title: Pharmacodynamics - Neonatal Intensive Care Drug Manual
text: Pharmacodynamics: Smits et al 2016 [15] in a dose-finding study in 50 neonates undergoing (semi-)the INSURE procedure reported the propofol ED50 (i.e. effective dose for 50% of patients) for successful intubation for preterm neonates <10 days of age varied between 0.713 and 1.350 mg/kg. Clinical recovery was not attained at the end of the 21-minute scoring period. Mean arterial blood pressure showed a median decrease between 28.5% and 39.1% from baseline with a brief decrease in peripheral and regional cerebral oxygen saturation. Summary: 67% of propofol clearance variability in neonates can be explained by PMA and PNA with very fast maturation of clearance in neonatal life. Propofol doses should be reduced in early (PNA of <10 days) life. 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.
  Safety:
  Low dose propofol bolus 1 mg/kg results in moderate reductions in blood pressure with a brief decrease in peripheral and regional cerebral oxygen saturation.[15] Higher doses (mean 3.3 mg/kg) were associated with hypotension in 39% of infants undergoing endotracheal intubation.[5] In infants and children undergoing procedures in Paediatric Critical Care Units, transient respiratory depression and hypotension were associated with propofol delivered by continuous infusion after a loading bolus dose.[16]
  Propofol infusion syndrome (PRIS) is a sudden onset of treatment-resistant bradycardia leading to asystole, combined with at least one of the following symptoms: lipaemic plasma, clinically enlarged or fat infiltrated liver, metabolic acidosis or rhabdomyolysis. The syndrome was associated with long-duration >48 hours, high-dose >4 mg/kg/h propofol infusions in children under 12 years.[10, 17]
  In animals, all currently available anaesthetics and sedatives that have been studied, such as ketamine, midazolam, diazepam, clonazepam, propofol, pentobarbital, chloral hydrate, halothane, isoflurane, sevoflurane, enflurane, nitrous oxide and xenon, have been demonstrated to trigger widespread neurodegeneration in the immature brain.[18] No clinical trials of propofol analgesia/sedation report the neurodevelopmental outcome of newborns. In adults, compared with sevoflurane-based general anaesthesia, propofol-based general anaesthesia might decrease the incidence of delayed neurocognitive recovery in older adults after major cancer surgery.[19]
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