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Treatment of “febrile seizures”
164
Letters to the Editor
about one quarter, or 8% of those on the drug, reacted in a serious manner? So I think most physicians would feel such a screening justified. To get a more precise incidence rate is not possible since we must rely on anecdotal reports, like this one, and the drug company-authored Physicians" Desk Reference for our information on iatrogenic deaths. In their short reporting period the F D A Adverse Drug Reporting Program lists 15 cases of coma and three deaths from Compazine alone. It is unfortunate that this is only a voluntary program, and that its existences, is not well known. I urge physicians to use it for all severe drug reactions. No matter what the incidence, prevention is an admirable goal. 1 hope that results of Chassimos and associates will be supported by further research in other metabolic labs. Then we might be able to prevent such tragedies as occurred in our child.
Virginia Feldman, M.D. (formerly) Pediatric Resident University of Oregon Medical School Portland, Ore. (presently) Pediatrician Kaiser Permanente Medical Group 5055 N. Greeley Portland, Ore. 97219 REFERENCES
1. Cassimos C, Tsiuris J, Danielides B, and Malaka-Zafiriu K: Urinary D-glucaric acid excretion in children with dystonic reactions caused by antiemetic drugs, J PEDIATR 87:981, 1975. 2. Shaw EB, et al: Phenothiazine tranquilizers as cause of 9severe seizures Pediatrics 23:485, 1959. 3. Garlitis I, et al: Alarming neuromuscular reactions due to Compazine. Ann Intern Med 52:538, 1960. 4. Federal Supplements: 284, p 259, 1967. Smith vs. The United States. 5. Hall RA, et al: Neurotoxic reactions resulting from chlorpromazine administration, JAMA: 161:214, 1956. 6. Ayde FJ: A Survey of drug induced extrapyramidal reactions, .IAMA 175:1054, 1961.
Treatment of "'febrile seizures" To the Editor: The investigation by Asnes and associates, 1which revealed that "practicing pediatricians vary widely in their approach to the diagnostic evaluation and therapeutic management of children with first febrile seizures" stimulated Sakaf-' to briefly cite some of the relevant literature concerning the value of intermittent and continuous phenobarbital therapy as a prophylaxis against the recurrence of "febrile convulsions" and to make therapeutic recommendations. In our opinion, Sakai was unsuccessful in his endeavor to resolve the problems of therapy for seizures associated with fever, because he failed to define the term "febrile convulsions," and, therefore, the reader cannot be certain whether his evaluations
The Journal of Pediatrics July 1976 and recommendations are directed to Asnes and co-workers' "Category I epileptic seizures precipitated by fever" or "Category II-simp:le febrile convulsions." Without amplification or elaboration, the term "febrile convulsions" is essentially meaningless, because it refers to all seizures associated with an elevation of temperature, without regard to the duration (several minutes to hours) or character (generalized or focal) of the episode, EEG findings, etc. Inconsistency in classifying "febrile seizures" is unquestionably responsible for some of the contradictory and perplexing reports relative to the treatment of seizures associated with fever in young children, and we believe that Sakai's communication does little more than compound and perpetuate the existing confusion. Since there is universal agreement that epileptic seizures precipitated by fever be treated with daily anticonvulsant medication, we must assume that Sakai's recommendations are directed to simple febrile convulsions. Therefore, his conclusion, "if one decides to treat the child prophylactically, the treatment of choice should be continuous therapy with phenobarbital," is highly questionable and subject to serious criticism, because it is based upon the results of an investigation by Faero and associates 3 who utilized a group of patients that exhibited different types of febrile seizures, rather than a homogeneous series of children with simple febrile convulsions. Obviously, the findings of this study, in which at least 25% of the patients had epileptic seizures precipitated by fever (prolonged and/or focal), coupled with an exceedingly brief period of follow-up (6 months), cannot be summarily, and certainly not judiciously, applied to children with simple febrile convulsions. In evaluating the results of therapy in children with convulsions associated with fever, a follow-up period of six lnonths is practically worthless, because, as is well known by all pediatricians, many children with simple febrile convulsions have only one or two such attacks annually. Moreover, the small size of the study group (60 patients) and the paucity of clinical an,d: laboratory data concerning the patient material do not aItow formation of definite conclusions from this investigation. We also question Sal~ai's statement that "the controlled study by Millichap and associates ~ appears to be a focal point for the support of intermittent therapy over continuous therapy." This investigation demonstrated no difference in the rate of recurrence of febrile seizures in a group treated intermittently with phenobarbital and one that received continuous phenobarbital therapy, and the casual reader may assume that good results relative to seizure prophylaxis were obtained in both groups. This, however, was not the case, and Millichap himself stated that "control of febrile seizures was poor and of questionable degree in both groups."