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New synthetic opioid cyclopropylfentanyl together with other novel synthetic opioids in respiratory insufficient comatose patients detected by toxicological analysis.
Clin Toxicol (Phila). 2019 Sep; 57(9):806-812.CT

Abstract

Introduction: Fentanyl derivatives like cyclopropylfentanyl have recently appeared on the recreational drug market. Cyclopropylfentanyl is probably a highly potent opioid, but human toxicological data are not available so far. Similar to other fentanyl derivatives the most serious acute health risk due to the use of cyclopropylfentanyl is likely to be respiratory depression. In case of overdose, this may lead to apnoea, respiratory arrest and death. In this paper, we present three cases of severe intoxication with cyclopropylfentanyl.

Methods:

Observational case series including three intoxications treated in the Emergency Department at the University Medical Centre in 2017. In all cases, the consumption of any drugs was denied by the patients and relatives. Toxicological analyses using GC-MS, LC-QTOF-MS and LC-MS-MS of serum, urine samples and in one case of a powder sample, found in the hospital room, were performed. Medical records were reviewed to obtain clinical data.

Results:

Clinical effects of severe opioid intoxications comprising loss of consciousness, bradypnea, hypercapnia, arterial hypotension and miosis were recorded. In all cases, the novel fentanyl analogue cyclopropylfentanyl was detected in body fluids. In two cases further synthetic opioids (U-47700, methoxyacetylfentanyl, butyrfentanyl, 2-fluoroiso- or 4-fluoroisobutyrfentanyl) and mitragynine or desoxypipradrol were found. A discovered powder sample contained cyclopropylfentanyl, cyclopropylnorfentanyl, acetylfentanyl, 4-ANPP, U-47700 and caffeine. Except for acetylfentanyl all ingredients could be detected in the respective blood and urine sample. In two cases a cyclopropylfentanyl serum concentration of 51 and 76 ng/ml was determined. Discussion: In three cases of severe potentially life-threatening intoxication, cyclopropylfentanyl was verified using different analytical procedures. The ingested substance, as well as the excreted metabolites, were detected by application of various mass spectrometric techniques.

Conclusions:

In cases of intoxication without a medical history, the detailed toxicological analysis may reveal new psychoactive substances which are not detected by standard toxicological screening approaches. The high pharmacological potency of new products with unknown toxicological data and unknown synergistic effects may easily lead to a life-threatening overdose.

Authors+Show Affiliations

a Clinical Toxicological Laboratory, GIZ-Nord Poisons Centre, University Medical Center Göttingen, Georg-August-University , Göttingen , Germany.a Clinical Toxicological Laboratory, GIZ-Nord Poisons Centre, University Medical Center Göttingen, Georg-August-University , Göttingen , Germany.b Faculty of Medicine, Department of Forensic Toxicology, Institute of Forensic Medicine, Medical Center - University of Freiburg, University of Freiburg , Freiburg , Germany.b Faculty of Medicine, Department of Forensic Toxicology, Institute of Forensic Medicine, Medical Center - University of Freiburg, University of Freiburg , Freiburg , Germany. c Hermann Staudinger Graduate School, University of Freiburg , Freiburg , Germany.b Faculty of Medicine, Department of Forensic Toxicology, Institute of Forensic Medicine, Medical Center - University of Freiburg, University of Freiburg , Freiburg , Germany.d Emergency Department, University Medical Center Göttingen, Georg-August-University , Göttingen , Germany.e Forensic Toxicological Laboratory, University Medical Center Göttingen, Georg-August-University , Göttingen , Germany.

Pub Type(s)

