Synthetic Fentanyl and Xylazine—The New Rogue Wave of the Opioid Crisis: A Neuroimaging Case Series of “Tranq-Dope” Overdoses
Nirmala Ghimirey1, Vinh Nguyen2, Christopher Newey4, Harinoor Mann5, Madihah Hepburn3
1Internal Medicine, 2Critical Care, 3Neurology, Summa Health, 4Neurology, Cleveland Clinic, 5Neurology, Summa Health System Akron Campus Building 3, East Pavilion
Objective:
A case series of synthetic fentanyl-xylazine overdoses; highlighting the unique clinical and neuroimaging features caused by central nervous system (CNS) toxicity.
Background:
Abuse of synthetic fentanyl has been on the frontline of the opioid crisis in the USA with overdose-related deaths increasing by ~45% since 2016. A new public health crisis has emerged with xylazine; horse anesthetic also known as “tranq dope” being mixed with fentanyl. Xylazine is a central α2-adrenergic agonist that penetrates the blood-brain barrier, decreasing neurotransmitter (dopamine) release and resulting in severe CNS depression leading to respiratory and hemodynamic compromise. Adding xylazine to illicit-fentanyl increases the risk of brain injury by decreasing CNS autoregulatory responses needed to compensate for hypoxia during periods of respiratory depression. Diagnosis of xylazine mixed in synthetic fentanyl is suspected when a patient presents with fentanyl overdose unresponsive to naloxone and rhabdomyolysis despite a short down-time; since there are no commercially available diagnostic tests.
Design/Methods:
Series of three patients found comatose with respiratory depression from witnessed fentanyl overdose. Despite administration of naloxone by first responders at the scene, there was no improvement in their mental status or respiratory failure. Lab evaluation was significant for rhabdomyolysis despite short downtime in the field. Clinical examination with varying degrees of coma, intact brainstem reflexes, limb spasticity, and autonomic dysfunction. Common neuroimaging themes include symmetrical involvement with cytotoxic and vasogenic edema of subcortical white matter, extrapyramidal motor system, and cortex. Cerebral herniation treated with hyperosmolar agents and goal-directed management of intracranial pressure. Two of the three patients discharged to subacute rehabilitation with meaningful neurological recovery.
Conclusions:
Illicit fentanyl-xylazine overdoses can cause toxic leukoencephalopathy and severe hypoxic-ischemic injury to cortical and subcortical brain regions due to rapid CNS penetration and interference with neurotransmitter release. By decreasing the protective cerebral autoregulatory mechanisms, there is increased vulnerability to systemic hypoxia and hypotension.