Do the pharmacokinetics and pharmacodynamics of anesthetic drugs differ in this population as compared with adults?

Do the pharmacokinetics and pharmacodynamics of anesthetic drugs differ in this population as compared with adults?

Pharmacokinetics refers to the changes in drug concen-tration in blood over time. In children, especially neonates and infants, pharmacokinetics is very different from that in adults. These differences are due to many factors including differences in the size of the fluid compartments, smaller muscle mass and fat stores, and the immature or absent hepatic enzyme systems necessary for metabolism of certain drugs. These hepatic enzyme systems mature at different rates; therefore the pharmacokinetics of all drugs do not progress toward the adult model at the same pace. The kidney is where most drugs or their metabolites are eliminated. The renal clearance of many drugs is altered because of the decreased GFR and other immature aspects of renal function in the neonate, such as secretion and resorption.

Neonates and infants have a faster uptake of inhaled anesthetics, which results in a more rapid induction of gen-eral anesthesia. There are several factors that contribute to this: the increased V_A/FRC ratio and the greater percentage of cardiac output that goes to the brain, which is part of the vessel-rich group. The minimum alveolar concentration (MAC) for the inhaled agents in a full-term infant is the same as for an adult. It is decreased in the preterm infant and increases until about 6 months of age. After 6 months, the MAC begins to decrease toward the adult level.

The respiratory and cardiovascular effects of inhaled agents are similar in adults and children. Respiratory and myocardial depression occur in a dose-dependent fashion. However, the blood pressure tends to decrease more in neonates than in adults. This may be due to the immature baroreceptors that prevent an appropriate compensatory response. Any anesthetic that decreases heart rate or car-diac contractility will cause hemodynamic instability until the child’s cardiac output is no longer rate-dependent.

In conclusion, the pharmacology of anesthetic agents changes as a neonate becomes an infant, an infant becomes a child, and a child becomes an adult. As a result, drug dosages must be individualized to take into account the changes that occur in the many pharmacokinetic parame-ters as the neonate grows.