This document provides information on acute radiation syndrome (ARS), including its clinical presentation, diagnosis, and treatment. It describes the various syndromes (hematopoietic, gastrointestinal, neurovascular) that can occur depending on radiation dose. It discusses factors that influence severity and outlines medical management approaches like isolation, infection prevention, total parenteral nutrition, cytokine therapy, and conventional therapy for thrombocytopenia. The goal of treatment is to reduce the depth and duration of symptoms like leukopenia and allow hematopoietic recovery.

1. ACUTE RADIATION SYNDROME
CLINICAL PICTURE, DIAGNOSIS AND
TREATMENT
NAME : Mohammad Nour Alsaeed
GROUP : 3

2. 2
Introduction
ARS threat
Discharged medical irradiators
Industrial radiography units
Commercial irradiators
Terrorist detonation
Nuclear fuel processing
Nuclear reactors
Acute radiation syndrome (ARS): Combination of
clinical syndromes occuring in stages hours to weeks
after exposure as injury to various tissues and organs
is expressed

3. 3
Early deterministic effects
<0.1 Gy, whole body - No detectable difference
in exposed vs non-exposed patients
0.1-0.2 Gy, whole body - Detectable increase in
chromosome aberrations. No clinical signs or
symptoms
>0.12 Gy, whole body - Sperm count decreases
to minimum about day 45
0.5 Gy, whole body - Detectable bone marrow
depression with lymphopenia

4. 4
Exposure levels at which healthy
adults are affected
_________________________________________________________________
Health effects Acute dose (Gy)
_________________________________________________________________
Blood count changes 0.50
Vomiting (threshold) 1.00
Mortality (threshold) 1.50
LD50/60 (minimal supportive care) 3.2-3.6
LD50/60 (supportive medical treatment) 4.8-5.4
LD50/60 (autologous bone marrow or
stem cell transplant) >5.4_____________________________________________________________________
Source: NCRP Report 98 "Guidance on Radiation Received in Space Activities", NCRP,
Bethesda (MD) (1989).

5. 5
Factors
decreasing LD50/60
Coexisting trauma combined injury
Chronic nutritional deficit
Coexisting infection
Contribution of high LET radiation

6. 6
Phases of ARS
 Initial or prodromal phase
 Latent phase
 Manifest illness phase
 Recovery phase

7. 7
Manifestations of ARS
Haematopoietic syndrome (HPS)
Gastrointestinal syndrome (GIS)
Neurovascular syndrome (NVS)

8. 8
Haematopoietic syndrome
Normal bone marrow cells

9. 9
Survival potential
Bone marrow damaged by radiation injury

10. 10
Haematological response to 1 Gy, whole
body exposure to ionizing radiation

11. 11
Haematological response to 3
Gy, whole body exposure

12. 12
Phases of haematopoietic
syndrome (HPS)
 Prodromal phase symptoms nausea and
vomiting lasts only a few hours, with time of
onset from later than one hour to about 24 hours
after exposure
 Latent phase lasts up to a month. Relatively
asymptomatic except for some fatigue and
weakness
 Manifest illness phase, characterized by
neutropenic fevers, systemic and localized
infections, sepsis, and haemorrhage

13. 13
Gastrointestinal (GI)
syndrome (8-30 Gy)
 Depletion of the epithelial
cells lining lumen of
gastrointestinal tract
 Intestinal bacteria gain free
access to body
 Haemorrhage through
denuded areas
 Loss of absorptive capacity
Irradiated GI Mucosa
Pathophysiology of the GI
Syndrome

14. 14
Phases of Gl syndrome
Prodromal period: Severe nausea and vomiting,
watery diarrhoea and cramps. Occurs within hours
after exposure
Latent (subacute) phase: Asymptomatic for hours to
days, severe tiredness, weakness
Manifest illness: Return of severe diarrhoea,
vomiting with fever; progression to bloody diarrhoea,
shock and death without aggressive medical
intervention

15. 15
Systemic effects of
GI syndrome
Malabsorptionmalnutrition
Fluid and electrolyte shiftsdehydration,
acute renal failure, cardiovascular collapse
GI bleedinganaemia
Sepsis
Paralytic ileusvomiting, abdominal
distention

16. 16
Pulmonary effects
Irradiated lung tissue Pulmonary fibrosis

17. 17
 At 30 Gy and above
 Endothelial cell damage
Neurovascular syndrome
(NVS)

18. 18
NVS
prodromal perıod
 Burning sensation within minutes of
exposure
 Nausea and vomiting within first hour
 Loss of balance, confusion with
prostration
 Hypotension, hyperpyrexia

19. 19
NVS
latent period
 Apparent
improvement lasting
several hours
–May be lucid and in
no pain but weak

20. 20
NVS
overt clinical picture
 Rapid onset
 Watery diarrhoea
 Respiratory distress
 Gross CNS signs
 Wide pulse pressure
 Hypotension

21. 21
ARS
Neurovascular Syndrome
SymptomsRadiation
dose (Gy)
Life threatening
injuries
Death of
patients
16
20
25
30
Loss of
consciousness
Neurovascular
damage
5-12 days
2-5 days

22. 22
Triage of
injured persons (degrees )

