In children requiring procedural sedation, what are the appropriate doses, onset times, durations, contraindications, and monitoring for chloral hydrate versus midazolam, and how should I choose between these agents?

Chloral Hydrate and Midazolam Dosing for Pediatric Procedural Sedation

For pediatric procedural sedation, chloral hydrate at 50 mg/kg orally is superior to midazolam, achieving 95-100% sedation success compared to only 19-51% with midazolam, making chloral hydrate the preferred first-line agent for non-painful diagnostic procedures in children. 1, 2

Dosing Recommendations

Chloral Hydrate (Preferred Agent)

• Dose: 50-100 mg/kg orally (maximum 2 grams) 1, 2
• Low-dose option: 10-25 mg/kg when combined with other sedating medications 1
• Onset: 15-20 minutes (median 20 minutes, range 15-27 minutes) 1, 3, 4
• Duration: Approximately 81 minutes sedation time, with discharge around 100-103 minutes 1
• Success rate: 95-100% for diagnostic imaging procedures 1, 5, 2

Midazolam (Alternative Agent)

• Oral dose: 0.5-0.75 mg/kg (maximum 0.6 mg/kg or approximately 13 mg for average child) 6
• Intranasal dose: 0.2 mg/kg 3
• Sublingual dose: 0.3 mg/kg 7
• IV dose: Peak EEG effect at 4.8 minutes; requires titration 1
• Onset: 14 minutes (intranasal), 30-60 minutes (oral) 6, 3
• Duration: 30-60 minutes recovery time (oral), 68 minutes (intranasal) 6, 3
• Success rate: Only 19-51% for imaging procedures when used alone 1, 5, 2

Clinical Decision Algorithm

When to Choose Chloral Hydrate:

• Non-painful diagnostic procedures (MRI, CT, echocardiography, auditory brainstem response testing) 1, 5, 2
• Children under 8 years old and weighing less than 50 kg (highest success rates) 1, 8
• When deeper sedation is required for comprehensive imaging 7
• ASA class I-II patients 1

When to Choose Midazolam:

• Anxiolysis only (minimal sedation needs) 8, 6
• When faster recovery is essential (30-60 minutes vs 100+ minutes) 6, 3
• High-risk patients where lighter sedation is safer 7
• When combined with other agents (though this increases respiratory depression risk) 1

When to Avoid These Agents:

• Midazolam alone should NOT be used for moderate-to-deep sedation in imaging procedures due to 81% failure rate 1
• Chloral hydrate is no longer commercially available as liquid formulation; requires hospital pharmacy compounding 1
• Children over 12 years or weighing more than 50 kg have reduced success with both agents 1

Critical Safety Monitoring

Required Equipment (Must Be Immediately Available):

• Age-appropriate airway equipment: oral/nasal airways, bag-valve-mask, laryngoscope, endotracheal tubes 1
• Flumazenil for midazolam reversal (for life-threatening respiratory depression) 6
• Continuous pulse oximetry throughout sedation and recovery 1
• Blood pressure monitoring at intervals 1

Respiratory Complications:

• Chloral hydrate: 1.7% adverse event rate; 4 patients (of 675) had oxygen desaturation requiring airway repositioning, 1 required bag-valve-mask ventilation 1
• Midazolam: Risk of respiratory depression increases significantly when combined with opioids or other sedatives 6
• Both agents: Oxygen desaturation typically responds to head repositioning or supplemental oxygen 1

Common Pitfalls and How to Avoid Them

Pitfall #1: Using Midazolam Alone for Imaging

The Evidence: IV midazolam achieved only 19% success for CT imaging versus 97% with pentobarbital 1. Oral/intranasal midazolam showed 50-51% success versus 95-100% with chloral hydrate 5, 2.

Solution: Reserve midazolam for anxiolysis only, not as sole agent for procedural sedation requiring immobility 8, 6.

Pitfall #2: Inadequate Observation After Discharge

The Evidence: Long-acting agents like chloral hydrate can cause re-sedation after discharge, particularly dangerous in infants in car seats 1.

Solution: Observe for minimum 2 hours after sedation; require two adults to accompany infants/toddlers in car seats 1.

Pitfall #3: Supplemental Dosing Too Early

The Evidence: Chloral hydrate onset is 15-27 minutes; midazolam peaks at 4.8 minutes (IV) but 30-60 minutes (oral) 1, 6, 3.

Solution: Wait full 30 minutes before administering second dose (half the initial dose) 2, 7.

Pitfall #4: Combining Agents Without Dose Reduction

The Evidence: Adding midazolam to pentobarbital provided no benefit but increased sedation time by 1.5 minutes and discharge time by 14 minutes 1.

Solution: When combining sedatives, reduce each component dose and continuously monitor respiratory function 1.

Contraindications and Special Populations

Chloral Hydrate Specific:

• Gastrointestinal side effects: 11.7% nausea/vomiting rate (significantly higher than midazolam at 0-2.8%) 3
• Paradoxical reactions: Irritability and hyperactivity reported in 1.7% 1
• Best for: Children under 1 year old at 50-100 mg/kg 8

Midazolam Specific:

• Underdosing risk: Oral route requires 0.5-0.75 mg/kg (not 0.05-0.1 mg/kg like IV) due to first-pass metabolism 6
• Better acceptance: Less resistance to sublingual/intranasal administration versus oral chloral hydrate 3, 7
• Faster onset with intranasal route: 14 minutes versus 40 minutes for chloral hydrate 3

High-Risk Patients (ASA III-IV):

• Require individual consideration and anesthesiology consultation 1
• Anatomic airway abnormalities or moderate-to-severe tonsillar hypertrophy need additional evaluation 1
• Consider lighter sedation with midazolam to avoid deep sedation complications 7

Pre-Procedural Requirements

Fasting Status:

• Minimum 2 hours clear liquid fasting before procedures 8
• NPO status minimizes aspiration risk during sedation 6

Rescue Skills Required:

• Practitioners must be able to rescue from one level deeper than intended sedation 1
• If planning moderate sedation, must have deep sedation rescue skills 1
• Emergency cart with age-appropriate resuscitation equipment mandatory 1