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