title: Intoxications involving acrylfentanyl and other novel designer fentanyls - results from the Swedish STRIDA project.
abstract: BACKGROUND
  The number of new psychoactive substances (NPS) introduced through the online recreational drugs market increases continuously. This report from the Swedish STRIDA project describes analytically confirmed intoxications involving the novel fentanyl analogs acrylfentanyl, 4-chloroisobutyrfentanyl (4Cl-iBF), 4-fluoroisobutyrfentanyl (4F-iBF), and tetrahydrofuranfentanyl (THF-F), and cyclopentylfentanyl in a drug product.
  
  
  METHODS
  Patients with suspected NPS exposure presenting in emergency departments (ED) or intensive care units (ICU) in Sweden and requiring hospital care are invited to the STRIDA project. NPS analysis of serum and urine samples was performed by multi-component liquid chromatography-mass spectrometry. Data on clinical features were retrieved from telephone consultations with the Swedish Poisons Information Centre and from medical records.
  
  
  RESULTS
  Between April and October 2016, eleven intoxications involving acrylfentanyl (8 cases), acrylfentanyl together with 4Cl-iBF (1), 4F-iBF (1), and THF-F (1) were analytically confirmed. Patients were aged 19-51 (median 28) years and 91% were men. Six (55%) were monitored at the ED, and five admitted to the ICU. Typical clinical features were decreased consciousness, respiratory depression, and miosis. In 8 cases, the antidote naloxone was administered to counter the opioid effects. The 4F-iBF positive patient eventually died of brain edema. The serum acrylfentanyl concentration (n = 8) ranged 0.5-2.1 (median 0.9) ng/mL, and in urine (n = 9) 0.2-10.5 (mean 4.6, median 5.2) μg/mmol creatinine. For 4Cl-iBF, 4F-iBF, and THF-F (n = 1 each), higher serum (5-45 ng/mL) and urine (11-136 μg/mmol creatinine) concentrations were found. Other NPS (e.g., flunitrazolam) and/or classical drugs were detected in five cases. In early 2016, nasal sprays with a claimed content of acrylfentanyl brought to hospital by patients or obtained by test purchase were demonstrated to instead contain fentanyl.
  
  
  CONCLUSIONS
  Potentially life-threatening opioid toxicity was seen in 11 acute intoxications involving the fentanyl analogs acrylfentanyl, 4Cl-iBF, 4F-iBF, and THF-F, which are available through open Internet trading. All patients were supported with acute and intensive hospital care, and naloxone was effective to reverse the opioid symptoms. One patient died of brain edema.
authors.affiliation: a Department of Laboratory Medicine , Karolinska Institutet , Stockholm , Sweden.|b Clinical Pharmacology, Karolinska University Laboratory , Stockholm , Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Helander
authors.affiliation: c Swedish Poisons Information Centre , Stockholm , Sweden.
authors.forename: Matilda
authors.initials: M
authors.lastname: Bäckberg
authors.affiliation: b Clinical Pharmacology, Karolinska University Laboratory , Stockholm , Sweden.
authors.forename: Patrick
authors.initials: P
authors.lastname: Signell
authors.affiliation: a Department of Laboratory Medicine , Karolinska Institutet , Stockholm , Sweden.|b Clinical Pharmacology, Karolinska University Laboratory , Stockholm , Sweden.
authors.forename: Olof
authors.initials: O
authors.lastname: Beck
mesh_terms: D000328:Adult; D000701:Analgesics, Opioid / Q000737:chemistry / Q000506:poisoning*; D000931:Antidotes / Q000008:administration & dosage; D002853:Chromatography, Liquid / Q000379:methods; D015198:Designer Drugs / Q000737:chemistry / Q000506:poisoning*; D004636:Emergency Service, Hospital; D005260:Female; D005283:Fentanyl / Q000031:analogs & derivatives / Q000737:chemistry / Q000506:poisoning*; D006801:Humans; D013287:Illicit Drugs / Q000737:chemistry / Q000506:poisoning*; D007362:Intensive Care Units; D020407:Internet; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D008875:Middle Aged; D009270:Naloxone / Q000008:administration & dosage; D011039:Poison Control Centers; D015813:Substance Abuse Detection / Q000379:methods; D013548:Sweden / Q000453:epidemiology; D055815:Young Adult
chemical_list: D000701:Analgesics, Opioid; D000931:Antidotes; D015198:Designer Drugs; D013287:Illicit Drugs; D009270:Naloxone; D005283:Fentanyl
keywords: 4-chloroisobutyrfentanyl; 4-fluoroisobutyrfentanyl; Acrylfentanyl; NPS; cyclopentylfentanyl; fentanyl; furanylfentanyl; internet drug; mass spectrometry method; new psychoactive substance; opioid analgesic drug; tetrahydrofuranfentanyl