Acute Radiation Syndrome (A Spectrum of Disease) Doran Christensen, DO Associate Director, REAC/TS.

Acute Radiation Syndrome Acute Radiation Syndrome (A Spectrum of Disease)(A Spectrum of Disease)

Acute Radiation Syndrome Acute Radiation Syndrome (A Spectrum of Disease)(A Spectrum of Disease)

Doran Christensen, DODoran Christensen, DOAssociate Director, REAC/TSAssociate Director, REAC/TS

Acute Radiation Acute Radiation SyndromeSyndromeAcute Radiation Acute Radiation SyndromeSyndrome

Systemic Effects from Acute Radiation Systemic Effects from Acute Radiation ExposureExposure

Multi-Faceted Spectrum of Disease Multi-Faceted Spectrum of Disease

Involvement of One or more Organ SystemsInvolvement of One or more Organ Systems

Systemic Effects from Acute Radiation Systemic Effects from Acute Radiation ExposureExposure

Multi-Faceted Spectrum of Disease Multi-Faceted Spectrum of Disease

Involvement of One or more Organ SystemsInvolvement of One or more Organ Systems

Ionization ProcessIonization ProcessIonization ProcessIonization ProcessDensity of Ionization TrailDensity of Ionization Trail

Chemical BondsChemical BondsDNA DamageDNA DamageSubcellular componentsSubcellular components

Mitotic DelayMitotic DelayRepairRepair

CompleteCompleteIncompleteIncompleteResidual Damage? Measureable?Residual Damage? Measureable?

Density of Ionization TrailDensity of Ionization TrailChemical BondsChemical BondsDNA DamageDNA DamageSubcellular componentsSubcellular components

Mitotic DelayMitotic DelayRepairRepair

CompleteCompleteIncompleteIncompleteResidual Damage? Measureable?Residual Damage? Measureable?

Exposure PrinciplesExposure PrinciplesExposure PrinciplesExposure Principles

Total vs. Partial Body IrradiationTotal vs. Partial Body IrradiationThreshold Effect of DoseThreshold Effect of Dose

ThresholdThresholdDD5050 Dose Dose

Dose RateDose RateDose Protraction or FractionationDose Protraction or Fractionation

Total vs. Partial Body IrradiationTotal vs. Partial Body IrradiationThreshold Effect of DoseThreshold Effect of Dose

ThresholdThresholdDD5050 Dose Dose

Dose RateDose RateDose Protraction or FractionationDose Protraction or Fractionation

Radiation EffectsRadiation EffectsRadiation EffectsRadiation EffectsStochasticStochastic - “All-or-Nothing” Effect - “All-or-Nothing” Effect

Occurrence Probability is Occurrence Probability is Function of DoseFunction of DoseIncreased Risk of Developing CancerIncreased Risk of Developing CancerInheritable MutationsInheritable Mutations

DeterministicDeterministic - - Effect Severity is a Function of Dose Effect Severity is a Function of Dose (Commonly Associated with Threshold)(Commonly Associated with Threshold)Inflammatory ResponseInflammatory ResponseOrgan FailureOrgan FailureFibrosisFibrosis

StochasticStochastic - “All-or-Nothing” Effect - “All-or-Nothing” Effect Occurrence Probability is Occurrence Probability is Function of DoseFunction of DoseIncreased Risk of Developing CancerIncreased Risk of Developing CancerInheritable MutationsInheritable Mutations

DeterministicDeterministic - - Effect Severity is a Function of Dose Effect Severity is a Function of Dose (Commonly Associated with Threshold)(Commonly Associated with Threshold)Inflammatory ResponseInflammatory ResponseOrgan FailureOrgan FailureFibrosisFibrosis

Radiation EffectsRadiation EffectsRadiation EffectsRadiation Effects

0

0.2

0.4

0.6

0.8

1

Effect

Dose

Deterministic

0

0.2

0.4

0.6

0.8

1

Effect

Dose

Stochastic

Law of Bergonié and Tribondeau Law of Bergonié and Tribondeau (1906)(1906)Law of Bergonié and Tribondeau Law of Bergonié and Tribondeau (1906)(1906)

More Differentiated Cells are Less SensitiveMore Differentiated Cells are Less Sensitive

Actively Proliferating Cells are More SensitiveActively Proliferating Cells are More Sensitive

Radiosensitivity is Proportional to Mitotic and Radiosensitivity is Proportional to Mitotic and Developmental Activity DurationDevelopmental Activity Duration

More Differentiated Cells are Less SensitiveMore Differentiated Cells are Less Sensitive

Actively Proliferating Cells are More SensitiveActively Proliferating Cells are More Sensitive

Radiosensitivity is Proportional to Mitotic and Radiosensitivity is Proportional to Mitotic and Developmental Activity DurationDevelopmental Activity Duration

