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The use of chloral hydrate in pediatric
electroencephalography
Mohammed M.S. Jan, MBChB, FRCP (C), Marilou F. Aquino, EEG Tech.
Objective:
Sleep is a known activator of epileptiform interval=4.5-21). Chloral hydrate was effective in inducing discharges on electroencephalography. Chloral hydrate is sleep in 97%, however, 34% of the children woke up used frequently for electroencephalography sedation. Our spontaneously before the test was completed, particularly objectives were to study the value and limitations of those with chronic neurological abnormalities (p=0.0003).
A second dose was necessary in 13%. Recording an initialperiod of wakefulness followed by sleep onset was more Methods:
likely achieved in natural sleep electroencephalograms pediatric electroencephalograms were included when compared to the sedated group (82% vs 10%, prospectively. One electroencephalography technologist p<0.0001). These electroencephalograms were more likely collected chloral hydrate related data.
to contain epileptiform discharges (p<0.001).
Electroencephalogram requisitions and recordings werereviewed separately by one certified Conclusion:
Although chloral hydrate was effective in sleep induction, the sleep onset was frequently missed andthe hypnotic effects were not sustained, particularly in Results:
The children’s ages ranged between 8 days to children with chronic neurological abnormalities. 19 years (mean=5.7 years). Natural sleep was recorded in 11% and only 2% were sleep deprived. Sedation was given Keywords:
Sedation, sleep, electroencephalogram, child, to 45% mostly using chloral hydrate (96%). Children with chronic neurological abnormalities were more likely to receive chloral hydrate (odds ratio=9.8, 95% confidence Neurosciences 2001; Vol. 6 (2): 99-102
leep is one of the well-known procedures of Occasionally, achieving natural sleep is difficult activating focal and generalized epileptiform and drugs need to be used. In fact, sedation is discharges on electroencephalography (EEG).1,2 frequently used in young and uncooperative children When the clinical suspicion of epilepsy is high and and several sedative hypnotic agents have been used.
the awake EEG is normal, sleep EEG usually 3-5 Benzodiazepines and barbiturates should not be provides additional diagnostic information.1 Falling utilized because of their antiepileptic properties and asleep normally is always superior to drug induced sleep as spike activation may occur mainly in the Chloral hydrate (CH) is used frequently for EEG lighter stages of sleep.2 Sleep deprivation is therefore sedation.3,4,7 It improves the EEG quality because of decreased muscle and movement artifacts and From the Department of Neurosciences (Jan), King Faisal Specialist Hospital and Research Center and The Neurophysiology Unit (Aquino), KingAbdulaziz University Hospital, Jeddah, Kingdom of Saudi Arabia. Received 29th August 2000. Accepted for publication in final form 12th December 2000. Address correspondence and reprint request to: Dr Mohammed M.S. Jan, Department of Neurosciences, King Faisal Specialist Hospital & ResearchCenter, MCB J-76, PO Box 40047, Jeddah 21499, Kingdom of Saudi Arabia. Tel. 00 966 2 667 7777 Ext 5819. Fax. 00966 2 667 7777 Ext 5813.
Sedation in pediatric EEG . Jan & Aquino improved organization of normal sleep features.8 Table 1 - Summary of important items included in the data collection
However, CH may result in significant reduction of epileptiform activities and therefore may alter EEGinterpretation.7 In fact, some authors suggested that it might have an antiepileptic property.9 Other studiesin children found it ineffective as an antiepileptic drug.10 The reduction in epileptiform activities is Natural sleep record (no sedation or sleep deprivation) more likely related to recording deeper stages ofsleep in well sedated children. The use of sedation is also not without complications. Serious cardiac and respiratory effects and excessive sedation have beenassociated with sedating agents, even when normal Time of the day when the EEG was done
doses are used.3 Several cases of childhood poisoningand cardiorespiratory arrest following CH aspirationwere reported.11,12 Duration of night sleep
For all these reasons, the use of CH should not be routine. The objectives of this study were to examine Time from the last night sleep or nap
the value of CH for EEG sedation and assess itsefficacy in sleep induction, and effects on EEG Time from the last meal
abnormalities. We hypothesized that CH may not beuniversally effective and may result in attenuation of Sedation
epileptiform activities as a result of recording deeper Methods. Consecutive pediatric EEGs performed at the Neurophysiology Unit of King Abdulaziz University Hospital (KAUH) were includedprospectively. All EEGs were recorded betweenMarch 19 and July 18, 2000. King Abdulaziz University Hospital is a multispecialty adult and Was the child awake throughout the record pediatric hospital providing primary care to the Was the child asleep throughout the record Jeddah area, as well as secondary and tertiary care fora regional population of western Saudi Arabia. King Was the child awake initially then fell asleep Abdulaziz University Hospital is the main teaching Was the child asleep then awoken spontaneously center of western Saudi Arabia in collaboration withKing Faisal Specialist Hospital & Research Centre.
