1. Developmental Pharmacology
   1. Age may have a substantial effect on the absorption of certain drugs, for example, because gastric juice is closer to neutral pH (pH ~6) at birth and does not reach adult levels of acidity until about 3 years of age.
   2. The albumin concentration is low in children, and α ₁-acid glycoprotein concentration is also reduced at birth and increases slowly with increasing age as well as during periods of stress. (Free fraction of medications such as lidocaine is greater in young infants than older children because the concentration of α ₁-acid glycoprotein in the former is reduced.)
   3. Apart from a few enzyme systems that hold importance in fetal life (CYP450 3A7), the activities of the vast majority of CYP450 enzyme systems (CYP450 3A4, 2E1, and 2D6) increase with age from birth but at divergent rates (Fig. 42-1: Developmental changes in common cytochromes of interest in pediatric anesthesia).
   4. The glomerular filtration rate is markedly reduced in neonates but matures throughout childhood, reaching adult rates by 5 to 15 years of age.
2. Inhalational Anesthetics
   1. The widespread appeal of the current inhalational anesthetics may be attributed to their physicochemical properties, which provide a rapid onset and offset of action, cardiorespiratory homeostasis, and limited metabolism and toxicity (Table 42-4: Factors Increasing The Washin of Inhalatonal Anesthetics in Children Compared with Adults).
   2. Sevoflurane is the induction agent of choice in infants and children. Desflurane offers the most favorable pharmacokinetic and in vivo metabolic characteristics in terms of its minimal blood and tissue solubilities and resistance to metabolism, although its use as an induction agent in children is proscribed because it irritates the upper airway.
3. Pharmacokinetics
   1. The greater ratio of alveolar ventilation to functional residual capacity (FRC) in infants and children compared with adults speeds the equilibration of inspired to alveolar anesthetic partial pressures. The net effect of a greater ventilation: FRC ratio is a reduction in the time constant, from 0.7 in adults to 0.2 in infants, which explains the speed of equilibration (sudden and rapid responses observed to inhalational anesthetic in infants and children compared with adults).
   2. The greater cardiac output in infants speeds the equilibration of alveolar to inspired anesthetic partial pressures in the vessel-rich group, which takes up most of the anesthetic during the first couple of hours of anesthesia.
   3. The solubility of all inhalational anesthetics is reduced in tissues in infants compared with adults, including in the brain, muscle, and heart.
4. Pharmacodynamics
   1. As a fetus matures and reaches birth, the minimum alveolar concentration (MAC) increases, peaking in infants 1 to 6 months of age isoflurane and then decreases steadily thereafter with increasing age (Fig. 42-2: Age and the minimum alveolar concentration (MAC) of isoflurane from premature infants to adults). (The reason for the age-dependent differences in MAC is unclear.)
   2. The MAC of desflurane in adult redheads is 20% greater than in nonredheads; the same response would be expected in children of similar genetic predisposition.

Pediatric Anesthesia

1. Anatomy and Physiology
2. Pharmacology
3. Respiration
4. Cardiovascular
5. Central Nervous System
6. Renal
7. Hepatic
8. In Vivo Metabolism
9. Intravenous
10. Sedatives
11. Preoperative Assessment
12. Induction of Anesthesia
13. Preoperative Preparation
14. Induction Techniques
15. Maintenance of Anesthesia
16. Emergency and Recovery from Anesthesia
17. Transfer to the Postanesthesia Care Unit (PACU)