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Chemical terrorism
GENERAL ASPECTS OF POISONING
Chemical terrorism
Key points
Stevan R Emmett
C
The threat of chemical terrorism is reported to be increasing globally
C
Organophosphate nerve agents, chlorine, cyanide and opioids are reportedly potential candidates
C
Recognition of clinical features consistent and awareness of appropriate early management (including available antidotes) are essential knowledge for healthcare staff
Peter G Blain
Abstract The OPCW (Organisation for the Prohibition of Chemical Weapons) has recognized that threat of deliberate exposure of the population to chemical agents by terrorists is increasing. There are limited medical countermeasures (antidotes) to the range of potential toxic chemicals that might be used, so high-quality clinical care remains key. The effective treatment for specific chemical agents is considered.
These are several magnitudes more potent than fentanyl itself and exist in various physicochemical forms. The US National Institute of Environmental Health Sciences has reported that human exposure via accidental release during a drug house raid, from a ruptured plastic bag in an automobile accident or via a direct inoculation from a sharp/needle are possible owing to the prevalence of these compounds in the criminal drug market.
Keywords CBRN; chemical; MRCP; terrorism
Background Terrorism is the deliberate use of indiscriminate methods to create social disruption and terror. The intent may be ideological, economic, religious or political. Terrorists have deployed chemicals, biological agents or radioactive material, but guns and explosives remain their most common weapon.1 Although chemical, biological, radiological and nuclear (CBRN) weapons (Figure 1) were primarily developed for warfare, in recent years terrorist groups have increasingly used toxic industrial chemicals/pharmaceuticals and classical chemical weapons to attack populations. State-sponsored terrorism can be subcontracted to terrorist groups or sympathizers; when targeted at specific individuals, this is better described as directed assassination (e.g. the alleged murder of Kim Jong-Nam, half-brother of Kim Jongun (Supreme Leader of North Korea), using VX nerve agent). Emergency responders are trained and resourced to recognize and manage a deliberate chemical release and treat casualties on site. The range of toxic chemicals that might be deployed is broad but only a limited number of effective medical countermeasures exist. Possible toxic chemical candidates are organophosphate nerve agents, chlorine, cyanide and opioids. Sarin (a nerve agent) and chlorine have been allegedly deployed in Syria, and sulphur mustard (a vesicant) used by the Da’ish terrorist group. Sarin was released in the Tokyo subway by the terrorist sect Aum Shinrikyo. Cyanide poisoning is most likely to occur in an industrial accident or from smoke inhalation, but the ease of production raises its terrorist threat potential. In the USA, and increasingly in Europe, novel fentanyl analogues are appearing in large quantities on the illicit drug market.
Cyanide Release of hydrogen cyanide gas in a confined space is a serious and immediate threat to life; in the open this is much less. Lowdose inhalation exposure produces nausea, drowsiness and hyperventilation; higher dose exposure rapidly results in reduced conscious level, vomiting, convulsions, hypotension and raised blood lactate concentrations (>10 mmol/litre). The clinical signs progress to coma, with fixed dilated pupils, cardiovascular collapse, respiratory failure and death. There are effective antidotes for cyanide poisoning; use depends on the severity of poisoning. In low-level exposure, oxygen/fresh air can be sufficient, but administration of an antidote is recommended when there is concern about the level of exposure based on clinical features. The first-line treatment used to be dicobalt edetate (KelocyanorÒ) but it was announced in June 2019 that this would no longer be manufactured. Hydroxocobalamin is recommended by the Royal College of Emergency Medicine and the National Poisons Information Service as an effective alternative treatment in severe exposures. Recent studies suggest that very large doses are required.2 After a dose of 5 g (200 ml of 25 mg/ml hydroxocobalamin intravenously over 15 minutes), a second dose of 5 g may be needed depending on the patient’s response. Hydroxocobalamin is effective in smoke inhalation. Sodium nitrite (10 ml of 3% solution (300 mg) intravenously over 5e20 minutes) followed by 12.5 g of sodium thiosulfate (25 ml of 50% or 50 ml of 25% solution) intravenously over 10 minutes is an alternative. This is not recommended in children as sodium nitrite acts by increasing methaemoglobin concentrations.
