This thesis assesses multiple monitoring modalities that can be used in the peri-operative period to reduce respiratory adverse events associated with the use of anesthetic drugs, particularly... Show moreThis thesis assesses multiple monitoring modalities that can be used in the peri-operative period to reduce respiratory adverse events associated with the use of anesthetic drugs, particularly opioids and neuromuscular blocking drugs. Monitors of analgesia, neuromuscular block and ventilation are studied in both healthy volunteers and surgical patient populations to assess proof of concept, efficacy, feasibility of clinical use and effect on clinical outcomes. Show less
The overarching clinical aim of this thesis was to improve pharmacological pain management by characterizing the pharmacodynamics of analgesics. To achieve this aim, available advanced... Show moreThe overarching clinical aim of this thesis was to improve pharmacological pain management by characterizing the pharmacodynamics of analgesics. To achieve this aim, available advanced pharmacometric modelling approaches are used to maximize the information that can be obtained from the available clinical data. To address methodological gaps for pharmacodynamic analysis, we introduced two new model development tools, as well as two new pharmacodynamics modelling approaches for the characterization of iatrogenic withdrawal syndrome in children.In addition to expanding our pharmacodynamic knowledge, this work can increase the clinical applicability of existing pharmacokinetic models: knowing what drug concentrations will give desirable clinical outcomes, we can use pharmacokinetic models to evaluate if an analgesic dose regimen is likely to produce this concentration. The models developed in this thesis can serve as a starting point for further research into the pharmacodynamics of analgesics by extending these models to include additional patient populations or other analgesics. Moreover, the novel pharmacometric techniques that were introduced in this thesis can support future analyses in a variety of settings: repeated time-to-event data, iatrogenic withdrawal syndrome data, and composite clinical scale data. Show less
