Pharmacokinetics in children

Negative correlation between age and the t½ of active metabolites (trichloroethanol), creating a longer recovery phase in young children. The exact role of chloral hydrate compared to trichloroethanol as a sedative is unknown. Chloral hydrate itself also appears to be important, even though it is converted quickly. The following t½ values were found [Mayers 1991]

Age	Chloralhydrate	Trichloro-ethanol
Prematures (31-37 wk)	1,0 ± 1,0 hour	39.8 ± 14.3 hour
Term neonates (38-42 wk)	3,0 ± 5.8 hour	27.8 ± 21.3 hour
1-13,6 year	9.7 ± 7.7 hour	9.7 ± 1.7 hour

 

dose recommendation of formulary compared to licensed use (on-label versus off-label)

No information is present at this moment.

Available formulations

No information is present at this moment.

Dosages

(Procedural) sedation; treatment of epileptic episodes

Rectal Term neonate 30 mg/kg/dose, once only repeat if necessary with 15-30 mg/kg/dose after 30 min. Watch out for hypoxia No studies have been carried out into the use of chloral hydrate for treating epileptic seizures. The recommendation is based on expert opinion. 1 month up to 12 months 50 mg/kg/dose, once only repeat if necessary with 25 mg/kg/dose after 30 minutes. Max single dose: 1.000 mg/dose. Watch out for hypoxia No studies have been carried out into the use of chloral hydrate for treating epileptic seizures. The recommendation is based on expert opinion. 1 year up to 18 years 50 mg/kg/dose, once only repeat if necessary with 25-50 mg/kg/dose after 30 min. Max single dose: 2.000 mg/dose. Watch out for hypoxia No studies have been carried out into the use of chloral hydrate for treating epileptic seizures. The recommendation is based on expert opinion. Oral Term neonate 30 mg/kg/dose, once only repeat if necessary with 15-30 mg/kg/dose after 30 min. Watch out for hypoxia No studies have been carried out into the use of chloral hydrate for treating epileptic seizures. The recommendation is based on expert opinion. 1 month up to 12 months 50 mg/kg/dose, once only repeat if necessary with 25 mg/kg/dose after 30 min. Max single dose: 1.000 mg/dose. Watch out for hypoxia No studies have been carried out into the use of chloral hydrate for treating epileptic seizures. The recommendation is based on expert opinion. 1 year up to 18 years 50 mg/kg/dose, once only repeat if necessary with 25-50 mg/kg/dose after 30 min. Max single dose: 2.000 mg/dose. Watch out for hypoxia No studies have been carried out into the use of chloral hydrate for treating epileptic seizures. The recommendation is based on expert opinion.

Renal impaiment in children > 3 months

Adjustment in renal impairment as specified:

GFR 50-80 ml/min/1.73 m2

Dose adjustment is not required

GFR 30-50 ml/min/1.73 m2

Do not administer

GFR 10-30 ml/min/1.73 m2

Do not administer

GFR < 10 ml/min/1.73 m2

Do not administer

The complete list of all undesirable drug reactions can be found in the national Summary of Product Characteristics (SmPC) – click here

Side effects in children

Hyperactivity, nausea, vomiting, respiratory depression and hypoxemia, motor disorders, restlessness, gastrointestinal complaints.

Long term exposure to high dosages of chloralhydrate can be carcinogenic [Steinberg 1993]

The complete list of all contra-indications can be found in the national Summary of Product Characteristics (SmPC) – click here

Contra-indications

No information available on specific contra indications in children.

The complete list of all warnings and precautions can be found in the national Summary of Product Characteristics (SmPC) – click here

Warnings & precautions in children

Active metabolites have longer half-lives that can cause accumulation with repeated doses. Monitor the haemodynamics in patients. The effect can be stronger in some situations. More chloral hydrate is needed in patients with an empty stomach. When used in outpatient treatment: only let the child go home once they are properly awake (miniumum >4 h of monitoring after application [German Society for Anesthesiology and Intensive Care Medicine]).

Interactions

The complete list of all interactions can be found in the national Summary of Product Characteristics (SmPC) – click here

• NERVOUS SYSTEM
• PSYCHOLEPTICS

HYPNOTICS AND SEDATIVES

This pages provides a list of drugs from the same ATC class for comparison. This does not necessarily mean that these drugs are interchangeable.

