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Basics of Treatment of Victims of Radiation Terrorism or Accidents. Niel Wald, M.D. Dept. of Environmental and Occupational Health University of Pittsburgh. Medical Radiation Problems. External Radiation Source: Local Radiation Injury Acute Radiation Syndrome

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Basics of Treatment of Victims of Radiation Terrorism or Accidents

Niel Wald, M.D.

Dept. of Environmental and Occupational Health

University of Pittsburgh


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Medical AccidentsRadiation Problems

External Radiation Source:

  • Local Radiation Injury

  • Acute Radiation Syndrome

    Radionuclide Contamination:

  • External

  • Localized in Wound

  • Internal


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LOCAL RADIATION INJURY: RADIODERMATITIS Accidents

TypeManifestation

I Erythema

II Transepidermal Injury

III Dermal Radionecrosis

IV Chronic Radiodermatitis


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Local Injury: Transepidermal Accidents (Beta Radiation + Thermal Burns)



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Local Radiation Injury AccidentsPXD 22


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Local Radiation Injury AccidentsPXD 90


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Local Radiation Injury Therapy Accidents

AMPUTATION STAGES

Upper Extremities

Left

Right

4

mo

5

mo

5

mo

5

mo

6

mo

7

mo

7

mo

10

mo

12

mo

17

mo




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Local Radiation Injury AccidentsPXD 29


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Local Radiation Injury AccidentsPXD 92


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Local Radiation Injury Diagnosis Accidents

  • Inspection: Erythema

  • Blood Flow: Thermography; Isotope scanning (201Tl scintigraphy); Skin laser Doppler.

  • Tissue Density and Hydration: MRI; CT;

    67Ga scintigraphy; 111In-labeled anti-myosin

    antibody scan.

    .


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Useful Steps in Clinical Care of Accidents Local Radiation Injury

  • History and Physical Examination

  • Serial Blood Counts

  • Chromosome Analysis

  • Re-enactment of Accident

  • Frequent Color Photographs

  • Baseline Extremity X-rays

  • Ophthalmologic Slit Lamp Examination

  • Sperm Counts

  • Surgical Consult


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Local Radiation Injury Therapy Accidents

  • Analgesics, Antipruritics

  • Anti-inflammatories

  • Antibiotics as needed

  • Skin Growth Factors

  • Synthetic Occlusive Dressings

  • Surgical Intervention:

    • Debridement

    • Excision and Grafting

    • Amputation




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Acute Radiation Syndromes Accidentsand Their Management

  • Key underlying pathophysiology at the cell and organ level

  • Description of syndromes

  • Diagnostic procedures

  • Clinical care

589-1


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Acute Radiation Syndromes Accidents

  • Underlying Cellular Radiation Effects

    • Mitotic inhibition

    • Cell killing

    • Organ malfunction

    • Vascular reactions

  • Clinical Manifestations

    • Hematological

    • Gastrointestinal

    • Neurovascular

    • Pulmonary



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Prodromal AccidentsSymptoms & Signs

NeurogenicVascular

Anorexia Conjunctivitis

Nausea Skin Erythema

Vomiting

Diarrhea

Fever

Weakness


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Radiation Erythema Accidents(PXD 10)


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Radiation Epilation Accidents(PXD 23)





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Hematopoietic Syndrome Systemic Effects Accidents

  • Immunodysfunction

    • Increased Infectious Complications

  • Hemorrhage

    • Anemia

  • Impaired Wound Healing



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Mechanism of GI Syndrome Accidents(Gunter-Smith Hypothesis)

627-1


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GI Syndrome Systemic Effects Accidents

  • Malabsorption

  • Ileus

    • Vomiting

    • Abdominal distention

  • Fluid and Electrolyte Shifts

    • Dehydration

    • Acute renal failure

    • Cardiovascular

  • GI Bleeding

  • Sepsis


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ARS: Neurovascular Form Accidents

EXCITATION

PHASE

38-E



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HYPOTHALAMIC SYSTEM Accidents

322-1


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Neurovascular Syndrome Systemic Effects Accidents

  • Vomiting and Diarrhea within Minutes

  • Confusion and Disorientation

  • Severe Hypotension

  • Hyperpyrexia

  • Cerebral Edema

  • Convulsions - Coma

  • Fatal within 24 to 48 Hours



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ARS- Pulmonary Form Accidents (exudative stage)


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ARS- Pulmonary Form Accidents(fibrotic stage)


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Pulmonary Syndrome Systemic Effects Accidents

  • Early Phase

    • Dyspnea

    • Cough

    • Pulmonary Edema

    • Acute Respiratory Distress Syndrome

  • Late Phase

    • Interstitial Fibrosis

    • Interstitial Pneumonitis

    • Chronic Respiratory Distress Syndrome


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Acute Radiation Syndrome Accidents

Clinical Management Problems

  • Psychological Stress

  • Infection

    • Bacterial, viral, fungal, CMV, herpes

  • Hemorrhage

  • Radiation Enterocolitis

  • Radiation Pneumonitis

  • Combined Injuries

    • Radiation plus trauma, burns, etc.

