• Gerdien A Zeilmaker, Paula Pokorna, Paola Mian, Enno D Wildschut, Knibbe Catherijne A J CAJ d Division of Pharmacology , LACDR, Leiden University , Leiden , The Netherlands. , Krekels Elke H J EHJ d Division of Pharmacology , LACDR, Leiden University , Leiden , The Netherlands., Karel Allegaert, and Dick Tibboel.
• a Intensive Care and Department of Pediatric Surgery , Erasmus MC-Sophia Children's Hospital , Rotterdam , The Netherlands.
• Expert Opin Drug Metab Toxicol. 2018 Apr 1; 14 (4): 417-428.

IntroductionAdequate postoperative analgesia in pediatric patients in the intensive care unit (ICU) matters, since untreated pain is associated with negative outcomes. Compared to routine postoperative patients, children undergoing hypothermia (HT) or extracorporeal membrane oxygenation (ECMO), or recovering after cardiac surgery likely display non-maturational differences in pharmacokinetics (PK) and pharmacodynamics (PD). These differences warrant additional dosing recommendations to optimize pain treatment. Areas covered: Specific populations within the ICU will be discussed with respect to expected variations in PK and PD for various analgesics. We hereby move beyond maturational changes and focus on why PK/PD may be different in children undergoing HT, ECMO or cardiac surgery. We provide a stepwise manner to develop PK-based dosing regimens using population PK approaches in these populations. Expert opinion: A one-dose to size-fits-all for analgesia is suboptimal, but for several commonly used analgesics the impact of HT, ECMO or cardiac surgery on average PK parameters in children is not yet sufficiently known. Parameters considering both maturational and non-maturational covariates are important to develop population PK-based dosing advices as part of a strategy to optimize pain treatment.

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