Chloral Hydrate

Pharmacologic Category

Dosing: Adult

Procedural sedation: Oral: 500 to 1,000 mg 30 minutes prior to procedure

Dosing: Renal Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling. Use is contraindicated in patients with marked renal impairment.

Dialysis: Dialyzable

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling. Use is contraindicated in patients with marked hepatic impairment.

Dosing: Pediatric

Sedation, mechanically-ventilated patients: Very limited data available: Infants, Children, and Adolescents: Oral: Initial: 8 to 25 mg/kg/dose every 6 to 8 hours; titrate to effect based on patient response up to 50 mg/kg/dose every 6 hours; maximum dose: 1,000 mg/dose (AHFS 1993; Parkinson 1997). Dosing based on randomized control trial of 44 patients (age range: 1 day to 15 years) that compared continuous infusion midazolam (n=20) to promethazine plus chloral hydrate (n=23) at dose of 25 mg/kg/dose every 6 hours for sedation in ventilated patients. If sedation unsatisfactory, doses could be increased up to 50 mg/kg/dose every 6 hours. The total number of satisfactory sedation assessments was significantly higher in the chloral hydrate/promethazine group (61%) compared to the midazolam group (48%) (Parkinson 1997).

Sedation, procedural (eg, echocardiogram or EEG): Limited data available: Infants and Children (best results in children <3 years): Oral: 25 to 100 mg/kg/dose 30 minutes prior to procedure; maximum dose 1,000 mg/dose; may repeat after 30 minutes with 25 to 50 mg/kg/dose if necessary. Maximum total dose: 100 mg/kg/procedure or 2,000 mg/procedure (Heistein 2006; Krauss 2006; Napoli 1996; Wheeler 2001). Note: Although dosing may be used in adolescent patients, use in these patients is not common; older children and adolescent patients may not require sedation for echocardiogram and other agents used for EEG.

Dosing: Renal Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling. Use is contraindicated in patients with marked renal impairment.

Dialysis: Dialyzable

Dosing: Hepatic Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling. Use is contraindicated in patients with marked hepatic impairment.

Calculations

Use: Labeled Indications

Note: Not approved in the US

Procedural sedation: Sedative/hypnotic for surgeries and diagnostic procedures; sedative prior to EEG evaluations

Note: The manufacturer labeling includes indications for pain control; alcohol, opioid or barbiturate withdrawal; and short-term treatment of insomnia; however, chloral hydrate is no longer recommended to be used this way (Schutte-Rodin 2008; VA/DoD 2015).

Administration: Oral

May dilute syrup in water or other oral liquid (eg, fruit juice or ginger ale) to minimize gastric irritation.

Administration: Pediatric

Oral: Minimize unpleasant taste and gastric irritation by administering with water, infant formula, fruit juice, or ginger ale.

Storage/Stability

Store syrup at controlled room temperature in a light-resistant, airtight container; protect from freezing.

Medication Patient Education with HCAHPS Considerations

What is this drug used for?

• It is used to treat sleep problems.

• It is used to calm you before a procedure.

• It may be given to you for other reasons. Talk with the doctor.

Frequently reported side effects of this drug

• Fatigue next day

• Passing gas

• Bad taste

• Nausea

• Vomiting

• Diarrhea

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Severe dizziness

• Passing out

• Abnormal heartbeat

• Sore throat

• Chills

• Behavioral changes

• Severe abdominal pain

• Confusion

• Slow breathing

• Shallow breathing

• Trouble breathing

• Driving, eating, or having intercourse and not being fully awake or not remembering

• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Medication Safety Issues

High alert medication:

Contraindications

Hypersensitivity to chloral hydrate or any component of the formulation; marked hepatic or renal impairment

Warnings/Precautions

Concerns related to adverse effects:

• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery or driving).

Disease-related concerns:

• Cardiac disease: Avoid use in patients with severe cardiac disease; larger doses may precipitate arrhythmias and hypotension.

• Gastrointestinal disorders: Because of irritant properties, avoid use in patients with gastritis, esophagitis, or gastric/duodenal ulcer.

• Porphyria: Use with caution in patients with porphyria.