-' In our experience, almost all pediatricians agree that intermittent therapy for "febrile convulsions" is essentially ineffective as a prophylactic measure. Our recommendations relative to the treatment of "febrile convulsions" are based on the findings of three studies? -~ The patients in these investigations received (1) continuous phenobarbital therapy; (2) intermittent therapy with phenobarbital and aspirin; (3) continuous placebo therapy; or (4) intermittent therapy with placebo and aspirin. The dosage of phenobarbital employed in these studies was sufficient to have yielded serum
Volume 89 Number 1
drug concentrations of at least 15 /~g/mlY The results of these studies revealed no significant difference in the recurrence rate of simple febrile convulsions among the four groups; the majority of children experienced a recurrence of one to four such seizures annually, regardless of the form of therapy employed, until four or five years of age, and subsequently no recurrence &seizures o f any type. We emphasize that children who suffer with convulsions associated with an elevation of temperature of the type we classify as "epileptic seizures precipitated by fever" must be treated with daily antiepiteptic medication in the same manner as patients who have epileptic seizures unassociated with fever. Samuel Livingston, M.D. Lydia L. Pauli, M.D. The Samuel Livingston Epilepsy Diagnostic and Treatment Center 1039 St. Paul St. Baltimore, Md. 21202
REFERENCES
1. Asnes RS, Novick LF, Nealis J, and Nguyen M: The first febrile seizure: A study of current pediatric practice, J PEDIATR 87:485, 1975. 2. Sakai RI: Chronic versus intermittent phenobarbital therapy, J PEOIATR 88:363, 1976. 3. Faero O, Kastrup KW, Lykkegaard Nielsen E, Melchior JC, and Thorn I: Successful prophylaxis of febrile convulsions with phenobarbital , Epilepsia 13:279, 1972. 4. Millichap JG, Aledort LM, and Madsen JA: A critical evaluation of therapy of febrile seizures, J PEDIATR 56:364, 1960. 5. Millichap JG: Febrile convulsions, New York, 1968, The Macmillan Company, 1968, p 122. 6. Livingston S, Bridge EM, and Kajdi L: Febrile convulsions;
Letters to the Editor
7.
8.
9.
165
a clinical study with special reference to heredity and prognosis, J PEDIATR 31:509, 1947. Livingston S: Convulsive disorders in infants and children; in Levine SZ editor: Advances in pediatrics, vol 10, Chicago, 1958, Year Book, Medical Publishers, Inc, pp 114-119. Livingston S: Comprehensive management of epilepsy in infancy, Childhood and Adolescence. Springfield, Ill., Thomas, 1972, page 27. Svensmark O, and Buchthal F: Diphenylhydantoin and phenobarbital: serum levies in children, Am J Dis Child 108:82, 1964.
Reptz To the Editor: The importance of common terminology, as pointed out by Drs. Livingston and Pauli, is a valid point. I was referring to those patients with simple febrile convulsions and felt that mos~ pediatricians would realize this. Livingston and Pauli seemed to have missed the point of my letter. It was not to discuss whether or not prophylactic therapy is warranted for simple febrile convulsions, but rather to show the benefits of continuous over intermittent phenobarbital therapy once it has been decided to treat the patient. I am glad that Livingston and Pauli agree w i t h me that intermittent phenobarbital is ineffective in preventing recurrence of simple febrile convulsions. Richard L Sakai, Pharm.D. Fellow, Pediatric Clinical Pharmacy Children's Hospital Division o f Clinical Pharmacy 219 Bryant St. Buffalo, N.Y. 14222
Letters to the Editor
about one quarter, or 8% of those on the drug, reacted in a serious manner? So I think most physicians would feel such a screening justified. To get a more precise incidence rate is not possible since we must rely on anecdotal reports, like this one, and the drug company-authored Physicians" Desk Reference for our information on iatrogenic deaths. In their short reporting period the F D A Adverse Drug Reporting Program lists 15 cases of coma and three deaths from Compazine alone. It is unfortunate that this is only a voluntary program, and that its existences, is not well known. I urge physicians to use it for all severe drug reactions. No matter what the incidence, prevention is an admirable goal. 1 hope that results of Chassimos and associates will be supported by further research in other metabolic labs. Then we might be able to prevent such tragedies as occurred in our child.