Rapidly Dividing Cells that Are Poorly Differentiated Rapidly Dividing Cells that Are Poorly Differentiated and Have a Long Mitotic Period Are Very Radiosensitiveand Have a Long Mitotic Period Are Very Radiosensitive

Exceptions:Exceptions:Exceptions:Exceptions:

LymphocyteLymphocyte - Most Radiosensitive Cell - Most Radiosensitive CellOocyteOocyte - Non Mitotic Cell - Non Mitotic Cell

LymphocyteLymphocyte - Most Radiosensitive Cell - Most Radiosensitive CellOocyteOocyte - Non Mitotic Cell - Non Mitotic Cell

Radiosensitive CellsRadiosensitive CellsRadiosensitive CellsRadiosensitive Cells

Red MarrowRed MarrowEpithelial Cells of GI System, LungEpithelial Cells of GI System, LungEpithelium of LensEpithelium of LensGerminative Cells of Testis and OvaryGerminative Cells of Testis and OvaryEndothelial Cells of Blood VesselsEndothelial Cells of Blood Vessels

Red MarrowRed MarrowEpithelial Cells of GI System, LungEpithelial Cells of GI System, LungEpithelium of LensEpithelium of LensGerminative Cells of Testis and OvaryGerminative Cells of Testis and OvaryEndothelial Cells of Blood VesselsEndothelial Cells of Blood Vessels

Radiosensitive Cells Radiosensitive Cells (cont’d)(cont’d)Radiosensitive Cells Radiosensitive Cells (cont’d)(cont’d)

Pluripotential Stem CellsPluripotential Stem Cells Rapid Mitotic RateRapid Mitotic Rate Form Intermdiate Precursors and then Form Intermdiate Precursors and then

Mature Elements.Mature Elements. Cells with Large Nuclei Cells with Large Nuclei

Interphase DeathInterphase Death Lymphocyte, Oocyte and Salivary GlandLymphocyte, Oocyte and Salivary Gland

Pluripotential Stem CellsPluripotential Stem Cells Rapid Mitotic RateRapid Mitotic Rate Form Intermdiate Precursors and then Form Intermdiate Precursors and then

Mature Elements.Mature Elements. Cells with Large Nuclei Cells with Large Nuclei

Interphase DeathInterphase Death Lymphocyte, Oocyte and Salivary GlandLymphocyte, Oocyte and Salivary Gland

Effects of Radiation Effects of Radiation ProtractionProtractionEffects of Radiation Effects of Radiation ProtractionProtraction

Prodromal ComponentProdromal Component(Gy)(Gy)

VomitingVomiting Diarrhea DiarrheaBriefBrief ProtractedProtracted BriefBrief ProtractedProtracted

ExposureExposure ExposureExposure ExposureExposure ExposureExposure

DD5050 22 55 33 66

ThresholdThreshold 0.50.5 1.51.5 11 2.52.5NUREG / CR 4214, Part II, p. 21NUREG / CR 4214, Part II, p. 21

GI Cellular HierarchyGI Cellular HierarchyGI Cellular HierarchyGI Cellular Hierarchy

IAEA – UNSCEAR 1988

Skin Cellular HierarchySkin Cellular HierarchySkin Cellular HierarchySkin Cellular Hierarchy

IAEA – UNSCEAR 1988

Phases of Acute Radiation Phases of Acute Radiation Syndrome Syndrome Phases of Acute Radiation Phases of Acute Radiation Syndrome Syndrome

ProdromalStage

ProdromalStage

LatentStage

LatentStage

ManifestIllness

ManifestIllness RecoveryRecovery

Time (60 days)Time (60 days)Time (60 days)Time (60 days)

ExposureExposureExposureExposure

Acute Radiation Acute Radiation SyndromeSyndromeAcute Radiation Acute Radiation SyndromeSyndrome

Components of Radiation Effects:Components of Radiation Effects:Prodromal Prodromal (0.5 - 3 Gy) (0.5 - 3 Gy) Hematological Hematological (1.5 - 6 Gy)(1.5 - 6 Gy)Respiratory Respiratory (5 - 310 Gy)(5 - 310 Gy)CutaneousCutaneous (5 - 10 Gy)(5 - 10 Gy)Gastrointestinal Gastrointestinal (8 - 15 Gy)(8 - 15 Gy)Neurovascular Neurovascular (6 - 50 Gy)(6 - 50 Gy)

Combined InjuryCombined Injury

Components of Radiation Effects:Components of Radiation Effects:Prodromal Prodromal (0.5 - 3 Gy) (0.5 - 3 Gy) Hematological Hematological (1.5 - 6 Gy)(1.5 - 6 Gy)Respiratory Respiratory (5 - 310 Gy)(5 - 310 Gy)CutaneousCutaneous (5 - 10 Gy)(5 - 10 Gy)Gastrointestinal Gastrointestinal (8 - 15 Gy)(8 - 15 Gy)Neurovascular Neurovascular (6 - 50 Gy)(6 - 50 Gy)

