Clinical Issues with hazardous chemicals, biological agents and nuclear radiationDr Aroop Mozumder CBFRCGP FFPH DMCC MSc DTM&H DAvMed FRAeS
Dean Worshipful Society of Apothecaries
Research Fellow University of Oxford
Chemical agents - Classification
CASUALTY EFFECT
Lethal AgentsKill
eg Phosgene (CG), Hydrogen Cyanide (AC), Nerve
Damaging (Casualty) AgentsMainly non-lethal, but long-term disablement likely
eg Blister Agents
Incapacitating AgentsNon-lethal short-term disablement
eg CS, BZ
Choking AgentsAttack the lungs, filling them with fluid
Chlorine, Phosgene (CG)
Onset of effects delayed
Treatment
Remove to clean air
Absolute rest
Oxygen
Hospitalisation
Chlorine
Old warfare agent : WW1, Iraq 2003-11, Syria 2014
Cheap and efffective
Yellow-green gas, heavy
Pungent odour
Chlorine on moist tissues can produce hydrochloric acid
Blurred vision
Burning of eyes, chest, bronchospasm
Severe breathing difficulty
Severe Pulmonary oedema (few hours)
Treatment of Chlorine poisoningSupportive treatment
Remove clothes and shower – full decontamination as for corrosive chemicals (tepid soapy water)
Ocular washout with saline
Oxygen
Bronchodilators
Monitor fluid balance (and blood gases)
Monitor cardio-vascular state
Treat wounds – irrigation, analgesia
Blood Agents
Interfere with handover of oxygen from blood to tissues
Hydrogen Cyanide (AC), Cyanogen Chloride (CK)
Supportive treatment only
Oxygen
Ventilatory and CVS support
Blister (Vesicant) AgentsAttack the skin, causing painful, slow-healing blisters
Mustard (H, HN), Lewisite (L)
Damaging agents, very persistent
Treatment Removal from contamination
Decontamination
Nerve Agents
Interfere with synaptic junction between the brain and voluntary muscles
Damages Acetylcholinesterase
Synapse flooded with neurotransmitter acetylcholine
Tabun (GA), Sarin (GB), Soman (GD), Cyclosarin (GF), VX,
Novichok
Treatment is complex and specific, and outcome is improved by pre-treatment (prophylaxis)
Clinical picture: Very rapid onset of symptomsCyanide
Rapid breathing/gasping/respiratory arrestSinus tachycardiaCardio-respiratory arrestCNS- dizziness, headache, convulsions ,comaFixed unreactive pupils
From thermal decomposition of polyurethane
Hydrogen SulphideRespiratory and eye irritationSymptoms similar to cyanides
Rapid onset of symptoms (minutes-hours)
Nerve agent
Tight chest
Secretions +++
Sinus bradycardia
Painful dim vision
Pin point pupils
Muscle weakness fasciculation
Involuntary defaecation/urination
Good response to atropine is highly suggestive
Rapid onset of symptoms (minutes-hours)
Opioids/fentanylRespiratory depression leading to respiratory arrestDepressed level of consciousnessComa and convulsions in late stagesPin point pupils in severe toxicityCholinergic crisis- invol contraction of skeletal musclesGood response to naloxone is suggestive
Toxic Industrial ChemicalsOften distinctive smellRespiratory irritationEye irritationDyspnoena/stridorBronchospasm
Nerve Agents – Pre-treatment
Current pre-treatment utilizes carbamate anticholinesterases, e.g., pyridostigmine.
They bind cholinesterases reversibly, preventing the organophosphate (OP)within the nerve agent binding to the enzyme.
There is NO pre-treatment available for BZ and its analogues.
Nerve Agents - Treatment
Symptomatic treatment may be all that is necessary for many casualties, depending on their level of exposure.
Pharmacologically, use:Anticholinergics (Atropine) to antagonise the muscarinic effects .Oximes to reactivate inhibited enzyme and antagonise the nicotinic effects.Anticonvulsants to prevent seizure activity and protect against subsequent CNS damage. BZ casualties may be treated with Physostigmine.
