- Email: [email protected]
Intranasal midazolam for childhood seizures
RESEARCH LETTERS
This case-control study gave estimates of the odds ratio which are in agreement with the risk-ratio estimate with a case-population approach, 1 and this adds consistency to our results. Our findings suggest a risk of aplastic anaemia associated with nifedipine. According to a Medline search for 1980–97, no cases of aplastic anaemia attributed to nifedipine have been reported. In 1986, the final report of the ISAAA included three cases (2·0%) and 26 controls (1·2%) exposed to nifedipine. 2 Our results suggest that the risk of aplastic anaemia associated with nifedipine is of a similar magnitude to that associated with chloramphenicol (1·7 per 100 000 exposed patients)3 and that associated with phenylbutazone (2·2 per 100 000 exposed patients).4 We conclude that the use of nifedipine is associated with a significant relative risk of aplastic anaemia, which translates into an absolute risk of 1·2 per 100 000 patient-years. We thank the patients who contributed and the haematologists for their collaboration: E Abella, R Ayats, C Besses, S Brunet, N Crespo, I De Diego, A Domingo, J Estella, M García, A Julià, P Marín, F Millà, B Nomdedéu, T Olivé, L Ortega, E Pérez, I Roig, A Solé, R Soto, and T Toll. 1
2
3
4
Capellà D, Laporte J-R, Vidal X, et al. European network for the case-population surveillance of rare diseases (Euronet): a prospective feasibility study. Eur J Clin Pharmacol 1998; 53: 299–302. Kaufman DW, Kelly JP, Levy M, Shapiro S. The drug etiology of agranulocytosis and aplastic anemia. New York: Oxford University Press, 1991. Smick KM, Condit PK, Proctor RL, Sutcher V. Fatal aplastic anemia. An epidemiological study of its relationship to the drug chloramphenicol. J Chron Dis 1964; 17: 899–914. Inman WHW. Study of fatal bone marrow depression with special reference to phenylbutazone and oxyphenbutazone. BMJ 1977; i: 1500–05.
Institut Català de Farmacologia, Vall d’Hebron Hospitals, Universitat Autònoma de Barcelona, 08035-Barcelona, Spain (J-R Laporte; e-mail [email protected])
Intranasal midazolam for childhood seizures
12 children had a history of seizures and were taking antiepileptic drugs; underlying diseases included cerebral palsy, idiopathic epilepsy, cerebral dysgenesis, and neurocutaneous syndrome. Eight children presented with their first seizure, four had idiopathic epilepsy, two bacterial meningitis,and two viral encephalitis. Seizure control was achieved in all children except for one in whom intravenous diazepam was ineffective and seizure control achieved after 30 min with intravenous phenytoin. Estimated duration of seizures before midazolam was 10–25 min (mean 17 [4·0]). Mean time to seizure control was 3·5 (0·8) min (range 2·5–5). There were no recurrences of seizures within 60 min after treatment. This study shows that intranasal midazolam is effective for the management of acute childhood seizures. Sublingual midazolam has been shown to be safe and effective in treating seizures in children.5 However, this route is impossible in tonic seizures and it is against the rules of treating people with epilepsy to forcefully open their mouths. Intranasal midazolam could be useful in physicians’ offices, special educational institutions and, with appropriate instructions, as a first aid technique for parents of epileptic children. 1 2
3
4
5
Dieckmann RA. Rectal diazepam for prehospital pediatric status epilepticus. Ann Emerg Med 1994; 13: 218–24. Chamberlain JM, Altieri MA, Futterman C, Young GM, Ochsenchlager DW, Waisman Y. A prospective, randomized study comparing intramuscular midazolam with intravenous diazepam for the treatment of seizures in children. Pediatr Emerg Care 1997; 13: 92–94. Lacon A, Reddy VG. Nasal midazolam and ketamine for pediatric sedation during computerized tomography. Acta Anesthesiol Scand 1994; 38: 259–61. O’Regan ME, Brown JK, Clarke M. Nasal rather than rectal benzodiazepines in the management of acute childhood seizures? Develop Med Child Neurol 1996; 38: 1037–45. Scott RC, Neville BGR, Besag FMC, Boyd SG. Nasal rather than rectal benzodiazepines in the management of acute childhood seizures? Develop Med Child Neurol 1997; 39: 137–38.