Stevan R Emmett BSc MB ChB DPhil (Oxon) DoHNs DPM MRSB MFPM is Principal Medical Officer at the Defence Science and Technology Laboratories, Porton Down, Salisbury, UK. Competing interests: none declared.
Opioids There are almost daily reports of the public health crisis in North America arising largely from excessive consumption of opioids and the availability of high-potency fentanyl analogues (e.g. carfentanil) on the illicit drug market. These fentanyl analogues
Peter G Blain CBE BMedSci MB BS PhD FBTS FRBS FFOM FRCP(Lon) FRCP(Edin) is Professor of Environmental Medicine at the Medical Toxicology Centre, Newcastle University, UK. Competing interests: none declared.
MEDICINE xxx:xxx
1
Ó 2019 Published by Elsevier Ltd.
Please cite this article as: Emmett SR, Blain PG, Chemical terrorism, Medicine, https://doi.org/10.1016/j.mpmed.2019.12.008
GENERAL ASPECTS OF POISONING
Figure 1
are transported in bags containing many kilogrammes of fine powder. After airborne release, these highly potent opioid (m) receptor agonists can produce rapid and severe incapacitation in exposed individuals (see Dubrovka Theatre incident, e.g. https:// en.wikipedia.org/wiki/Moscow_theater_hostage_crisis). Unconsciousness can occur within minutes, potentially followed by death from respiratory depression. The diagnostic triad of miosis, respiratory depression and altered conscious state is highly suggestive, but organophosphate exposure must be considered (see below). Decontamination is important, and immediate treatment with high-dose intravenous or intramuscular naloxone (2e5 mg) is vital and is highly effective. Higher doses can be necessary, repeated within 30e40 minutes and continued as a naloxone infusion titrated to the patient’s response. The World Health Organization has noted the long duration of action of some fentanyls, such as carfentanyl, can exceed that of naloxone. Longer acting antidotes, such as naltrexone and nalmefene, are available.
Novichok can result in the same overall toxidrome but one that can be delayed in onset or have a modified symptomatology profile. An intelligence picture, evidence of the toxidrome and positive detection by equipment at the scene can all aid clinical decision-making and differential diagnosis (c.f. opioids). However, it should not delay the use of healthcare worker personal protective equipment and casualty decontamination in the form of clothing removal and dryewet processes (e.g. Fuller’s earth then water).3 ‘Off-gassing’ from casualties is a real concern with volatile agents. It is well established early antidote administration is important and consists of the anticholinergic atropine (2 e5 mg intravenously/orally or 2 mg intramuscularly), as a repeat administration with the dose doubled if required. To avoid irreversible enzyme changes, the oximes pralidoxime (2 g or 30 mg/ kg intravenously/intraosseously by slow infusion) or obidoxime (8 mg/kg intravenously) should be used early as they can reactivate some agents. Anticonvulsants such as diazepam or midazolam can control nerve agent-induced seizures and act as a neuroprotective.
Nerve agents These are a class of potent organophosphorus compounds that irreversibly inhibit the catalytic actions of cholinesterases, resulting in cholinergic excess at neuromuscular and central synapses. Organophosphorus compounds were initially developed for use as pesticides and insecticides (see Poisoning by pesticides on pages xxexx of this issue), but in the 1930s several were found to be highly potent and have the potential for malicious terrorist or assassination use. As recognized by the OPCW these potent agents have different chemical properties (e.g. boiling point, volatility, viscosity) that dictate effective use, and therefore route of exposure of casualties (e.g. gaseous release, liquid application, ingestion), influencing the symptomatology. Sarin has a high vapour pressure (i.e. is volatile), and in temperate or hot conditions is likely to exist as a vapour, so casualties present with the classic cholinergic toxidrome of miosis, bradycardia and bronchorrhoea/bronchoconstriction (seizures, fasciculations); respiratory signs are likely to predominate because of the inhalational route. Conversely, percutaneous exposure to low-volatility agents like VX or
MEDICINE xxx:xxx
Chlorine Chlorine is a greenish-yellow gas at normal room temperature, or is transported as an amber liquid. Liberation as a gas can result from mixing any basic compound containing chlorine substance with an acid. The resulting fumes are highly reactive at moist epithelial surfaces such as those of the eyes, respiratory tract and skin. Tissue damage occurs from generation of hypochlorous and hydrochloric acid and formation of oxygen free radicals. With deliberate release, there can be a spectrum of symptoms and signs depending on the exposure dose. The sensitivity of the respiratory tract means individuals present with chest tightness, cough, wheeze, sore throat and dyspnoea. Low oxygen saturation and hypoxia can be apparent, and there can be evidence of dermal erythema, pain and even chemical burns. The mainstay of clinical management involves decontamination of the casualty by removal of clothing (copious water irrigation) and supportive measures including administration of oxygen and bronchodilators, with the potential addition of
2
Ó 2019 Published by Elsevier Ltd.
