Hydrochloride Salts in Anesthesia: Role and Clinical Applications
Clarification of Terminology
Hydrochloride (chlorhydrate) refers to the salt form of medications, not a distinct anesthetic agent. Many anesthetic and sedative drugs are formulated as hydrochloride salts to improve water solubility and stability—examples include lidocaine hydrochloride, bupivacaine hydrochloride, and ketamine hydrochloride 1. The hydrochloride component itself has no pharmacologic activity; it simply allows the active drug to dissolve in aqueous solutions for injection 1.
If your question concerns chloral hydrate (a distinct sedative agent), the following information applies:
Chloral Hydrate: Role in Procedural Sedation
Primary Indication and Efficacy
Chloral hydrate is a first-line oral sedative for non-painful diagnostic imaging in children under 8 years and weighing less than 50 kg, achieving 95–100% sedation success rates. 2 It is indicated specifically for procedures such as MRI, CT, echocardiography, and auditory brainstem response testing where anxiolysis and immobility—not analgesia—are required 2.
- Chloral hydrate vastly outperforms midazolam for moderate-to-deep sedation in imaging: midazolam fails in approximately 81% of cases when used as a sole agent, whereas chloral hydrate succeeds in 95–100% 2.
- In a direct comparison of 675 pediatric patients, chloral hydrate and pentobarbital showed similar efficacy (both ~99% success), time to sedation (166 vs. 196 minutes), and adverse event rates (1.7% vs. 1.6%) 3.
Dosing and Pharmacokinetics
- Standard oral dose: 50–100 mg/kg (maximum 2 g) 2.
- Low-dose regimen: 10–25 mg/kg when combined with other sedatives 2.
- Onset of action: Median 20 minutes (range 15–27 minutes) 2.
- Duration of sedation: Averages 81 minutes, with discharge typically at 100–103 minutes 2.
- Chloral hydrate is rapidly absorbed from the gastrointestinal tract, with sedative effects appearing in 20–60 minutes 4. The active metabolite trichloroethanol (TCE) has a half-life of 8–12 hours, while trichloroacetic acid (TCA) persists for 67 hours 4.
Patient Selection Criteria
Ideal candidates are ASA class I–II children under 8 years, weighing less than 50 kg, without high-risk airway anatomy or significant comorbidities. 2 Children older than 12 years or heavier than 50 kg experience markedly reduced sedation success with chloral hydrate 2.
- Contraindications include gastric ulcers, hepatic insufficiency, porphyria, respiratory insufficiency, and hypersensitivity 4.
- High-risk patients (ASA III–IV, airway anomalies, severe tonsillar hypertrophy) require individualized assessment and often anesthesiology consultation 2.
Safety Profile and Adverse Events
Chloral hydrate carries a 1.7% overall adverse event rate, primarily mild oxygen desaturation responding to simple airway maneuvers. 2 In a study of 675 children, 4 experienced oxygen desaturation requiring airway repositioning, and 1 required bag-valve-mask ventilation 3, 2. Paradoxical reactions (irritability, hyperactivity) occur in approximately 1.7% of cases 2.
- Transient respiratory depression to oxygen saturation less than 10% below baseline has been documented but typically resolves with head positioning or supplemental oxygen 3.
- Serious toxicity occurs with doses around 10 g, though fatalities have been reported with as little as 5 g 4.
- Long-term concerns include potential genotoxicity and carcinogenicity, leading to withdrawal of chloral hydrate from many dermatologic and stomatologic formulations in France 4.
Monitoring Requirements
Continuous pulse oximetry and intermittent blood pressure monitoring are mandatory throughout sedation and recovery. 2 Age-appropriate airway equipment (oral/nasal airways, bag-valve-mask, laryngoscope, endotracheal tubes) must be immediately available 2. Practitioners must be capable of rescuing a patient one sedation level deeper than intended 2.
Pre-Procedural Requirements
- Minimum fasting: 2 hours for clear liquids to minimize aspiration risk 2.
- An emergency cart with age-appropriate resuscitation equipment must be readily available 2.
Practical Limitations
Chloral hydrate is no longer commercially available as a liquid formulation and must be compounded by hospital pharmacies. 2 This creates potential for compounding errors and limits accessibility 5.
Alternative Sedative Agents
Midazolam
Midazolam should not be used as the sole agent for moderate-to-deep sedation in imaging procedures due to its 81% failure rate. 2 It is appropriate only when anxiolysis alone is required or when faster recovery is essential (30–60 minutes versus >100 minutes with chloral hydrate) 2.
- Oral dose: 0.5–0.75 mg/kg (maximum ~13 mg) 2.
- Intravenous dose: Titrated to effect, with peak EEG effect at 4.8 minutes 2.
- Onset: Intranasal ~14 minutes; oral 30–60 minutes 2.
- Flumazenil should be stocked for reversal of life-threatening respiratory depression 2. Risk of respiratory depression increases markedly when midazolam is combined with opioids or other sedatives 2.
Pentobarbital
Pentobarbital achieves 97–99.5% success rates for pediatric sedation in imaging studies 3. However, it has longer recovery times (356 minutes) and time to discharge (406 minutes) compared to propofol 3. Emergence reactions (hyperactivity) occur in 5–8.4% of children, particularly those older than 8 years 3.
Common Hydrochloride Salt Formulations in Anesthesia
Local Anesthetics
Local anesthetics are classified by potency, onset, and duration 1:
- Low potency, short duration: Procaine hydrochloride, chloroprocaine hydrochloride 1.
- Moderate potency and duration: Lidocaine hydrochloride, mepivacaine hydrochloride, prilocaine hydrochloride 1.
- High potency, long duration: Tetracaine (amethocaine) hydrochloride, bupivacaine hydrochloride, etidocaine hydrochloride 1.
Lipid solubility determines potency, protein binding influences duration, and pKa correlates with onset of action 1.
Anaphylaxis Considerations
Chlorhexidine (often formulated as chlorhexidine hydrochloride) is an increasingly recognized cause of perioperative anaphylaxis. 3 Reactions range from contact dermatitis to life-threatening anaphylaxis, particularly when used for urological, gynecological, or central venous catheter insertion 3. It is prudent to allow skin disinfectant to completely dry before beginning invasive procedures 3.
- In suspected anaphylaxis, remove all potential causative agents (including IV colloids, latex, and chlorhexidine) and administer adrenaline intravenously: initial adult dose 50 µg (0.5 ml of 1:10,000 solution) 3.
- Secondary management includes chlorphenamine 10 mg IV and hydrocortisone 200 mg IV (adult doses) 3.
Key Clinical Pitfalls
- Do not use chloral hydrate in children with neurologic disorders: failure rates increase from 4% in normal children to 27% in neurologically impaired children 6.
- Do not use midazolam alone for imaging sedation: its 81% failure rate makes it unsuitable for this purpose 2.
- Do not exceed chloral hydrate dosing limits: toxicity and death occur with doses ≥10 g, and compounding errors are a real risk 4, 5.
- Do not use chloral hydrate for painful procedures: it provides sedation but no analgesia 2.