Pediatric Neurology Unit (E Lahat), Pediatric Division and Clinical Pharmacology and Toxicology Unit, Assaf Harofeh Medical Center, Zerifin 70300, Israel
E Lahat, M Goldman, J Barr, G Eshel, M Berkovitch
Diazepam is widely used to treat acute seizures in adults and children. However, it has a short duration of action, it is usually given intravenously, and it tends to accumulate if repeated doses are given. Diazepam and other benzodiazepines may be given rectally, but absorption may be delayed1 and the procedure is unpleasant. Midazolam, a water-soluble benzodiazepine, is an effective anticonvulstant given intramuscularly.2 Intranasal midazolam is a safe and effective anaesthetic in children3 and can suppress epileptic activity.4 We assessed intranasal midazolam in the treatment of acute childhood seizures. For 3 months, all children between age 1 month and 16 years who came to our paediatric emergency department with generalised motor seizures of at least 10 min duration were eligible for inclusion. Children with an intravenous line or who had received anticonvulsive medication were excluded. Parents gave verbal consent and later signed their approval. The study was approved by the hospital’s ethics committee. Midazolam solution (5 mg/mL) at a dose of 0·2 mg/kg bodyweight was dropped into both nostrils immediately before an intravenous line was inserted. Treatment was taken to be successful if the child’s seizure stopped within 5 min, delayed if between 5 min and 10 min, and a failure if seizures did not stop within 10 min, when diazepam 0·3 mg/kg was given intravenously. 20 children were eligible—12 boys and eight girls, aged 6 months to 16 years (mean 5·8 [SD 5·0] years, median 3·5 years).
620
␥-band electroencephalographic oscillations in a patient with somatic hallucinations Torsten Baldeweg, Sean Spence, Steven R Hirsch, John Gruzelier
Despite advances in neuroimaging, the physiological basis of abnormal human perceptions, such as hallucinations, has remained elusive. Electrophysiological studies in animals suggest that synchronous high-frequency cortical oscillations (40 Hz or ␥-band electroencephalogram [EEG]) may reflect the process of perception. 1 Analogous oscillations in the human EEG are generally of low voltage and are, therefore, difficult to distinguish. We saw high-amplitude ␥-band EEG oscillations in a man aged 36 years while he experienced bizarre somatic hallucinations. EEG was recorded (32 channels, silver/silverchloride electrodes, ECI conductive gel, band pass 0–70 Hz) on two occasions during investigations into psychotic phenomena. The first EEG was done when the patient was on no medication, and was repeated after 3 weeks when he was taking trifluoperazine 10 mg per day. We obtained written informed consent before investigation. At the time of testing, the patient repeatedly reported popping sensations in his left cervical, temporal, and
THE LANCET • Vol 352 • August 22, 1998
This case-control study gave estimates of the odds ratio which are in agreement with the risk-ratio estimate with a case-population approach, 1 and this adds consistency to our results. Our findings suggest a risk of aplastic anaemia associated with nifedipine. According to a Medline search for 1980–97, no cases of aplastic anaemia attributed to nifedipine have been reported. In 1986, the final report of the ISAAA included three cases (2·0%) and 26 controls (1·2%) exposed to nifedipine. 2 Our results suggest that the risk of aplastic anaemia associated with nifedipine is of a similar magnitude to that associated with chloramphenicol (1·7 per 100 000 exposed patients)3 and that associated with phenylbutazone (2·2 per 100 000 exposed patients).4 We conclude that the use of nifedipine is associated with a significant relative risk of aplastic anaemia, which translates into an absolute risk of 1·2 per 100 000 patient-years. We thank the patients who contributed and the haematologists for their collaboration: E Abella, R Ayats, C Besses, S Brunet, N Crespo, I De Diego, A Domingo, J Estella, M García, A Julià, P Marín, F Millà, B Nomdedéu, T Olivé, L Ortega, E Pérez, I Roig, A Solé, R Soto, and T Toll. 1
2
3
4
Capellà D, Laporte J-R, Vidal X, et al. European network for the case-population surveillance of rare diseases (Euronet): a prospective feasibility study. Eur J Clin Pharmacol 1998; 53: 299–302. Kaufman DW, Kelly JP, Levy M, Shapiro S. The drug etiology of agranulocytosis and aplastic anemia. New York: Oxford University Press, 1991. Smick KM, Condit PK, Proctor RL, Sutcher V. Fatal aplastic anemia. An epidemiological study of its relationship to the drug chloramphenicol. J Chron Dis 1964; 17: 899–914. Inman WHW. Study of fatal bone marrow depression with special reference to phenylbutazone and oxyphenbutazone. BMJ 1977; i: 1500–05.
