 min, followed by a continuous i.v. infusion of 1 mg/min followed by 2 mglmin. The EEG response to treatment is shown in Fig. 1 . Lidocaine successfully eliminated all ictal EEG activity, and the patient gradually awakened. Followup EEGs showed progressive background normalization. Clinical and electrical S E did not recur. Patient 2 A 37-year-old, 80-kg man with a recurrent left temporal astrocytoma and left temporal onset secondarily generalized seizures was admitted for Pneumocystis pneumonia and intubated for respiratory failure. The patient was successfully extubated but continuous right-sided clonic jerking and clonic eye deviation to the right developed acutely; he was unresponsive to verbal and painful stimulus. Lorazepam i.v. stopped clinical seizure activity, but the patient remained unresponsive. Continuous EEG monitoring showed a continuous left hemispheric sharp and slow wave pattern consistent with EEG SE. PB 1,700 mg was infused i.v. (21 mg/kg), but a continuous ictal pattern persisted. Lidocaine as an 80-mg i.v. bolus ( 1 mg/kg) was administered, followed by a continuous i.v. infusion at a rate of 1 mg/min. The EEG SE was terminated within 54 min after the i.v. lidocaine infusion was started. Figure 2 shows the EEG response to treatment.
DISCUSSION Lidocaine, a local anesthetic, anticonvulsant, and antiarrhythmic agent, was introduced in 1948. It primarily blocks sodium channels, thereby decreasing membrane excitability (Stone and Javid, 1988). Lidocaine effectively blocks seizures induced by ouabain (a sodium/potassium pump antagonist), and is effective against glutamate-induced seizures but is ineffective against penicillin and pentylenetetrazol seizures (Stone and Javid, 1988). Overall, lidocaine has an anticonvulsant spectrum of activity similar to phenytoin, and blocks sodium-dependent epileptiform spike activity (Stone and Javid, 1988). Lidocaine i.v. is rapidly distributed, with a distribution half-life (tY2) of 8-17 min; elimination t?h is 1-8 h (Lindsay, 1989; Goodman Gilman et al., 1990). Effective antiarrhythmic concentrations are achieved with a bolus of 1-1.5 mg/kg, followed by half the dose in 5 min (Goodman Gilman et al., 1990). Infusion rates of 1 - 4 mg/min result in plasma levels of 1-5 pg/ml (Goodman Gilman et al., 1990). CNS toxicity, including confusion, stupor, respiratory arrest, or seizures, occur at levels >5 pg/ml, Epilepsiu, Vol. 33, N o . 5 , 1992
usually in chronic heart failure, severe hepatic disease, or shock; in the elderly, lower infusion rates are necessary (Lindsay, 1989; Goodman Gilman et al., 1990). Seizures secondary to lidocaine have been reported, but the actual risk is low (Buckman et al., 1980; Forrenge et al., 1986). Buckman et al. (1990), in a prospective study correlating blood levels with toxicity, reported lidocaine-induced seizures in 1 of 50 patients, an alcoholic patient with lidocaine levels of 9.3 pg/ml. CNS toxicity (confusion, drowsiness, tremulousness, tinnitus, and psychosis) was reported in 26 patients at levels >2.9 pg/ml. These symptoms occurred in all patients with levels >5.9 pg/ml. Rodman et al. (1984), in another large study comparing computer-assisted infusion with conventional therapy, reported no seizures in 156 patients. In addition to heart and liver disease, neuromuscular blockade may also increase the risk for toxicity. Simon et al. (1984) reported that neuromuscular blockade results in partitioning of lidocaine into the CNS, resulting in potentially toxic CNS levels, significantly higher than plasma levels would indicate. To our knowledge, there are no reports of additional seizures or of prolongation or recurrence of SE when lidocaine was administered as an anticonvulsant Many short literature reports document the efficacy of lidocaine in SE (Bernhard et al., 1955; Taverner and Bain, 1958; Lemmen et al., 1978; Morris, 1979; Browne, 1983; Pascual et al., 1988). Bernhard et al. (1955) first reported the efficacy of lidocaine for SE. Taverner and Bain (1958) reported the only prospective blinded study of lidocaine for SE that clearly showed efficacy when lidocaine was compared with saline in 3 patients. Lidocaine or saline was infused after a seizure, and the interval to the next seizure was measured, with lidocaine clearly prolonging the time to the next seizure. By 1979, lidocaine was recognized as a “neglected anticonvulsant” (Morris, 1979). Browne (1983) reviewed 148 reported cases of SE treated with lidocaine and concluded that lidocaine is effective in SE and may control SE when diazepam, PHT, PB, and paraldehyde fail. He noted that the antiepileptic effect is rapid (20-30 s) and short-lived, which may necessitate a continuous infusion. A prospective study by Pascual et al. (1988) confirms this conclusion. We believe that ours is the first report of lidocaine efficacy in RSE, documented by continuous EEG monitoring, which is essential in documenting success of treatment in SE and in diagnosing nonconvulsive SE. NCSE subsequent to generalized convulsive SE is an increasingly recognized phenomenon (Treiman et al., 1984, 1987, 1990;
C . M . DE GIORGIO ET AL.
