Neonatal Intensive Care Drug Manual

Preparation is light sensitive; store in a dark container.

Chloral hydrate has no analgesic properties, excitement may occur in patients with pain.

Despite being restricted in some countries (e.g. France) as a result of potential carcinogenicity, the American Academy of Pediatrics has judged the evidence insufficient to avoid single doses of chloral hydrate for this reason alone.³

Chloral hydrate is effective for sedation for painless procedures^4,5(Level II, Grade C)

There are insufficient data to promote the regular use of chloral hydrate as a sedative for neonates undergoing intensive care⁶. (Level III, Grade C).
Safety

Chloral hydrate overdose may produce cardiac arrhythmias including torsades de pointes.⁷

Administration of chloral hydrate in former premature infants causes significant post-procedural bradycardia¹ (Level III, Grade C).

Prolonged use warrants monitoring of serum bilirubin level⁸. (Level III Grade C).

Death/severe permanent neurologic injuries have been reported in children, either alone or in combination with other sedatives.⁹
Pharmacokinetics

Chloral hydrate is rapidly and effectively absorbed via the oral route and is immediately metabolised by liver enzymes (alcohol dehydrogenase) to the active hypnotic metabolite trichloroethanol (TCE). It is eventually excreted in the urine after glucuronidation in the liver. Plasma concentration peaks within 30 minutes to an hour. It is also metabolised to trichloroacetic acid (TCA). Both TCE (8–64 hours) and TCA (days) have long plasma half-lives in neonates and accumulate with repeated doses⁸. (Level III Grade C)

1. 
   Allegaert K, Daniels H, Naulaers G, et al. Pharmacodynamics of chloral hydrate in former preterm infants. Eur J Pediatr 2005;164:403-7
   
2. 
   Litman, RS, Soin, K, Salam A. Chloral Hydrate Sedation in Term and Preterm Infants: An Analysis of Efficacy and Complications. Anesthesia & Analgesia 2010;110(3):739-46.
   
3. 
   American Academy of Pediatrics, Committee on drugs and environment health: Use of Chloral Hydrate for sedation in children. Pediatrics 1993;92;471
   
4. 
   D'Agostino J, Terndrup TE. Chloral hydrate versus midazolam for sedation of children for neuroimaging: a randomized clinical trial. Pediatr Emerg Care 2000;16:1-4.
   
5. 
   Wheeler DS, Jensen RA, Poss WB. A randomized, blinded comparison of chloral hydrate and midazolam sedation in children undergoing echocardiography. Clin Pediatr 2001;40:381-7.
   
6. 
   Cruise S, Tam-Chan D, Harrison D, Johnston L. Prospective clinical audit of chloral hydrate administration practices in a neonatal unit. Journal of paediatrics and child health. Nov 2012;48(11):1010-1015.
   
7. 
   Pershad J, Palmisano P, Nichols M. Chloral hydrate: the good and the bad. Pediatr Emerg Care 1999;15:432-5.
   
8. 
   Reimche LD, Shankaran K, Hindmarsh KW et al: Chloral hydrate sedation in neonates and infants: clinical and pharmacological considerations. Dev Pharmacol Ther 1989;12:57.
   
9. 
   Cote CJ, Notterman DA, Karl HW, Weinberg JA, McCloskey C. Adverse sedation events in pediatrics: a critical incident analysis of contributing factors. Pediatrics 2000;105(4 Pt 1):805-14.
   
10. 
    Hijazi OM, Ahmed AE, Anazi JA, Al-Hashemi HE, Al-Jeraisy MI. Chloral hydrate versus midazolam as sedative agents for diagnostic procedures in children. Saudi Med J 2014;35(2):123-31.
    
11. 
    Esmaeili A, Keinhorst AK, Schuster T, Beske F, Schlosser R, Bastanier C. Treatment of neonatal abstinence syndrome with clonidine and chloral hydrate. Acta Paediatr 2010;99(2):209-14.