SANITÄTSDIENST DIFFERENTIATING NERVE AGENT POISONING FROM OPIOID POISONING – CLINICAL SIGNS, DETECTION AND DIAGNOSTICS PD Dr. Timo Wille LtCol (MC) German Armed Forces Bundeswehr Institute of Pharmacology and Toxicology Disclosures Presenter’s has no relevant financial or non-financial interests to disclose. Disclosure will be made when a product is discussed for an unapproved use. This continuing education activity is managed and accredited by AffinityCE in collaboration with AMSUS. AffinityCE and AMSUS staff as well as Planners and Reviewers, have no relevant financial or non-financial interests to disclose. Commercial Support was not received for this activity Objectives • List clinical signs of nerve agent and opioid poisoning • Know that highly potent opioids might be misused as chemical weapon • Know on-site devices for diagnosis of opioid and nerve agent poisoning NERVE AGENTS – RELEVANCE Tabun (GA) Sarin (GB) Soman (GD) Cyclosarin (GF) Salisbury / Amesbury 2018: one death, min. four injured Kuala Lumpur 2017: one death Syria 2013-2017: thousands dead and injured Halabja 1988: 5.000 deaths, 10.000 injured VX Novichok? 5 S a n i t ä t s d i e n s MECHANt ISM OF NERVE AGENT POISONING – INHIBITION OF ACETYLCHOLINESTERASE Physiology: Pathophysiology: Acetylcholinesterase (AChE) cleaves Binding of OP to AChE, renders the enzyme inactive acetylcholine in acetate and choline and ACh overflow at muscarinic and nicotinic synapses terminates its action as a neurotransmitter muscarinic nicotinic cns diarrhea muscle fasciculations seizures bradycardia cramps bronchorrhea, severe muscle respiratory bronchoconstriction dysfunction disturbance londonlungcancer.com dailymail.co.uk aic.cuhk.edu.hk/Muscle faculty.pasadena.edu S6 a n i HIFlemingGHLY‘sPGOoldfingerTENT OP(novelIOIDS19AS59 C/ movieHEMIC1964AL)WEAPON – FICTION t ä t s d i e n • Goldfinger advocates “a highly concentrated s t opiate….the symptoms are a deep and instant sleep” to enable a raid on Fort Knox • 1960: discovery of fentanyl by Janssen Images: bondmovies.com; goldfinger.neocities.org S7 a n i OPMIOosIDScow–ThNEWeater Si CegeHEMIC2002 AL THREAT Fentanyls t ä t s d i e n Terrorists take > 800 hostages s aerosol pumped by SOF: Toxicol 2012, 36, t 33 dead terrorists 125 dead hostages Deadly doses Fentanyl = 2 mg (VX = 4 mg) Science 2017, 355, 1364-6 I dpa I J Anal 647-56 S8 a n i TherapMECHy: ANISM OF OPIOID POISONOpioiING d–toINxidroHIBmIe:TORY GPCR t µ-agonism results in analgesia Miosis, CNS depression, respiratory depression, ä t s d i wikimedia.org dailymail.co.uk e n s delta kappa mu t analgesia analgesia, analgesia, miosis, miosis, sedation respiratory disturbance Nature 2012, 485, 321-326 S9 a n i SIMILAR CLINICAL SIGNS FOR„WhenOPIOyIoDSu heaANDr hooNEvesR:VEThinkAGHENTSorses not Zebras“ t Initial Toxidromes in Order of Onset ä Continuous; depends on route of uptake and dose t Class Primary Secondary Tertiary Later Signs s Nerve mental-status increased shallow convulsions, d agents changes, secretions, breaths coma, i fasciculations, miosis respiratory e muscle arrest n weakness, s Covered bench near shopping center in paralysis t Salisbury where collapsed victims were Opioids confusion, bradypnea, coma respiratory found miosis sedation, arrest, apnea bradycardia, tentative diagnosis: opioid poisoning hypotension Ciottone, N Engl J Med 2018, 378: 1611-20 ST1 ai0 nt ie ASSUMPTIONS – OPIOID VS NERVE AGENT POISONING tl. Toxidrome-based triage might fail in discrimination of opioids and nerve agents ä t. Nerve agents and opioids are lethal if not quickly diagnosed s. Nerve agents and opioids require different antidotes d i e Need for discrimination of both groups early detection and n identification on surfaces and/or skin s t ST1 ai1 nt SKIN DETECTION - KEY ASSET IN MANAGEMENT OF CHEMICAL MASS ie CASUALTIES tl ä t s d i e n s t Gap: detection of nerve agents with low vapor pressure and high percutaneous toxicity such as V-agents ST1 ai2 SKIN DETECTION - KEY ASSET IN MANAGEMENT OF CHEMICAL MASS CASUALTIES nt ie Kit covers all AChE inhibitors! This image cannot currently be displayed. tl ä t s d i e n s t This image cannot currently be displayed. OP Skin Disclosure Kit is in advanced development ! ST1 ai3 nt This image cannot currently be displayed. This image cannot currently be displayed. This image cannot currently be displayed. ie DIAGNOSIS OF OP POISONING – PORTABLE DEVICE FOR FIELD USE tl ä t s d i e n s Development of medical product: t ChE check mobile: covers all AChE inhibitors, easy to use, robust, field- usable, COTS Nerve agent poisoning: Yes or No ST1 ai4 nt ie FENTANYLS – ON SITE DEVICES - Detection: Mass Spectrometry (MS; MX908), flameThis imagesp cannot currently be displayed. ectrometry (AP4C) tl This image cannot currently be displayed. This image cannot currently be displayed. ä t s d i e n s- Diagnosis (ELISA for saliva, sweat, urine; spectrum?) t This image cannot currently be displayed. ST1 ai5 t n CONCLUSION ie• Highly potent opioids (fentanyls) might be mis-used as chemical weapons tl • synthesis of fentanyls is comparable easy (convenient one pot synthesis of fentanyl) ä t s• Toxicity of fentanyls is comparable to toxicity of nerve agents – both lethal if not treated quickly d • both groups pose risk for first responders i e• Opioids and nerve agents might show similar signs - but differ largely in antidotal treatment n • tool for skin detection of nerve agents is under advanced development s • tool for diagnosis of nerve agent exposure is available t • tools for detection and diagnosis of fentanyls available (spectrum?) • supportive care may ultimately be life-saving (ventilation) ST1 ai6 t n CONTINUING EDUCATION ie• How to Earn CE If you would like to earn continuing education credit for this activity, please tl visit: http://amsus.cds.pesgce.com ä t Hurry, CE Certificates will only be available for 30 Days after this event! s d i e n s t ST1 DIFFERENTIATING NERVE AGENT ai7 POISONING FROM OPIOID nt POISONING – ie CLINICAL SIGNS, DETECTION AND tl Thank you for your attention! ä DIAGNOSTICSThis image cannot currently be displayed. t s d i e n s t Questions?.