ArticleClinical pharmacology and therapeutics2021
Tolerance to Opioid-Induced Respiratory Depression in Chronic High-Dose Opioid Users: A Model-Based Comparison With Opioid-Naïve Individuals.
Article in Clinical pharmacology and therapeutics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05338632 (Reversal of Opioid-induced Respiratory Depression With Opioid Antagonists - a Study in Opioid naïve Individuals and Chronic Opioid Users Under Real-life Conditions), which is not on this map. Cited by 37 papers, 2 of them syntheses that pooled it.
What it found
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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.
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.
Reversal of Opioid-induced Respiratory Depression With Opioid Antagonists - a Study in Opioid naïve Individuals and Chronic Opioid Users Under Real-life Conditions
Who cites it
37 citing papers in PubMed, 2 syntheses or guidelines pooled it, 54 citations in OpenAlex.
- Oxygen Saturation Thresholds for Opioid-induced Respiratory Depression: A Systematic Review.The western journal of emergency medicine · 2026Pooled it
- Sensitivity and specificity of International Classification of Diseases algorithms (ICD-9 and ICD-10) used to identify opioid-related overdose cases: A systematic review and an example of estimation using Bayesian latent class models in the absence of gold standards.Canadian journal of public health = Revue canadienne de sante publique · 2024Pooled it
- Time Course of Reversal of Fentanyl-Induced Respiratory Depression in Healthy Subjects by Intramuscular Nalmefene and Intramuscular and Intranasal Naloxone.Journal of clinical pharmacology · 2025Trial
- Intranasal Naloxone Repeat Dosing Strategies and Fentanyl Overdose: A Simulation-Based Randomized Clinical Trial.JAMA network open · 2024Trial
- Trial
- Effects of opioids and stimulants on the respiratory system.European respiratory review : an official journal of the European Respiratory Society · 2026Review
- Fentanyl purity and overdose decline: A reexamination of geographic trends.Science advances · 2026Article
- Fentanyl Purity and Overdose Decline: A Reexamination of Geographic Trends.medRxiv : the preprint server for health sciences · 2026Article
- Modeling Supports Combinatorial Effects Between Pharmacological and Non-Pharmacological Interventions to Prevent Opioid-Induced Cardiac Arrest.Clinical pharmacology and therapeutics · 2026Article
- Double Jeopardy: Risks of Opioid-Benzodiazepine Co-prescription in Older Adults with Gastrointestinal Cancer.Annals of surgical oncology · 2026Article
- Intranasal Naloxone Reversal of Opioid-induced Respiratory Depression in Opioid-naive Individuals and Self-reported Daily Opioid Users.Anesthesiology · 2026Article
- A model to simulate cardio-respiratory responses to fentanyl analgesia after traumatic injury.Frontiers in physiology · 2026Article
- The influence of magnesium ions on the electrophysiological, analgesic, and BDNF-induced neuromodulation of morphine effects in diabetic rats.Frontiers in pharmacology · 2026Article
- Relationship between morphine rescue dose and respiratory safety during breakthrough cancer pain in lung cancer patients treated with high-dose opioids.American journal of cancer research · 2026Article
- Naloxone reversal of fentanyl-induced respiratory depression versus naloxone-induced precipitated withdrawal: anFrontiers in pharmacology · 2026Article
- Design, Syntheses, and Pharmacological Evaluations of Core Ring Expanded Fentanyl Analogues as Potential Counteracting Agents Against Fentanyl Induced Respiratory Depression.Journal of medicinal chemistry · 2025Article
- "We knew it was coming: we didn't act" perspectives from people who use drugs and substance use workforce on the impact of delays in implementation of the supervised injection facility and drug checking interventions.Harm reduction journal · 2025Article
- Divergent ventilatory responses during opioid-induced respiratory depression in response to repeated fentanyl use.American journal of physiology. Lung cellular and molecular physiology · 2025Article
- Treating Opioid Use Disorder and Opioid Withdrawal in the Context of Fentanyl.Annual review of clinical psychology · 2025Review
- A pH-sensitive opioid does not exhibit analgesic tolerance in a mouse model of colonic inflammation.British journal of pharmacology · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chronic opioid consumption is associated with addiction, physical dependence, and tolerance. Tolerance results in dose escalation to maintain the desired opioid effect. Intake of high-dose or potent opioids may cause life-threatening respiratory depression, an effect that may be reduced by tolerance. We performed a pharmacokinetic-pharmacodynamic analysis of the respiratory effects of fentanyl in chronic opioid users and opioid-naïve subjects to quantify tolerance to respiratory depression. Fourteen opioid-naïve individuals and eight chronic opioid users received escalating doses of intravenous fentanyl (opioid-naïve subjects: 75-350 µg/70 kg; chronic users: 250-700 µg/70 kg). Isohypercapnic ventilation was measured and the fentanyl plasma concentration-ventilation data were analyzed using nonlinear mixed-effects modeling. Apneic events occurred in opioid-naïve subjects after a cumulative fentanyl dose (per 70 kg) of 225 (n = 3) and 475 µg (n = 6), and in 7 chronic opioid users after a cumulative dose of 600 (n = 2), 1,100 (n = 2), and 1,800 µg (n = 3). The time course of fentanyl's respiratory depressant effect was characterized using a biophase equilibration model in combination with an inhibitory maximum effect (E
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Registered trials
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.