Combined InjuryCombined Injury

Prodromal ComponentProdromal Component(0.5 - 3 Gy and higher)(0.5 - 3 Gy and higher)Prodromal ComponentProdromal Component(0.5 - 3 Gy and higher)(0.5 - 3 Gy and higher)

Immediate Effect of Cell Membrane DamageImmediate Effect of Cell Membrane DamageMediated by Inflammatory Elements of Cell Mediated by Inflammatory Elements of Cell

DestructionDestructionMediated Neurologically by Mediated Neurologically by

Parasympathetic SystemParasympathetic System

Immediate Effect of Cell Membrane DamageImmediate Effect of Cell Membrane DamageMediated by Inflammatory Elements of Cell Mediated by Inflammatory Elements of Cell

DestructionDestructionMediated Neurologically by Mediated Neurologically by

Parasympathetic SystemParasympathetic System

Prodromal ComponentProdromal Component(Gy)(Gy)

VomitingVomiting Diarrhea DiarrheaBriefBrief ProtractedProtracted BriefBrief ProtractedProtracted

ExposureExposure ExposureExposure ExposureExposure ExposureExposure

DD5050 22 55 33 66

ThresholdThreshold 0.50.5 1.51.5 11 2.52.5NUREG / CR 4214, Part II, p. 21NUREG / CR 4214, Part II, p. 21

TBI Dose Estimates TBI Dose Estimates for Prodromal Symptomsfor Prodromal Symptoms

Hematopoietic Hematopoietic ComponentComponent(1.5 - 6 Gy and higher)(1.5 - 6 Gy and higher)

Hematopoietic Hematopoietic ComponentComponent(1.5 - 6 Gy and higher)(1.5 - 6 Gy and higher)

LymphocytesLymphocytesNeutrophilsNeutrophilsThrombocytesThrombocytesErythrocytesErythrocytes

LymphocytesLymphocytesNeutrophilsNeutrophilsThrombocytesThrombocytesErythrocytesErythrocytes

HemogramHemogram3 Gy (300 Rad) TBI Exposure 3 Gy (300 Rad) TBI Exposure HemogramHemogram3 Gy (300 Rad) TBI Exposure 3 Gy (300 Rad) TBI Exposure

Source – REAC / TS Diagram – Human Irradiation 3 Gy (300 Rads)

Gastrointestinal Gastrointestinal ComponentComponent(8 - 15 Gy and higher)(8 - 15 Gy and higher)

Gastrointestinal Gastrointestinal ComponentComponent(8 - 15 Gy and higher)(8 - 15 Gy and higher)

SymptomsSymptomsMechanismsMechanismsGI Epithelial Sterilization - 15 GyGI Epithelial Sterilization - 15 GyVeno-Occlusive Disease of LiverVeno-Occlusive Disease of Liver

SymptomsSymptomsMechanismsMechanismsGI Epithelial Sterilization - 15 GyGI Epithelial Sterilization - 15 GyVeno-Occlusive Disease of LiverVeno-Occlusive Disease of Liver

Respiratory ComponentRespiratory Component(5 - 310 Gy and higher)(5 - 310 Gy and higher)Respiratory ComponentRespiratory Component(5 - 310 Gy and higher)(5 - 310 Gy and higher)

Sensitive from Highly Vascular TissueSensitive from Highly Vascular TissueEndothelial CellsEndothelial CellsType II Alveolar CellType II Alveolar Cell

Effect is Dose-Rate RelatedEffect is Dose-Rate RelatedPneumonitisPneumonitisFibrosisFibrosis

Sensitive from Highly Vascular TissueSensitive from Highly Vascular TissueEndothelial CellsEndothelial CellsType II Alveolar CellType II Alveolar Cell

Effect is Dose-Rate RelatedEffect is Dose-Rate RelatedPneumonitisPneumonitisFibrosisFibrosis

Pulmonary Lethality Pulmonary Lethality SyndromeSyndromePulmonary Lethality Pulmonary Lethality SyndromeSyndrome

Dose Rate (Gy/hr)Dose Rate (Gy/hr) Threshold Threshold (Gy)(Gy)

Dose Rate (Gy/hr)Dose Rate (Gy/hr) Threshold Threshold (Gy)(Gy)0.05 310

0.1 160

0.5 40

1 20

10 7

100 5

0.05 310

0.1 160

0.5 40

1 20

10 7

100 5NUREG / CR-4214, Part II, p. 55

Neurovascular Neurovascular ComponentComponent(8 - 50 Gy and higher)(8 - 50 Gy and higher)

Neurovascular Neurovascular ComponentComponent(8 - 50 Gy and higher)(8 - 50 Gy and higher)