Please cite this article as: Emmett SR, Blain PG, Chemical terrorism, Medicine, https://doi.org/10.1016/j.mpmed.2019.12.008
GENERAL ASPECTS OF POISONING
inhaled corticosteroids. In severe exposure with evidence of hypoxia, emerging pulmonary oedema (at 2e6 hours after exposure) and failure to respond to oxygen, continuous positive airway pressure or intubation and ventilation may be required using acute respiratory distress syndrome protocols. A
2 Thompson A, Dunn M, Jefferson R, et al. Modest and variable efficacy of pre-exposure hydroxocobalamin and dicobalt edetate in a porcine model of acute cyanide salt poisoning. Clin Toxicol 2019; Aug 7: 1e11. https://doi.org/10.1080/15563650.2019.1628969 [Epub ahead of print]. 3 Hulse EJ, Haslam JD, Emmett SR, Woolley T. Organophosphorus nerve agent poisoning: managing the poisoned patient. Br J Anaesth 2019; 123: 457e63.
KEY REFERENCES 1 Byers M, Greaves I. Respiratory protection for health care workers. J R Army Med Corps 2006; 152: 225e30.
MEDICINE xxx:xxx
3
Ó 2019 Published by Elsevier Ltd.
Please cite this article as: Emmett SR, Blain PG, Chemical terrorism, Medicine, https://doi.org/10.1016/j.mpmed.2019.12.008
Chemical terrorism
Key points
Stevan R Emmett
C
The threat of chemical terrorism is reported to be increasing globally
C
Organophosphate nerve agents, chlorine, cyanide and opioids are reportedly potential candidates
C
Recognition of clinical features consistent and awareness of appropriate early management (including available antidotes) are essential knowledge for healthcare staff
Peter G Blain
Abstract The OPCW (Organisation for the Prohibition of Chemical Weapons) has recognized that threat of deliberate exposure of the population to chemical agents by terrorists is increasing. There are limited medical countermeasures (antidotes) to the range of potential toxic chemicals that might be used, so high-quality clinical care remains key. The effective treatment for specific chemical agents is considered.
These are several magnitudes more potent than fentanyl itself and exist in various physicochemical forms. The US National Institute of Environmental Health Sciences has reported that human exposure via accidental release during a drug house raid, from a ruptured plastic bag in an automobile accident or via a direct inoculation from a sharp/needle are possible owing to the prevalence of these compounds in the criminal drug market.
Keywords CBRN; chemical; MRCP; terrorism
Background Terrorism is the deliberate use of indiscriminate methods to create social disruption and terror. The intent may be ideological, economic, religious or political. Terrorists have deployed chemicals, biological agents or radioactive material, but guns and explosives remain their most common weapon.1 Although chemical, biological, radiological and nuclear (CBRN) weapons (Figure 1) were primarily developed for warfare, in recent years terrorist groups have increasingly used toxic industrial chemicals/pharmaceuticals and classical chemical weapons to attack populations. State-sponsored terrorism can be subcontracted to terrorist groups or sympathizers; when targeted at specific individuals, this is better described as directed assassination (e.g. the alleged murder of Kim Jong-Nam, half-brother of Kim Jongun (Supreme Leader of North Korea), using VX nerve agent). Emergency responders are trained and resourced to recognize and manage a deliberate chemical release and treat casualties on site. The range of toxic chemicals that might be deployed is broad but only a limited number of effective medical countermeasures exist. Possible toxic chemical candidates are organophosphate nerve agents, chlorine, cyanide and opioids. Sarin (a nerve agent) and chlorine have been allegedly deployed in Syria, and sulphur mustard (a vesicant) used by the Da’ish terrorist group. Sarin was released in the Tokyo subway by the terrorist sect Aum Shinrikyo. Cyanide poisoning is most likely to occur in an industrial accident or from smoke inhalation, but the ease of production raises its terrorist threat potential. In the USA, and increasingly in Europe, novel fentanyl analogues are appearing in large quantities on the illicit drug market.
