# Treatment of Fentanyl Overdose-Induced Respiratory Failure by Low-Dose Dexmedetomidine

> **NIH NIH R61** · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · 2020 · $708,424

## Abstract

SUMMARY
The objective of our proposal is to demonstrate that the restoration of respiratory mechanics and of the
metabolism by low doses of the central alpha-2 agonist dexmedetomidine results in an increase in ventilation
and prevents the fatal outcome of an opioid overdose.
Death by opioid overdose is the consequence of an acute respiratory failure mediated by a direct and indirect
inhibition of the medullary respiratory neurons. This inhibition is associated with immediate and prolonged tetanic
contractions of the inspiratory and expiratory muscles and an increase in upper-airway resistance that impede
respiratory movements for hours. Opioid-induced muscle “rigidity” is produced via neurons in the locus coeruleus
and can be suppressed by central alpha-2 agonist agents. Our preliminary results, obtained in sedated and non-
sedated rats, show that infusion of low doses of the central alpha-2 agonist dexmedetomidine restores chest
wall compliance and suppresses the hypermetabolism produced by fentanyl-induced muscle rigidity, while
increasing minute ventilation.
The objective of our proposal is to demonstrate that administration of dexmedetomidine, after opioid exposure,
prevents a fatal outcome. If efficacy is demonstrated in rodents, we intend to pursue efficacy studies in a non-
anesthetized sheep model of fentanyl overdose. This model will allow us to establish the doses of
dexmedetomidine needed to produce a beneficial effect without sedation. The effects of intravenous and
intranasal dexmedetomidine will be examined. Our intention is to obtain, via 505(b)2 pathway, an FDA approval
for non-sedative doses of dexmedetomidine as a treatment of opioid overdose.

## Key facts

- **NIH application ID:** 10132101
- **Project number:** 1R61HL156248-01
- **Recipient organization:** PENNSYLVANIA STATE UNIV HERSHEY MED CTR
- **Principal Investigator:** Philippe A Haouzi
- **Activity code:** R61 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $708,424
- **Award type:** 1
- **Project period:** 2020-09-20 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10132101

## Citation

> US National Institutes of Health, RePORTER application 10132101, Treatment of Fentanyl Overdose-Induced Respiratory Failure by Low-Dose Dexmedetomidine (1R61HL156248-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10132101. Licensed CC0.

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