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Chloral Hydrate Sedation in Children Savithiri Ratnapalan CLIN PEDIATR published online 6 November 2013 DOI: 10.1177/0009922813508000 The online version of this article can be found at: http://cpj.sagepub.com/content/early/2013/11/02/0009922813508000 A more recent version of this article was published on - Jul 31, 2014

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CPJXXX10.1177/0009922813508000Clinical PediatricsRatnapalan

Commentary

Chloral Hydrate Sedation in Children

Clinical Pediatrics XX(X) 1­–4 © The Author(s) 2013 Reprints and permissions: sagepub.com/journalsPermissions.nav DOI: 10.1177/0009922813508000 cpj.sagepub.com

Savithiri Ratnapalan, MBBS MEd1 Background Chloral hydrate, discovered in 1832, is one of the oldest sedatives in the market that has fallen in to disrepute at the beginning of this century in parts of Europe.1 Although, used for sedating children in North America for several years, interest for using it as a sedative was rekindled after a systematic review of chloral hydrate sedations of pediatric patients in the emergency department was published in 2008 by the American College of Emergency Physicians.2 Chloral hydrate is well absorbed orally and rectally, is rapidly metabolized by alcohol dehydrogenase in the liver and erythrocytes to trichloroethanol, its active metabolite and is often used to produce immobility for nonpainful diagnostic procedures such as radiological procedures, echocardiographies, and electroencephalograms, in infants and young children.3 Trichloroethanol has a high plasma protein binding capacity of 70% to 80% and is well distributed in all body tissues, including the cerebrospinal fluid, breast milk, and placenta.3 The onset of action of chloral hydrate is 30 to 60 minutes after both oral and rectal administrations and the duration of action may vary from 2 to 8 hours; however, individual responses may vary and sedative effects may last up to 24 hours.3,4 The elimination half-life is age dependent and varies from 4 to 12 hours and may extend to 37 hours in preterm and 28 hours in term infants.3 Chloral hydrate may produce residual effects up to 24 hours after administration as it has the potential for resedation effects after initial recovery from sedation.3 Although it is not a potent respiratory depressant, its sedative effects can cause airway obstruction and as such monitoring is required.2 It should be used with caution in preterm and term infants because of the accumulation of active metabolites, the development of metabolic acidosis, and the potential to predispose newborns to conjugated and unconjugated hyperbilirubinemia.2,3 Chloral hydrate should be avoided in patients with moderate to severe renal failure (creatinine clearance 97%) and effects with regards to time to sedation, time to discharge, and adverse reactions during sedation for diagnostic imaging.10 Chloral hydrate at a dose of 75 mg/kg compared with pentobarbital at a dosage of 5 mg/kg sedations for magnetic resonance imaging had a slightly longer onset of sedation and more need for supplementary sedation; however, the incidence of motor imbalance, paradoxical reactions, and agitation were lower with chloral hydrate, and there was faster return to baseline activity.11 In infants younger than 1 year sedated for magnetic resonance imaging, the incidence of adverse events were significantly reduced with pentobarbital although both medications were equally effective in providing successful sedation.12 For echocardiography in young children aged 1 month to 3 years, chloral hydrate at a dose of 80 mg/kg has been shown to produce adequate motion control in 78% of patients.5 In this study, 38% of children were American Society of Anesthesiologists class 3 and 4.5 When compared with chloral hydrate use in sedation for echocardiography, oral midazolam provides a significantly shorter recovery time but chloral hydrate provided a significantly deeper level of sedation and a more comprehensive diagnostic evaluation.13 Chloral hydrate sedation is preferred over sedation with benzodiazepines or barbiturates for electroencephalographies as both benzodiazepines and barbiturates

have antiepileptic properties and induce of faster electroencephalography frequencies.14 Although, some have suggested that chloral hydrate also has antiepileptic activity, it has been shown that chloral hydrate is not an effective antiseizure medication.15-17 It has been shown to be less effective in children with neurodevelopment delay and sedative effects are not sustained long enough to complete the procedure.18-20 A study examining chloral hydrate sedation for electroencephalography monitoring suggests that children with neurodevelopment delay may need a repeat dose of chloral to complete the procedure.20

