Chemical Burns

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Chemical Burns Radiation Injuries

• Moritz Haager
• Dec. 04, 2003

2
Objectives

• Approach to chemical burns
• Acids, alkali, HF
• Approach to radiation injuries
• Chemical nuclear warfare agents

3
Perspective

• gt 65,000 chemicals in use 60,000 new ones added
  yearly
• Impossible to know each of these
• Health effects mostly unknown
• Important to have a general approach
• Know the common agents
• Important to make use of MSDS sheets Poison
  Centers

4
Chemical Exposure

• Dermal
• Ocular
• Inhalation
• Ingestion
• Systemic effects

5
Determinants of injury severity

• Chemical agent(s)
• Duration of exposure / Penetration
• Concentration pH
• Type of exposure

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Acids vs. Alkali

• Alkali
• Liquefaction necrosis
• Combine w/ proteins saponify lipids
• Deep ongoing tissue penetration
• Difficult to access with hydrotherapy
• Strong bases have pH gt 11

• Acids
• Coagulation necrosis
• Coagulate proteins forming barrier to further
  penetration
• More superficial burns
• Tissues have intrinsic acid buffering capacity
• Strong acids have pH lt 2

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General Approach

• Prehospital
• ED care
• Post-ED care

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Pre-hospital Management

• Scene safety
• Remove pt from danger
• ABCs primary survey
• Immediate decontamination
• Remove contaminated clothing
• Brush off dry chemicals first
• Copious low pressure irrigation
• Identify agent(s) obtain MSDS sheets if possible

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ED Care

• Continue hydrotherapy
• Strong acids 2-3 hrs
• Strong alkali 12 hrs or more!!
• Copious amounts to offset any exothermic reaction
  maximally dilute
• Low pressure to prevent spray contamination

10
ED Care

• Provide analgesia
• Antibiotic prophylaxis Tetanus prn
• Identify Tx Systemic Sx
• Poison center consult to guide ongoing management

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Case 1

• 12 mo M spilled Resolve multi-purpose cleaner
  on his leg
• Mom did not notice for 15 min
• Presents w/ obvious erythema and areas of
  excoriation on R ant leg R wrist
• Also lips red cracked
• No stridor, wheeze, or resp distress
• Vitals normal, rest of exam normal

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Case 1

• MSDS sheet
• Ethylene glycol monobutyl ether, trisodium
  phosphate, nonoxynol-10
• pH 12.0

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Case 1

• Management
• Flush, flush, flush
• Observe cautiously for airway involvement
• IV placed for analgesia possible airway
  management
• Lytes incl. Mg, Ca
• PADIS consult (prior to obtaining MSDS)

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Case 2

• 17 yo M comes in c/o severe pain in all digits of
  his hand worsening since y/d
• Cleaning rusty bicycle chain with rust cleaner
  y/d
• Indurated, tough, whitish finger tips

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Hydrofluoric Acid

• Found in rust cleaners, metal cleaners
• Also used for glass etching electronics
  manufacturing
• Dilute solutions penetrate deeply cause delayed
  Sx onset more severe burn pain can last days
• 14.5 w/v ? immediate Sx
• 12 w/v ? Sx w/in 1hr
• lt 7 w/v ? hrs before Sx develop

16
Hydrofluoric Acid

• Mechanism of Injury
• Corrosive burn (H ions)
• Chemical burn (Fluoride ions)
• Penetrate tissue form insoluble salts w/ Mg2
  Ca2
• Local (tissue destruction necrosis) systemic
  effects (hypocalcemia, hypomagnesemia,
  hyperkalemia) ? arrhythmias
• Concentrated HF (gt50) to 2.5 BSA has been fatal

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HF Approach

• Determine type timing of exposure
• Concentration contact time
• Rule out co-exposures
• Rule out monitor for systemic effects
• Cardiac monitor
• Trousseaus Chvosteks signs, tetany
• Lytes, Ca2, Mg2, ECG (QT)
• Tx for local systemic toxicity

