Question

• A pediatric patient is found to have a murmur that is judged to be significant enough to investigate by echocardiography.  Is chloral hydrate a safe and effective choice for sedation for the study?

Clinical Bottom Lines

1. Sedation during echocardiography in the young pediatric population is a necessary step in assuring an adequate study to evaluate cardiac anatomy and function. 
2. Randomized, placebo controlled studies are not possible due to the nature of chloral hydrate and the reason for using it. 
3. Chloral hydrate is a safe and effective agent in the sedation of children undergoing echocardiography for known or suspected heart disease.

Summary of Key Evidence

1. 405 patients, age 3 weeks to 14 years old with known or suspected heart disease were given chloral hydrate in doses ranging from 50-100 mg/kg orally.¹ 
2. Pulse ox and heart rate were monitored continuously throughout the procedure and respiratory rate, blood pressure, O2 sat and heart rate were recorded both before and after sedation. 
3. Efficacy of chloral hydrate was measured in different groups based on age and dosage.  Safety was measured by heart rate and O2 sat changes in groups based on cyanosis, age and dosage. 
4. Children less than 3 years old were sedated more successfully than those greater than 3 years old. 
5. The higher doses did have an increased time to sedation and a greater failure rate. 
6. Heart rate and blood pressure were not significantly altered in any of the three groups. 
7. O2 saturation was decreased by >5% in 6% of successfully sedated children. 

Additional Comments

• A study focusing on side effects of chloral hydrate showed a higher dose led to a higher incidence of paradoxical excitement.  In addition, the excitement was more commonly seen in older children.²
• Even though no significant adverse effects were observed in these studies, one still needs to consider that other oral sedatives do exist and comparison studies to these agents would be very useful in determining the use of chloral hydrate.
• A study comparing propofol and chloral hydrate found that there was a 19% incidence of chloral hydrate causing excitement and 3% incidence of respiratory depression;  the incidence of both of these adverse events for propofol were 0%.³  However, propofol is not as viable an alternative for use with outpatient echocardiography.
• The AAP guidelines do make mention of the concern of carcinogenesis of chloral hydrate.  There are no studies in humans.  The studies in mice that showed an increased risk of hepatic tumors was in mice who received daily chloral hydrate for 2 years.  Some benzodiazepine and barbiturate sedatives have been shown to be carcinogenic in animal studies as well.⁴
• The AAP policy statement also raises concern that repetitive dosing of chloral hydrate is concerning due to the accumulation of metabolites which may produce excessive central nervous system depression, predispose newborns to conjugated and nonconjugated hyperbilirubinemia, decreased albumin binding of bilirubin and contribute to acidosis.

Citation

1. Napoli KL, Ingall CG, Martin GR.  Safety and ffficacy of chloral hydrate sedation in children undergoing echocardiography.  Journal of Pediatrics 1996:129(2):287-291.
2. Lipshitz M, Marino BL, Sanders ST.  Chloral hydrate side effects in young children: Causes and management.  Heart and Lung 1993: 408-414.
3. Merola C, Albarracin C, Lebowitz P, Bienkowski RS, Barst SM.  An audit of adverse events in children sedated with chloral hydrate or propofol during imaging studies.  Paediatric Anaesthesia 1995: 5(6): 375-378.
4. American Academy of Pediatrics.  Use of chloral hydrate for sedation in children.  Pediatrics 1993: 92(3): 471-473.
   

CAT Author: Patti Buck, MD

CAT Appraisers: John Frohna, MD

Date appraised: January 10, 2000