The last decades it is increasingly recognized that acute as well as chronic postoperative pain is an important problem. Treatment and prevention of postoperative pain is a challenge, especially in... Show moreThe last decades it is increasingly recognized that acute as well as chronic postoperative pain is an important problem. Treatment and prevention of postoperative pain is a challenge, especially in special patient populations where there is only limited guidance on how to optimally use opioids. In this thesis we focused on the perioperative use of opioids in three different populations. First, the influence of the opioids remifentanil versus fentanyl on acute and chronic postoperative pain was investigated in adult cardiac surgery patients. Second, pharmacodynamic modelling methods were applied to analyze the postoperative use of morphine in children after cardiac surgery. Finally, a pharmacokinetic model was developed to investigate the influence of obesity on the pharmacokinetics of morphine and its metabolites. Pain remains a complex puzzle among biological, psychological, behavioral and social-cultural factors. The high inter-individual variation in all of these factors results in postoperative pain still being a major issue while the ultimate goal is to stay without pain after a surgical procedure. Therefore, the answer to the question: “Does it still hurt?” is: YES unfortunately. This thesis adds pieces to this complex puzzle by focusing on the use of opioids in three different patient populations. Show less
Although ketamine can be considered to be an “old” drug, a definitive model explainingketamine pharmacokinetics for a wide range of patient populations, dosing regimens and ketamine administrations... Show moreAlthough ketamine can be considered to be an “old” drug, a definitive model explainingketamine pharmacokinetics for a wide range of patient populations, dosing regimens and ketamine administrations forms is lacking. Currently, a large number of ketamine population pharmacokinetic models is published. However, the large number of ketamine pharmacokinetic models based on data from all types of study populations,ketamine dosing regimens and administration forms, can prove to become a serious challenge for clinical decision makers, since it may not always be easy to pick the model that best suits their patient population. In this thesis, we focus on unraveling the complex pharmacokinetics and pharmacodynamics that characterize ketamine, in order to get a step closer to a final “all encompassing” pharmacokinetic-pharmacodynamic model. For the pharmacodynamic outcomes, we especially focus on the effects of ketamine on neuropathic pain, nociceptive pain (pressure pain) and psychedelic outcomes. Show less