Brain Cells are Fixed, Post-Mitotic CellsBrain Cells are Fixed, Post-Mitotic Cells

Weak Link -- Stromal CellsWeak Link -- Stromal Cells

Endothelial Cells Turnover Endothelial Cells Turnover 2 Months to 3 Years (3 Days)2 Months to 3 Years (3 Days)

EEG Changes Doses as Low as 1 GyEEG Changes Doses as Low as 1 Gy

Brain Cells are Fixed, Post-Mitotic CellsBrain Cells are Fixed, Post-Mitotic Cells

Weak Link -- Stromal CellsWeak Link -- Stromal Cells

Endothelial Cells Turnover Endothelial Cells Turnover 2 Months to 3 Years (3 Days)2 Months to 3 Years (3 Days)

EEG Changes Doses as Low as 1 GyEEG Changes Doses as Low as 1 Gy

Neurovascular Neurovascular Component Component (continued)(continued)

Neurovascular Neurovascular Component Component (continued)(continued)

1 - 6 Gy 1 - 6 Gy - Glial Cell Damage- Glial Cell Damage 10 Gy 10 Gy - Morphologic Changes- Morphologic Changes 10 - 20 Gy10 - 20 Gy - Vascular Lesions - Vascular Lesions 40 Gy 40 Gy - White Matter Necrosis- White Matter Necrosis 60 Gy 60 Gy - Demyelinization- Demyelinization

1 - 6 Gy 1 - 6 Gy - Glial Cell Damage- Glial Cell Damage 10 Gy 10 Gy - Morphologic Changes- Morphologic Changes 10 - 20 Gy10 - 20 Gy - Vascular Lesions - Vascular Lesions 40 Gy 40 Gy - White Matter Necrosis- White Matter Necrosis 60 Gy 60 Gy - Demyelinization- Demyelinization

Ovarian FunctionOvarian FunctionOvarian FunctionOvarian Function Ovarian Dose (Gy) Results

0.6 - No Deleterious Effect

1.5 - Some Risk for Ovulatory Suppression in Women over 40

2.5 - 5.0 - 60% Women Aged 15-40 Have Permanent SuppressionRemainder have Temporary Amennorrhea 100% Women Over 40 have Permanent Suppression

5.0 - 8.0 - 60-70% Women Aged 15-40 Have Permanent SuppressionRemainder have Temporary Amennorrhea

>8.0 - 100% Permanent Ovulatory Suppression

Ovarian Dose (Gy) Results

0.6 - No Deleterious Effect

1.5 - Some Risk for Ovulatory Suppression in Women over 40

2.5 - 5.0 - 60% Women Aged 15-40 Have Permanent SuppressionRemainder have Temporary Amennorrhea 100% Women Over 40 have Permanent Suppression

5.0 - 8.0 - 60-70% Women Aged 15-40 Have Permanent SuppressionRemainder have Temporary Amennorrhea

>8.0 - 100% Permanent Ovulatory Suppression

NUREG / CR-4214, p II-70NUREG / CR-4214, p II-70NUREG / CR-4214, p II-70NUREG / CR-4214, p II-70

Sperm ProductionSperm ProductionSperm ProductionSperm Production Testicular Dose (Gy) Results

0.1 - 0.3 - Temporary Oligospermia

0.3 - 0.5 - 100% Temporary Aspermia from 4 - 12 mo Post-IrradiationFull Recovery by 48 mo

0.5 - 1.0 - 100% Temporary Aspermia from 3 - 17 moFull Recovery Beginning at 8 - 38 mo

1 - 2 - 100% Temporary Aspermia from 2 - 15 moRecovery Beginning at 11 - 20 mo

2 - 3 - 100% Aspermia Beginning at 1 - 2 moNo Recovery Observed after 40 mo

Testicular Dose (Gy) Results

0.1 - 0.3 - Temporary Oligospermia

0.3 - 0.5 - 100% Temporary Aspermia from 4 - 12 mo Post-IrradiationFull Recovery by 48 mo

0.5 - 1.0 - 100% Temporary Aspermia from 3 - 17 moFull Recovery Beginning at 8 - 38 mo

1 - 2 - 100% Temporary Aspermia from 2 - 15 moRecovery Beginning at 11 - 20 mo

2 - 3 - 100% Aspermia Beginning at 1 - 2 moNo Recovery Observed after 40 mo

NUREG / CR-4214, p II-73NUREG / CR-4214, p II-73NUREG / CR-4214, p II-73NUREG / CR-4214, p II-73

Radiation Skin InjuryRadiation Skin InjuryRadiation Skin InjuryRadiation Skin Injury

EffectsEffects

Time FrameTime Frame

Injury CourseInjury Course

EffectsEffects

Time FrameTime Frame

Injury CourseInjury Course

Radiation Skin InjuryRadiation Skin InjuryRadiation Skin InjuryRadiation Skin Injury

