Evaluation of Intravenous Lipid Emulsion as an Adjunctive Antidote in Experimental Fentanyl Toxicity: Comparison with Naloxone in a Rat Model.

Fentanyl is an extremely potent and highly lipophilic synthetic opioid, whose toxicity is marked by significant respiratory depression and central nervous system impairment. Naloxone is the primary antidote for opioid overdose; however, there is an increasing interest in intravenous lipid emulsion (ILE) as a supplementary therapeutic approach for poisoning with lipophilic agents. This study aimed to assess the antidotal effect of ILE in cases of experimental fentanyl toxicity and to compare its effectiveness with that of naloxone, both when administered alone and in combination. The research was performed on male Wistar rats. Various parameters were monitored, including heart rate, respiratory rate, nociceptive response (Hot Plate test), motor coordination (Rota-rod test), and behavioral metrics (Open Field test). Fentanyl induced significant cardiorespiratory depression and analgesia. Naloxone successfully counteracted the respiratory and nociceptive effects. ILE demonstrated positive effects on specific cardiorespiratory parameters, especially in the initial recovery phase, although its influence on analgesia was less pronounced and occurred later. The combination of naloxone and ILE appeared to promote earlier cardiorespiratory enhancement compared to naloxone used alone; nevertheless, these variations must be viewed with caution due to the brief duration of fentanyl's effects and the absence of evidence supporting an increased maximal therapeutic benefit. These findings endorse the potential role of ILE as an adjunctive, rather than a standalone, antidotal treatment for acute fentanyl poisoning.