Virginia Feldman, M.D. (formerly) Pediatric Resident University of Oregon Medical School Portland, Ore. (presently) Pediatrician Kaiser Permanente Medical Group 5055 N. Greeley Portland, Ore. 97219 REFERENCES
1. Cassimos C, Tsiuris J, Danielides B, and Malaka-Zafiriu K: Urinary D-glucaric acid excretion in children with dystonic reactions caused by antiemetic drugs, J PEDIATR 87:981, 1975. 2. Shaw EB, et al: Phenothiazine tranquilizers as cause of 9severe seizures Pediatrics 23:485, 1959. 3. Garlitis I, et al: Alarming neuromuscular reactions due to Compazine. Ann Intern Med 52:538, 1960. 4. Federal Supplements: 284, p 259, 1967. Smith vs. The United States. 5. Hall RA, et al: Neurotoxic reactions resulting from chlorpromazine administration, JAMA: 161:214, 1956. 6. Ayde FJ: A Survey of drug induced extrapyramidal reactions, .IAMA 175:1054, 1961.
Treatment of "'febrile seizures" To the Editor: The investigation by Asnes and associates, 1which revealed that "practicing pediatricians vary widely in their approach to the diagnostic evaluation and therapeutic management of children with first febrile seizures" stimulated Sakaf-' to briefly cite some of the relevant literature concerning the value of intermittent and continuous phenobarbital therapy as a prophylaxis against the recurrence of "febrile convulsions" and to make therapeutic recommendations. In our opinion, Sakai was unsuccessful in his endeavor to resolve the problems of therapy for seizures associated with fever, because he failed to define the term "febrile convulsions," and, therefore, the reader cannot be certain whether his evaluations
The Journal of Pediatrics July 1976 and recommendations are directed to Asnes and co-workers' "Category I epileptic seizures precipitated by fever" or "Category II-simp:le febrile convulsions." Without amplification or elaboration, the term "febrile convulsions" is essentially meaningless, because it refers to all seizures associated with an elevation of temperature, without regard to the duration (several minutes to hours) or character (generalized or focal) of the episode, EEG findings, etc. Inconsistency in classifying "febrile seizures" is unquestionably responsible for some of the contradictory and perplexing reports relative to the treatment of seizures associated with fever in young children, and we believe that Sakai's communication does little more than compound and perpetuate the existing confusion. Since there is universal agreement that epileptic seizures precipitated by fever be treated with daily anticonvulsant medication, we must assume that Sakai's recommendations are directed to simple febrile convulsions. Therefore, his conclusion, "if one decides to treat the child prophylactically, the treatment of choice should be continuous therapy with phenobarbital," is highly questionable and subject to serious criticism, because it is based upon the results of an investigation by Faero and associates 3 who utilized a group of patients that exhibited different types of febrile seizures, rather than a homogeneous series of children with simple febrile convulsions. Obviously, the findings of this study, in which at least 25% of the patients had epileptic seizures precipitated by fever (prolonged and/or focal), coupled with an exceedingly brief period of follow-up (6 months), cannot be summarily, and certainly not judiciously, applied to children with simple febrile convulsions. In evaluating the results of therapy in children with convulsions associated with fever, a follow-up period of six lnonths is practically worthless, because, as is well known by all pediatricians, many children with simple febrile convulsions have only one or two such attacks annually. Moreover, the small size of the study group (60 patients) and the paucity of clinical an,d: laboratory data concerning the patient material do not aItow formation of definite conclusions from this investigation. We also question Sal~ai's statement that "the controlled study by Millichap and associates ~ appears to be a focal point for the support of intermittent therapy over continuous therapy." This investigation demonstrated no difference in the rate of recurrence of febrile seizures in a group treated intermittently with phenobarbital and one that received continuous phenobarbital therapy, and the casual reader may assume that good results relative to seizure prophylaxis were obtained in both groups. This, however, was not the case, and Millichap himself stated that "control of febrile seizures was poor and of questionable degree in both groups."