What a Riot! – Toxicology Blog

Author: Chris Riviello, DO, Emergency Medicine Resident PGY1
Fellow: Alexis Cates, DO, Medical Toxicology Fellow PGY6
Faculty: David Goldberger, MD, Medical Toxicology / Emergency Medicine Attending


The Case:

You are a resident working in a busy level 1 trauma center on election day.  Several hours after the results are released you overhear the television report that multiple local protests have turned violent.   As the news breaks, the first of many patients begin to present to your Emergency Department (ED).  A 27 year old male presents via fire rescue with chief complaint of “I can’t see!”  He is uncomfortable appearing due to pain and relatively uncooperative with your history.  He does however report that less than 30 minutes prior to arrival he was at a protest when an unknown gas was used in order to disperse the crowd.  In addition to an ocular exposure, the  patient believes he was exposed via inhalation.  He now complains of burning and redness of his skin, difficulty seeing, burning of his eyes, severe nausea/vomiting, and a sensation of shortness of breath with burning/tightness in his chest.  On physical exam, his vital signs are within normal limits, there is mild erythema of his skin diffusely, as well as multiple small abrasions to his extremities. His exam is significant for copious lacrimation associated with rhinorrhea, periorbital edema, conjunctival injection and bilateral blepharospasm.  He is tolerating secretions and there is no evidence of airway edema or stridor and no evidence of acute pulmonary edema.  The patient is requesting you do anything to treat his discomfort and restore his vision.


Learning point 1: Introduction to Irritant Incapacitating Agents

  • Irritant incapacitating agents include “tear gases” such as 2-Chloroacetophenone (CN) also known as mace, as well as o-chlorobenzylidene malonitrile (CS).
  • Oleoresin capsicum (OC) also known as “pepper spray” is derived from oils of herbs/shrubs of the capsicum genus (cayenne peppers, chili peppers, etc). (Figure 1)
  • Considered a non-lethal means of crowd control and is most known for its ophthalmologic, dermal and pulmonary effects.
  • Banned in warfare (with exception of special circumstances) during the 1993 Geneva convention; however, still permitted for use by law enforcement domestically.
  • Referred to by multiple names including “tear gas,” “riot control agents” and “lacrimators.”
  • While the term “tear gas” is used frequently, the far majority of irritant incapacitating agents are aerosols of fine particles.
  • Deployment technologies such as high temperature dispersion (700C) can create gaseous forms of these agents.
  • More severe toxicities have been associated with pyrogenic/explosive deployment strategies OR prolonged exposures to high concentrations in poorly ventilated areas:
    • Blindness, bronchospasm, laryngospasm, pulmonary edema, severe blistering/burns
  • Structurally, the three agents above (CN, CS, OC) are lipophilic due to their hydrocarbon base and benzene rings allowing for tissue penetration. (Figure 2)
  • Melting points for these agents are not generally in the range of ambient temperature, making removal of fine particulates more amenable to irrigation rather than vaporization in the liquid form.
  • Emergency Medicine (EM) physicians are often the first point of contact following these exposures.
  • Pre-hospital and military settings may serve as an additional site of exposure for EM providers.
  • Anti-government protests have increased 11.5% per year on average since 2009, so the EM physician should be comfortable with recognizing the toxicity of and the management of irritant incapacitating agents.

Figure 1:   Capsicum annuum  

Figure 2: Chemical structures of CN (A), CS (B) and OC (C)

                       
   

Learning Point 2:
Understanding Toxicity of Riot Control Agents

  • Irritant incapacitating agents exert their toxicity via activation of endogenous receptors/mechanisms.
  • CN and CS are alkylating agents (electrophiles) and as such can rapidly deplete redox systems within cells and modify structures of nucleic acids and proteins.
  • It is this same ability to modify protein that allows CN and CS to exert their effects on Transient Receptor Potential A1 (TRPA1).
  • TRPA1 can be found within the sensory afferents of nociceptors in the skin, conjunctiva, as well as the upper and lower respiratory tract.  
    • Normally activated with noxious heat (>109F) or acidification as a physiological warning of impending tissue damage/destruction.
  • Covalent modification of cysteine residues of TRPA1 promotes neuronal depolarization via sodium and calcium cation influx.
  • Additionally, CN and CS promote release of substance P and bradykinin which promote a mild inflammatory response and pain.

Figure 3: TRPA1 is the molecular target of CN & CS which act to covalently modify cysteine residues of the receptor and promote Na+/Ca2+ influx. This inflow of electrolytes promotes neuronal depolarization along nociceptors of sensory afferents while also contributing to release of bradykinin and substance P. (Source: Skerratt, S. (2017). Recent Progress in the Discovery and Development of TRPA1 Modulators. Progress in Medicinal Chemistry, 81-115. doi:10.1016/bs.pmch.2016.11.003)

  • OC acts predominantly at TRPV1 which is located within nociceptors of the skin, cornea, conjunctiva, upper and lower respiratory tract, as well as nociceptive sensory afferents in the trigeminal, vagal and dorsal root ganglion.
    • Suggests both a central and peripheral mechanism of action
  • Secondary to lipophilicity of OC, it can also penetrate cell membranes and cause intracellular dysfunction by binding electron rich groups (nucleic acids and proteins).
  • Binding of OC results in the influx of the calcium which promotes sensation of pain and inflammation in the aforementioned systems.
  • Ca2+ influx potentiates effects at TRPA1 and, much like CN & CS, also promotes release of substance P and bradykinin.