.75 Gy.75 Gy - Hair Follicles Change- Hair Follicles Change

3 Gy 3 Gy - Epilation- Epilation

6 Gy 6 Gy - Erythema- Erythema

10 Gy 10 Gy - Dry Desquamation- Dry Desquamation

20 Gy 20 Gy - Wet Desquamation - Wet Desquamation (Transepithelial Injury)(Transepithelial Injury)

.75 Gy.75 Gy - Hair Follicles Change- Hair Follicles Change

3 Gy 3 Gy - Epilation- Epilation

6 Gy 6 Gy - Erythema- Erythema

10 Gy 10 Gy - Dry Desquamation- Dry Desquamation

20 Gy 20 Gy - Wet Desquamation - Wet Desquamation (Transepithelial Injury)(Transepithelial Injury)

Skin EffectsSkin EffectsSkin EffectsSkin Effects

EffectEffect ParameterParameter Brief Brief Protracted Protracted ExposureExposure Exposure Exposure

ErythemaErythema ThresholdThreshold 33 66DD5050 66 2020

TransepithelialTransepithelial ThresholdThreshold 1010 4040InjuryInjury DD5050 2020 8080

EffectEffect ParameterParameter Brief Brief Protracted Protracted ExposureExposure Exposure Exposure

ErythemaErythema ThresholdThreshold 33 66DD5050 66 2020

TransepithelialTransepithelial ThresholdThreshold 1010 4040InjuryInjury DD5050 2020 8080

NUREG / CR-4214, p II-68NUREG / CR-4214, p II-68

Skin EffectsSkin EffectsSkin EffectsSkin Effects

EffectEffect Single Single Onset Onset Dose (Gy)Dose (Gy) Time Time

EpilationEpilation 3 - 73 - 7 ~18 days~18 days

ErythemaErythema 10 - 2010 - 20 12 - 17 days12 - 17 days

PigmentationPigmentation 10 - 2010 - 20

Dry DesquamationDry Desquamation 10 - 2010 - 20 30 - 70 days30 - 70 days

Moist DesquamationMoist Desquamation 20 - 2420 - 24 30 - 50 days30 - 50 days That HealsThat Heals

TelangiectasiaTelangiectasia 17 - 2417 - 24 6 mo - years6 mo - years

Nonhealing NecrosisNonhealing Necrosis > 60 > 60 months, years months, years

EffectEffect Single Single Onset Onset

Dose (Gy)Dose (Gy) Time Time

EpilationEpilation 3 - 73 - 7 ~18 days~18 days

ErythemaErythema 10 - 2010 - 20 12 - 17 days12 - 17 days

PigmentationPigmentation 10 - 2010 - 20

Dry DesquamationDry Desquamation 10 - 2010 - 20 30 - 70 days30 - 70 days

Moist DesquamationMoist Desquamation 20 - 2420 - 24 30 - 50 days30 - 50 days That HealsThat Heals

TelangiectasiaTelangiectasia 17 - 2417 - 24 6 mo - years6 mo - years

Nonhealing NecrosisNonhealing Necrosis > 60 > 60 months, years months, years NUREG / CR-4214, p II-68NUREG / CR-4214, p II-68

El Salvador Patient + 32 El Salvador Patient + 32 DaysDaysEl Salvador Patient + 32 El Salvador Patient + 32 DaysDays

Hyperpigmentation ( Bronzing )

El Salvador Patient + 32 El Salvador Patient + 32 DaysDaysEl Salvador Patient + 32 El Salvador Patient + 32 DaysDays

Dry Desquamation

El Salvador Patient + 32 El Salvador Patient + 32 DaysDaysEl Salvador Patient + 32 El Salvador Patient + 32 DaysDays

Transition to Wet Desquamation

El Salvador Patient + 32 El Salvador Patient + 32 DaysDaysEl Salvador Patient + 32 El Salvador Patient + 32 DaysDays

Wet Desquamation

TriageTriageTriageTriage

By Conventional InjuriesBy Conventional InjuriesTraumaTraumaBurnsBurns

By Radiation InjuryBy Radiation InjuryProdromal SymptomsProdromal SymptomsHematologic PictureHematologic Picture

By Conventional InjuriesBy Conventional InjuriesTraumaTraumaBurnsBurns

By Radiation InjuryBy Radiation InjuryProdromal SymptomsProdromal SymptomsHematologic PictureHematologic Picture

Modified USSR Classification Modified USSR Classification (1986)(1986)Modified USSR Classification Modified USSR Classification (1986)(1986)