Cyanide Release of hydrogen cyanide gas in a confined space is a serious and immediate threat to life; in the open this is much less. Lowdose inhalation exposure produces nausea, drowsiness and hyperventilation; higher dose exposure rapidly results in reduced conscious level, vomiting, convulsions, hypotension and raised blood lactate concentrations (>10 mmol/litre). The clinical signs progress to coma, with fixed dilated pupils, cardiovascular collapse, respiratory failure and death. There are effective antidotes for cyanide poisoning; use depends on the severity of poisoning. In low-level exposure, oxygen/fresh air can be sufficient, but administration of an antidote is recommended when there is concern about the level of exposure based on clinical features. The first-line treatment used to be dicobalt edetate (KelocyanorÒ) but it was announced in June 2019 that this would no longer be manufactured. Hydroxocobalamin is recommended by the Royal College of Emergency Medicine and the National Poisons Information Service as an effective alternative treatment in severe exposures. Recent studies suggest that very large doses are required.2 After a dose of 5 g (200 ml of 25 mg/ml hydroxocobalamin intravenously over 15 minutes), a second dose of 5 g may be needed depending on the patient’s response. Hydroxocobalamin is effective in smoke inhalation. Sodium nitrite (10 ml of 3% solution (300 mg) intravenously over 5e20 minutes) followed by 12.5 g of sodium thiosulfate (25 ml of 50% or 50 ml of 25% solution) intravenously over 10 minutes is an alternative. This is not recommended in children as sodium nitrite acts by increasing methaemoglobin concentrations.
Stevan R Emmett BSc MB ChB DPhil (Oxon) DoHNs DPM MRSB MFPM is Principal Medical Officer at the Defence Science and Technology Laboratories, Porton Down, Salisbury, UK. Competing interests: none declared.
Opioids There are almost daily reports of the public health crisis in North America arising largely from excessive consumption of opioids and the availability of high-potency fentanyl analogues (e.g. carfentanil) on the illicit drug market. These fentanyl analogues
Peter G Blain CBE BMedSci MB BS PhD FBTS FRBS FFOM FRCP(Lon) FRCP(Edin) is Professor of Environmental Medicine at the Medical Toxicology Centre, Newcastle University, UK. Competing interests: none declared.
MEDICINE xxx:xxx
1
Ó 2019 Published by Elsevier Ltd.
Please cite this article as: Emmett SR, Blain PG, Chemical terrorism, Medicine, https://doi.org/10.1016/j.mpmed.2019.12.008
GENERAL ASPECTS OF POISONING
Figure 1
are transported in bags containing many kilogrammes of fine powder. After airborne release, these highly potent opioid (m) receptor agonists can produce rapid and severe incapacitation in exposed individuals (see Dubrovka Theatre incident, e.g. https:// en.wikipedia.org/wiki/Moscow_theater_hostage_crisis). Unconsciousness can occur within minutes, potentially followed by death from respiratory depression. The diagnostic triad of miosis, respiratory depression and altered conscious state is highly suggestive, but organophosphate exposure must be considered (see below). Decontamination is important, and immediate treatment with high-dose intravenous or intramuscular naloxone (2e5 mg) is vital and is highly effective. Higher doses can be necessary, repeated within 30e40 minutes and continued as a naloxone infusion titrated to the patient’s response. The World Health Organization has noted the long duration of action of some fentanyls, such as carfentanyl, can exceed that of naloxone. Longer acting antidotes, such as naltrexone and nalmefene, are available.