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Fagan and Lee, 1990). Several EEG patterns have been reported to be associated with NCSE (Fagan and Lee, 1990; Treiman et al., 1990). These patterns are remarkably similar to those reported in our 2 patients (patient 1, Fagan and Lee, 1990, Fig. 2; patient 2, Treiman et.al., 1990, Fig. 3A). The resolution of these two ictal patterns confirms the efficacy of lidocaine. We believe that the relative risks of lidocaine may be less than those of pentobarbital and recommend a prospective comparison of pentobarbital and lidocaine in RSE. Our results support the recommendation by Delgado-Escueta et al. (1982) that lidocaine may be used as an alternative drug for SE after diazepam, PHT, and PB have failed. Note: We remind readers that SE is not a U.S. FDAapproved indication for lidocaine.
Acknowledgment: A.L.R. received support from the Garnier Trust for Epilepsy Research.
REFERENCES Bauer G, Aichner F , Mayr U. Nonconvulsive status epilepticus following generalized tonic-clonic seizures. Eur Neurol 1982; 21:411-9. Bernhard GC, Bohm E, Hojeberg S. A new treatment of status epilepticus, intravenous injections of a local anesthetic (lidocaine). Arch Neurol Psychiatry 1955;74:208-14. Browne TR. Paraldehyde, chlormethiorale, and lidocaine for treatment of status epilepticus. In: Delgado-Escueta AV, Wasterlain CG, Treiman DM, Porter RJ, eds. Status epilepficus. Mechanisms of brain damage and treatment. Raven Press: New York, 1983:509-17. (Advances in neurology; vol. 34.) Buckman K, Claiborne K, deGuzman M, Walberg CB, Haywood J. Lidocaine efficacy and toxicity assessed by a new rapid method. Clin Pharmacol Ther 1980;28:177-81. De Giorgio CM, Tomiyasu U , Gott PS, Treiman DM. Hippocampal pyramidal cell loss in human status epilepticus. Epilepsia 1992;33:23-7. Delgado-Escueta AV, Wasterlain C, Treiman DM, Porter RJ. Current concepts in neurology: management of status epilepticus. N Engl J Med 1982;306:133740. Fagan KJ, Lee SI. Prolonged confusion following convulsions due to generalized nonconvulsive status epilepticus. Neurology 1990;40: 1689-94. Forrenge E, Covinsky JO, Multen C. A seizure induced by concurrent lidocaine-tocainamide therapy. Is it just a case of additive toxicity? Drug Intel1 Clin Pharmacol 1986;20:5&9. Goodman Gilman A, Rall TW, Niej AJ, Taylor P. In: The pharmacological basis of therapeutics, 8th ed. New York: 1990:320, 861. Guberman A, Cantu-Reyna G, Stuss D, Broughton R. Nonconvulsive generalized status epilepticus-clinical features, neuropsychological testing, and long-term follow-up. Neurology 1986;36:1284-91. Lemmen LJ, Klassen M, Duiser B. Intravenous lidocaine in the treatment of convulsions. J A M A 1978;239:2025. Leppik I . Status epilepticus. Neurol Clin 1986;4:63343. Leppik I . Status epilepticus: the next decade. Neurology 1990; 4O(suppl 2):&9. Lindsay BD. Cardiac arrhythmias. In: Dunagon WC, Ridner ML, eds. Manual of medical therapeutics, 26th ed. Boston: Little Brown, 1989:159. Epilepsia, Vol. 33, No. 5 , 1992
