Opioid use in the United States and abroad is an endemic part of society with yearly increases in overdose rates and deaths. As rates of overdose incidence increase, the use of the safe and effective reversal agent, naloxone, in the form of a nasal rescue spray is being fielded and used by emergency medical technicians (EMTs) at a greater and greater rate. Despite advances in the deployment of these rescue products, deaths are continuing to increase. There is evidence that repeated dosing of a naloxone nasal spray (such as Narcan) is becoming more common due to the amount and type of opiate being administered. Despite the benefits of naloxone related to opioid reversals, we lack repeated dosing guidelines as a function of opiates and the amount the patient has taken. Goal-directed rescue dosing, where respiratory markers such as oxygen saturation or end-tidal carbon dioxide, are being used as an indication of the patient's recovery. These rescue methods require time, training, and understanding by the EMT to administer with most patients receiving naloxone doses with no follow-up or additional monitoring. To measure repeat dosing guidelines, we construct a whole-body model of the pharmacokinetics and dynamics of an opiate, fentanyl on respiratory depression. We then construct a model of nasal deposition and administration of naloxone to investigate repeat dosing requirements for large overdose scenarios. We demonstrate that naloxone is highly effective at reversing the respiratory symptoms of the patient and recommend dosing requirements as a function of the fentanyl amount administered. By designing the model to include circulation and respiration we investigate physiological markers that may be used in goal-directed therapy rescue treatments.

Data was collected via the BioGears physiology engine. Python code used to generate data is included in the zip.