Novichok can result in the same overall toxidrome but one that can be delayed in onset or have a modified symptomatology profile. An intelligence picture, evidence of the toxidrome and positive detection by equipment at the scene can all aid clinical decision-making and differential diagnosis (c.f. opioids). However, it should not delay the use of healthcare worker personal protective equipment and casualty decontamination in the form of clothing removal and dryewet processes (e.g. Fuller’s earth then water).3 ‘Off-gassing’ from casualties is a real concern with volatile agents. It is well established early antidote administration is important and consists of the anticholinergic atropine (2 e5 mg intravenously/orally or 2 mg intramuscularly), as a repeat administration with the dose doubled if required. To avoid irreversible enzyme changes, the oximes pralidoxime (2 g or 30 mg/ kg intravenously/intraosseously by slow infusion) or obidoxime (8 mg/kg intravenously) should be used early as they can reactivate some agents. Anticonvulsants such as diazepam or midazolam can control nerve agent-induced seizures and act as a neuroprotective.
Nerve agents These are a class of potent organophosphorus compounds that irreversibly inhibit the catalytic actions of cholinesterases, resulting in cholinergic excess at neuromuscular and central synapses. Organophosphorus compounds were initially developed for use as pesticides and insecticides (see Poisoning by pesticides on pages xxexx of this issue), but in the 1930s several were found to be highly potent and have the potential for malicious terrorist or assassination use. As recognized by the OPCW these potent agents have different chemical properties (e.g. boiling point, volatility, viscosity) that dictate effective use, and therefore route of exposure of casualties (e.g. gaseous release, liquid application, ingestion), influencing the symptomatology. Sarin has a high vapour pressure (i.e. is volatile), and in temperate or hot conditions is likely to exist as a vapour, so casualties present with the classic cholinergic toxidrome of miosis, bradycardia and bronchorrhoea/bronchoconstriction (seizures, fasciculations); respiratory signs are likely to predominate because of the inhalational route. Conversely, percutaneous exposure to low-volatility agents like VX or
MEDICINE xxx:xxx
Chlorine Chlorine is a greenish-yellow gas at normal room temperature, or is transported as an amber liquid. Liberation as a gas can result from mixing any basic compound containing chlorine substance with an acid. The resulting fumes are highly reactive at moist epithelial surfaces such as those of the eyes, respiratory tract and skin. Tissue damage occurs from generation of hypochlorous and hydrochloric acid and formation of oxygen free radicals. With deliberate release, there can be a spectrum of symptoms and signs depending on the exposure dose. The sensitivity of the respiratory tract means individuals present with chest tightness, cough, wheeze, sore throat and dyspnoea. Low oxygen saturation and hypoxia can be apparent, and there can be evidence of dermal erythema, pain and even chemical burns. The mainstay of clinical management involves decontamination of the casualty by removal of clothing (copious water irrigation) and supportive measures including administration of oxygen and bronchodilators, with the potential addition of
2
Ó 2019 Published by Elsevier Ltd.
Please cite this article as: Emmett SR, Blain PG, Chemical terrorism, Medicine, https://doi.org/10.1016/j.mpmed.2019.12.008
GENERAL ASPECTS OF POISONING
inhaled corticosteroids. In severe exposure with evidence of hypoxia, emerging pulmonary oedema (at 2e6 hours after exposure) and failure to respond to oxygen, continuous positive airway pressure or intubation and ventilation may be required using acute respiratory distress syndrome protocols. A
2 Thompson A, Dunn M, Jefferson R, et al. Modest and variable efficacy of pre-exposure hydroxocobalamin and dicobalt edetate in a porcine model of acute cyanide salt poisoning. Clin Toxicol 2019; Aug 7: 1e11. https://doi.org/10.1080/15563650.2019.1628969 [Epub ahead of print]. 3 Hulse EJ, Haslam JD, Emmett SR, Woolley T. Organophosphorus nerve agent poisoning: managing the poisoned patient. Br J Anaesth 2019; 123: 457e63.
KEY REFERENCES 1 Byers M, Greaves I. Respiratory protection for health care workers. J R Army Med Corps 2006; 152: 225e30.
MEDICINE xxx:xxx
3
Ó 2019 Published by Elsevier Ltd.
Please cite this article as: Emmett SR, Blain PG, Chemical terrorism, Medicine, https://doi.org/10.1016/j.mpmed.2019.12.008