Lowenstein DH, Aminoff MJ, Simon RP. Barbiturate anesthesia in the treatment of refractory status epilepticus. Neurology 1988;38:395-400. Morris HH. Lidocaine: a neglected anticonvulsant? South Med J 1979;72:1564-5. Orlowski JP, Erenberg G, Lueders H, Cruse RP. Hypothermia and barbiturate coma for refractory status epilepticus. Crit Care Med 1984;12:367-372. Pascual J, Sedano MJ, Polo JM, Berciano J . Intravenous lidocaine for status epilepticus. Epilepsia 1988;29:584-9. Rashkin MC, Youngs C, Penovich P. Pentobarbital treatment of refractory status epilepticus. Neurology 1987;37:50&3. Rodman JH, Jelliffe RW, Kolb E , et al. Clinical studies with computer-assisted initial lidocaine therapy. Arch Intern Med 1984;144:703-9. Simon RP, Benowitz NL, Culala S. Motor paralysis increases brain uptake of lidocaine during status epilepticus. Neurology 1984;34:384-7. Stone WE, Javid MJ. Anticonvulsive and convulsive effects of lidocaine: comparison with those of phenytoin, and implications for mechanism of action concepts. Neurol Res 1988;lO: 161-8. Taverner D, Bain WA. Intravenous lidocaine as an anticonvulsant. In status epilepticus and serial epilepsy. Lancet 1958; 2:1145-7. Treiman DM, De Giorgio CM, Salusbury SM, Wickboldt CL. Subtle generalized convulsive status epilepticus. Epilepsiu 1984;25:653. Treiman DM, Walton N Y , Wickboldt C , De Giorgio CM. Predictable sequence of EEG changes during generalized convulsive status epilepticus in man and three experimental models of status epilepticus in the rat. Neurology 1987;37(suppl 1):244. Treiman DM, Walton NY, Kendrick C. A progressive sequence of electroencephalographic changes during generalized convulsive status epilepticus. Epilepsy Res 1990;5:4940. Uthman BM, Wilder BJ. Emergency management of seizures: an overview. Epilepsia 1989;30(suppl 2):S33-7.
RESUME L a llidocaine s’est revtlee efficace chez 2 patients presentant un Ctat de ma1 Cpileptique refractaire, qui n’avait pas rCpondu a plusieurs medicaments antikpileptiques, y compris a des doses ClevCes de barbituriques. Les auteurs confirment, pour la premiere fois chez l’adulte, sous monitorage EEG continu, I’efficacitk de la lidocaine. Lorsqu’elle est utilisee de faGon adaptee, la lidocaine peut representer une option therapeutique dans l’ktat de ma1 epileptique rebelle. (P. Genton, Marseille)
RESUMEN La lidocaina ha sido eficaz en 2 pacientes con status epilCptico refractario al tratamiento con varias medicaciones antiepilkpticas incluyendo dosis altas de barbituricos. Los autores confirman, por primera vez en adultos, la eficacia de la lidocaina administrada durante una monitorizacion continua con EEG. L a lidocaina cuando se usa de mod0 apropiado puede ser el tratamiento opcional en el status epiltptico refractario. (A. Portera-SBnchez, Madrid)
ZUSAMMENFASSUNG Lidocain war bei 2 Patienten mit therapieresistentem Status epileptikus wirksam, der nicht auf verschiedene Antiepileptika und hohe Dosen Barbiturat ansprachen. Zum erstenmal bestatigen wir fur das Erwachsenenalter die Wirksamkeit von Lidocain durch kontinuierliches EEG-Monitoring. Bei richtiger Anwendung stellt Lidocain eine Behandlungsmoglichkeit des therapieresistenten Status Epileptikus dar. (C. G. Lipinski, HeidelberglNeckargemiind)
