What are the recommended pharmacokinetics and pharmacodynamics for pediatric anesthesia?

Pharmacokinetics and Pharmacodynamics of Paediatric Anaesthesia

Paediatric patients require fundamentally different anaesthetic dosing than adults due to age-dependent differences in drug clearance, volume of distribution, protein binding, and organ maturity—with neonates under 6 months requiring 30% dose reductions for amide local anaesthetics and infants demonstrating 2-fold higher remifentanil clearance compared to adults. 1, 2, 3

Key Pharmacokinetic Principles by Age Group

Neonates and Infants (<6 months)

• Reduce all amide local anaesthetic doses by 30% due to immature hepatic metabolism and altered protein binding 1, 4, 2
• Remifentanil clearance is highly variable but averages 2 times higher than young adults, necessitating starting infusion rates of 0.4 mcg/kg/min with potential need for increased rates and additional boluses 3
• Protein binding is markedly decreased, increasing free drug fraction and risk of toxicity 5
• Hepatic clearance of bupivacaine and ropivacaine is reduced during the first year of life 5

Infants (6-12 months)

• MAC (minimum alveolar concentration) for volatile anaesthetics is 1.5-1.8 times higher than in 40-year-old adults, peaking around 6 months of age 5
• Propofol clearance and volume of distribution are greater than adults, requiring three times the initial adult dose to achieve similar plasma concentrations 5

Children (1-12 years)

• Propofol demonstrates superior recovery characteristics with lowest incidence of emergence agitation compared to volatile agents 6
• Regional anaesthesia dosing follows weight-based calculations with ropivacaine 0.2% maximum dose of 3 mg/kg with epinephrine 1, 2

Adolescents and Elderly (>65 years)

• Geriatric patients show twice the sensitivity to remifentanil's pharmacodynamic effects despite unchanged elimination half-life, requiring 50% dose reduction 3
• Clearance of remifentanil is reduced approximately 25% in elderly patients 3

Intraoperative Anaesthetic Dosing

Induction and Maintenance Agents

• Remifentanil maintenance infusion: 0.05-0.3 mcg/kg/min for paediatric patients 2
• Fentanyl intraoperative dosing: 1-2 mcg/kg 2
• Morphine intraoperative dosing: 25-100 mcg/kg depending on age, titrated to effect 2
• Propofol for sedation: 0.5-1 mg/kg intermittent bolus 2
• Propofol for MRI sedation: 2-3.7 mg/kg bolus (lower dose if weight >10 kg), 7.1-10.1 mg/kg/h infusion 7

Non-Opioid Analgesics

• Paracetamol IV loading dose: 15-20 mg/kg 2
• Ibuprofen oral: 10 mg/kg every 8 hours 2
• Diclofenac oral: 1 mg/kg every 8 hours 2
• Metamizole should be used as first-line rescue analgesic where available 7

Adjuvant Medications

• Dexmedetomidine IV bolus: 0.5-1 mcg/kg 2
• Dexamethasone: 0.15-0.25 mg/kg (maximum 0.5 mg/kg) to reduce postoperative swelling 7, 2
• Intraoperative ketamine as co-analgesic enhances analgesia 7
• Alpha-2 agonists (clonidine) intraoperatively improve outcomes 7

Regional Anaesthesia Pharmacokinetics

Local Anaesthetic Maximum Doses

Critical safety principle: Calculate maximum allowable dose in milligrams before starting any procedure 1, 4

Ropivacaine 0.2%

• Maximum dose with epinephrine: 3 mg/kg 1, 2
• Maximum dose without epinephrine: 2 mg/kg 1
• Caudal block: 1.0 mL/kg 7, 1, 2
• Lumbar epidural: 0.5 mL/kg (maximum 15 mL initially) 7, 1
• Thoracic epidural: 0.2-0.3 mL/kg 1
• Peripheral nerve blocks: 0.2-0.5 mL/kg 7, 1
• TAP/rectus sheath blocks: 0.2-0.5 mL/kg per side 7, 1

