Uptake and distribution: infant vs. adult

Infant’s Physiology

• Pediatric intravascular and extracellular fluid compartments are relatively larger than adults
• Hepatic biotransformation pathways are immature in neonates and young infants
• Protein binding is decreased
• Metabolic rate is higher than adults
• Infants have proportionately higher total body water than adults (70-75% vs. 50-60%) secondary to relatively higher fat content and smaller muscle mass.

Inhaled anesthetics

Infants have higher alveolar ventilation and lower FRC compared to adults. This higher minute ventilation-to-FRC ratio along with higher blood flow to vessel rich organs leads to rapid rise in alveolar concentration, speeding induction. MAC requirements are highest at six months (except for sevoflurane, which are highest at birth and decrease at all age groups). This is why Neonatal Uptake is Faster (Barash).

Pulmonary

Higher ratio of MV to FRC (FRC is low thus gas concentrations rise quickly). Lower blood:gas partition coefficient in infants.

Cardiovascular

Greater cardiac output: More cardiac output goes to vessel-rich organs

Intravenous anesthetics

Higher total body water leads to larger volume of distribution per unit weight for most drugs. Smaller muscle mass prolongs the clinical termination of action by redistribution to muscle for drugs like thiopental and fentanyl. Neonates and young infants have decreased protein binding for thiopental and bupivacaine. For the former this results in increased potency and lower dose requirements; for the latter it may increase likelihood of systemic toxicity. The larger volume of distribution of infants results in higher dose requirements for propofol. Children also have shorter elimination half-lives and higher plasma clearance for propofol, resulting in faster emergence, particularly after infusions. As discussed above, the same principles apply to thiopental (note that in contrast to infants, neonates are more sensitive to barbiturates because of decreased protein binding and impaired ability to clear the drug).

Opioids

More potent in neonates and young infants, perhaps because they cross the blood brain barrier more readily in the very young. Respiratory centers may also be more sensitive. Older infants and children have high rates of biotransformation and elimination of opioids secondary to high hepatic blood flow, necessitating earlier re-dosing.

Muscle relaxants

All generally have shorter onset times because of shorter circulation times than adults. Infants require higher doses of succinylcholine because of the larger volume of distribution. Neonates and young infants have a large volume of distribution for the nondepolarizing relaxants, but are more sensitive to their effects because of immature neuromuscular junctions. These effects tend to cancel each other out, making doses generally the same as for adults. For most patients, duration of nondepolarizers tends to be slightly longer.

A few reminders about infants when considering pharmacology: 1) pediatric intravascular and extracellular fluid compartments are relatively larger than adults 2) hepatic biotransformation pathways are immature in neonates and young infants 3) protein binding is decreased 4) metabolic rate is higher than adults 5) infants have proportionately higher total body water than adults (70-75% vs. 50-60%) secondary to relatively higher fat content and smaller muscle mass.

Inhaled anesthetics: Infants have higher alveolar ventilation and lower FRC compared to adults. This higher minute ventilation-to-FRC ratio along with higher blood flow to vessel rich organs leads to rapid rise in alveolar concentration, speeding induction. MAC requirements are highest at six months (except for sevoflurane, which are highest at birth and decrease at all age groups).

Why Neonatal Uptake is Faster (Barash, p. 1191)

Pulmonary

Higher ratio of MV to FRC (FRC is low thus gas concentrations rise quickly)

Lower blood:gas partition coefficient in infantsCardiovascular

Greater cardiac output

More cardiac output goes to vessel-rich organs

Intravenous anesthetics: Higher total body water leads to larger volume of distribution per unit weight for most drugs. Smaller muscle mass prolongs the clinical termination of action by redistribution to muscle for drugs like thiopental and fentanyl. Neonates and young infants have decreased protein binding for thiopental and bupivacaine. For the former this results in increased potency and lower dose requirements; for the latter it may increase likelihood of systemic toxicity.

The larger volume of distribution of infants results in higher dose requirements for propofol. Children also have shorter elimination half-lives and higher plasma clearance for propofol, resulting in faster emergence, particularly after infusions. As discussed above, the same principles apply to thiopental (note that in contrast to infants, neonates are more sensitive to barbiturates because of decreased protein binding and impaired ability to clear the drug).

Opioids: more potent in neonates and young infants, perhaps because they cross the blood brain barrier more readily in the very young. Respiratory centers may also be more sensitive. Older infants and children have high rates of biotransformation and elimination of opioids secondary to high hepatic blood flow, necessitating earlier re-dosing.

Muscle relaxants: All generally have shorter onset times because of shorter circulation times than adults. Infants require higher doses of succinylcholine because of the larger volume of distribution. Neonates and young infants have a large volume of distribution for the nondepolarizing relaxants, but are more sensitive to their effects because of immature neuromuscular junctions. These effects tend to cancel each other out, making doses generally the same as for adults. For most patients, duration of nondepolarizers tends to be slightly longer.