Class 1 Class 1 Class Class 22

ProdromeProdrome >3 hrs>3 hrs** 1 - 3 hrs*1 - 3 hrs*Lymphs (3-6 days)Lymphs (3-6 days) 600 - 1000600 - 1000 300 - 500300 - 500TBI DoseTBI Dose 1 - 2 Gy1 - 2 Gy 2 - 4 Gy2 - 4 GySurvival EstimateSurvival Estimate Probable w / o txProbable w / o tx Possible w / o txPossible w / o tx

Class 3 Class 3 Class Class 44

ProdromeProdrome .5 - 1 hr .5 - 1 hr < .5 hr< .5 hrLymphs (3-6 days)Lymphs (3-6 days) 100 - 200 100 - 200 <100<100TBI DoseTBI Dose 4.2 - 6.3 Gy4.2 - 6.3 Gy 6 - 12, 16 Gy6 - 12, 16 GySurvival EstimateSurvival Estimate Probable w / txProbable w / tx Not LikelyNot Likely

Class 1 Class 1 Class Class 22

ProdromeProdrome >3 hrs>3 hrs** 1 - 3 hrs*1 - 3 hrs*Lymphs (3-6 days)Lymphs (3-6 days) 600 - 1000600 - 1000 300 - 500300 - 500TBI DoseTBI Dose 1 - 2 Gy1 - 2 Gy 2 - 4 Gy2 - 4 GySurvival EstimateSurvival Estimate Probable w / o txProbable w / o tx Possible w / o txPossible w / o tx

Class 3 Class 3 Class Class 44

ProdromeProdrome .5 - 1 hr .5 - 1 hr < .5 hr< .5 hrLymphs (3-6 days)Lymphs (3-6 days) 100 - 200 100 - 200 <100<100TBI DoseTBI Dose 4.2 - 6.3 Gy4.2 - 6.3 Gy 6 - 12, 16 Gy6 - 12, 16 GySurvival EstimateSurvival Estimate Probable w / txProbable w / tx Not LikelyNot Likely

Mettler FA, Kelsey CA, Ricks RC Eds. Mettler FA, Kelsey CA, Ricks RC Eds. Medical Management of Radiation Accidents.Medical Management of Radiation Accidents. Boca Raton: CRC Press, 1990, p. 72. Boca Raton: CRC Press, 1990, p. 72.*Barabanova A. *Barabanova A. REAC/TS Newsletter.REAC/TS Newsletter. Winter 1992, Oak Ridge, TN, p 1-2. Winter 1992, Oak Ridge, TN, p 1-2.

Mettler FA, Kelsey CA, Ricks RC Eds. Mettler FA, Kelsey CA, Ricks RC Eds. Medical Management of Radiation Accidents.Medical Management of Radiation Accidents. Boca Raton: CRC Press, 1990, p. 72. Boca Raton: CRC Press, 1990, p. 72.*Barabanova A. *Barabanova A. REAC/TS Newsletter.REAC/TS Newsletter. Winter 1992, Oak Ridge, TN, p 1-2. Winter 1992, Oak Ridge, TN, p 1-2.

Andrews LymphocyteAndrews LymphocyteNomogramNomogramAndrews LymphocyteAndrews LymphocyteNomogramNomogram

From From Andrews GA, Auxier JA, Lushbaugh CC: The Importance of Dosimetry to the Medical Management of Andrews GA, Auxier JA, Lushbaugh CC: The Importance of Dosimetry to the Medical Management of Persons Exposed to High Levels of Radiation. Persons Exposed to High Levels of Radiation. In In Personal Dosimetry for Radiation Accidents. Personal Dosimetry for Radiation Accidents. Vienna, International Atomic Energy Agency, 1965, pp 3- 16Vienna, International Atomic Energy Agency, 1965, pp 3- 16

From From Andrews GA, Auxier JA, Lushbaugh CC: The Importance of Dosimetry to the Medical Management of Andrews GA, Auxier JA, Lushbaugh CC: The Importance of Dosimetry to the Medical Management of Persons Exposed to High Levels of Radiation. Persons Exposed to High Levels of Radiation. In In Personal Dosimetry for Radiation Accidents. Personal Dosimetry for Radiation Accidents. Vienna, International Atomic Energy Agency, 1965, pp 3- 16Vienna, International Atomic Energy Agency, 1965, pp 3- 16

Confirms suspected Confirms suspected radiation exposureradiation exposure

Determines significant Determines significant hematological hematological involvementinvolvement

Serial CBCs every 6 hSerial CBCs every 6 h

Confirms suspected Confirms suspected radiation exposureradiation exposure

Determines significant Determines significant hematological hematological involvementinvolvement

Serial CBCs every 6 hSerial CBCs every 6 h

Goans Nomogram – The Next Goans Nomogram – The Next AdvanceAdvanceGoans Nomogram – The Next Goans Nomogram – The Next AdvanceAdvance

Goans, RE, “Clinical Care of the Radiation-Accident Patient: Patient Presentation, Assessment, and Initial Diagnosis” in Ricks RC, Berger ME, O’Hara FM, The Medical Basis for Radiation Accident Preparedness – The Clinical Care of Victims, p18.

