Fentanyl overdose increases risk of acute lung injury and multiorgan damage

PURPOSE: Survivors of opioid overdose often require intensive care treatment and have recently been shown to be at higher risk for developing acute lung injury (ALI). The precise pathogenesis and importance of naloxone reversal in ALI risk in this population is unknown. This study aimed to develop a rat model of fentanyl overdose, with and without rescue naloxone use, to investigate fentanyl and naloxone’s contribution to ALI. METHODS: Rats were given a single overdose of fentanyl, with or without naloxone, at 15 minutes, and then monitored for 4 hours. Continuous endpoints included oxygen saturation (SpO2), heart rate (HR), respiratory rate (RR), as well as muscle rigidity, activity and breathing scores. Laryngospasm and respiratory secretion amounts were recorded every 30 minutes. At 4 hours, animals were euthanized, blood assayed for Clinical Chemistry, and lungs collected for wet to dry ratio assessment and histopathology. RESULTS: Fentanyl overdose caused significant abnormalities within 15 minutes of exposure, including: sustained decreases in SpO2 and RR; whole-body rigidity with absence of activity; shallow breathing; laryngospasm; and increased oral/nasal secretions. Naloxone treatment normalized all clinical parameters, except oral/nasal secretions, with improvements sustained for 4 hours. Elevated liver and kidney enzymes were seen, as well as mild lung edema and proteinaceous exudate, without improvements after naloxone. CONCLUSION: Fentanyl overdose resulted in a multitude of abnormal clinical signs, which were reversed with naloxone treatment. Multiorgan injury was seen, without benefit from naloxone. Signs of ALI were present, with increased prevalence and severity after naloxone.