PhD Defense: Protecting critically ill patients from drug-related harm and adverse neuropsychiatric outcomes

Patients admitted to the intensive care unit (ICU) are critically ill and depend on life-sustaining therapies. To deliver these therapies, they are exposed to multiple potent intravenous drugs, which places them at high risk of drug-related harm and adverse outcomes. This thesis aimed to improve outcomes of critically ill patients by protecting them from two specific risks: harm caused by medication and adverse neuropsychiatric outcomes such as delirium, post-traumatic stress, anxiety and depression.
The first part of the thesis examined interventions across the entire medication use process in adult, pediatric and neonatal ICUs. A clinical decision support system tailored to the pediatric ICU significantly reduced prescribing errors. Replacing aseptically prepared ready-to-administer syringes with prefilled sterilized syringes in an adult ICU reduced drug waste from 31% to 5%, lowering harm at the system level through more sustainable care. In the neonatal ICU, compatibility testing showed that alprostadil and vancomycin can safely be co-administered with parenteral nutrition, whereas insulin aspart and lidocaine cannot without an in-line filter. A case report of severe benzylpenicillin neurotoxicity provided a plausible toxicity threshold to guide therapeutic drug monitoring.
The second part focused on neuropsychiatric outcomes. Deep sedation with midazolam, alone or combined with propofol, was associated with a higher risk of ICU delirium than propofol alone. Glucocorticoid exposure during ICU admission was not associated with post-traumatic stress one year later, but interleukin-6 inhibitors in critically ill COVID-19 patients were associated with fewer psychiatric symptoms.
Together, these findings support a safer, more sustainable ICU.