Atropine Poisoning
Dry mouth
Large pupils (nb Belladonna)
Blurred vision
Tachycardia
Hallucinations
Delirium
Nerve Agents - TreatmentAtropine 2mg iv every 5 minutes Toxic dose of atropine is close to therapeutic doseMonitor dose against bronchospasm
Pralidoxime chloride 30mg/kg iv then bolusesPrevents “ageing” of acetylcholinesterase and some reactivation (not
Novichok)
Diazepam 10mg iv as required – for convulsionsVentilatory support and oxygenLasting nerve damage reported
NB Organophosphorus insecticides – similar but slower onsetMuscarinic effects – GI and respiratory, headacheThousands of annual deaths Treat with atropine
Novichok – Russian for “newcomer”
4th generation nerve agent developed in USSR/Russia
10 times potency of VX
Binary weapon – needs mixing from two relatively safe pre-cursors, beats CW Convention
Difficult to detect
Persistent agent
Treat as any other nerve agent
Novichok
Lasting nerve damage
Russian laboratory workers
Permanent disability
Chronic weakness
Toxic hepatitis leading to cirrhosis
Epilepsy and depressive illness
Wilfred Owen: Dulce and Decorum Est Bent double, like old beggars under sacks,Knock-kneed, coughing like hags, we cursed through sludge,Gas!(7) Gas! Quick, boys! – An ecstasy of fumbling,Fitting the clumsy helmets(8) just in time;But someone still was yelling out and stumbling,And flound'ring like a man in fire or lime(9) . . .Dim, through the misty panes(10) and thick green light,As under a green sea, I saw him drowning.In all my dreams, before my helpless sight,He plunges at me, guttering,(11) choking, drowning.If in some smothering dreams you too could paceBehind the wagon that we flung him in,And watch the white eyes writhing in his face,His hanging face, like a devil's sick of sin;If you could hear, at every jolt, the bloodCome gargling from the froth-corrupted lungs,Obscene as cancer, bitter as the cud(12)Of vile, incurable sores on innocent tongues,My friend, you would not tell with such high zest(13)To children ardent(14) for some desperate glory,The old Lie; Dulce et Decorum estPro patria mori.(15)
Thought to have been written between 8 October 1917 and March, 1918
Biological AgentsBIOLOGICAL WARFARE (BW) is the deliberate
dissemination of micro-organisms to cause LETHAL or INCAPACITATING EFFECTS in the armed forces or civilian population of an adversary or to destroy domestic animals or food crops
Favoured BW AgentsOrganism
Bacillus anthracis
Francisella tularensis
Yersinia pestis
Brucella spp
Variola major
VEE
Clostridium botulinum
Ricin
Disease
Anthrax
Tularaemia
Plague
Brucellosis
Smallpox
VEE
Botulism
Critical BW AgentsCategory
1. Highly infectious or easy dissemination; high mortality and major public health crisis
2. Moderately easy to disseminate, moderate impact
3. Emerging and possible genetically engineered agents
Pathogens
Anthrax, Smallpox, Botulism, Plague
Q fever, Brucellosis, influenza, water borne pathogens
VHFs, drug resistant TB, Encepahalitis viruses
AnthraxBacillus Anthracis
Gram positive rods
Contaminated wool, hides
Cutaneous anthrax fairly common
Cutaneous anthrax treatable
Anthrax spores readily weaponised
High survivability in weapons
LD50 – 10,000 inhaled spores per person
Known to be weaponised in Russia and Iraq
Sudden onset flu-like symptoms
Proceeding to severe cough, myalgia, then shock, tachycardia and cyanosis
Death within 24 hrs of acute phase onset
Untreated pulmonary anthrax CFR >90%
PlagueBacterial zoonosis
Causative organism is Yersinia pestis, a Gm-ve rod-shaped coccobacillus.