-' In our experience, almost all pediatricians agree that intermittent therapy for "febrile convulsions" is essentially ineffective as a prophylactic measure. Our recommendations relative to the treatment of "febrile convulsions" are based on the findings of three studies? -~ The patients in these investigations received (1) continuous phenobarbital therapy; (2) intermittent therapy with phenobarbital and aspirin; (3) continuous placebo therapy; or (4) intermittent therapy with placebo and aspirin. The dosage of phenobarbital employed in these studies was sufficient to have yielded serum
Volume 89 Number 1
drug concentrations of at least 15 /~g/mlY The results of these studies revealed no significant difference in the recurrence rate of simple febrile convulsions among the four groups; the majority of children experienced a recurrence of one to four such seizures annually, regardless of the form of therapy employed, until four or five years of age, and subsequently no recurrence &seizures o f any type. We emphasize that children who suffer with convulsions associated with an elevation of temperature of the type we classify as "epileptic seizures precipitated by fever" must be treated with daily antiepiteptic medication in the same manner as patients who have epileptic seizures unassociated with fever. Samuel Livingston, M.D. Lydia L. Pauli, M.D. The Samuel Livingston Epilepsy Diagnostic and Treatment Center 1039 St. Paul St. Baltimore, Md. 21202
REFERENCES
1. Asnes RS, Novick LF, Nealis J, and Nguyen M: The first febrile seizure: A study of current pediatric practice, J PEDIATR 87:485, 1975. 2. Sakai RI: Chronic versus intermittent phenobarbital therapy, J PEOIATR 88:363, 1976. 3. Faero O, Kastrup KW, Lykkegaard Nielsen E, Melchior JC, and Thorn I: Successful prophylaxis of febrile convulsions with phenobarbital , Epilepsia 13:279, 1972. 4. Millichap JG, Aledort LM, and Madsen JA: A critical evaluation of therapy of febrile seizures, J PEDIATR 56:364, 1960. 5. Millichap JG: Febrile convulsions, New York, 1968, The Macmillan Company, 1968, p 122. 6. Livingston S, Bridge EM, and Kajdi L: Febrile convulsions;
Letters to the Editor
7.
8.
9.
165
a clinical study with special reference to heredity and prognosis, J PEDIATR 31:509, 1947. Livingston S: Convulsive disorders in infants and children; in Levine SZ editor: Advances in pediatrics, vol 10, Chicago, 1958, Year Book, Medical Publishers, Inc, pp 114-119. Livingston S: Comprehensive management of epilepsy in infancy, Childhood and Adolescence. Springfield, Ill., Thomas, 1972, page 27. Svensmark O, and Buchthal F: Diphenylhydantoin and phenobarbital: serum levies in children, Am J Dis Child 108:82, 1964.
Reptz To the Editor: The importance of common terminology, as pointed out by Drs. Livingston and Pauli, is a valid point. I was referring to those patients with simple febrile convulsions and felt that mos~ pediatricians would realize this. Livingston and Pauli seemed to have missed the point of my letter. It was not to discuss whether or not prophylactic therapy is warranted for simple febrile convulsions, but rather to show the benefits of continuous over intermittent phenobarbital therapy once it has been decided to treat the patient. I am glad that Livingston and Pauli agree w i t h me that intermittent phenobarbital is ineffective in preventing recurrence of simple febrile convulsions. Richard L Sakai, Pharm.D. Fellow, Pediatric Clinical Pharmacy Children's Hospital Division o f Clinical Pharmacy 219 Bryant St. Buffalo, N.Y. 14222