DOI: 10.5061/dryad.3tx95x6pr
title: Whole-body physiology model to simulate respiratory depression of fentanyl and associated naloxone reversal

description: 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.
description: Data was collected via the BioGears physiology engine. Python
 code used to generate data is included in the zip.
description: # Whole-body physiology model to simulate respiratory depression of
 fentanyl and associated naloxone reversal
 [https://doi.org/10.5061/dryad.3tx95x6pr](https://doi.org/10.5061/dryad.3tx95x6pr) Experimental and simulated data to investigate respiratory depression associated with fentanyl overdose and naloxone reversal administration. ## Description of the data and file structure The data, once unzipped is in the following structure: * Data * Naloxone PK data * /reversal * /RepeatExperiment - Naloxone reversal data (units included in files) with Python notebook to generate figures * /bolus - Fentanyl bolus data * /Opiod - Experimental fentanyl data, extracted from cited publications and notebook to generate figures * /modelData - Experimental and simulated data for CO2 responses and respiratory depression * /StepInfusionResults - Figures from a single simulated experiment ## Sharing/Access information The data is also available on GitHub (link in the Related Works section). ## Code/Software All data was generated using the BioGears physiology engine. The HowTo file to generate all reversal scenarios is included in the core engine repository at the GitHub site. All Python notebooks are included in this data to re-create all figures in the manuscript.