In the present study, researchers examined the patients with the acute amnestic syndrome to determine the presence of Fentanyl traces in urine through Immunoassays

Between 2012 and 2016, a total of 14 patients in Massachusetts with a history of substance use had an acute anterograde amnestic syndrome that lasted for months (or longer in some patients); this amnestic syndrome was characterized by a hyperintense signal involving both hippocampi on magnetic resonance imaging diffusion-weighted sequences.

The patients were also variably observed to have deficits in other cognitive domains, including orientation and attention. Thirteen of these 14 patients had a positive toxicologic test for opioids or had a history of opioid use, but none underwent testing for synthetic opioids such as fentanyl.

Although synthetic opioids are currently often combined with heroin, they are not typically identified on routine assays for morphine, heroin metabolites, or oxycodone.

This amnestic syndrome also occurred in a patient who overdosed in Maryland and was ultimately transferred to a tertiary care center in West Virginia, where the case was reported; this patient had a history of heroin use and tested positive for norfentanyl and cocaine. 

 Researchers report four additional cases in patients (age range, 28 to 37 years) who had a history of heroin use and presented with this acute amnestic syndrome in Massachusetts in 2017.

Confirmatory toxicologic tests in all four patients were positive for fentanyl and its metabolite norfentanyl in either urine (three patients; range of fentanyl level, 1.8 to >200 ng per milliliter) or serum (one patient; fentanyl level, 1.87 ng per milliliter). These patients were not known to have used fentanyl. 

Routine screening immunoassays for opiates in the urine were negative in three patients, but an immunoassay was positive in the fourth after the patient received morphine in the hospital. The urine immunoassay for the heroin metabolite 6-monoacetylmorphine was negative in this fourth patient.

In one patient, a routine urine toxicologic screening test was also positive for cocaine, benzodiazepines, and amphetamines, and a confirmatory urine test was positive for a metabolite of buprenorphine. However, expanded confirmatory testing panels for fentanyl analogs (synthetic opioids structurally similar to fentanyl) and “designer” opioids in the urine and serum of this patient were negative.

Interpretation of the cause of the amnestic syndrome was limited by the drugs for which testing was performed. Another unidentified drug, adulterant, or contaminant cannot be excluded as a cause of the amnestic syndrome.

However, the presence of fentanyl in the four additional patients described here strengthens an association of fentanyl with Acute amnestic syndrome, and fentanyl was the only drug detected in two of the four patients. We may be observing this syndrome now because of the increasing presence of fentanyl in the supply of illicit drugs.

Potential mechanisms of fentanyl-related hippocampal injury include cerebral ischemia or hypoxemia as a result of overdose or excitotoxicity since fentanyl. Expanded toxicologic screening for fentanyl and its analogs should be considered in patients with a history of substance use who present with this amnestic syndrome.