Pedi and Aged 2024 Presentation Slides.pptx

The Use of Drugs in Pediatric and Aged Patients DNAP 707 Amy Wielar, DNAP, CRNA Department of Nurse Anesthesia College of Health Professions Virginia Commonwealth University [email protected] Most Often Manifested As: Exaggerated drug effects Cumulative drug effects Prolonged elimination half-time D...

The Use of Drugs in Pediatric and Aged Patients DNAP 707 Amy Wielar, DNAP, CRNA Department of Nurse Anesthesia College of Health Professions Virginia Commonwealth University [email protected] Most Often Manifested As: Exaggerated drug effects Cumulative drug effects Prolonged elimination half-time Due to: Increased amount of available drug Increased volume of distribution Decreased clearance 05/03/2024 2 Remember...Pharmacokine tics What the body does to the drug o Absorption o Distribution o Metabolism o Excretion Remember...Pharmacodyn amics What the drug does to the body. o The study of the biochemical, physiologic, and molecular effects of drugs on the body and involves receptor binding (including receptor sensitivity), post-receptor effects, and chemical interactions. Drug Use in Pediatrics 05/03/2024 5 Choice of Drugs in Pediatric Patients is Affected by the following: 05/03/2024 Significant physiologic differences Differences in anesthetic requirement Differences in response to muscle relaxants Altered pharmacokinetics (Distribution and elimination) 6 Definition Neonate – newborn to one month of age (premature or full term) Infant – 1-12 months Child – 1 year to puberty 05/03/2024 7 Growth and Developm ent in 1st Several Months 05/03/2024 Rapid growth and development of organ function Circulatory and ventilatory adaptations Thermoregulation If patients are hypothermic the anesthetic will last longer because of reducing metabolic rate. 8 Shifts in body fluid compartments Skeletal muscle mass developing Development of hepatic enzymes (responsible for metabolism) Maturation of renal function 05/03/2024 9 By the time an infant is 3 months of age the major tasks of maturation have been accomplished Over the next 1-1.5 years they are/are NOT transformed into *Mini Adults ?!?!* 05/03/2024 10 Comparison of Body Compartments Percentage (%) of Body Weight Premature Infant Child Adult Total Body Water 80-90 73 65-70 60 Extra Cellular Fluid 50-60 44 30 15-20 Blood Volume 8-10 7 Intracellular Water 25 33 Muscle Mass 15 20 50 Fat 3 12 18 05/03/2024 40 40 11 Volume of Distribution in Neonates and Infants Affects dose and elimination Total body water content and ECV increased (40% vs 20%) By 18-24 months ECV is similar to adults Larger volume of distribution of watersoluble drugs and relatively smaller volume of distribution of lipid soluble drugs in neonates and infants 05/03/2024 12 Pharmacodynamics Lowered anesthetic requirements in neonates related to: Immaturity of the CNS Elevated levels of progesterone and beta endorphins 05/03/2024 13 Immature Blood Brain Barrier May increase the sensitivity of the neonate to the effects of barbiturates and opiates Membrane permeability and myelination that counteracts drug passage not fully developed 05/03/2024 14 Protein Binding Decreased in Infants Higher plasma levels of unbound and active drug Increased pharmacologic effect 05/03/2024 15 Neonatal serum albumin is low Albumin has lower binding capacity and affinity for drugs Free fatty acids, bilirubin, maternal steroids, and medications may reduce protein binding 05/03/2024 16 Twice the amount of Morphine and thiopental accumulates in the CNS of a neonate due to decreased protein binding and less effective blood-brain barrier. 05/03/2024 17 Pharmacokinetics Diminished hepatic and renal clearance in neonates and infants, due to immature liver and kidneys This can cause prolonged effects of most drugs Hepatic and renal functions increase to adult levels by 5-6 months of age GFR of neonates is 40% of adult; less than 34 weeks gestation even less. This is due to incomplete glomerular development. Later in childhood, metabolism may exceed adult levels due to a larger liver mass relative to the body. 05/03/2024 What about glycogen stores? 18 Pharmacokinet ics  Enzymes that oxidize (thiopental, methohexital, narcotics and muscle relaxants), reduce, hydrolyze, and conjugate (morphine, barbiturates) drugs are present but relatively inactive  Immature P450 system in children under 2 years.  Neonate have decreased ability to metabolize barbiturates 05/03/2024 19 Pharmacokinet ics Conjugation develops rapidly and increases 30-fold during first 3 weeks of life  Short acting barbiturates (methohexital, thiopental) have more rapid uptake, effect more quickly achieved and metabolism, excretion and recovery more prompt in infants and children (because of proportionately greater amount of vessel-rich tissue) 05/03/2024 20 Children between 5-15 Require higher doses of IV drugs for induction of anesthesia Elimination halftimes may be shorter than adults due to more rapid hepatic clearance Recovery after larger or repeated doses may be more rapid 05/03/2024 21 May see prolonged duration of action due to decreased hepatic and renal function, in the premature, neonates and infants Hoffmann elimination and ester hydrolysis are not affected by age related effects on renal and hepatic function Antagonism reliable 05/03/2024 22 Incidence of bradycardia, hypotension and cardiac arrest during induction of inhalation anesthesia is higher in infants and children due to: 05/03/2024 Sensitivity of the cardiovascular system Age-related differences in uptake Anesthetic requirements 23 Sensitivity of Cardiovascular System Contractile components immature; less capable of generating a response to an increase in stroke volume Neonates dependent on HR for cardiac output and blood pressure Decreased ability to vasoconstrict in response to hemorrhage 05/03/2024 24 Increase in O2 Consumption 6ml/kg which is 2x an adult Tidal volume on a weight basis does not differ Only way to accommodate the increased O2 consumption is to increase respiratory rate 05/03/2024 25 Alveolar ventilation is doubled Alveolar ventilation relative to FRC two to three times (5:1) greater than adults (1.5:1) = MORE RAPID UPTAKE of Inhalation Anesthetics 05/03/2024 27 Increased Cardiac Output Normally increased CO delays equilibration of alveolar to inspired anesthetic partial pressures An increased CO in infants actually speeds the equilibration of partial pressures Faster circulation times for delivering and removing drugs to and from site of action 05/03/2024 28 This Paradoxical Effect is Attributed to: Vessel-rich group (i.e.. Brain, liver, kidneys, and endocrine glands) represent 18% of body weight in infants compared to 8% in adults. Compounded by limited muscle and fat mass in infant 05/03/2024 29 Lower solubility of inhalational anesthetics in blood and tissues in neonate compared to adult speeds equilibration of alveolar to inspired anesthetic partial pressures 05/03/2024 30 Effect of Shunting A right to left shunt slows the uptake More pronounced with less soluble anesthetics Sevoflurane may better preserve cardiovascular homeostasis than halothane Removal of anesthetic may be prolonged 05/03/2024 31 Effect of Left-to-Right Shunt Variable Large (>80%) left-to-right shunt increases the rate of uptake of anesthetic from FRC to arterial blood Smaller shunts (