Evidence map›Paper›PMID 41520183›Full record

ArticleClinical pharmacology and therapeutics2026

Modeling Supports Combinatorial Effects Between Pharmacological and Non-Pharmacological Interventions to Prevent Opioid-Induced Cardiac Arrest.

Bradlee Thrasher, John Mann, Anik Chaturbedi, Shilpa Chakravartula, Hamed Meshkin, Affan Affan, Alexander Galluppi, Ji Young Kim, Nigar Karimli, Yue Han and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Clinical pharmacology and therapeutics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Review
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Bradlee ThrasherDivision of Applied Regulatory Science, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, USA.ORCID 0000-0001-5877-7419
John MannDivision of Applied Regulatory Science, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, USA.
Anik ChaturbediDivision of Applied Regulatory Science, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, USA.ORCID 0000-0002-8114-5820
Shilpa ChakravartulaDivision of Applied Regulatory Science, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, USA.ORCID 0009-0003-1664-0977
Hamed MeshkinDivision of Applied Regulatory Science, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, USA.ORCID 0000-0001-7269-4687
Affan AffanDivision of Applied Regulatory Science, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, USA.ORCID 0000-0002-0666-7696
Alexander GalluppiDivision of Applied Regulatory Science, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, USA.ORCID 0000-0002-0788-4166
Ji Young KimDivision of Applied Regulatory Science, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, USA.ORCID 0009-0005-4062-8040
Nigar KarimliDivision of Applied Regulatory Science, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, USA.ORCID 0009-0000-8644-067X
Yue HanDivision of Applied Regulatory Science, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, USA.ORCID 0000-0001-7372-6724
Zachary DezmanDivision of Anesthesiology, Addiction Medicine, and Pain Medicine, Office of Neuroscience, Office of New Drugs, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, USA.ORCID 0000-0001-6405-724X
Jeffry FlorianDivision of Applied Regulatory Science, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, USA.ORCID 0009-0000-1984-8026
Zhihua LiDivision of Applied Regulatory Science, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, USA.ORCID 0000-0002-2772-0839

Funding

Intramural FDA HHS FD999999
6 · The paper itself

Abstract

Few studies have quantified the effects of non-pharmacological interventions (e.g., rescue breathing) in the setting of community opioid overdose. We extended a previously validated model for opioid antagonists by incorporating the mechanism of rescue breathing, and quantified combinatorial effects between rescue breathing and various formulations of naloxone under different fentanyl overdose scenarios in a virtual patient population suffering from opioid-induced respiratory failure. We defined successful reversal of an overdose as fewer than 5% of the virtual population experiencing cardiac arrest after intervention. Our model showed that timely rescue breathing reduced the naloxone dose needed for successful overdose reversal from greater than 8 mg (intranasal) to less than 2 mg (intramuscular) and extended the naloxone rescue window to 10 minutes under a median fentanyl intravenous overdose scenario. Administration of 4 mg naloxone intranasally reduced the duration of rescue breathing needed from 11 hours to 5 minutes under a median fentanyl transmucosal overdose scenario. High-quality (as delivered by well-trained rescuers), but not low-quality (as delivered by laypersons), rescue breathing could successfully rescue severe opioid overdose scenarios. Even in cases where virtual subjects survived without naloxone, 4 mg intranasal naloxone provided benefit by shortening the time to recovery of spontaneous. Our results highlight the importance of utilizing both pharmacological and non-pharmacological interventions in reversal of overdose.

Indexed as

Analgesics, OpioidFentanylHeart ArrestNaloxoneNarcotic AntagonistsOpiate OverdoseAdministration, IntranasalDrug OverdoseHumansRespiratory InsufficiencyAnalgesics, OpioidFentanylNaloxoneNarcotic Antagonists

Identifiers

PMID41520183
PMCPMC12962354

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.