• Respiratory disease: Closely monitor patients with respiratory insufficiency.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Children: Life-threatening respiratory obstruction and deaths have been reported with use in children; use with extreme caution.

• Elderly: Excessive sedation or other adverse effects may be more likely to occur in elderly patients; avoid use in older adults.

• Neonates: Prolonged use in neonates is associated with direct hyperbilirubinemia (active metabolite [TCE] competes with bilirubin for glucuronide conjugation in the liver).

Dosage form specific issues:

• Benzyl alcohol and derivatives: Some dosage forms may contain sodium benzoate/benzoic acid; benzoic acid (benzoate) is a metabolite of benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP ["Inactive" 1997]; CDC 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol derivative with caution in neonates. See manufacturer’s labeling.

Geriatric Considerations

Chloral hydrate is not a hypnotic agent of choice in the elderly.

Warnings: Additional Pediatric Considerations

Deaths and permanent neurologic injury from respiratory compromise have been reported in children sedated with chloral hydrate; respiratory obstruction may occur in children with tonsillar and adenoidal hypertrophy, obstructive sleep apnea, and Leigh's encephalopathy, and in ASA class III children; depressed levels of consciousness may occur; chloral hydrate should not be administered for sedation by nonmedical personnel or in a nonsupervised medical environment; sedation with chloral hydrate requires careful patient monitoring (Coté 2000). Animal studies suggest that chloral hydrate may depress the genioglossus muscle and other airway-maintaining muscles in patients who are already at risk for life-threatening airway obstruction (eg, obstructive sleep apnea); alternative sedative agents should be considered for these patients (Hershenson 1984).

Pregnancy Considerations

Animal reproduction studies have not been conducted. Chloral hydrate crosses the placenta, and long-term use may lead to withdrawal symptoms in the neonate.

Breast-Feeding Considerations

Chloral hydrate is excreted in breast milk; use by breast-feeding women may cause sedation in the infant.

Briggs' Drugs in Pregnancy & Lactation

Chloral Hydrate

Adverse Reactions

Frequency not defined.

Cardiovascular: Atrial arrhythmia, depression of myocardial contractility, hypotension, shortening of refractory periods, torsades de pointes, ventricular arrhythmia

Central nervous system: Abnormal gait, ataxia, confusion, delirium, dizziness, drowsiness, drug dependence (physical and psychological; with prolonged use or large doses), hallucinations, hangover effect, malaise, nightmares, paradoxical excitation, somnambulism, vertigo

Dermatologic: Skin rash (including erythema, eczematoid dermatitis, urticaria, scarlatiniform exanthems)

Endocrine & metabolic: Acute porphyria, ketonuria

Gastrointestinal: Diarrhea, flatulence, gastric irritation, nausea, vomiting

Hematologic & oncologic: Acute porphyria, eosinophilia, leukopenia

Ophthalmic: Allergic conjunctivitis, blepharoptosis, keratoconjunctivitis

Otic: Increased middle ear pressure (infants and children)

Respiratory: Airway obstruction (young children), laryngeal edema (children)

Miscellaneous: Drug tolerance

Allergy and Idiosyncratic Reactions

Chloral Hydrate Allergy

Metabolism/Transport Effects

None known.

Drug Interactions Open Interactions

Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy

Alizapride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Azelastine (Nasal): CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal). Risk X: Avoid combination

Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Risk D: Consider therapy modification

Brexanolone: CNS Depressants may enhance the CNS depressant effect of Brexanolone. Risk C: Monitor therapy

Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Bromopride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Bromperidol: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Buprenorphine: CNS Depressants may enhance the CNS depressant effect of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine at lower doses in patients already receiving CNS depressants. Risk D: Consider therapy modification

Cannabidiol: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Cannabis: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Chlormethiazole: May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Risk D: Consider therapy modification

Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Risk C: Monitor therapy

CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Risk C: Monitor therapy

Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Doxylamine: May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended. Risk C: Monitor therapy

Dronabinol: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Risk D: Consider therapy modification

Esketamine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Risk D: Consider therapy modification

Furosemide: May enhance the adverse/toxic effect of Chloral Hydrate. Risk X: Avoid combination

HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Kava Kava: May enhance the adverse/toxic effect of CNS Depressants. Risk C: Monitor therapy

Lemborexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dosage adjustments of lemborexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive CNS depressant effects. Close monitoring for CNS depressant effects is necessary. Risk D: Consider therapy modification

Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Risk C: Monitor therapy

Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Melatonin: May enhance the sedative effect of Hypnotics (Nonbenzodiazepine). Risk C: Monitor therapy

Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. Risk D: Consider therapy modification

MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Risk C: Monitor therapy

Minocycline (Systemic): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Nabilone: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Opioid Agonists: CNS Depressants may enhance the CNS depressant effect of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification

Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Risk X: Avoid combination

Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification

Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Risk X: Avoid combination

Perampanel: May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination. Risk D: Consider therapy modification

Piribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil. Risk C: Monitor therapy

Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Risk C: Monitor therapy

ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Risk C: Monitor therapy

Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Risk C: Monitor therapy

Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Risk C: Monitor therapy

Selective Serotonin Reuptake Inhibitors: CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Risk C: Monitor therapy

Sodium Oxybate: Hypnotics (Nonbenzodiazepine) may enhance the CNS depressant effect of Sodium Oxybate. Risk X: Avoid combination

Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modification

Tetrahydrocannabinol: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Tetrahydrocannabinol and Cannabidiol: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Risk X: Avoid combination

Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Vitamin K Antagonists (eg, warfarin): Chloral Hydrate may increase the serum concentration of Vitamin K Antagonists. Risk C: Monitor therapy

Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Risk D: Consider therapy modification

Test Interactions

May interfere with copper sulfate tests for glycosuria or with fluorometric urine catecholamine and urinary 17-hydroxycorticosteroid tests.

Monitoring Parameters

Vital signs, O₂ saturation and blood pressure with doses used for conscious sedation

Product Availability

Not available in the US

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule, Oral:

Generic: 500 mg

Syrup, Oral:

Generic: 500 mg/5 mL (500 mL)

Anatomic Therapeutic Chemical (ATC) Classification

N05CC01

Generic Available (US)

Mechanism of Action

Central nervous system depressant effects are due to its active metabolite trichloroethanol, mechanism unknown

Pharmacodynamics/Kinetics

Onset of action: 15 to 30 minutes (Krauss 2006)

Duration: 1 to 2 hours (Krauss 2006)

Absorption: Oral: Well absorbed

Protein binding: Trichloroethanol: 35% to 40%; trichloroacetic acid: ∼94% (may compete with bilirubin for albumin binding sites)

Metabolism: Rapidly metabolized in the liver by alcohol dehydrogenase to trichloroethanol (active metabolite); trichloroethanol undergoes glucuronidation in the liver; variable amounts hepatically and renally to trichloroacetic acid (inactive)

Half-life elimination:

Chloral hydrate (Mayer 1991):

Preterm infants (postmenstrual age [PMA] 31 to 37 weeks): 1.01 ± 0.97 hours

Term infants (PMA 38 to 42 weeks): 3.01 ± 5.81 hours

Children and Adolescents <14 years: 9.68 ± 7.73 hours

Active metabolite (trichloroethanol) (Mayers 1991):

Preterm infants (PMA 31 to 37 weeks): 39.82 ± 14.27 hours

Term infants (PMA 38 to 42 weeks): 27.8 ± 21.32 hours

Children and Adolescents <14 years: 9.67 ± 1.72 hours

Adults: 8 to 12 hours (Fuhrman 2011)

Trichloroacetic acid: Adults: 67 hours (Furhman 2011)

Excretion: Urine (as metabolites); feces (small amounts)

Dental Use

Short-term sedative/hypnotic for dental procedures

Local Anesthetic/Vasoconstrictor Precautions

No information available to require special precautions

Effects on Dental Treatment

No significant effects or complications reported

Effects on Bleeding

No information available to require special precautions

Dental Usual Dosing

Conscious sedation: Children: Oral: 25-50 mg/kg/dose 30 minutes prior to procedure; repeated dosing is not recommended by AAPD (American Academy of Pediatric Dentistry).