Combined-Injury Triage whenCombined-Injury Triage whenRadiation Doses are Known*Radiation Doses are Known*Combined-Injury Triage whenCombined-Injury Triage whenRadiation Doses are Known*Radiation Doses are Known*

Conventional Triage Changes in Expected Triage CategoryCategories if Injuries are followingOnly Trauma Whole-Body Radiation Dose (Gy)

No Radiation Exists < 1.5 (150 rad) 1.5-4.5 (150-450 rad) > 4.5 (450 rad)Prodrome Onset < 3 h 1 – 3 h < 1 h

Immediate Immediate Immediate ExpectantDelayed Delayed Expectant ExpectantMinimal Minimal Expectant ExpectantExpectant Expectant Expectant Expectant

*Decision based on whole-body radiation dose, assuming all casualties are wearing personal dosimetersSource: Medical Consequences of Nuclear Warfare, 1989, p. 39

Combined InjuryCombined InjuryCombined InjuryCombined Injury

Combined Injury -Combined Injury -Total Body Irradiation + Total Body Irradiation + BurnsBurns

Combined Injury -Combined Injury -Total Body Irradiation + Total Body Irradiation + BurnsBurns

100 R 250 R 500 R

50

0

70

50

0

95

50

20

100

0

10

20

30

40

50

60

70

80

90

100

Percent Lethality

100 R 250 R 500 R

Burns

Radiation

Combined

100 R 250 R 500 R

50

0

70

50

0

95

50

20

100

0

10

20

30

40

50

60

70

80

90

100

Percent Lethality

100 R 250 R 500 R

Burns

Radiation

Combined

Rat ModelRat Model

AFRRI AFRRI Medical Effects of Nuclear Weapons Medical Effects of Nuclear Weapons Course “Triage and Treatnent of Radiation Casualties” Lecture, slide 35Course “Triage and Treatnent of Radiation Casualties” Lecture, slide 35AFRRI AFRRI Medical Effects of Nuclear Weapons Medical Effects of Nuclear Weapons Course “Triage and Treatnent of Radiation Casualties” Lecture, slide 35Course “Triage and Treatnent of Radiation Casualties” Lecture, slide 35

Treatment OverviewTreatment OverviewTreatment OverviewTreatment OverviewSupportive CareSupportive CareSurgical RecommendationsSurgical RecommendationsSelective Gut DecontaminationSelective Gut DecontaminationBone Marrow Transplants (not as successful)Bone Marrow Transplants (not as successful)Biological Response ModifiersBiological Response ModifiersCytokines (more successful)Cytokines (more successful)Complications of Acute Radiation SyndromeComplications of Acute Radiation Syndrome

Supportive CareSupportive CareSurgical RecommendationsSurgical RecommendationsSelective Gut DecontaminationSelective Gut DecontaminationBone Marrow Transplants (not as successful)Bone Marrow Transplants (not as successful)Biological Response ModifiersBiological Response ModifiersCytokines (more successful)Cytokines (more successful)Complications of Acute Radiation SyndromeComplications of Acute Radiation Syndrome

Supportive CareSupportive CareSupportive CareSupportive Care

Fluid and Electrolyte ReplacementFluid and Electrolyte ReplacementReverse IsolationReverse IsolationTotal Parenteral NutritionTotal Parenteral NutritionEmpiric Antibiotics for Documented InfectionEmpiric Antibiotics for Documented Infection

Fluid and Electrolyte ReplacementFluid and Electrolyte ReplacementReverse IsolationReverse IsolationTotal Parenteral NutritionTotal Parenteral NutritionEmpiric Antibiotics for Documented InfectionEmpiric Antibiotics for Documented Infection

Supportive Care Supportive Care (cont’d)(cont’d)Supportive Care Supportive Care (cont’d)(cont’d)

Irradiated Blood ProductsIrradiated Blood ProductsEnteral FeedingsEnteral Feedings Intravenous GlutamineIntravenous GlutamineSucralfateSucralfate

Irradiated Blood ProductsIrradiated Blood ProductsEnteral FeedingsEnteral Feedings Intravenous GlutamineIntravenous GlutamineSucralfateSucralfate

Surgical RecommendationsSurgical RecommendationsSurgical RecommendationsSurgical RecommendationsBased on Immunocompetence Status Based on Immunocompetence Status

(neutropenia immunocompetence)(neutropenia immunocompetence)Life-Saving / Major Surgery within 36 - 48 hLife-Saving / Major Surgery within 36 - 48 hElective Procedures until 45 - 60 days Elective Procedures until 45 - 60 days

Following Hematopoietic RecoveryFollowing Hematopoietic Recovery

Based on Immunocompetence Status Based on Immunocompetence Status (neutropenia immunocompetence)(neutropenia immunocompetence)

