Due to altered body composition and immature renal and hepatic function, drug administration produces different effects in children than in adults (Table 127-1). With growth and development, drug pharmacology changes, and dosages must be adjusted accordingly.
TABLE 127-1Trends in Physiological Systems and Clinical Implications for Anesthesia ||Download (.pdf) TABLE 127-1 Trends in Physiological Systems and Clinical Implications for Anesthesia
|Physiology ||Trends ||Implications |
|Body composition ||Decreased fat and muscle, increased water in neonates ||Increased volume of distribution, duration of action for water-soluble drugs |
|Plasma protein binding ||Decreased plasma protein concentrations in neonates ||Increased unbound fraction, potential for drug toxicity |
|Hepatic function || |
Immature cytochrome P450 enzymes in neonates and infants
Increased hepatic mass in children 2–6 years of age
Decreased metabolic clearance, increased dosing intervals in neonates and infants
Increased metabolic clearance, decreased dosing intervals in children 2–6
|Renal function ||Decreased glomerular filtration rate in neonates and infants ||Accumulation of renally excreted drugs, increased dosing intervals in neonates and infants |
Neonates have a larger body proportion of water than adults, resulting in an increased volume of distribution, delayed excretion, and larger initial dose requirement for water-soluble drugs. Neonates exhibit longer times of action for drugs terminating through redistribution into muscle or fat stores.
Oral absorption of drugs is generally slower in children due to slower gastric emptying. Gastric pH is slightly higher in children than in adults, leading to higher absorption rate and bioavailability of orally administered acid-labile compounds. Intestinal motility is decreased in neonates but increased in children relative to adults.
Intramuscular (IM) bioavailability is higher in neonates and infants than in older children due to higher density of skeletal muscle capillaries. However, decreased muscular blood flow and reduced muscular mass cause IM administration to be unreliable in neonates.
Permeability of the blood–brain barrier is increased in neonates as a result of decreased myelination. Some hydrophilic drugs can therefore enter the cerebrospinal fluid (CSF), leading to higher concentrations and lower dosage requirements in neonates.
Plasma protein binding is lower in children than adults due to decreased total serum protein and albumin levels. As a result, the amount of “free” drug is increased in children. Hepatic metabolism is not fully developed in neonates. Clearance of hepatically metabolized medications is reduced in infants under the age of 2 due to immature cytochrome P450 (CYP) enzyme function. Meanwhile, clearance is increased in children aged 2–6 due to larger liver mass relative to body size, resulting in requirement of more frequent doses. Hepatic clearance usually reaches adult levels during adolescence.
Renal function is decreased in infants relative to adults due to incomplete glomerular development, inadequate osmotic load, and low perfusion pressure, leading to decreased clearance for drugs that are primarily excreted by the kidneys. Glomerular filtration rate increases ...