A common misconception of dosing anesthetics in pediatric patients is that children are miniature adults. Although there are substantial physiologic changes with early development and maturation (Table 21–1; Figures 21–1 through 21–3),1-6 they are not rigorously accounted for in published dosing guidelines for pediatric patients. Ideally, dosing recommendations would be based on studies in children at various phases of maturation and characterize drug kinetic and dynamic behavior as a function of age and body composition. Without a scientific basis, anesthesiologists are left to make assumptions and educated guesses when formulating a dosing regimen and then rely on the forgiving nature of most anesthetics that have a wide therapeutic margin.
Table 21–1Body composition, absorption, distribution, metabolism, and renal excretion in young children.1-6 ||Download (.pdf) Table 21–1 Body composition, absorption, distribution, metabolism, and renal excretion in young children.1-6
|Physiologic Function ||Differences in Young Children |
|Absorption || |
|Gastric motility ||Gastric emptying is delayed in newborn infants and approaches adult values by 6 to 8 months of age.1 |
|Gastric pH ||Neutral at birth and then reaches adult levels by age 2 years.2 Important in absorption of acid-labile drugs.3 |
|Body composition || |
|Total body water ||Declines from 95% of total body weight in the premature infant to 60% in young adults. |
|Extracellular water ||Declines from 60% in premature infants to 20% in young adults. |
|Intracellular water ||Rises from 25% in premature infants to 45% in young adults (Figure 21–1).4 |
|Percent body fat ||Rises from infancy, peaks at age 1, then reaches adult percentages of 15% (Figure 21–2).5 |
|Volume of distribution ||Decreases up to 50% for water soluble drugs (eg, muscle relaxants).3 |
|Metabolism || |
Hepatic microsomal enzymes: low concentrations at birth that reach adult levels by 6 to 12 months of age.
Hepatic conjugation (glucuronidation and acetylation): low at birth that reaches adult functionality by 3 to 6 months of age.3
|Renal excretion ||Glomerular filtration rate rises from 11 in the premature infant to 20 mL/min/1.73 m2 in the young adult (Figure 21–3). |
Estimated total, intracelluar, and extracelluar water as a percentage of total body weight by age.1-6
Body fat as a percentage of total body weight versus age.1-6
Glomerular filtration rate (GFR) as a function of age.1-6
A major reason for the paucity of data characterizing anesthetic drug behavior in pediatric patients is drug development cost. Pharmaceutical companies that market drugs in the United States seek approval from the Food and Drug Administration (FDA) for adults but do not pursue approval in children because of prohibitive costs (up to $800 million for one ...