648-4


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General Treatment Plan for External Exposure Accidents

  • Provide Psychological Support

    • Professional

    • Family

    • Clergy

  • Use Symptomatic Treatment

    • Antiemetics

    • Analgesics

  • Prevent Infection and Hemorrhage

    • Reverse Isolation

    • Antibiotics

    • Blood Products


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General Treatment Plan (cont.) Accidents

  • Maintain Hydration and Nutrition

    • Fluids

    • Electrolytes

    • Nutrients

  • Encourage Cell Renewal

    • Growth Factors

    • Stem Cells

  • Control Inflammatory Response

    • Steroids

    • Vasodilators


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Psychological Stress Reducers Accidents

  • One Responsible Decision-Maker

  • Realistic Appraisal of Problem and Clear Communication

  • Credible Action Plan and Adequate Resources

  • Pre-Emergency Education


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Infection Problems Secondary to Radiation Pancytopenia

  • Invasion and colonization of rectal or colonic wall by normal flora

  • Activation of latent infections

  • Opportunistic infections

    • Gram Negative

    • Staphylococcus Aureus

56-J


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General Anti-Infection Measures in Radiation Pancytopenia Pancytopenia

  • Control Bacterial and Fungal Flora of

    • Naso-Oro-Pharyngeal Tract

    • Gastrointestinal Tract

  • Avoid Disruption of Skin and Mucosa

  • Introduce Environmental Control

  • Use Optimal Regimen vs. Overt Infection


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Selective Bacterial Decontamination Pancytopenia

  • Some Oral Agents that have been used:

    Nasopharyngeal Tract:

    • B-Lactam Resistant Penicillins p.o. and Bacitracin to nares

      Gastrointestinal Tract:

    • Trimethoprim-Sulfamethoxazole or Polymixin + above, or Polymixin + Nalidixic Acid and Amphotericin or Nystatin p.o.

    • CONSULT INFECTIOUS DISEASE, TRANSPLANT, or HEMATOLOGY/ONCOLOGY SPECIALISTS for BEST CURRENT THERAPY for IMMUNOSUPPRESSED PATIENTS


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Environmental Control in PancytopeniaRadiation Pancytopenia

  • Air Filtration and Positive Pressure

  • Reverse Isolation Procedures

  • Dietary Considerations

  • Special Precautions for Skin Punctures

  • Limitation of Attending Personnel




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Preparation For Hematologic Complications In Radiation Pancytopenia

Transfusions: Erythrocytes

Platelets

Growth Factors: GSF, GMCF,

IL2, etc.

Stem Cell Transplants: Autografts

(Marrow, cord, PB) Isografts

Homografts

Xenografts (?)


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Infection Therapy in Radiation Pancytopenia Pancytopenia

Some Systemic Agents that have been used:

  • Aminoglycosides (Gentamicin,etc.)

    • most effective

  • Ureido-Penicillins (Ticarcillin,etc.)

    • synergistic vs. gram-negative

  • Monobactams

    • effective vs. gram-negative & no renal toxicity

  • B-Lactam Resistant Penicillins (Methicillin,etc.)

    • effective vs. S.aureus

      CONSULT INFECTIOUS DISEASE, TRANSPLANT, or HEMATOLOGY/ ONCOLOGY SPECIALISTS for BEST CURRENT THERAPY for IMMUNOSUPPRESSED PATIENTS

434-2


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Uses of Hematopoietic Growth Factors Pancytopenia

  • Mobilize peripheral-blood progenitor cells

  • Expand hematopoietic cell population

  • Speed and enhance hematopoietic recovery

  • Early hematopoietic recovery will reduce nonhematological toxicity (infection, mucositis, pneumonia, etc.)

  • Augment transplant using smaller number of hematopoietic cells

583-3


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Marrow Transplantation Procedure Pancytopenia(after E.D. Thomas and C.D. Buckner)

  • Donor:

    • Compatability matching.

    • General anesthesia.

    • 100 sites aspirated in sternum, ant. & post. Iliac crests.

  • Marrow:

    • 4cc aspirates into TC 199 + 5,000 U Connaught preservative-free heparin.

    • 9 X 109 marrow cells in 400cc passed through 300u and 200u S.S. screens.

  • Recipient:

    • Given marrow I.V. rapidly from Fenwall bag.

58-D



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ARS: Current Treatment Challenges - Gastrointestinal PancytopeniaSyndrome Therapy

  • 5HT3 (5-hydroxytriptamine) receptor antagonist

  • Radioprotectants (WR-2721)

  • Cytokines (IL-1, G-CSF)

  • Prostaglandin antagonists

  • Sucralfate

  • Gut microbial and fungal suppression

  • Vasopressin

  • Elemental Diet (amino acids, sucrose, limited fat)

  • Glutamine




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ARS: General Therapeutic Approach Pancytopenia

  • Provide Psychological Support

  • Use Symptomatic Treatment

  • Prevent Infection and Hemorrhage

  • Maintain Hydration and Nutrition

  • Encourage Cell Renewal

  • Control Inflammatory Response


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ARS: Therapy Summary Pancytopenia

583-7



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Internal Exposure Variables Pancytopenia

Routes of Entry:

  • Inhalation, Ingestion, Injection and Absorption

    Decay Rates and energies

    Chemical Compounds, Solubility, Particle Size, etc.