Fasting Guidelines for Chloral Hydrate Although there are no clear guidelines for pre-procedural fasting for chloral hydrate, many children coming for elective procedures have fasted the recommended 8 hours for solids. They are often also fasted 6 to 8 hours for liquids despite recommendation that they may have clear liquids 2 hours prior to the procedure.21 There is evidence that mandatory fasting for chloral hydrate has no benefit where 2 studies demonstrated that the fasting state of a child affected the dose of chloral hydrate, with fed children demonstrating a quicker onset and a lower dose than fasted children.2,22,23 The greater dose requirement in fasted children was thought to be related to the longer duration to onset, which also resulted in a longer duration of action. In one study, the efficacy of chloral hydrate was increased when timed to coincide with nap times.23 As such, fasting children prior to receiving chloral hydrate should be reconsidered and these children may be encouraged to take at least clear fluids 2 hours before the procedure to improve the chance of successful sedation with chloral hydrate without breaking institutional fasting protocols for chloral sedation.

Monitoring Although chloral hydrate has been routinely treated as mild sedation with no monitoring it is recommended that the child has baseline vital signs and pulse oximetry monitored.2 Appropriately trained personal to manage potential adverse events such as respiratory depression and hypoxia should be available for chloral sedations.2 The addition of other sedative such as nitrous oxide should be avoided in children receiving chloral hydrate as adding nitrous oxide in concentrations of 30% to 50% to children who have received chloral hydrate at a dose of 70 mg/kg leads to deep sedation in the majority (94%) of them.24

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Ratnapalan In summary, chloral hydrate is safe and effective for sedating children younger than 48 months undergoing painless diagnostic procedures. Chloral hydrate has also been used safely to sedate children with congenital heart disease undergoing painless diagnostic procedures. Caution should be exercised for children with neurological or genetic disorders and premature babies and ex-premature babies. It is recommended that all children undergoing sedation have baseline vital signs and pulse oximetry monitored.

Key Points 1. Chloral hydrate is an effective sedative for children younger than 48 months undergoing painless diagnostic studies. 2. Children receiving chloral hydrate need proper monitoring and should be managed by appropriately trained personal as they are at risk for respiratory depression and hypoxia. 3. Children fasted prior to receiving chloral hydrate have higher sedation failure rates. 4. Chloral hydrate may produce residual effects up to 24 hours after administration as it has the potential for resedation effects after initial recovery from sedation. 5. Children with congenital cardiac anomalies undergoing painless diagnostic procedures may be safely sedated with chloral hydrate. Children with neurodevelopmental disorders have increased incidence of adverse effects and decreased efficacy as compared with healthy children. Declaration of Conflicting Interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding The author(s) received no financial support for the research, authorship, and/or publication of this article.

