Review of pharmacokinetics—developmental principles of absorption, distribution, metabolism, and elimination
Review of pharmacodynamics
Review of anesthesia-specific medications with a neonatal perspective
As one considers the anesthetic to be delivered to a neonatal patient, it is prudent to give special attention to the ontogeny that will affect this plan. Neonates are children typically defined as age birth to 1 month. However, if born prematurely, as early as 24 weeks, this “neonatal” period is extended. Since neonates are not simply small adults, one must review the developmental aspects of pharmacokinetics and pharmacodynamics prior to administering anesthesia.
The emphasis on a neonatal tailored anesthetic originates from the very basic facts. Start with growth and maturation. Compared with adults, neonates have larger heads, shorter extremities, and larger torsos. Their skin as a vital organ accounts for a much larger percentage of body weight playing a significant role in pharmacokinetics. The rest of their organs are immature in function affecting a drug’s ultimate action. With advances in neonatal critical care, infants are born at birth weight of 500 g and gestational age of 24 weeks creating a different physiologic state than previously seen.
When caring for a premature infant, a clinician must respect developmental nuances that make essential a thorough review of neonatal pharmacology prior to anesthetic administration. All infants, but especially premature ones, undergo rapid developmental changes in the postnatal period, which affect each aspect of pharmacokinetics. Pharmacokinetics refers to the disposition of a drug in the body and the processes that affect its course. These processes include drug absorption, distribution, metabolism, and elimination. We will review each process through the neonatal perspective. Fundamental parameters common among these processes include volume of distribution (Vd), clearance, and half-life.1
Vd is a concept used to define the volume required to contain the total amount of a drug at a concentration equal to that in plasma. This “volume” is affected by hydrophilicity and lipophilicity. When a drug is highly water-soluble, it will have a small Vd because it must remain in the intravascular space only. Conversely, when a drug is lipophilic, it is distributed to the entire body and its Vd is much larger. Neonates are considered to have a much larger volume of distribution for hydrophilic drugs compared to a smaller volume of distribution for lipophilic drugs.
Clearance is the organ’s ability to clear or eliminate a drug from an amount of fluid (blood or plasma). This is a concept that will be further elaborated in the section on elimination. This capability is also affected by the eliminating organ’s maturity, whether it will be the liver or the kidney.
Half-life is the time required for half the amount of a drug in the blood to be removed from the body2