Barbiturates, plain
	Pentobarbital Related Medicines Menu">	N05CA01

Benzodiazepine derivatives
	Midazolam Related Medicines Menu">	N05CD08
	Nitrazepam Related Medicines Menu">	N05CD02
	Temazepam Related Medicines Menu">	N05CD07

Other hypnotics and sedatives
	Dexmedetomidine Related Medicines Menu">	N05CM18
	Doxylamin	N05CM21

Melatonin receptor agonists
	Melatonin Related Medicines Menu">	N05CH01

References

1. Mayers DJ, et al, Sedative/hypnotic effects of chloral hydrate in the neonate: trichloroethanol or parent drug, Dev Pharmacol Ther, 1992, 19(2-3), 141-6
2. Informatorium Medicamentorum (Interacties), 2008
3. Mayers DJ, et al, Chloral hydrate disposition following single-dose administration to critically ill neonates and children, Dev Pharmacol Ther, 1991, 16(2), 71-7
4. Saarnivaara L, et al, Comparison of chloral hydrate and midazolam by mouth as premedicants in children undergoing otolaryngological surgery, Br J Anaesth, 1988, Oct;61(4), 390-6
5. Malviya S, et al, Prolonged recovery and delayed side effects of sedation for diagnostic imaging studies in children, Pediatrics, 2000, Mar;105(3), E42
6. Greenberg SB, et al, High-dose chloral hydrate sedation for children undergoing MR imaging: safety and efficacy in relation to age, AJR Am J Roentgenol, 1993, Sep;161(3), 639-41
7. Kantovitz KR, et al, Sedative effect of oral diazepam and chloral hydrate in the dental treatment of children, J Indian Soc Pedod Prev Dent, 2007, Apr-Jun;25(2), 69-75
8. Layangool T, et al, A comparison of oral chloral hydrate and sublingual midazolam sedation for echocardiogram in children, J Med Assoc Thai, 2008, Oct;91 Suppl 3, S45-52
9. D'Agostino J, et al, Chloral hydrate versus midazolam for sedation of children for neuroimaging: a randomized clinical trial, Pediatr Emerg Care, 2000, Feb;16(1), 1-4
10. Ronchera CL, et al, Administration of oral chloral hydrate to paediatric patients undergoing magnetic resonance imaging, Pharm Weekbl Sci, 1992, Dec 11;14(6), 349-52
11. Vade A, et al, Chloral hydrate sedation of children undergoing CT and MR imaging: safety as judged by American Academy of Pediatrics guidelines, AJR Am J Roentgenol, 1995, Oct;165(4), 905-9
12. Steinberg AD., Should chloral hydrate be banned?, Pediatrics, 1993, Sep;92(3), 442-6
13. Centraal Begeleidings Orgaan (CBO), Concept richtlijn sedatie en/of analgesie op lokaties buiten de operatiekamer, 2008
14. Nederlandse Vereniging voor Anesthesiologie, (NVA), and (NVK) Nederlandse Vereniging voor Kindergeneeskunde., Richtlijn sedatie en/of analgesie (PSA) op locaties buiten de operatiekamer. Deel III: bij kinderen., www.nvk.nl, 2009
15. Hindley, D. et al, Audit of the use of chloral hydrate as an acute treatment for childhood seizures', Dev Med Child Neuro, 2005, 47 (3), 212-3.
16. Finnemore, A. et al, Chloral hydrate sedation for magnetic resonance imaging in newborn infants.", Paediatr Anaesth, 2014, 24 (2), 190-5
17. Fong, C. Y. et al, Chloral hydrate as a sedating agent for neurodiagnostic procedures in children, Cochrane Database Syst Rev, 2021, Aug 16;8(8), CD011786
18. Delgado, J et al, Chloral hydrate in pediatric magnetic resonance imaging: evaluation of a 10-year sedation experience administered by radiologists., Pediatr Radiol, 2015, 45 (1), 108-14.
19. Chen, M. L. et al, Safety and efficacy of chloral hydrate for conscious sedation of infants in the pediatric cardiovascular intensive care unit., Medicine (Baltimore), 2017, 96 (1), e5842
20. Bracken, J et al, Chloral hydrate sedation in radiology: retrospective audit of reduced dose, Pediatr Radiol, 2012, 42 (3), 349-54
21. Avlonitou, E, Use of chloral hydrate as a sedative for auditory brainstem response testing in a pediatric population., Int J Pediatr Otorhinolaryngol, 2011, 75 (6), 760-3.
22. Allegaert, K. et al, Pharmacodynamics of chloral hydrate in former preterm infants., Eur J Pediatr, 2005, 164 (7), 403-7

Changes

Therapeutic Drug Monitoring

Overdose