The pediatric neurology group is a major referral chronic CNS disorders (e.g. mental retardation, center for the western region, particularly the Jeddah autism, attention disorder). The same EEGer area. One certified electroencephalographer (EEGer) epileptiform or background abnormalities, and sleep A data collection sheet regarding the use of staging. The EEG abnormalities were coded as sedation was designed as shown in Table 1. One follow: 1) Focal epileptiform discharges, 2) EEG technologist (co-author Marilou Aquino) Multifocal epileptiform discharges, 3) Generalized completed these forms during the EEG recording epileptiform discharges, 4) Focal background sessions. All EEG requisitions and recordings were disturbance, and 5) Diffuse background disturbance.
reviewed sparately by one EEGer. He examined the Statistical analyses were performed using Epi Info, requisitions to identify the referral source, EEG version 6.13,14 Categorical variables were examined in number, child’s age, EEG indication, history of 2x2 tables using Chi-square statistics. The magnitude epilepsy, and current antiepileptic drugs. Based on of significant associations is presented as p values, the description of the child’s events and the odds ratios (OR), and the 95% confidence interval for underlying clinical scenario, the most likelydiagnosis responsible for requesting the EEG was coded as follow: 1) Established epilepsy, 2) Probableseizure or seizures of new onset, 3) Non epileptic Results. During the study period, 159 EEGs were paroxysmal events (e.g. migraine, syncope, breath included. The children’s ages ranged between 8 days holding spells), 4) Acute central nervous system to 19 years (mean 5.7 years, standard deviation 4.6).
(CNS) disorders (e.g. toxic, metabolic, infectious, or The first EEG was studied in 109 (69%) of the cases hypoxic encephalopathy), and 5) Non epileptic and 31% were repeat EEGs. Seventy-six children
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Sedation in pediatric EEG . Jan & Aquino Table 2 - Some EEG variables in the non sedated and sedated EEG.
EEG related variables
No sedation
Sedation
Number/Total
Number/Total
Requesting physician
Indication
Abnormal EEG result
(48%) had established epilepsy and 46% were when compared to the sedated group (62% versus receiving antiepileptic drugs. Chronic neurological 19%, p=0.004). Recording an initial period of abnormalities (e.g. cerebral palsy, developmental, or wakefulness followed by sleep onset was even more chromosomal abnormalities) were documented in likely achieved in the natural sleep group (82% 46%. Natural sleep was recorded in 17 (11%) EEGs.
versus 10%, p<0.0001). These EEGs were much Only 2% were sleep deprived. Sedation was given in more likely to contain epileptiform discharges when 71 (45%) and CH was used in 96% of these cases.
compared to the continous sleep recordings (91% Two children had diazepam, 2 had promethazine, 1 versus 27%, p=0.0007). Twenty four (34%) of the had midazolam, and 1 child had chlorpromazine for children who received CH woke up spontaneously EEG sedation. Most children (85%) had a CH dose before the test was completed, particularily those ranging between 25-75 mg/kg, which was given less with chronic neurological abnormalities (p=0.0003).
than one hour before the test in 91%. No side effects This was not related to the CH dose, however, a were noted. Children less than 2 years of age were 12 times more likely to receive CH when compared to Table 2 shows a summary of the EEG sources, older children (95% confidence interval (CI) 5-30, indications, and results in the two groups with and p<0.0001). As well, children with chronicneurological abnormalities (e.g. cerebral palsy) were without sedation. Eighty four (53%) EEGs were 9.8 times more likely to receive CH when compared reported as abnormal. Sleep EEGs were more likely to neurologicaly normal children (95% CI 4.5-21, to be abnormal (odds ratio (OR) 5.3, 95% CI 2.5-11).
p<0.0001). The use of antiepileptic drugs and the Sedation also correlated with abnormal EEG results, number of EEG (first or repeat) did not correlate with however, generalized epileptiform discharges were more likely noted in the non sedated EEGs (Table 2).