    Time and Duration

    Radionuclides and Forms

    Metabolic Behavior

  • Deposition, Retention, Elimination and Critical Organs


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Initial Management of the Externally Contaminated Patient Pancytopenia

FIRST AID prn. for SHOCK, BLEEDING and ACUTE RESPIRATORY DISTRESS

Gross Decontamination

Removal of Contaminated Clothing

  • Washing and removal of Contaminated Hair

  • Removal of Gross Wound Contamination

    Intermediate Stage (at clean location,if necessary)

  • Removal of Contaminated Clothing

  • Further Local Decontamination, Swabs of Body Orifices

    Final Stage

  • Patient Discharged with Fresh Clothing

  • More Definitive Decontamination (surgical) and Other Therapy at Dispensary or Hospital


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Decontaminating Agents Pancytopenia

  • Soap and Water

  • Abrasive Soap and Water

  • Detergents

    • (10%) Dreft, Tide; Phisohex, Hemosol

  • Oxidizers

    • Chlorox (20%), KMnO4

  • Complexers

    • Citric Acid (1%)

  • Chelators

    • Versene (1%) EDTA, DTPA


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Early Treatment For Radionuclide Inhalation Pancytopenia

  • Irrigate Nose, Mouth and Pharynx

  • No Effective Medical Means to enhance lung clearance

  • Consider Bronchopulmonary Lavage for Major Long-Lived High-Hazard Lung Contamination


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Early Treatment For Radionuclide Ingestion Pancytopenia

  • Irrigate Nose, Mouth and Pharynx

  • Remove Gastric Contents

  • Give Purgative (10gm MgSO4 in 100 ml water)

  • Give Chemical Antidote for Blocking, Diluting or Chelating


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Early Treatment For Contaminated Wounds Pancytopenia

  • Irrigate Wound

    • Saline

    • Water

  • Decontaminate Skin (But Do Not Injure)

    • Detergent

  • Continue Wound Irrigation Until Radiation Level Is Zero or Constant

  • Treat Wound as Usual

    • Consider Excision of Embedded Long- Lived High-Hazard Contaminants





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Treatment of Internal Contamination Pancytopenia

  • Reduce G.I. Absorption

  • Hasten Excretion

  • Use Blocking or Diluting Agents When Appropriate

  • Use Mobilizing Agents

  • Use Chelating Agents If Available


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Therapy For Isotope Decorporation Pancytopenia

  • Dilution

    • 3H: Water

    • 32P: Phosphorus (Neutraphos)

  • Blocking

    • 137Cs: Prussian Blue

    • 131I, 99Tc: KI (Lugol’s)

    • 90Sr, 85Sr: Na-Alginate (Gaviscon), Al-Phosphate or Hydroxide Gel

      (Phosphajel or Amphojel)


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Therapy For Isotope Decorporation Pancytopenia(cont.)

Mobilization

  • 86Rb: Chlorthalidone (Hygroton)

    Chelation

  • 252Cf, 242Cm, 241Am, 239Pu, 144Ce,

    Rare Earths, 143Pm, 140La, 90Y,

    65Zn, 46Sc: DTPA

  • 210Pb: EDTA, Penicillamine

  • 210Po: Dimercaprol (BAL)

  • 203Hg, 60Co: Penicillamine


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Prevention of Health Effects in PancytopeniaRadionuclide Contamination Event

  • Physical:

    • Shelter

    • Evacuation

  • Biomedical:

    • Thyroid Blocking

    • Personal Decontamination

    • Control of Intake


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Bibliography Pancytopenia

  • The Medical Basis for Radiation-Accident Preparedness: The Clinical Care of Victims. Ricks, R.C., Berger, M.E. and O’Hara, Jr., F.M.,Editors. Parthenon Publishing Group, New York, 2002.

  • Medical Management of Radiation Accidents. Gusev, I.A., Guskova, A.K. and Mettler Jr., F.A., Editors, CRC Press, Boca Raton, FL, 2001.

  • NCRP Report No. 138. Management of Terrorist Events Involving Radioactivity. National Council on Radiation Protection and Measurements Committee 46-14, John W. Poston, Sr. Chairman; NCRP, Washington, DC, 2001.


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Advances in the Biosciences: Advances in the Treatment of Radiation Injuries. MacVittie, T.J., Weiss, J.F., and Browne, D., Pergamon Press, New York, 1996.

Medical Effects of Ionizing Radiation. 2nd Edition. Mettler, F.A.Jr, and Upton, A.C., W.B. Saunders, Philadelphia, PA, 1995.

NCRP Report No. 65, Management of Persons Accidentally Contaminated with Radionuclides. National Council on Radiation Protection and Measurements Committee, George L. Voelz, Chairman; NCRP, Washington, DC, 1980.


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