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3. Canadian Pharmacists Association. Compendium of Pharmaceuticals and Specialties 2012. The Canadian Drug Reference for Health Professionals. Ottawa, Ontario, Canada; Canadian Pharmacists Association; 2012. 4. Treluyer JM, Andre C, Carp PF, et al. Sedation in children undergoing CT scan or MRI: effect of time-course and tolerance of rectal chloral hydrate. Fundam Clin Pharmacol. 2004;18:347-350. 5. Heistein LC, Ramaciotti C, Scott WA, Coursey M, Sheeran PW, Lemler MS. Chloral hydrate sedation for pediatric echocardiography: physiologic responses, adverse events, and risk factors. Pediatrics. 2006;117: e434-e441. 6. Greenberg SB, Faerber EN, Aspinall CL, Adams RC. High-dose chloral hydrate sedation for children undergoing MR imaging: safety and efficacy in relation to age. AJR Am J Roentgenol. 1993;161:639-641. 7. Biban P, Baraldi E, Petteenazzo A, Filippone M, Zacchello F. Adverse effect of chloral hydrate in two young children with obstructive sleep apnea. Pediatrics. 1993;92:461-463. 8. Nordenberg A, Delisle G, Izukawa T. Cardiac arrhythmia in a child due to chloral hydrate ingestion. Pediatrics. 1971;47:134-135. 9. Krauss B, Green SM. Procedural sedation and analgesia in children. Lancet. 2006;367:766-780. 10. Rooks VJ, Chung T, Connor L, et al. Comparison of oral pentobarbital sodium (nembutal) and oral chloral hydrate for sedation of infants during radiologic imaging: preliminary results. AJR Am J Roentgenol. 2003;180: 1125-1128. 11. Malviya S, Voepel-Lewis T, Tait AR, et al. Pentobarbital vs chloral hydrate for sedation of children undergoing MRI: efficacy and recovery characteristics. Paediatr Anaesth. 2004;14:589-595. 12. Mason KP, Sanborn P, Zurakowski D, et al. Superiority of pentobarbital versus chloral hydrate for sedation in infants during imaging. Radiology. 2004;230:537-542. 13. Wheeler DS, Jensen RA, Poss WB. A randomized, blinded comparison of chloral hydrate and midazolam sedation in children undergoing echocardiography. Clin Pediatr (Phila). 2001;40:381-387. 14. Mandema JW, Danhof M. Electroencephalogram effect measures and relationships between pharmacokinetics and pharmacodynamics of centrally acting drugs. Clin Pharmacokinet. 1992;23:191-215. 15. Thoresen M, Henriksen O, Wannag E, Laegreid L. Does a sedative dose of chloral hydrate modify the EEG of children with epilepsy? Electroencephalogr Clin Neurophysiol. 1997;102:152-157. 16. Castro CB, Chiste MA, Vizioli JF, et al. Comparison between the EEG of natural sleep and the induced by chloral hydrate in relation to paroxysmal changes and baseline rhythm [in Portuguese]. Arq Neuropsiquiatr. 1994;52:326-329. 17. Lampl Y, Eshel Y, Gilad R, Sarova-Pinchas I. Chloral hydrate in intractable status epilepticus. Ann Emerg Med. 1990;19:674-676.

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18. Allegaert K, Daniels H, Naulaers G, Tibboel D, Devlieger H. Pharmacodynamics of chloral hydrate in former preterm infants. Eur J Pediatr. 2005;164:403-407. 19. Mayers DJ, Hindmarsh KW, Sankaran K, Gorecki DK, Kasian GF. Chloral hydrate disposition following singledose administration to critically ill neonates and children. Dev Pharmacol Ther. 1991;16:71-77. 20. Jan MMS, Aquino MF. The use of chloral hydrate in pediatric electroencephalography. Neurosciences. 2001;6: 99-102. 21. Green SM, Roback MG, Miner JR, Burton JH, Krauss B. Fasting and emergency department procedural sedation and analgesia: a consensus-based

clinical practice advisory. Ann Emerg Med. 2007;49: 454-461. 22. Keidan I, Gozal D, Minuskin T, Weinberg M, Barkaly H, Augarten A. The effect of fasting practice on sedation with chloral hydrate. Pediatr Emerg Care. 2004;20: 805-807. 23. Lipshitz M, Marino BL, Sanders ST. Chloral hydrate side effects in young children: causes and management. Heart Lung. 1993;22:408-414. 24. Litman RS, Kottra JA, Verga KA, Berkowitz RJ, Ward DS. Chloral hydrate sedation: the additive sedative and respiratory depressant effects of nitrous oxide. Anesth Analg. 1998;86:724-728.

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Chloral hydrate sedation in children.

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