Chloral hydrate was effective in inducing sleep in The only sleep factor (as listed in Table 1) that 97%. Stage 1 sleep was recorded in 19%, stage 2 in correlated with achieving sleep during the EEG, 60%, and stage 3 in 21% of the EEGs. Stage 1 sleep independent of CH use, was the duration of the was more likely recorded in the natural sleep EEGs preceeding noctornal sleep. Children who slept less
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Sedation in pediatric EEG . Jan & Aquino than 4 hours were more likely to sleep when which was non-intentional in this group. compared to those who slept more than 4 hours at We conclude that chloral hydrate is a safe and effective agent for sleep induction. However, thesleep onset was frequently missed which may alter the EEG interpretation. The sedative effect was not sustained in many children, particularly those with observations regarding the value of CH in EEG chronic neurological abnormalities. Sleep deprivation sedation. Chloral hydrate was safe and very effective is underutilized and needs to be used more in sleep induction. This is similar to the findings of Rumm et al, who found CH effective in 86% ofchildren on first attempt with no side effects.15 A recent study compared the hypnotic effects of CHwith other sedatives and found no statistically 1. El-Ad B, Neufeld MY, Korczyn AD. Should sleep EEG significant differences in the effect on sleep induction record always be performed after sleep deprivation.
or sleep activation effects.16 This means that CH is Electroencephalogr Clin Neurophysiol 1994; 90: 313-5.
not only safe, but also as effective as other agents.
2. Dinner DS. Sleep and pediatric epilepsy. Cleve Clin J Med However, children with neurological disorders had a 3. Nahata MC. Sedation in pediatric patients undergoing much greater failure rate when compared to diagnostic procedures. Drug Intell Clin Pharm 1988; 22: neurologicaly normal children (27% versus 4%).15 We did not encounter this high failure rate, however, 4. Lasagna L. Hypnotic drugs. N Engl J Med 1972; 7: 1182-4.
one third of our children woke up spontaneously 5. Milstein V, Small JG, Spencer DW. Melatonin for sleep EEG. Clin Electroencephalogr 1998; 29: 49-53.
before the test was completed, particularily those 6. Mandema JW, Danhof M. Electroencephalogram effect with chronic neurological abnormalities. This was measures and relationships between pharmacokinetics and not dose related, however, a second CH dose (i.e.
pharmacodynamics of centrally acting drugs. Clin higher total dose) may be necessary in some of these 7. Thoresen M, Henriksen O, Wannag E, Laegreid L. Does a sedative dose of chloral hydrate modify the EEG of children In our study, sedation was not given routinely as with epilepsy? Electroencephalogr Clin Neurophysiol 1997; 55% of the children were not sedated for EEG.
Children with chronic neurological abnormalities and 8. Castro CB, Chiste MA, Vizioli JF, Cordova NM, Ohlweiler L, Lago IS, et al. Comparison between the EEG of natural young infants were more likely to receive CH. This sleep and the induced by chloral hydrate in relation to suggests that physicians used CH rather selectively, paroxysmal changes and baseline rhythm. Arq particularly in out-patients who were less likely to receive CH. Very few children received inappropriate 9. Lampl Y, Eshel Y, Gilad R, Sarova-Pinchas I. Chloral hydrate in intractable status epilepticus. Ann Emerg Med sedatives such as benzodiazepines reflecting increased physician’s awareness about this issue. 10. Hakeem VF, Wallace SJ. EEG monitoring of therapy for Overall, sleep EEGs were more likely to be neonatal seizures. Dev Med Child Neurol 1990; 32: 858-54.
abnormal and the use of CH correlated with 11. Lansky LL. An unusual case of childhood chloral hydrate poisoning. Am J Dis Child 1974; 127: 275-6.
abnormal EEG results. However, lighter stages of 12. Granoff DM, McDaniel DB, Borkowf SP. Cardiorespiratory sleep were more likely recorded in the natural sleep arrest following aspiration of chloral hydrate. Am J Dis EEGs. Recording an initial period of wakefulness followed by sleep onset was even more likely 13. Dean AG, Dean JA, Burton A, Dicker R. Epi Info: A achieved in the natural sleep group. These EEGs general-purpose microcomputer program for public healthinformation systems. Am J Prev Med 1991; 7: 178-182.
were much more likely to contain epileptiform 14. Dean AG, Dean JA, Coulombier D. Epi Info, Version 6: a discharges when compared to continous sleep word processing, database, and statistics program for public recordings. This is one of the limitations of drug health on IBM-compatible microcomputers. Centers for induced deep sleep as spike activation may occur Disease Control and Prevention, Atlanta, Georgia, USA,1995.
mainly in the lighter stages of sleep.2 Sleep 15. Rumm PD, Takao RT, Fox DJ, Atkinson SW. Efficacy of deprivation is a good solution to this problem, but sedation of children with chloral hydrate. South Med J 1990; was used very infrequently in our sample. In fact, the children who slept less than 4 hours the night prior to 16. Takasaka Y, Ishikawa T, Mizuno K, Nakamura C, Yamaguchi A, Furuyama M et al. Methods of sleep EEG were more likely to sleep regardless of whether induction for EEG recordings: comparison between three hypnotics and natural sleep. No To Hattatsu 1999; 31: 153- effectiveness sleep deprivation in achieving sleep,
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