Pharmacological Considerations in Pediatrics

Pediatric PK/PD - Tiny Bodies, Big Changes

• Absorption (A):
  • Neonates: Gastric pH ↑, GI transit variable, IM absorption erratic, skin permeability ↑.
• Distribution (D):
  • Total Body Water (TBW) ↑ (70-80% vs. 60% adult) & Extracellular Fluid (ECF) ↑ → ↑ Volume of Distribution (Vd) for water-soluble drugs.
  • Fat content ↓ → ↓ Vd for lipid-soluble drugs.
  • Protein binding ↓ (e.g., albumin) → ↑ free drug fraction.
• Metabolism (M):
  • CYP450 enzyme system immature; Phase I reactions (e.g., oxidation) slower.
  • Phase II glucuronidation ↓ significantly in neonates. 📌 Neonates Generally Lack UDPGT (UDP-glucuronosyltransferase).
• Excretion (E):
  • Glomerular Filtration Rate (GFR) ↓ in neonates/infants (reaches adult values by 6-12 months).
• Pharmacodynamics (PD):
  • Receptor density & affinity may differ.
  • Paradoxical drug responses (e.g., benzodiazepines causing agitation).

⭐ Minimum Alveolar Concentration (MAC) values for volatile anesthetics are highest in infants (peak at 1-6 months), often ~1.5x adult values (e.g., Sevoflurane).

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Inhalational Agents - Sweet Dreams, Safe Air

• MAC (Minimum Alveolar Concentration): Peaks at ~6 months (Sevoflurane/Isoflurane); lower in neonates & older children vs. infants.
• Kinetics: Faster induction/emergence (↑ $V_A$/FRC, ↑ CO to VRG, ↓ blood:gas solubility effect).
• Agents:
  • Sevoflurane: Choice for induction; non-pungent.
  • Desflurane: Airway irritant; rapid recovery. Not for induction.
  • Halothane: Historical; halothane hepatitis risk.
  • Nitrous Oxide ($N_2O$): Diffusion hypoxia risk (administer 100% O₂ post-use).

⭐ Sevoflurane is preferred for pediatric inhalational induction due to low pungency and rapid onset.

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IV Anesthetics & Opioids - Vein Voyage, Pain Vanquishers

• Propofol:
  • Induction/maintenance. Neonates: ↑ Vd, ↑ dose (2.5-3.5 mg/kg).
  • ⚠️ Risk: Propofol Infusion Syndrome (PRIS).
• Ketamine:
  • Dissociative anesthesia, potent analgesia, bronchodilation.
  • Dose (IV): Induction 1-2 mg/kg; Analgesia 0.25-0.5 mg/kg.
  • ⚠️ Emergence delirium; ↓ with benzodiazepines.
• Opioids:
  • Morphine: Neonates: ↓ clearance, prolonged effect. Dose: 0.05-0.1 mg/kg.
  • Fentanyl: Neonates: ↑ sensitivity. Dose: 1-2 mcg/kg. ⚠️ Chest wall rigidity with high doses/rapid injection.
  • Remifentanil: Ultra-short acting; plasma esterase metabolism. Ideal for TIVA.
• Dexmedetomidine:
  • α2-agonist: sedative, analgesic. Minimal respiratory depression.
  • Loading dose: 0.5-1 mcg/kg over 10 min; Maintenance: 0.2-0.7 mcg/kg/hr.

⭐ Fentanyl is approximately 100 times more potent than morphine.

Muscle Relaxants & Reversal - Still Muscles, Swift Wake-up

• Succinylcholine (SCh): 1-2 mg/kg IV. Risks: MH, hyperkalemia, masseter spasm; atropine for bradycardia.
• Non-depolarizers (NDMRs):
  • Rocuronium: 0.6-1.2 mg/kg. Reversal: Sugammadex.
  • Atracurium/Cisatracurium: Hoffman/ester hydrolysis.
• Pediatric Considerations:
  • Neonates: ↑ sensitivity to NDMRs, ↓ plasma cholinesterase.
• Reversal:
  • Neostigmine (0.05-0.07 mg/kg) + Glycopyrrolate (0.01-0.02 mg/kg).
  • Sugammadex (for Rocuronium).

⭐ Neonates: ↑ NDMR sensitivity, ↓ plasma cholinesterase (prolongs SCh).

Local Anesthetics & Dosing - Numb & Numbered Right

• Max Doses (mg/kg):
  • Lidocaine: Plain 3-5; With Epi 5-7
  • Bupivacaine: Plain ~2
  • Ropivacaine: Plain ~2-3
• Neonates: ↓ protein binding (↑ free fraction), ↓ metabolism.
• LAST (Local Anesthetic Systemic Toxicity):
  • Signs: CNS (tinnitus, seizures) → CVS (arrhythmias, collapse).
  • Management: Intralipid 20%.

• Common Applications: Caudal blocks, EMLA cream.

⭐ For LAST, Intralipid 20% initial bolus is 1.5 mL/kg (ideal body weight) over 1 min; may repeat bolus 1-2 times for persistent asystole/CV collapse.

High‑Yield Points - ⚡ Biggest Takeaways

• Neonates/Infants: ↑ Vd for water-soluble drugs (e.g., succinylcholine) means higher mg/kg doses.
• Immature hepatic metabolism (glucuronidation) prolongs effects of opioids (morphine) & benzodiazepines.
• Reduced GFR in neonates slows renal drug excretion (e.g., aminoglycosides).
• MAC values are higher in infants (peak ~6 months); sevoflurane highest in neonates.
• Marked sensitivity to respiratory depression from opioids and sedatives.
• Rapid inhalational induction/emergence due to ↑ alveolar ventilation/FRC ratio.
• Propofol: Higher induction doses (mg/kg) due to larger Vd & faster clearance.