Institut Català de Farmacologia, Vall d’Hebron Hospitals, Universitat Autònoma de Barcelona, 08035-Barcelona, Spain (J-R Laporte; e-mail [email protected])
Intranasal midazolam for childhood seizures
12 children had a history of seizures and were taking antiepileptic drugs; underlying diseases included cerebral palsy, idiopathic epilepsy, cerebral dysgenesis, and neurocutaneous syndrome. Eight children presented with their first seizure, four had idiopathic epilepsy, two bacterial meningitis,and two viral encephalitis. Seizure control was achieved in all children except for one in whom intravenous diazepam was ineffective and seizure control achieved after 30 min with intravenous phenytoin. Estimated duration of seizures before midazolam was 10–25 min (mean 17 [4·0]). Mean time to seizure control was 3·5 (0·8) min (range 2·5–5). There were no recurrences of seizures within 60 min after treatment. This study shows that intranasal midazolam is effective for the management of acute childhood seizures. Sublingual midazolam has been shown to be safe and effective in treating seizures in children.5 However, this route is impossible in tonic seizures and it is against the rules of treating people with epilepsy to forcefully open their mouths. Intranasal midazolam could be useful in physicians’ offices, special educational institutions and, with appropriate instructions, as a first aid technique for parents of epileptic children. 1 2
3
4
5
Dieckmann RA. Rectal diazepam for prehospital pediatric status epilepticus. Ann Emerg Med 1994; 13: 218–24. Chamberlain JM, Altieri MA, Futterman C, Young GM, Ochsenchlager DW, Waisman Y. A prospective, randomized study comparing intramuscular midazolam with intravenous diazepam for the treatment of seizures in children. Pediatr Emerg Care 1997; 13: 92–94. Lacon A, Reddy VG. Nasal midazolam and ketamine for pediatric sedation during computerized tomography. Acta Anesthesiol Scand 1994; 38: 259–61. O’Regan ME, Brown JK, Clarke M. Nasal rather than rectal benzodiazepines in the management of acute childhood seizures? Develop Med Child Neurol 1996; 38: 1037–45. Scott RC, Neville BGR, Besag FMC, Boyd SG. Nasal rather than rectal benzodiazepines in the management of acute childhood seizures? Develop Med Child Neurol 1997; 39: 137–38.
Pediatric Neurology Unit (E Lahat), Pediatric Division and Clinical Pharmacology and Toxicology Unit, Assaf Harofeh Medical Center, Zerifin 70300, Israel
E Lahat, M Goldman, J Barr, G Eshel, M Berkovitch
Diazepam is widely used to treat acute seizures in adults and children. However, it has a short duration of action, it is usually given intravenously, and it tends to accumulate if repeated doses are given. Diazepam and other benzodiazepines may be given rectally, but absorption may be delayed1 and the procedure is unpleasant. Midazolam, a water-soluble benzodiazepine, is an effective anticonvulstant given intramuscularly.2 Intranasal midazolam is a safe and effective anaesthetic in children3 and can suppress epileptic activity.4 We assessed intranasal midazolam in the treatment of acute childhood seizures. For 3 months, all children between age 1 month and 16 years who came to our paediatric emergency department with generalised motor seizures of at least 10 min duration were eligible for inclusion. Children with an intravenous line or who had received anticonvulsive medication were excluded. Parents gave verbal consent and later signed their approval. The study was approved by the hospital’s ethics committee. Midazolam solution (5 mg/mL) at a dose of 0·2 mg/kg bodyweight was dropped into both nostrils immediately before an intravenous line was inserted. Treatment was taken to be successful if the child’s seizure stopped within 5 min, delayed if between 5 min and 10 min, and a failure if seizures did not stop within 10 min, when diazepam 0·3 mg/kg was given intravenously. 20 children were eligible—12 boys and eight girls, aged 6 months to 16 years (mean 5·8 [SD 5·0] years, median 3·5 years).
620
␥-band electroencephalographic oscillations in a patient with somatic hallucinations Torsten Baldeweg, Sean Spence, Steven R Hirsch, John Gruzelier
Despite advances in neuroimaging, the physiological basis of abnormal human perceptions, such as hallucinations, has remained elusive. Electrophysiological studies in animals suggest that synchronous high-frequency cortical oscillations (40 Hz or ␥-band electroencephalogram [EEG]) may reflect the process of perception. 1 Analogous oscillations in the human EEG are generally of low voltage and are, therefore, difficult to distinguish. We saw high-amplitude ␥-band EEG oscillations in a man aged 36 years while he experienced bizarre somatic hallucinations. EEG was recorded (32 channels, silver/silverchloride electrodes, ECI conductive gel, band pass 0–70 Hz) on two occasions during investigations into psychotic phenomena. The first EEG was done when the patient was on no medication, and was repeated after 3 weeks when he was taking trifluoperazine 10 mg per day. We obtained written informed consent before investigation. At the time of testing, the patient repeatedly reported popping sensations in his left cervical, temporal, and
THE LANCET • Vol 352 • August 22, 1998