Life-Saving / Major Surgery within 36 - 48 hLife-Saving / Major Surgery within 36 - 48 hElective Procedures until 45 - 60 days Elective Procedures until 45 - 60 days

Following Hematopoietic RecoveryFollowing Hematopoietic Recovery

Browne D, Weiss JF, MacVittie TJ, Pillai MV (eds) Treatment of Radiation Injuries, 1990, Plenum Press, New York, p. 229Browne D, Weiss JF, MacVittie TJ, Pillai MV (eds) Treatment of Radiation Injuries, 1990, Plenum Press, New York, p. 229

Selective Gut DecontaminationSelective Gut DecontaminationSelective Gut DecontaminationSelective Gut Decontamination

Historical BackgroundHistorical BackgroundNon-Systemic Abx vs. Systemic AbxNon-Systemic Abx vs. Systemic AbxFluoroquinolones Fluoroquinolones

Ciprofloxacin, OfloxacinCiprofloxacin, OfloxacinNorfloxacin Norfloxacin

Historical BackgroundHistorical BackgroundNon-Systemic Abx vs. Systemic AbxNon-Systemic Abx vs. Systemic AbxFluoroquinolones Fluoroquinolones

Ciprofloxacin, OfloxacinCiprofloxacin, OfloxacinNorfloxacin Norfloxacin

Cytokine CombinationsCytokine CombinationsCytokine CombinationsCytokine Combinations

IL-3/G-CSFIL-3/G-CSF IL-3/GM-CSFIL-3/GM-CSF

IL-3/G-CSFIL-3/G-CSF IL-3/GM-CSFIL-3/GM-CSF

Acute Radiation Syndrome Acute Radiation Syndrome ComplicationsComplicationsAcute Radiation Syndrome Acute Radiation Syndrome ComplicationsComplications

Hematologic/GastrointestinalHematologic/Gastrointestinal Interstitial Pulmonary FibrosisInterstitial Pulmonary FibrosisVeno-occlusive Disease of the LiverVeno-occlusive Disease of the LiverHerpes Simplex (HSV) ReactivationHerpes Simplex (HSV) ReactivationCytomegalovirus (CMV) ReactivationCytomegalovirus (CMV) ReactivationCombined InjuriesCombined Injuries

Hematologic/GastrointestinalHematologic/Gastrointestinal Interstitial Pulmonary FibrosisInterstitial Pulmonary FibrosisVeno-occlusive Disease of the LiverVeno-occlusive Disease of the LiverHerpes Simplex (HSV) ReactivationHerpes Simplex (HSV) ReactivationCytomegalovirus (CMV) ReactivationCytomegalovirus (CMV) ReactivationCombined InjuriesCombined Injuries

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ReferencesReferencesReferencesReferencesNUREG / CR-4214, Health Effects Models for Nuclear Power PlantAccident Consequence Analysis: Low LET Radiation, Part II: Scientific Bases for Health Effects Models, US Nuclear Regulatory Commission, 1989.

Browne D, Weiss JF, MacVittie TJ, Pillai MV (eds)Treatment of Radiation Injuries, 1990, Plenum Press, New York, p. 229

AFRRI Medical Effects of Nuclear Weapons Course “Triage and Treatnent of Radiation Casualties” Lecture, slide 35

IAEA, The Radiological Accident in San Salvador, 1989

Ricks RC, Berger ME, O’Hara FM, The Medical Basis for Radiation-AccidentPreparedness – The Clinical Care of Victims, Parthenon Publishing Group, Inc:New York:2002.

Saenger EL, Andrews GA, Linnemann RE, Wald N: Radiation Accident Preparedness-Medical and Managerial Aspects. Science-Thru-Media: New York 1981, p 15.

NUREG / CR-4214, Health Effects Models for Nuclear Power PlantAccident Consequence Analysis: Low LET Radiation, Part II: Scientific Bases for Health Effects Models, US Nuclear Regulatory Commission, 1989.

Browne D, Weiss JF, MacVittie TJ, Pillai MV (eds)Treatment of Radiation Injuries, 1990, Plenum Press, New York, p. 229

AFRRI Medical Effects of Nuclear Weapons Course “Triage and Treatnent of Radiation Casualties” Lecture, slide 35

IAEA, The Radiological Accident in San Salvador, 1989

Ricks RC, Berger ME, O’Hara FM, The Medical Basis for Radiation-AccidentPreparedness – The Clinical Care of Victims, Parthenon Publishing Group, Inc:New York:2002.

Saenger EL, Andrews GA, Linnemann RE, Wald N: Radiation Accident Preparedness-Medical and Managerial Aspects. Science-Thru-Media: New York 1981, p 15.

Revision 6.1 – 17 Apr 2004