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HF Local Treatment

• Copious irrigation 15-30 min
• Persistent pain indicates deep penetration ? need
  to eliminate Fluoride ion
• Debride blisters necrotic tissue
• Fluoride chelation
• Ocular burns
• sterile water or saline irrigation (may need
  local anesthetic drops)
• Persistent pain ? 1 calcium gluconate irrigation
  (10 solution in 10x volume of NS)
• Inhalation burns
• 100 oxygen by mask, 2.5 calcium gluconate by
  nebulizer
• Watch for pulmonary edema
• Ingestions (Usually fatal)
• Consider gastric lavage with calcium chloride
  (i.e., 20 mmol calcium in 1000 cc NS) if early
  presentation
• Intubate prior to lavage

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Fluoride Chelation Calcium gluconate

• Topical gel
• 2.5 10 Ca gluconate in 3x volume of muco or
  KY jelly e.g. 25 ml in 75 ml muco) in latex glove
  persistent pain after 30 min indicates need for
  SC or intraarterial Ca2
• Wear glove for 24 hrs
• SC infiltration of 5-10 Ca gluconate at 0.5
  ml/cm2
• Consider regional anesthesia b/c severe pain
• Intraarterial infusion
• 10 ml 10 Ca gluconate in 50 ml D5W over 4 hrs
  into radial or ulnar artery repeat if pain
  persists / returns within 4 hrs
• 20 ml of 20 Ca gluconate in 80 ml D5W repeat in
  12 hrs prn
• Watch for pain, arterial spasm, thrombosis ?
  tissue necrosis and digit loss have occurred
  following extravasation of calcium salts
• NB KCL is more irritating damaging therefore
  use Ca gluconate

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HF Systemic Treatment

• Evidence of hypocalcemia
• 10 ml of 10 CaCL IV empirically
• Repeat prn
• Follow w/ serial lytes ECG until normalizes

21
Case 3

• 24 yo F grad student spilled phenol on her sleeve
  brief rinse then continued to work
• Presents feeling lightheaded, nauseated, and
  drowsy

22
Phenol

• Aromatic acidic alcohol
• Plasticizer, antiseptic, used for DNA extraction
  in labs
• Dilute solutions less likely to cause papillary
  necrosis therefore tend to penetrate more quickly
• Locally causes acidic burn
• Systemic absorption leads to CNS depression ?
  coma resp arrest, as well as hypotension,
  metabolic acidosis, hypothermia

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Phenol Treatment

• Copious irrigation
• Polyethylene glycol 200 or 400 or isopropyl
  alcohol most effective, but can use water (just
  use LOTS)
• PEG can be used for ocular exposures
• Physiologic support for systemic Sx
• Tx in well ventilated room

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Case 4

• You are w/ MSF in the jungles of Cambodia
• A young boy is brought in w/ severe burns after a
  friend stepped on unexploded ordinance which then
  blew up in a brilliant white flash killing his
  friend and showering him with burning debris

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Phosphorus

• Waxy yellow solid spontaneous ignition in air gt
  34oC
• Used in munitions, insecticides, rodenticides,
  pesticides
• Will continue to burn on skin
• Firebombing of Dresden in WWII
• Primarily causes thermal burns
• Systemic effects metabolic in nature
• Hypocalcemia, hyperphosphatemia ?
  bradyarrhythmias

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Phosphorus

• Treatment
• Submerse affected areas in COOL water, or cover
  in wet towels
• Wash off w/ 5 Na bicarb 3 CuSO4 in 1
  hydroxyethyl cellulose solution
• Phosphorus particles turn black
• Phosphorus particles fluoresce under UV light

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Highlights

• Formic acid
• Bicarb for acidosis, may need HD or exchange
  transfusions for systemic toxicity
• Anhydrous ammonia
• Alkali burns
• High danger of inhalational injury
• Elemental metals
• Na K react w/ water to produce heat H2 gas
  OH-
• Remove metal fragments place in mineral oil or
  isopropyl alcohol (Na) or terbutyl alcohol (K)

