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.

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 drug⁷). As a result, several anesthetics are administered to children “off label” with drug adult doses scaled to pediatric patients.

To address this void, the National Institute for Childhood Health and Human Development in the United States formed the Pediatric Pharmacology Research Unit Network in 1994. This network encouraged the inclusion of pediatric patients during drug development.⁸ The 1997 FDA Modernization Act further provided an incentive to pediatric pharmacology research by requiring drugs frequently prescribed to children to have FDA approval and allowing additional 6 months of market exclusivity for approved drugs.⁹

Over the years, clinical pharmacologists have explored numerous approaches to more accurately dose pediatric patients with formulas that incorporate age, weight, body surface area (BSA), or allometric scaling (Table 21–2). Although an improvement, none of them account for maturation and development in early childhood.

For example, early approaches used age to scale adult doses to children. Although easy to calculate, they were highly unreliable because of the large variability in weight at a given age. For a 3-year-old male child, the 3rd to 97th percentile for weight ranges from 12.5 to 19 kg (a comparable range in an adult would be 70 to 106 kg). A single anesthetic dose administered to patients over this weight range would likely lead to overdosing or underdosing.

Weight-based dosing techniques are most common. Although easy to calculate, dosing normalized to weight assumes that (1) people of different sizes and age have the same body composition and similar metabolism and excretion, and that (2) drug effects are similar regardless of age. This may be acceptable in children 2 years of age and older. But for younger infants and neonates, the physiologic differences described in Table 21–1 can substantially alter drug behavior.

Another approach is to scale adult doses by BSA. BSA assumes physiologic processes are nearly constant when expressed per unit of body surface area.¹² Although BSA is used to estimate organ size and fluid compartment volumes,¹⁰ physiologic processes are not the same in infants, toddlers, and young children. Dosing scaled to BSA may lead to larger doses than with weight-based approaches in certain age groups. As an example, consider dosing fentanyl for a 15-kg, 76-cm, 2-year-old (BSA = 0.56 m²) according to weight versus BSA. With a 2-mcg/kg (150-mcg) dose for a 75-kg adult (BSA = 1.73 m²), the weight- and BSA-scaled doses are 30 and 50 mcg, respectively (70% increase).

The clinical implications of differences between weight- and BSA-based dosing are not clear. Perhaps scaling to BSA better captures differences in body composition not accounted for by weight. By contrast, scaling to either BSA or weight may ignore important maturation processes as a function of age that directly influence drug clearance and lead to excessive dosing. A dramatic example of this involves the antimicrobial chloramphenicol. When dosed according to body weight, chloramphenicol caused cardiovascular collapse and “gray baby syndrome.”^13,14 Newborn infants metabolize chloramphenicol by glucuronidation. This process is immature in newborns and proceeds at a slower rate than in adults—half life of 20 versus 4 hours.

An additional approach is allometric scaling. This technique scales clearance from adults to children as a function of body weight and assumes clearance is the same in young children and adults. Because of this assumption, it is limited to children 8 years of age or older when clearance becomes similar to adults¹⁵; however, many researchers suggest that it should not be used at all.¹⁶

At present, most dosing recommendations for anesthetics in pediatric patients are simply weight based (ie, mg/kg), whereas some recommendations provide unique weight normalized dose for premature infants, neonates, toddlers, and children (Table 21–3). Selected anesthetics are discussed in more detail below.