Usually found in small mammals & their fleas
Humans can be infected through:the bite of infected vector fleasunprotected contact with infectious bodily fluids or
contaminated materialsthe inhalation of respiratory droplets/small particles
from a patient with pneumonic plague
Very dangerous disease in humans:CFR
30-60% for untreated bubonic plagueCa. 100% for untreated septicaemic & pneumonic plague
Photo: doc-stock.com
Treatment of Plague in 17thC
Doctrine of 4 humours
Blood letting and purging
Mithridantium
Up to 41 herbal ingredients from Galen 2ndC
Theriac
Up to 64 ingredients
Treatment of plague- 21stC
Antibiotics & supportive therapy are effective if patients are diagnosed in time
CFR:bubonic plague: 1–15% in treated vs 30 - 60% in untreated casessepticaemic plague: 4–15% in treated vs 40 - 100% in untreated casespneumonic plague: 1-10% in treated vs ca. 100% in untreated cases
pneumonic plague can be fatal within 18 - 24 hours of onset if untreated
Several classes of antibiotics are effectiveaminoglycosides (streptomycin & gentamicin)tetracyclines(especially doxycycline)fluoroquinolone (ciprofloxacin)
Supportive treatment includes oxygen and intravenous fluids
Plague as a Bio Weapon?WW2 Japan developed “Flea-bomb” Uji-50
Plague fleas and flour
Flour attracted rats
Used on Manchurian villages -dead rats and bubonic plague spread
? Kamikaze bombers plan for San Diego “Operation Cherry Blossoms at Night”
1995 White supremacist in Ohio acquired Y.Pestis
1970 report WHO – 50kg Y Pestis bacteria sprayed over a city of 5m could cause 150k cases and 36k deaths
Signs, symptoms and types
Pneumonic plaguethe most virulent formincubation can be ca.24 hours cases can transmit the disease via droplets to
other humans can be fatal if not diagnosed & treated early.
Recovery rates high if detected & treated within 24 hours of symptom onset
Septicaemic plaguerare but highly lethal form patients can develop an overwhelming
septicaemia with DIC
Simulation of BW releaseAnthrax powder from a truck passing a sports stadium of 74,000
!6,000 potentially infected
25% mortality
WHO 1970-
500k city
Potential for 100k deaths if aerosolised and delivered by air at high doses
Plague can be disseminated by air
or by infected rats
Real example - Japanese use in Manchuria in 1930s –flour bombs contaminated with infected fleas
Radiation Facts- Ionising Alpha Particles
- charged- few cm- Inhaled/ingested
Beta Particles –- charged - Ingested/ inhaled hazard, PPE some protection
Gamma Rays- High energy photons-organ damage
Radiation FactsRadioactivity measured in Bequerels (1Bq = 1 Radioactive decay per second)
Absorbed dose of radiation measured in Grays
1Gy = 1 joule/kg of tissue
Weighting factor for types of radiation, so absorbed dose measured in Sieverts accounts for this
Eg X Rays and Gamma rays weighting factor is 1
Therefore 1Gy= 1Sv
CXR = 20microSV
Annual background radiation in UK 2,700 mcSv
Acute radiation injury – above 1SV
LD 50 is around 4.5 SV
Radiation Dispersal Devices –‘Dirty Bombs’IAEA – ‘..up to 1 000 sources go missing every year’
Mainly from Former Soviet Union
Organised crime involvement
Terrorist organisations
‘Red mercury’
‘Nuclear hand grenades’
Explosive charge combined with a suitable source.
Radiation InjuriesMost harm to rapidly dividing cells
Bone marrow
Skin
GI tract
Alopecia
One serious incident a year average –death or serious injury
Dirty bomb – explosive plus radioactive dispersal
Low yield nuclear device
Acute radiation injuryMost radiation accidents -partial injury:
Early erythema
Bullae
Skin necrosis
Acute radiation sickness (homogenous exposure)
Non specific nausea & vomiting
Bone marrow failure
GI/Skin injuries, alopecia
Survival with active treatment (eg bone marrow transplant) now around 12 Sv possible
Radiation injury treatmentCurable radiation injuries (2-15 Sv)
Bone marrow monitoring and transplant if required for haemopoetic syndrome
Symptomatic GI tract treatment
Reverse isolation
Manage vital signs
Enteral nutrition
Fluid balance
Monitor increased cancer risk
Radiation injury treatment
Incurable radiation injuries (>20 Sv)
Multi-organ failure
Vomiting
Severe headache
Symptom control only
Death in 1-3 days
Questions?References:
Centers for Disease Control (CDC):Emergency Preparedness and Response
Public Health England :Chemical, Biological, Radiological and Nuclear incidents Handbook
Jane’s Chem-Bio Handbook
Kumar & Clarks Textbook of Medicine
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