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Part II Chemical Warfare Agents
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Why we should know this

• Increased potential for terrorist use
• Relatively easy to make or obtain
• Most are simple derivatives of precursor
  compounds in manufacture of plastics, pesticides,
  fabrics
• Non-traditional chemical agents can be used as
  weapons in the right setting
• Bhopal methyl isocynate (2000 dead)

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Chemical Warfare Agents

• Choking (pulmonary) agents
• Chlorine, Phosgene
• Vesicants (Blister agents)
• Mustards, halogenated oximes
• Nerve agents
• G agents (Sarin, tabun, soman), VX
• Cyanide agents
• Improvised agents

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Vesicants

• 3 subclasses
• Mustards
• Arsenicals
• Halogented oximes
• Produce cutaneous, ocular, mucous membrane,
  pulmonary burns
• Less lethal (primarily kill via pulmonary
  involvement) but highly morbid
• Effects tend to be delayed
• Easy to manufacture or obtain

32
Mustard Agents

• Sulfur mustard prototype
• Designated H, or HD
• Easy inexpensive to produce
• Most dangerous agent in WWI
• Low lethality (1-3) but high morbidity
• Most recent use by Iraq in Iran-Iraq war
• Low volatility, high persistence
• Delayed Sx onset (may take up to 12 hrs) ?
  prolonged exposure

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Mustard MOA

• Radiomimetic
• Contaminates environment
• Penetrates clothing skin easily w/o visible or
  perceptible effects
• Precise cellular action unknown but acts similar
  to alkylating agents
• Inhibits glycolysis ? cellular death
• Primary tissue irritant
• DNA, RNA, protein damage
• Mutagenic, carcinogenic, teratogenic
• Poorly soluble in water dissolves readily in
  skin oils
• Predilection for moist areas of body
• (eyes gt resp tract gt scrotum gt face gt anus)

34
Mustard Clinical Effects

• Ocular
• Corneal ulceration, iritis, blindness
• Respiratory
• URT irritation, chemical pneumonitis respiratory
  failure, death
• GI
• N V
• Hematologic
• Bone marrow suppression, pancytopenia
• CVS
• CV collapse, shock, death
• Immune system
• Immunosupression, sepsis
• Dermal
• Cutaneous burns

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Mustard Treatment

• Decontamination
• Prior to entry into medical facility
• Protect workers
• Remove all clothing (contaminated)
• 0.5 hypochlorite (bleach) irrigation
• Debride decontaminate bullae
• US Military kits
• 2 sets of paper towels soaked with phenol
  hydroxide followed by chloramine
• Adsorbents (flour, talcum powder)
• Water less ideal b/c poor solubility but may use
  in large amounts if nothing else available
• Ocular exposures should be rinsed w/ 2.5
  thiosulfate soln then topical abx,
  cycloplegics ? optho consult

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Mustard Treatment

• No antidote Tx is supportive
• Bronchodilators, O2, steroids, bronchoscopy,
  mechanical ventilation
• Analgesia
• Tx cutaneous injuries like burns
• Most pts recover completely
• Factors associated w/ poor prognosis
• Erythema gt50 BSA
• Dyspnea w/in 4-6 hrs of exposure
• Respiratory failure
• Bone marrow suppression

37
Mustard Burns
38
Mustard as a terror weapon

• Difficult to detect, delayed onset
• Potent, w/ significant morbidity
• Easy to make, store, transport, deliver
• Bombs, aerosol, vapour, rockets, canisters
• 9 openly documented manufacturing methods that
  can be done with high school lab supplies in
  someone's basement (the MDA of terrorism if you
  will)
• Cheap
• Persistent difficult to clean up
• Sig. experience in mid-east due to use in
  Iran-Iraq war