Case Reports
Journal Article

Language

eng

PubMed ID

30775936

Citation

Müller, Dieter, et al. "New Synthetic Opioid Cyclopropylfentanyl Together With Other Novel Synthetic Opioids in Respiratory Insufficient Comatose Patients Detected By Toxicological Analysis." Clinical Toxicology (Philadelphia, Pa.), vol. 57, no. 9, 2019, pp. 806-812.
Müller D, Neurath H, Neukamm MA, et al. New synthetic opioid cyclopropylfentanyl together with other novel synthetic opioids in respiratory insufficient comatose patients detected by toxicological analysis. Clin Toxicol (Phila). 2019;57(9):806-812.
Müller, D., Neurath, H., Neukamm, M. A., Wilde, M., Despicht, C., Blaschke, S., & Grapp, M. (2019). New synthetic opioid cyclopropylfentanyl together with other novel synthetic opioids in respiratory insufficient comatose patients detected by toxicological analysis. Clinical Toxicology (Philadelphia, Pa.), 57(9), 806-812. https://doi.org/10.1080/15563650.2018.1554187
Müller D, et al. New Synthetic Opioid Cyclopropylfentanyl Together With Other Novel Synthetic Opioids in Respiratory Insufficient Comatose Patients Detected By Toxicological Analysis. Clin Toxicol (Phila). 2019;57(9):806-812. PubMed PMID: 30775936.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - New synthetic opioid cyclopropylfentanyl together with other novel synthetic opioids in respiratory insufficient comatose patients detected by toxicological analysis. AU - Müller,Dieter, AU - Neurath,Hartmud, AU - Neukamm,Merja A, AU - Wilde,Maurice, AU - Despicht,Caroline, AU - Blaschke,Sabine, AU - Grapp,Marcel, Y1 - 2019/02/18/ PY - 2019/2/19/pubmed PY - 2020/6/9/medline PY - 2019/2/19/entrez KW - Cyclopropylfentanyl KW - drugs of abuse KW - intoxication KW - novel synthetic opioids KW - systematic toxicological analysis SP - 806 EP - 812 JF - Clinical toxicology (Philadelphia, Pa.) JO - Clin Toxicol (Phila) VL - 57 IS - 9 N2 - Introduction: Fentanyl derivatives like cyclopropylfentanyl have recently appeared on the recreational drug market. Cyclopropylfentanyl is probably a highly potent opioid, but human toxicological data are not available so far. Similar to other fentanyl derivatives the most serious acute health risk due to the use of cyclopropylfentanyl is likely to be respiratory depression. In case of overdose, this may lead to apnoea, respiratory arrest and death. In this paper, we present three cases of severe intoxication with cyclopropylfentanyl. Methods: Observational case series including three intoxications treated in the Emergency Department at the University Medical Centre in 2017. In all cases, the consumption of any drugs was denied by the patients and relatives. Toxicological analyses using GC-MS, LC-QTOF-MS and LC-MS-MS of serum, urine samples and in one case of a powder sample, found in the hospital room, were performed. Medical records were reviewed to obtain clinical data. Results: Clinical effects of severe opioid intoxications comprising loss of consciousness, bradypnea, hypercapnia, arterial hypotension and miosis were recorded. In all cases, the novel fentanyl analogue cyclopropylfentanyl was detected in body fluids. In two cases further synthetic opioids (U-47700, methoxyacetylfentanyl, butyrfentanyl, 2-fluoroiso- or 4-fluoroisobutyrfentanyl) and mitragynine or desoxypipradrol were found. A discovered powder sample contained cyclopropylfentanyl, cyclopropylnorfentanyl, acetylfentanyl, 4-ANPP, U-47700 and caffeine. Except for acetylfentanyl all ingredients could be detected in the respective blood and urine sample. In two cases a cyclopropylfentanyl serum concentration of 51 and 76 ng/ml was determined. Discussion: In three cases of severe potentially life-threatening intoxication, cyclopropylfentanyl was verified using different analytical procedures. The ingested substance, as well as the excreted metabolites, were detected by application of various mass spectrometric techniques. Conclusions: In cases of intoxication without a medical history, the detailed toxicological analysis may reveal new psychoactive substances which are not detected by standard toxicological screening approaches. The high pharmacological potency of new products with unknown toxicological data and unknown synergistic effects may easily lead to a life-threatening overdose. SN - 1556-9519 UR - https://www.unboundmedicine.com/medline/citation/30775936/New_synthetic_opioid_cyclopropylfentanyl_together_with_other_novel_synthetic_opioids_in_respiratory_insufficient_comatose_patients_detected_by_toxicological_analysis_ L2 - https://www.tandfonline.com/doi/full/10.1080/15563650.2018.1554187 DB - PRIME DP - Unbound Medicine ER -