Sudden Death Induced by Rapid Intravenous Injection of Fentanyl in Conscious Rats

Abstract

The sudden death induced by rapid intravenous (IVr) injection of overdose FNT in clinical settings is commonly observed in conscious humans and more often in the males than females. Our previous study has shown that IVr injection of FNT induces a long-lasting apnea associated with bradycardia and hypotension in anesthetized rats (Zhuang et al. 2023 EB). This study aimed to determine whether a lethal dose of FNT could cause sudden death with the mortality being higher in male rats than female ones and whether the FNT-induced respiratory disorder, especially ventilatory arrest, but not cardiac arrest, was the trigger of the death. The rat previously instrumented with ECG electrodes and jugular vein cannulation was placed in a restraint tube that was connected to a plethysmograph chamber to record cardiorespiratory activities. We found that FNT at doses <2 mg/kg induced an immediate persistent apnea, lasting less than 1 min, associated with bradycardia. Following restoration of respiratory rhythm, the rats showed depressed VE and bradycardia for several hours and the cardiorespiratory variables recovered next day. A lethal dose of FNT at 3 mg/kg, compared to FNT at <2 mg/kg, induced an even longer apnea (lasting >1.5 min) accompanied with more severe bradycardia. This sustained apnea was usually interrupted by brief restoration of breathing, which was followed by ventilatory and cardiac arrest occurring at approximately 5 min and 10 min post injection respectively. Although the initial cardiorespiratory response to FNT appeared to be similar in both genders, the death rate was relatively higher in male rats than female ones. In conclusion, our study establishes an animal model of IVr injection of overdose FNT-induced sudden death occurring within minutes. The sudden death is the result of ventilatory, but not cardiac, arrest following a brief restoration of respiratory activity from a sustained apnea. Supported by NIH R01 grants HL163512 and DA059063. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.