Figure 4: Activation of TRPV1 also promotes Na+/Ca2+ influx leading neuronal depolarization and firing of nociceptive afferents. (Source: Anand, P., & Bley, K. (2011). Topical capsaicin for pain management: Therapeutic potential and mechanisms of action of the new high-concentration capsaicin 8% patch. British Journal of Anesthesia, 107, 490-502. doi:10.1093/bja/aer260)

  • This pathophysiology results in a variety of physical manifestations all of which typically manifest within 20-60 seconds and subside within 30-60 minutes of exposure.
    • Ocular Toxicity:
      • blepharospasm, photophobia, periorbital edema, conjunctival/scleral edema, conjunctival injection and lacrimation 
        • Leads to functional blindness
    • Pulmonary Toxicity:
      • Severe rhinorrhea/salivation, stinging/burning in nose/chest, coughing, sneezing 
      • Associated with development of respiratory illness within one week of exposure 
    • Dermal Toxicity:
      • Erythema, burning and transient edema
    • Other:
      • Rare cases of laryngospasm, pulmonary edema, severe burns associated with prolonged exposure at high concentration OR when deployed at close range with pyrogenic devices

The case continued.

Medics reports there will be many new patients entering the ED, all with similar symptoms and exposures.  They are experiencing clear nasal discharge, lacrimation, severe nausea and abdominal discomfort.  Some report a sensation of shortness of breath.  You turn to your colleagues and discuss appropriate precautions and management strategies for the large influx of patients you are expecting. 

Learning Point 3:
Management & Special Considerations

  • All healthcare professionals should follow contact precautions with appropriate Personal Protective Equipment (PPE): surgical masks, gowns, goggles and gloves.
  • While not always practically possible, patient decontamination should take place outdoors and involve removal of exposed clothing.
  • Contact lenses should be removed as they act as a reservoir for continued exposure to irritant incapacitating agents.
  • In the pre-hospital setting, an important consideration is that aerosol formulations are heavier than air, patients should therefore be removed from the ground and taken away from the exposure.
  • Treatment inside the ED should ideally occur in well-ventilated rooms.
  • No specific antidotes exist and management is largely supportive. 
    • Skin should be washed with soap and water 
      • Milk and baby shampoo have anecdotally been touted as effective remedies
      • Due to availability and non-inferiority, water should be considered the first line agent for decontamination
    • Ophthalmologic exposures should undergo irrigation 
      • In order to facilitate proper rinsing, consider prior application of anesthetic eye-drops in select patients
      • Symptoms persisting more than 10-20 minutes following irrigation should undergo prompt slit lamp evaluation and fluorescein staining 
    • Oxygen saturation should be monitored
      • Rare bronchospasm – consider short acting beta agonists
      • Rare laryngeal edema – consider supportive care with mechanical ventilation

The case concludes…

A station is established outside the ED, and is staffed by healthcare professionals with appropriate PPE where patients are successfully decontaminated and triaged for further treatment.  Your first patient is feeling better approximately one hour after his exposure.  You elected to treat with copious irrigation of his skin using soap and water, and thorough ocular irrigation.  His shortness of breath and wheezing successfully responded to a short course of albuterol in the ED.  The patient thanks you for your help to which you suavely respond – “Don’t sweat it, but remember … bad things happen in Philadelphia.” 

Resources:

  1. Akpunonu, P., Eagar, H., & Doty, B. (2020, June 05). Managing the Effects of Riot Control Agents. Retrieved October 12, 2020, from https://www.emra.org/emresident/article/riot-agents/
  2. Anand, P., & Bley, K. (2011). Topical capsaicin for pain management: Therapeutic potential and mechanisms of action of the new high-concentration capsaicin 8% patch. British Journal of Anesthesia, 107, 490-502. doi:10.1093/bja/aer260
  3. Brewster, M. S., & Gaudet, R. (2015). How the TRPA1 receptor transmits painful stimuli: Inner workings revealed by electron cryomicroscopy. BioEssays, 37(11), 1184-1192. doi:10.1002/bies.201500085
  4. Mcmahon, S. B., & Wood, J. N. (2006). Increasingly Irritable and Close to Tears: TRPA1 in Inflammatory Pain. Cell, 124(6), 1123-1125. doi:10.1016/j.cell.2006.03.006
  5. Political protests have become more widespread and more frequent. (n.d.). Retrieved October 12, 2020, from https://www.economist.com/graphic-detail/2020/03/10/political-protests-have-become-more-widespread-and-more-frequent
  6. Rothenberg, C., Achanta, S., Svendsen, E. R., & Jordt, S. (2016). Tear gas: An epidemiological and mechanistic reassessment. Annals of the New York Academy of Sciences, 1378(1), 96-107. doi:10.1111/nyas.13141
  7. Schep, L. J., Slaughter, R. J., & Mcbride, D. I. (2013). Riot control agents: The tear gases CN, CS and OC—a medical review. Journal of the Royal Army Medical Corps, 161(2), 94-99. doi:10.1136/jramc-2013-000165
  8. Skerratt, S. (2017). Recent Progress in the Discovery and Development of TRPA1 Modulators. Progress in Medicinal Chemistry, 81-115. doi:10.1016/bs.pmch.2016.11.003
  9. Tidwell, D. R. (2020, September 22). Tear Gas and Pepper Spray Toxicity. Retrieved October 13, 2020, from https://www.statpearls.com/articlelibrary/viewarticle/394/

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