Pharmacotherapy Pearls

Not an analgesic

Index Terms

Chloral; Hydrated Chloral; Trichloroacetaldehyde Monohydrate

References

Ahlfors CE. Benzyl alcohol, kernicterus, and unbound bilirubin. J Pediatr. 2001;139(2):317-319.[PubMed 11487763]

American Academy of Pediatric Dentistry. Guideline for monitoring and management of pediatric patients during and after sedation for diagnostic and therapeutic procedures. 2011;35(6):205-221.

American Academy of Pediatrics, Committee on Drugs and Committee on Environmental Health, “Use of Chloral Hydrate for Sedation in Children,” Pediatrics, 1993, 92(3):471-3.[PubMed 8361811]

American Geriatrics Society 2015 Beers Criteria Update Expert Panel. American Geriatrics Society 2015 Updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults [published online October 8, 2015]. J Am Geriatr Soc. 2015;63(11):2227-2246.[PubMed 26446832]10.1111/jgs.13702

Centers for Disease Control (CDC). Neonatal deaths associated with use of benzyl alcohol—United States. MMWR Morb Mortal Wkly Rep. 1982;31(22):290-291. http://www.cdc.gov/mmwr/preview/mmwrhtml/00001109.htm [PubMed 6810084]

Coté CJ, Karl HW, Notterman DA, et al. Adverse Sedation Events in Pediatrics: Analysis of Medications Used for Sedation. Pediatrics. 2000;106(4):633-644.[PubMed 11015502 ]

Fuhrman B, Zimmerman J, eds. Pediatric Critical Care. 4th ed. Philadelphia, PA: Elsevier Health; 2011.

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(3):e434-441.[PubMed 16481449]

Hershenson M, Brouillette RT, Olsen E, et al, “The Effect of Chloral Hydrate on Genioglossus and Diaphragmatic Activity,” Pediatr Res, 1984, 18(6):516-9.[PubMed 6739190]

"Inactive" ingredients in pharmaceutical products: update (subject review). American Academy of Pediatrics (AAP) Committee on Drugs. Pediatrics. 1997;99(2):268-278.[PubMed 9024461]

Krauss B, Green SM. Procedural sedation and analgesia in children. Lancet. 2006;367(9512):766-780. DOI: 10.1016/S0140-6736(06)68230-5.[PubMed 16517277]

Mayers DJ, Hindmarsh KW, Gorecki DK, et al, “Sedative/Hypnotic Effects of Chloral Hydrate in the Neonate: Trichloroethanol or Parent Drug?” Dev Pharmacol Ther, 1992, 19(2-3):141-6.[PubMed 1340434]

Mayers DJ, Hindmarsh KW, Sankaran K, Gorecki DK, Kasian GF. Chloral hydrate disposition following single-dose administration to critically ill neonates and children. Dev Pharmacol Ther. 1991;16(2):71-77.[PubMed 1914781]

McEvoy GK, Litvak K, Welsh O, et al, eds. AHFS Drug Information 1993. Bethesda, MD: American Society of Health-System Pharmacists Inc; 1993.

Napoli KL, Ingall CG, Martin GR. Safety and efficacy of chloral hydrate sedation in children undergoing echocardiography. J Pediatr. 1996;129(2):287-291.[PubMed 8765629]

Parkinson L, Hughes J, Gill A, Billingham I, Ratcliffe J, Choonara I. A randomized controlled trial of sedation in the critically ill. Paediatr Anaesth. 1997;7(5):405-410.[PubMed 9308065]

pms-Chloral hydrate [product monograph]. Montreal, Canada: Pharmascience; May 1998.

Rudolph A, Hoffman J, Rudolph C eds. Rudolph's Pediatrics. 20th ed. Stamford, CT: Appleton & Lange; 1996.

Schutte-Rodin S, Broch L, Buysse D, et al. Clinical guideline for the evaluation and management of chronic insomnia in adults. J Clin Sleep Med. 2008;4(5):487-504.[PubMed 18853708]

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(7):381-387.[PubMed 11491133]

Brand Names: International

Chloradorm (AU); Chloraldurat (DE, NL); Chloralhydrat 500 (ID); Escre (JP); Kloral (DK); Pocral (KR); Suppojuvent Sedante (ES); Welldorm (GB)

Last Updated 2/20/20

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