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Halogenated Oximes

• Phosgene oxime (CX, dichloroform oxime)
• Also known as urticariants or nettle gases
• Fair water solubility
• Immediate Sx onset unpleasant odor
• No confirmed battlefield use
• Penetrates clothing, rubber, skin rapidly
  (secs)
• Enhances penetration of other agents
• 2 proposed MOAs
• Direct injury due to corrosive effect enzyme
  inhibition
• Indirect injury due to alveolar macrophage
  activation secondary pulmonary injury (delayed)

40
CX Clinical effects

• Immediate effects absorption
• Mild irritation ? severe pain
• Skin has grayish blanched appearance
  surrounding erythema which can go on to blister
  or form hives pruritus
• Turns brown into dark eschar over 24h 1 wk
• Also immediate conjunctivitis ocular pain

41
CX Treatment

• No antidote
• Decontaminate Supportive Care
• US military
• M291 decontamination kits
• Flush w/ large amounts of water

42
Improvised Agents

• Military terrorist mission goals differ
• Many chemical deemed poor for warfare more than
  appropriate for terror attacks
• Thousands of commercial compounds can potentially
  become weapons
• E.g. 911 jetliners turned into bombs
• CDC threat list
• 11 categories of diverse potential biological
  chemical weapons
• Underscores need for generalized approach
  disaster planning

43
General Guidelines

• Prehospital decontamination ideal
• Assume decontamination has NOT occurred
• Protective clothing
• No PPC suit can protect against all agents, but
  Level A suits are best
• Latex gloves useless nitrile much better

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Part III Radiation Injury
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Quiz

• How large were the atomic (fission) bombs dropped
  on Hiroshima Nagasaki?
• Equivalent to 12,500 20,000 tons of TNT
  respectively
• 66, 000 people instantly died 69,000 injured in
  Hiroshima
• Blast radius was 3 miles in diameter
• What are modern (fusion) thermonuclear warhead
  yields?
• In the mega ton range (largest ever detonated 100
  MT)
• What was is the lethal radius of a 10 KT weapon?
  A 20 MT weapon?
• 3 miles vs. 35 miles
• How many nuclear devices have been detonated?
• A gt 2000 tests, gt500 above ground
• How many nuclear warheads were held at the height
  of the Cold War?
• Over 69,000 in 1985
• How many now?
• 32, 000 gt 10,000 MT TNT

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Basics

• Ionizing radiation
• Short wavelength, high frequency
• High energy 1 billion x that of non-ionizing
• UV, X, ? rays a ß particles neutrons
• Released by unstable atomic particle decay
  radioactivity
• Ability to knock electrons out of orbit of other
  atoms (ionize them)

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Ionizing Radiation
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Units

• SI Units
• Sievert (Sv) exposed dose or dose equivalent
• 1 Sv 1 Gy
• Gray (Gy) absorbed dose
• 1 Gy 1 joule energy absorbed / Kg tissue
• Becquerel (Bq) activity
• Older Units
• Rem radiation equivalent man
• 1 rem 0.01 Gy
• Rad radiation absorbed dose
• 1 rad 0.01 Sv
• Roentgen (R) exposure
• 1 R 0.01 Gy
• Curie (Ci) activity
• 1 Bq 27 pCi

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Real Life Examples

• 1 CXR 0.02 mSv
• Background radiation 3 mSv / yr (150 CXRs)
• AXR 1.5 mSv (75 CXRs)
• Abdominal CT 6 8 mSv (300-400 CXRs)
• Background radiation in affected parts of
  Belarus, Ukraine, Russia 6 -11 mSv / yr (300
  550 CXRs)
• Firefighters in Chernobyl 0.7 13 Sv (35,000
  650,000 CXRs)

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Types of exposure

• External radiation
• E.g. X-rays
• Only neutrons can produce radioactivity
• I.e. a pt exposed to other radiation is NOT
  radioactive poses no risk to others
• External contamination
• E.g. radioactive spill in lab
• Incorporation internal contamination
• Ingestion, inhalation, open wounds