Bupivacaine 0.25%

• Maximum dose with epinephrine: 3 mg/kg 4
• Maximum dose: 2.5 mg/kg (1 mL/kg of 0.25% solution) 2
• Same volume guidelines as ropivacaine for specific blocks 7

Lidocaine

• Maximum dose with epinephrine: 7 mg/kg 4
• Maximum dose without epinephrine: 4.5 mg/kg 4
• For children specifically: 4.5 mg/kg without epinephrine, 7 mg/kg with epinephrine 4
• IV regional anaesthesia (Bier block): reduced to 3-5 mg/kg 4

Adjuvants for Regional Blocks

• Preservative-free clonidine: 1-2 mcg/kg can be added to local anaesthetics for enhanced duration in epidural, caudal, and peripheral nerve blocks 7, 1, 2
• Morphine 30-50 mcg/kg can be added to caudal blocks (only with adequate monitoring) 7

Critical Safety Considerations

Local Anaesthetic Systemic Toxicity (LAST) Prevention

• Have 20% lipid emulsion immediately available when administering ropivacaine or other local anaesthetics into vascular tissues 1, 2
• Aspirate frequently before injection to avoid intravascular administration 1, 4
• Use lower doses in highly vascular areas due to increased systemic absorption 1, 4
• Never use ropivacaine or other long-acting local anaesthetics for IV regional anaesthesia due to excessive cardiac toxicity risk 1, 4

Monitoring Requirements

• Document vital signs every 5 minutes initially, then every 10-15 minutes once stable when using high-dose local anaesthetics 1, 2
• Early signs of toxicity include CNS excitation or depression, circumoral numbness, facial tingling, metallic taste, and cardiac depression 1, 4
• Progressive toxicity manifests as seizures or CNS depression 4

Special Population Adjustments

• Morbidly obese patients: Use ideal body weight for dose calculations, not actual body weight 4
• Patients with renal impairment: Exercise caution as remifentanil is substantially excreted by kidney 3
• Critically ill ICU patients: No data available for remifentanil use longer than 16 hours 3

Pharmacodynamic Considerations

Volatile Anaesthetics

• MAC is context-sensitive with little difference between age groups for pharmacokinetics 5
• Halothane has Michaelis-Menten kinetics with up to 40% hepatic metabolism 5
• Desflurane has highest incidence of emergence agitation and worst recovery characteristics 6
• Sevoflurane cases report highest incidence of analgesic requirement postoperatively 6

Propofol Advantages

• Propofol is recommended as the most efficient and safe anaesthetic in paediatric anaesthesia with fewest adverse effects including lowest emergence agitation rates 6
• Equipotent doses induce more marked deleterious haemodynamic effects in infants compared to children 5
• Risk of propofol infusion syndrome requires vigilance, particularly with prolonged infusions 8

Drug Interactions

• Enhanced sedative effects occur when maximum recommended doses of local anaesthetics are combined with opioids or other sedatives 4
• Combination of NSAID and paracetamol reduces opioid use 7
• Avoid IV lidocaine within 4 hours of other local anaesthetic interventions 4

Common Pitfalls and How to Avoid Them

• Failing to reduce doses in neonates: Always apply 30% reduction for amide local anaesthetics in infants <6 months 1, 2
• Using actual body weight instead of ideal body weight: Particularly problematic in obese patients and for IV lidocaine calculations 4
• Not calculating maximum dose before procedure: This leads to cumulative dosing errors 1, 4
• Inadequate administration of non-opioid drugs: Real-world data shows these foundational analgesics are frequently underdosed 7
• Overlooking increased MAC requirements in infants: Infants 6 months old require substantially higher volatile anaesthetic concentrations 5
• Assuming adult pharmacokinetics apply: Children have fundamentally different clearance, volume of distribution, and protein binding requiring distinct dosing strategies 9, 5