Experimental assessment of intravenous lipid emulsion in the management of acute fentanyl poisoning

Fentanyl is a highly potent and lipophilic μ-opioid receptor agonist associated with severe neurorespiratory toxicity and a growing incidence of overdose. Although naloxone remains the standard antidote, its relatively short half-life and exclusively pharmacodynamic mechanism of action may limit its efficacy in intoxications involving highly lipophilic opioids. The aim of this study was to evaluate the therapeutic effects of intravenous lipid emulsion (ILE), administered alone or in combination with naloxone, in a rat model of acute fentanyl toxicity. Thirty adult male Wistar rats were randomly assigned to five groups ( n = 6 per group): vehicle control; fentanyl (0.44 mg/kg, i.p.); fentanyl + naloxone (1.0 mg/kg, i.p.); fentanyl + ILE (20%, 1.5 mL/kg, i.p.); and fentanyl + naloxone + ILE. Survival and clinical manifestations (loss of righting reflex [LORR], catatonia-like behavior, respiratory impairment, and convulsions) were assessed over 120 min. Survival was analyzed using Kaplan–Meier methodology, and nonparametric tests were applied for ordinal outcomes. No statistically significant differences in survival were observed ( p = 0.406). However, combination therapy significantly reduced the incidence of LORR compared to fentanyl alone ( p = 0.0152) and produced the most pronounced improvement in catatonia and respiratory impairment scores ( p < 0.001, Kruskal–Wallis test). In conclusion, combined naloxone and lipid emulsion therapy demonstrated superior attenuation of fentanyl-induced neurobehavioral and respiratory toxicity compared to monotherapy, suggesting complementary pharmacodynamic and pharmacokinetic mechanisms. Further adequately powered studies are warranted.