Inspire or expire: a matter of life or death

Lemmen, M.A. van (2025)

Doctoral Thesis

The main focus of this thesis is opioid-induced respiratory depression. The research first explores the use of machine learning to detect the early warning signs of respiratory failure before it becomes fatal. It then rigorously evaluates the standard antidote, naloxone, reviewing its limitations against potent synthetic opioids. A key finding from its human trials is that intramuscular naloxone works faster and requires fewer doses to reverse severe, fentanyl-induced apnea compared to the common intranasal spray. Finally, the thesis explores mechanism-agnostic respiratory stimulants, drugs that could reverse respiratory depression from any substance, such as Danavorexton.

• Opioid-induced respiratory depression
• Naloxone
• Opioid antagonists
• Opioid crisis
• Fentanyl

• All authors: Lemmen, M.A. van
• Supervisor: Dahan, A.
• Co-supervisor: Velzen, M. van; Schrier, R.M. van der
• Committee: Kraaijvanger, A.M.M.; Bouvy, M.L.; Rathmell, J.P.; Sarton, E.Y.
• Qualification: Doctor (dr.)
• Awarding Institution: Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University
• Date: 2025-12-05
• ISBN (print): 9789465227078
• DOI: doi:10.60602/c57m-k535