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Radiation MOA

• Direct effects
• Ionization damage of molecules (e.g.
  cross-linking of DNA)
• 100 mGy -- get ssDNA damage (reparable)
• 0.5 - 5 Gy -- dsDNA damage (irreparable)
• Indirect effects
• Ionization of H2O to H2O radical ? decays to
  free radicals which react with damage other
  molecules

52
Determinants of severity

• Dose rate
• How fast a given dose is delivered
• Energy
• Total dose
• Total vs. partial exposure
• Tissue(s) exposed (radiosensitivity)

53
Radiosensitivity

• Three laws of radiosensitivity
• Bergonie Tribondeau, 1906
• Varies directly w/ rate of cell proliferation
• Varies directly w/ of future divisions
• Varies inversely w/ degree of morphologic
  functional differentiation
• Lymphocyte is the exception most
  radiation-sensitive cell in body

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Human Radiation Effects

• Deterministic (non-stochastic)
• Threshold dose
• Effect is not seen if threshold dose is not
  exceeded
• See dose-response curve
• Effects manifest w/in mins wks
• E.g. ARS

• Stochastic
• No threshold dose
• Controversial
• Not all exposed individuals manifest the effect
• No clear dose-response curve
• Effect less pronounced at high exposures
• E.g. radiation-induced carcinogenesis

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Radiation Injury Scenarios

• Nuclear device detonation
• Military use (e.g. Hiroshima, Nagasaki)
• Terrorist use
• Dirty bombs
• RDD (radiation dispersal device)
• Industrial accidents / spills
• Chernobyl, Three mile island
• Medical Research
• Radiation Tx, Radioisotope spills

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Nuclear Detonation

• Blast thermal effects
• Most significant injuries acutely therefore Tx
  conventional injuries first
• Megaton yield weapons ? lethal radius from blast
  thermal effect larger than that for radiation
  effect Radiation effects
• Radiation effects
• Intense neutron gamma ray release
• Fallout
• Radioactive particulate matter (soil etc)
  following significant radiation release or
  nuclear explosion
• Can poison food chain render area uninhabitable
  for yrs
• Can travel great distances (e.g. Chernobyl)

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Acute Radiation Syndrome

• Most common cause of death in 1st 60d following
  external whole body irradiation
• Divided into sequential subsyndromes
• Hematopoietic (1- 5 Gy)
• Gastrointestinal (6-30 Gy)
• CVS / CNS (gt30 Gy)
• 4 separate stages
• Prodromal, latent, manifest illness, recovery
• Timing of stages subsyndromes inversely related
  to dose received
• LD50 for radiation is estimated to be 4.1 Gy
  (95CI 2.55 5.5)

60
ARS Prodromal Latent Phase
Dose (Gy) Onset (h) Duration (h) Latency
0.5 2 6 lt 24 3 wks
2.1 3.5 2 6 12 24 2 3 wks
3.6 5.5 1 2 24 1 2.5 wks
gt 5.6 Mins 1 48 2 4 days
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ARS Prodromal Phase

• 1o Sx are N V, diarrhea (occ bloody)
• Anorexia, weakness, fatigability
• Time of onset inversely related to dose
• Duration severity directly related to dose
• Mild Sx occurring 2 hrs post-exposure lasting
  lt 24 h usually imply dose lt 2 Gy

62
ARS Latent Phase

• Duration inversely related to dose
• Hrs - wks
• May be asymptomatic w/ lower doses
• More at risk for infection
• Delayed wound healing
• Critical to monitor closely

63
ARS Illness Phase

• Hematopoetic (1 5 Gy)
• Delayed onset of pancytopenia due to stem cell
  irradiation
• Death due to sepsis /- hemorrhage
• Takes mos yrs to recover
• Lymphocyte platelet counts can be used to
  estimate exposure guide mgmt

