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 SyndromeRadionuclide Contamination:–External–Localized in Wound–Internal

LOCAL RADIATION INJURY: RADIODERMATITIS

Type Manifestation

I Erythema

II Transepidermal Injury

III Dermal Radionecrosis

IV Chronic Radiodermatitis

Local Injury: Transepidermal (Beta Radiation + Thermal Burns)

Local Radiation Injury PXD14

Local Radiation Injury PXD 22

Local Radiation Injury PXD 90

Local Radiation Injury Therapy

AMPUTATION STAGESUpper Extremities

5mo

4mo

5mo 6

mo5

mo7mo

7mo

10mo

17mo

12mo

RightLeft

Arteriole (post-irradiation)

Local Radiation Injury PXD22

Local Radiation Injury PXD 29

Local Radiation Injury PXD 92

Local Radiation Injury Diagnosis• 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.

.

Useful Steps in Clinical Care of 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

Local Radiation Injury Therapy• Analgesics, Antipruritics• Anti-inflammatories• Antibiotics as needed • Skin Growth Factors• Synthetic Occlusive Dressings• Surgical Intervention:

–Debridement–Excision and Grafting–Amputation

Diagnostic X-Ray Injury

Diagnostic X-ray Injury: Repaired

Acute Radiation Syndromes and Their Management

• Key underlying pathophysiology at the cell and organ level

• Description of syndromes• Diagnostic procedures• Clinical care

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Acute Radiation Syndromes• Underlying Cellular Radiation Effects

– Mitotic inhibition– Cell killing– Organ malfunction– Vascular reactions

• Clinical Manifestations– Hematological– Gastrointestinal– Neurovascular– Pulmonary

Three Stage Kinetic Model

Prodromal Symptoms & SignsNeurogenic Vascular

Anorexia ConjunctivitisNausea Skin ErythemaVomitingDiarrhea FeverWeakness

Radiation Erythema (PXD 10)

Radiation Epilation (PXD 23)

ARS: 45 Days post-Epilation

ARS: Hematopoietic Form

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ARS: Hematologic Course

Hematopoietic Syndrome Systemic Effects

• Immunodysfunction–Increased Infectious

Complications• Hemorrhage

–Anemia• Impaired Wound Healing

ARS: Gastrointestinal Form

38-D

Mechanism of GI Syndrome(Gunter-Smith Hypothesis)

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GI Syndrome Systemic Effects • Malabsorption• Ileus

–Vomiting–Abdominal distention

• Fluid and Electrolyte Shifts–Dehydration–Acute renal failure–Cardiovascular

• GI Bleeding• Sepsis

ARS: Neurovascular Form

38-E

EXCITATIONPHASE

Autonomic Nervous System

49-B

HYPOTHALAMIC SYSTEM

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Neurovascular Syndrome Systemic Effects

• Vomiting and Diarrhea within Minutes

• Confusion and Disorientation• Severe Hypotension• Hyperpyrexia• Cerebral Edema• Convulsions - Coma• Fatal within 24 to 48 Hours

ARS- Pulmonary Form (pre-exposure)

ARS- Pulmonary Form (exudative stage)

ARS- Pulmonary Form (fibrotic stage)

Pulmonary Syndrome Systemic Effects • Early Phase

–Dyspnea–Cough–Pulmonary Edema –Acute Respiratory Distress Syndrome

• Late Phase–Interstitial Fibrosis–Interstitial Pneumonitis–Chronic Respiratory Distress Syndrome

Acute Radiation Syndrome

• Psychological Stress• Infection

– Bacterial, viral, fungal, CMV, herpes• Hemorrhage• Radiation Enterocolitis• Radiation Pneumonitis• Combined Injuries

– Radiation plus trauma, burns, etc.

Clinical Management Problems

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General Treatment Plan for External Exposure• Provide Psychological Support

– Professional– Family – Clergy

• Use Symptomatic Treatment– Antiemetics– Analgesics

• Prevent Infection and Hemorrhage– Reverse Isolation– Antibiotics– Blood Products

General Treatment Plan (cont.)

