School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA
There are 4 steps that a given medication undergoes as it is administered: absorption, distribution, metabolism, and elimination. In the neonate most physiological processes are incompletely developed, and thus every step of the therapeutic pathway is influenced.
Oral absorption is hampered by increased gastric pH during the first days of life, decreased blood flow to the gastrointestinal tract during the first 2 weeks of life, spitting up or vomiting the medication, and diarrhea. During the neonatal period SC and IM administration of medications is unpredictable, as there is decreased peripheral blood flow and decreased muscle activity.
Distribution is dependent on the volume of distribution. There is increased body water content and decreased fat content in puppies and kittens, and their surface areas in relation to the body sizes are larger than those in adults. Thus, medications that are water-soluble may need to be given at a higher dose in young puppies and kittens to achieve the desired serum concentrations. On the other hand, drugs that are fat soluble may need to be given at lower doses which is particularly important for anesthetic drugs that tend to "disappear" into the brain (one of the larger masses of fat in the neonate and young pediatric patient). Plasma protein concentrations are also lower in pediatric patients. Drugs that are protein bound will saturate the system quicker than those that are not, and their concentrations may need to be adjusted to achieve the desired plasma concentration. In neonatal patients, the blood brain barrier may still be open and the mechanisms for removing potentially toxic substances are not developed resulting in undesired accumulation in the CNS.
Liver and kidney are immature at birth and some of the processes are not fully developed until 6 months of age. Therefore, drug data sheets should be carefully reviewed to determine a given drug's dependence on hepatic or renal metabolism and elimination.
When considering anesthesia, the pediatric patient loses heat at a higher rate than an adult (increased body surface to size ratio) and thus needs to be kept warm at all times. Due to higher oxygen consumption in the pediatric patient, respiratory rates may need to be elevated but inhalant overpressure should be avoided at all cost. Low blood pressure, high water content, and overall small volumes in the young pediatric patient impede circulation. Puppies and kittens have a lower ability to increase stroke volume in response to IV fluids. However, due to increased body water content, fluid requirements are higher and will therefore need to be administered judiciously. Young pediatric patients are unable to regulate serum glucose levels well. Therefore, they should not be excessively fasted.
Understanding physiological differences in pediatric patients is a prerequisite to formulating age appropriate therapy and anesthesia.