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Continuous Midazolam Infusion As Treatment of Status Epilepticus

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Continuous Midazolam Infusion As Treatment of Status Epilepticus Archives of Disease in Childhood 1997;76:445–448 445 Continuous midazolam infusion as treatment of Arch Dis Child: first published as 10.1136/adc.76.5.445 on 1 May 1997. Downloaded from status epilepticus Roshan Lal Koul, Guru Raj Aithala, Alexander Chacko, Rajendra Joshi, Mussalem Seif Elbualy Abstract Midazolam is a recently developed water In a tertiary referral centre, midazolam soluble benzodiazepine, commonly used as a infusion was tried as treatment for 20 preanaesthetic agent with remarkable anticon- children with status epilepticus over a vulsant action.5 It has been shown to have a period of two years. The mean age of the wide margin of safety and a broad therapeutic children was 4.07 years. Twelve children index. Furthermore, it diVuses rapidly across with refractory status epilepticus had the capillary wall into the central nervous received intravenous or per rectal di- system and can be mixed with saline or glucose azepam and intravenous phenytoin/ solutions to allow its administration as a phenobarbitone or both before midazolam continuous infusion.6 was given (0.15 mg/kg bolus followed by 1–5 µg/kg/min infusion). Eight children required only midazolam to control the Subjects and methods established status epilepticus. The sei- Twenty children suVering from status epilepti- zures were controlled in 19 children. The cus admitted to the paediatric ward from mean time required for complete cessa- November 1993 to November 1995 were tion of seizures was 0.9 hours. The mean included in this study. Eleven were already tak- infusion rate required was 2.0 µg/kg/min. ing various antiepileptic drugs. All children had regained full conscious- Status epilepticus was diagnosed according ness by a mean of 5.1 hours after discon- to the criteria of Engel, namely continuous sei- tinuation of midazolam treatment. No zures for 30 minutes or longer or several seizures occurring with impairment of con- metabolic derangement or compromise of 2 vital functions was noted in any of the sciousness between seizure activity. Refractory children. Midazolam infusion is thus an status epilepticus was the diagnosis if the eVective and safe therapeutic approach seizures continued, despite at least two doses of for the management of childhood status diazepam intravenously or rectally in succes- http://adc.bmj.com/ epilepticus. sion followed by phenytoin sodium/ (Arch Dis Child 1997;76:445–448) phenobarbitone or both 20 mg/kg given over 30 minutes as an infusion, or failure to respond Keywords: status epilepticus; refractory; midazolam to the latter alone or in combination. The duration of status before midazolam therapy was approximate, based on the history ob- Status epilepticus is a medical emergency that tained from the patient’s attendants and the requires prompt intervention. The term is referring physician’s notes. Electroencephalo- on September 29, 2021 by guest. Protected copyright. applied to situations in which seizures occur so graphy (EEG) was not used for the diagnosis. It frequently that complete recovery between fits was, however, performed after the seizures had does not take place.1 A more substantive been controlled to monitor the electrical definition is continuous seizures lasting for 30 suppression of seizure discharge. Continuous Division of Paediatric minutes or longer or recurrent seizures occur- EEG monitoring was not available. However, it Neurology, Department of Child ring with impairment of consciousness be- was used to diagnose non-convulsive status 2 Health, Sultan Qaboos tween seizure activity. Status epilepticus is epilepticus at onset. All children underwent University Hospital, more common in childhood, and the reported computed tomography scanning of the brain PO Box 35, Al Khod death rate varies between 3 and 20%.3 and other relevant investigations. 123, Sultanate of Prolonged seizure activity itself produces irre- All 20 children received intravenous mida- Oman R Lal Koul versible cerebral damage, independent of zolam at 0.15 mg/kg as a bolus followed by a accompanying hypoxia, acidosis, and conse- constant infusion starting at 1 µg/kg/min up to Department of Child quent biochemical derangements. The exces- 5 µg/kg/min increasing by 1 µg/kg/min every 15 Health, Sultan Qaboos sive metabolic demands of continuously firing minutes until complete control of seizures was University Hospital, Al neurones leading to depletion of essential achieved. The optimum rate of infusion at Khod, Sultanate of nutrients is currently thought to be the most which seizure control was achieved was main- Oman important factor leading to cell death during tained for a period of 24 hours. Subsequently G Raj Aithala 4 A Chacko continuous seizures. Although the majority of the midazolam infusion rate was gradually R Joshi children who suVer continuous seizures re- decreased (by 1 µg/kg/min every two hours) M Seif Elbualy spond to intravenously administered diazepam until tapering was completed. and phenytoin sodium, some require other Variables such as age, weight, sex, history of Correspondence to: modalities of treatment including general seizures, underlying diseases, and the time Dr Lal Koul. anaesthesia, which could lead to serious required for control of seizures were carefully Accepted 5 February 1997 adverse eVects. recorded for each patient. Vital parameters 446 Lal Koul, Raj Aithala, Chacko, Joshi, Seif Elbualy Table 1 Type,duration, and control of status epilepticus Arch Dis Child: first published as 10.1136/adc.76.5.445 on 1 May 1997. Downloaded from Status Midazolam Antiepileptic Rate Cessation Previous Duration drugs received to (µg/kg/ of seizures Side No Age Sex Diagnosis antiepileptic drugs Type (minutes) control min) (minutes) eVects Outcome 12 M Acute purulent Nil GTC 40 DZP PR, IV, 115NilNo months meningitis PHT IV recurrence 2 10 years M Idiopathic epilepsy SVA, VGB, GTC 45 DZP PR, IV 1 30 Nil No LTG, PHT, recurrence ETH 3 10 years F Idiopathic epilepsy — GTC 30 PHT IV 1 15 Nil No recurrence 4 4 years F Neurological SVA Partial 300 DZP PR 2.5 50 Nil Several degeneration motor/MYO 5 1 year M Postencephalitic PHT, PHB GTC 180 DZP IV (3) 2.5 60 Nil No sequalae recurrence 62 M Cerebrovascular SVA, PHT GTC 120 DZP IV 1.5 25 Nil No months accident recurrence 76 M Acute purulent — GTC 45 DZP IV, PHT 1.5 25 Nil No months meningitis IV recurrence 88 M Acute purulent — Partial motor 60 DZP IV, PHB 125NilNo months meningitis IV recurrence 9 5 years M Chronic SVA, CLZ GTC, MYO 1440 DZP PR, IV, 5 220 Nil Lost to follow encephalitis PHT IV up 10* 3 years M Idiopathic epilepsy CBZ MYO, T 90 DZP IV 2 40 Nil No recurrence 11 3 years M Idiopathic epilepsy — MYO, astatic 30 DZP PR 1 10 Nil Recurred twice 12 13 years M Cerebrovascular — GTC 40 DZP IV 2 60 Nil No accident recurrence 13* 4 years M Idiopathic epilepsy CBZ, SVA, CLZ MYO, T 120 DZP PR (2) 2 25 Nil No recurrence 14 9 years F Idiopathic epilepsy SVA, CBZ Complex 65 PHT IV 2 30 Nil No partial recurrence 15 3 years F Acute — Complex 60 PHT IV 2.5 50 Nil No meningoencephalitis partial recurrence 16 6 M Cerebral dysgenesis PHB, PHT, SVA GTC 720 DZP PR, PHT 5 240 Nil Recurred months IV twice 17 3 years M Idiopathic epilepsy SVA, PHT GTC, MYO 120 PHT IV 2 60 Nil No recurrence 18 7 years M Idiopathic epilepsy SVA, PHT GTC 45 PHT IV 2 60 Nil No recurrence 19 2 years F Acute — GTC 30 PHT IV, PHB 115SpO2 No meningoencephalitis IV 90% recurrence 20 2.5 M Acute — GTC, 60 PHT IV, PHB 1.5 25 SpO2 No years meningoencephalitis dystonic IV 90% recurrence GTC = generalised tonic-clonic; T = tonic; MYO = myoclonic; IV = intravenous; PR = per rectum; DZP = diazepam; PHT = phenytoin sodium; PHB = phenobar- http://adc.bmj.com/ bitone; SVA = sodium valproate; CBZ = carbamazepine; VGB = vigabatrin; LTG = lamotrigine; ETH = ethosuximide; SpO2 = oxygen saturation; * Lennox-Gastaut syndrome status. including respiratory rate, heart rate, and blood encephalitis, and the remainder had various pressure were documented. The oxygen satura- vascular or degenerative lesions of the brain. tion of each child was monitored continuously The type of status presented in the children by pulse oximetry. as follows: generalised tonic-clonic (n = 13), The children were also monitored for the partial seizure status (partial motor (n = 2), on September 29, 2021 by guest. Protected copyright. development of adverse eVects of benzodi- complex partial (n = 2)), myoclonic astatic (n = azepines including hypotension, hypoxia, and 1), and Lennox-Gastaut status (myoclonic + respiratory depression. In order to exclude tonic; n = 2). Myoclonic seizures were seen as electrolyte and metabolic disturbances as a a combination of myoclonus with generalised cause of the seizures, blood samples were taken tonic-clonic status in three others. Twelve on admission and at 24 hours to measure patients had refractory status epilepticus (table circulating sodium, potassium, calcium, glu- 2). Their seizures continued for more than 30 cose, and magnesium concentrations. minutes after administration of diazepam, followed by phenytoin sodium/phenobarbitone or both intravenously. Eight children being fol- Results lowed up in the outpatient department who Of the 20 children with status epilepticus were on various antiepileptic drugs were given admitted to our high dependency care unit, 15 midazolam infusion alone. were boys (table 1). The mean age was 4.07 years (range 2 months to 13 years). Eleven Table 2 Drugs given before midazolam in refractory children had a history of seizures and were status epilepticus already taking antiepileptic drugs, which in- cluded various combinations of sodium val- Drug No of cases proate (n = 9), carbamazepine (n = 3), pheno- Diazepam 12 IV 9 barbitone (n = 2), phenytoin sodium (n = 6), PR 7 clonazepam (n = 2), ethosuximide (n = 1), Combined 3 vigabatrin (n = 1), and lamotrigine (n = 1).
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