Lymphocyte count 24-48 h post-exposure (x1000 / mm3) Estimated Dose (Gy)
3.0 0.25
1.2 3.0 1 2
0.4 1.2 2 3.5
0.1 -0.4 3.5 5.5
lt 0.1 gt 5.5
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ARS Illness Phase

• Gastrointestinal (6 -30 Gy)
• GI stem cell death ? breakdown of intestinal
  mucosa w/ hemorrhages, fluid electrolyte
  shifts, bacterial translocation
• Sepsis
• Malnutrition
• Paralytic ileus
• Hypovolemia electrolyte imbalances

65
ARS Illness Phase

• CVS / CNS (gt 30 Gy)
• Direct damage to CNS CVS tissues
• C/o burning pain of skin w/in mins
• Pyrexia, ataxia, elevated ICP coma, hypotension
  w/in mins - hrs

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Other Radiation Injuries

• Skin burns
• Transient erythema w/in hrs
• Secondary erythema w/in 5 21d
• Timing inversely proportional to dose
• Low doses ? progress to dry desquamation
• High doses ? wet epidermitis blisters
• Tx same as thermal burns /- steroid creams
• Acute radiation pulmonitis
• Severe dyspnea, thundering creps
• High dose exposure almost universally fatal
• Psychological Impact
• Chronic Health effects

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Radiation Injuries Management

• Triage
• Radiation injury unlikely
• Absence of prodromal N V D
• Probable radiation injury (survivable)
• Group most likely to benefit from intensive
  medical care
• Severe radiation injury (usually fatal)
• Analgesics, comfort measures

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Radiation Injuries Management

• External Decontamination
• Should occur ASAP prehospital if possible
• Showering or washing w/ soap water achieves
  95 decontamination
• Debride clean open wounds
• Risk to medical personnel exposed to contaminated
  persons appears to be minimal
• Monitor w/ whole body radiation counters, Geiger
  counters, thyroid scanners bioassay sampling

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Radiation Injuries Management

• Internal Decontamination
• Knowledge of radioisotope important to guide
  management
• Decrease absorption
• Cathartics, SBL, charcoal, BAL for severe
  inhalation
• Increase elimination
• Chelation
• Block uptake / incorporation
• Antidotes E.g. potassium iodide (need to start
  w/in 12-24h at latest)
• Bioassay Geiger counts on urine feces to
  guide ongoing Tx

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Chelators Radioactive isotope (from D. Watts
talk)

• Prussian blue
• Penicillamine
• Chlorthalidone
• Deimercaprol
• Deferoxamine
• Ca-EDTA
• Zn-DTPA

• Cesium
• Cu, Co, Ag, Pb, Hg
• Rubidium
• Polonium
• Iron
• Cd, Cr, Pb, Zn
• All the weird ones American names

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Radiation Injuries Management

• Medical Tx
• Largely supportive
• Symptomatic Tx
• Infection control
• Serial CBCs
• Transfuse if plts lt 20
• CSF may be useful
• Bone marrow transplant may be necessary
• Any necessary surgery should occur either w/in 36
  hrs otherwise wait at least 3 mos
• Fibroblasts osteoblasts radiosensitive --
  impaired wound healing

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Radiation Injury Chronic Risk

• Stochastic effects
• Highly controversial topic
• While exposure to radiation appears to increase
  risk of CA, birth defects, and other health
  problems we still dont know what a safe dose
  is
• Most people think risk of exposure is cumulative
  but even this is not clear-cut
• One very large single dose likely more harmful
  than same dose over long time period
• Mutation rate in crops of contaminated regions in
  Europe 6x higher than elsewhere
• Increased incidence of thyroid CA
• Increased incidence of various CAs in atomic
  bomb survivors aftermath of Chernobyl w/
  exposures gt 50 - 100 mSv
• Studied hindered by methodological flaws --
  difficult to determine precise risk for an
  individual exposed to increased radiation

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