• Maintain Hydration and Nutrition– Fluids– Electrolytes– Nutrients

• Encourage Cell Renewal– Growth Factors– Stem Cells

• Control Inflammatory Response– Steroids– Vasodilators

Psychological Stress Reducers• One Responsible Decision-Maker

• Realistic Appraisal of Problem and Clear Communication

• Credible Action Plan and Adequate Resources

• Pre-Emergency Education

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

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General Anti-Infection Measures in Radiation 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

Selective Bacterial Decontamination• 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

Environmental Control in Radiation Pancytopenia

• Air Filtration and Positive Pressure

• Reverse Isolation Procedures

• Dietary Considerations

• Special Precautions for Skin Punctures

• Limitation of Attending Personnel

ARS: Environmental Control

Bedside Debriding of Local Radiation Injury

Preparation For Hematologic Complications In Radiation PancytopeniaTransfusions: Erythrocytes

Platelets

Growth Factors: GSF, GMCF,IL2, etc.

Stem Cell Transplants: Autografts(Marrow, cord, PB) Isografts

HomograftsXenografts (?)

Infection Therapy in Radiation Pancytopenia

• 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

Some Systemic Agents that have been used:

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Uses of Hematopoietic Growth Factors

• 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

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Marrow Transplantation Procedure (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.

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ARS: Hematologic Response to Stem Cells

ARS: Current Treatment Challenges - Gastrointestinal Syndrome 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

ARS: Current Treatment Challenge -Pulmonary

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Combined Injury: A-Bomb Patients

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Type of Injury % Died Before 20 px-days

% Alive at 20 or more px-days

Radiation 95.1 81.2

Severe Rad Sx 58.5 75.2

Thermal burns 57.2 25.1

Mechanical Trauma

57.2 61.8

ARS: General Therapeutic Approach

• Provide Psychological Support• Use Symptomatic Treatment• Prevent Infection and Hemorrhage • Maintain Hydration and Nutrition• Encourage Cell Renewal• Control Inflammatory Response

ARS: Therapy Summary

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Radiation Accident Management

Type of Accident

Worst Consequence

Preparation _ Time___

External Exposure

Death in 0-6 Weeks

1-2 Weeks After Accident

Internal Contamination

Cancer in 5-25 Years

Months-Years before Accident

Internal Exposure Variables Routes of Entry:– Inhalation, Ingestion, Injection and AbsorptionDecay Rates and energiesChemical Compounds, Solubility, Particle Size, etc.Time and Duration

Radionuclides and Forms Metabolic Behavior– Deposition, Retention, Elimination and Critical Organs

Initial Management of the Externally Contaminated Patient

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

Gross DecontaminationRemoval 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

Decontaminating Agents• 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

Early Treatment For Radionuclide Inhalation

• Irrigate Nose, Mouth and Pharynx

• No Effective Medical Means to enhance lung clearance

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

Early Treatment For Radionuclide Ingestion

• Irrigate Nose, Mouth and Pharynx• Remove Gastric Contents• Give Purgative (10gm MgSO4 in 100 ml

water)• Give Chemical Antidote for Blocking,

Diluting or Chelating

Early Treatment For Contaminated Wounds

• 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

Pu-Contaminated Lacerations

Pu-Contaminated Wound Monitoring

Plutonium in Scar Tissue

Treatment of Internal Contamination

• Reduce G.I. Absorption• Hasten Excretion• Use Blocking or Diluting Agents When

Appropriate• Use Mobilizing Agents• Use Chelating Agents If Available

Therapy For Isotope Decorporation• 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)

Therapy For Isotope Decorporation (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

Prevention of Health Effects inRadionuclide Contamination Event

• Physical:–Shelter–Evacuation

• Biomedical:–Thyroid Blocking–Personal Decontamination–Control of Intake

Bibliography

• 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.

• 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.