Pharmacokinetics and pharmacodynamics of medication in asphyxiated newborns during controlled hypothermia. The PharmaCool multicenter study

• DOI: 10.1186/1471-2431-12-45
• Publication Date: 2012-04-19T12:14:28Z
• Authors: Timo R de Haan; Yuma A Bijleveld; Johanna H van der...; Floris Groenendaal; Marcel PH van den...; Carin MA Rademaker; Henrica LM van St...; Mirjam M van Weis...; Jeroen R Vermeulen; Peter H Dijk; Jeroen Dudink; Monique Rijken; Arno van Heijst; Koen P Dijkman; Danilo Gavilanes; Anton H van Kaam; Martin Offringa; Ron AA Mathôt
• Keywords: Perinatal asphyxia; Pharmacodynamics; Neonatal Encephalopathy

In the Netherlands, perinatal asphyxia (severe oxygen shortage) necessitating newborn resuscitation occurs in at least 200 of 180-185.000 newly born infants per year. International randomized controlled trials have demonstrated an improved neurological outcome with therapeutic hypothermia. During hypothermia neonates receive sedative, analgesic, anti-epileptic and antibiotic drugs. So far little information is available how pharmacokinetics (PK) pharmacodynamics (PD) these drugs are influenced by post multi organ failure metabolic effects cooling treatment itself. As a result, evidence based dosing guidelines lacking. This multicenter observational cohort study was designed to answer question influences distribution, metabolism elimination commonly used neonatal intensive care.Multicenter study. All term treated for Hypoxic Ischemic Encephalopathy (HIE) resulting from all ten Dutch Neonatal Intensive Care Units (NICUs) will be eligible this rewarming blood samples taken indwelling catheters investigate concentrations several antibiotics, analgesics, sedatives For each individual drug population PK characterized using Nonlinear Mixed Effects Modelling (NONMEM). It investigated clearance volume distribution also taking maturation neonate into account. Similarly, integrated PK-PD models developed relating time course concentration pharmacodynamic parameters such as successful seizure treatment; pain assessment infection clearance.On basis derived application during treatment. The results lead hypothermic patients. Results published national web paediatric formulary, peer reviewed journals international references.NTR2529.