Inter-individual variability in propofol pharmacokinetics in preterm and term neonates

Abstract

PMA and PNA contribute to the inter-individual variability of propofol clearance with very fast maturation of clearance in neonatal life. This implicates that preterm neonates and neonates in the first week of postnatal life are at an increased risk for accumulation during either intermittent bolus or continuous administration of propofol.

Prevention and Management of Procedural Pain in the Neonate: An Update

“…The clearance of propofol in the neonatal population is inversely related to postmenstrual age, with significant variability in its pharmacokinetics in preterm and term neonates. 104 It has also been associated with bradycardia, desaturations, and prolonged hypotension in newborn infants. 105 Limited experience with dexmedetomidine in preterm and term infants suggests that it may provide effective sedation and analgesia.…”

Preterm Versus Term Children: Analysis of Sedation/Anesthesia Adverse Events and Longitudinal Risk

“…There is considerable variability in both the pharmacokinetics and pharmacodynamics of this drug, especially in preterm neonates, which may in part explain the occurrence of apnea. 20,21 In addition, abnormal respiratory function frequently observed in the preterm population is complex and not completely understood. The immaturity of the respiratory and central nervous systems, altered carotid chemoreceptor responses to hypoxia and hyperoxia, numerous neurotransmitters, genetic predisposition, and laryngeal chemoreflexes are a few of the mechanisms that have been implicated in the development of apnea and respiratory abnormalities in the preterm infant.…”

“…5,[8][9][10][27][28][29][30][31][32] This fact has been attributed to the variation in pharmacokinetics and pharmacodynamics of sedative and anesthetic drugs and to the limited physiologic reserve in children <1 year of age. 20,21,32,33 We postulated that preterm children were more susceptible to experiencing adverse events at a younger age, but that the risk would decrease as they grew older owing to the increase in physiologic reserve that occurs with increasing age. The finding that a decrease in frequency of adverse events did not occur in formerly preterm patients as they reached adulthood was unexpected.…”

The allometric exponent for scaling clearance varies with age: a study on seven propofol datasets ranging from preterm neonates to adults

“…Neonates [17] Twenty-five cardiovascularly and respiratory stable neonates with a median of bodyweight of 2.82 (range 0.68-4.03) kg, post-natal age of 8 (1-25) days and gestational age of 37 (26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40) weeks were given an intravenous bolus dose of propofol (3 mg kg −1 ) for the elective removal of chest tubes, (semi)elective chest tube placement or endotracheal intubation.…”