23. 23
Measurement of severity
 Prodromal effects
 Time of onset
 Degree of symptoms
 Haematological changes
 Lymphocyte counts
 Biological dosimetry
 Physical dosimetry
 Attendant readable

24. 24
Radiation dose under 5 Gy
 No immediate life-threatening hazard
exists
 Prodromal symptoms of moderate
severity
 Onset > 1 hour
 Duration < 24 hours

25. 25
Fatal radiation
 Nausea and vomiting within minutes (during the first hour)
 Within hours (on the first day):
 Explosive bloody diarrhoea
 Hyperthermia
 Hypotension
 Erythema
 Neurological signs

26. 26
Triage categories of radiation
injuries according to early
symptoms

27. 27
Guide for management of radiation
injuries on the basis of early symptoms
No vomiting
Vomiting 2-3 h
after exposure
Vomiting 1-2 h
after exposure
Vomiting
earlier than 1 h,
other severe
symptoms, like
hypotension
hyperthermia,
diarrhoea,
oedema,
erythema, CNS
symptoms
< 1 Gy
1-2 Gy
2-4 Gy
> 4 Gy
Outpatient with 5-week surveillance
Surveillance in a general hospital (or
outpatient for 3 weeks) followed by
hospitalization
Hospitalization in a haematological
department
Hospitalization in a well equipped
haematological or surgical department
with transfer to a specialized centre
for radiopathology

28. 28
Lymphocytes
3Gy
4-5Gy

29. 29
Change of lymphocyte counts in initial
days of ARS depending on dose of
acute WB exposure
Degree of
ARS
Dose
(Gy)
Lymphocyte counts
(cells/L)
6 days after first
exposure
Preclinical phase
Mild
Moderate
Severe
Very severe
Lethal
0.1-1.0
1.0-2.0
2.0-4.0
4.0-6.0
6.0-8.0
>8.0
1500-2500
700-1500
500-800
300-500
100-300
0-50

30. 30
Granulocyte counts and dose
relationship after irradiation

31. 31
Medical management
of
acute radiation syndrome

32. 32
Therapeutic support for
haematopoietic syndrome patient
Primary goal of haematopoietic support is
reduction in both depth and duration of
leukopenia
 Prevention and management of infection is mainstay
of therapy
 Quantitative relationship between degree of
neutropenia and increased risk of infectious
complications. Absolute neutrophil count (ANC) <
100/L is greatest risk factor

33. 33
Infection managment
General principles
 Prophylaxis
 Barrier/isolation
 Gut decontamination
 Antiviral agents
 Antifungal agents
 Pneumocystis prophylaxis
 Early cytokine therapy
 Close wounds
 Avoid invasive procedures
Direct therapy for
infections
Culture specific
antibiotics
Therapy for
leukopenia
Cytokine
administration

34. 34
Isolation
Treat ARS patients with estimated WB >2Gy in
isolated rooms. Warn nursing personnel of the need
for rigorous environmental control including:
 laminar flow isolation
 strict hand washing before and after patient
care
 surgical scrubs for staff
 gowns, caps, gloves, masks for staff
 double bagging of all disposables

35. 35
Prevention of infection
 Reduction of microbial acquisition
 Contact control (e.g. careful, frequent hand
washing)
 Low-microbial content food
 Acceptable water supply
 Air filtration to reduce aspergillus infection
 Reduction of invasive procedures (e.g.
nasogastric tubes, catheters)

36. 36
Approach to prevent
infection in immunocompromised patients
Suppression of micro-organisms
Selective gut decontamination
Administration of oral non-absorbable
antibacterial drugs (e.g.,Quinolones) that
preserve anaerobic bacteria
Awareness of resistant bacterial acquisition
during clinical course
Antivirals (Acyclovir) as guided by
positive anti-HSV (herpes simplex virus)
antibody or empirically if test not available

37. 37
Approach to prevent infection
in immunocompromised patients
 Suppression of micro-organisms
 Physiological interventions
Maintenance of gastric acidity
Avoidance of antiacids and H2 blokers
Use of sucralfate for stress ulcer prophylaxis when
indicated to reduce gastric colonization and
pneumonia
Early oral enteral nutrition (when feasible)
 Adequate personal hygiene
 Povidone-iodine (Betadine) or chlorhexidine for skin
disinfection, shampoo
 Oral hygiene (brushing and flossing)

38. 38
Approach to prevent infection in
immunocompromised patients
 Improvement of host defences
 Active vaccination for expected pathogens (e.g.
influenza)
 Passive immunization with immunoglobulins
(utility not yet established)
 Cytokine G-CSF administered prophylactically to
reduce duration of neutropenia and provide
adequate numbers of functional neutrophils

39. 39
Management of infection
 Survey for possible source, pancultures
 Administer antibiotics for absolute neutrophil
count (ANC) <500/mm3
 Use broad spectrum antibiotic coverage
 Add amphotericin for prolonged fever lasting 5-7
days after starting standard antibiotics
 Continue antibiotics for duration of ANC <1000

40. 40
 If there is evidence of resistant gram-positive
infection, add vancomycin
 If diarrhoea is present, examine stool cultures
for salmonella, shigella, camphylobacter and
yersinia
 Oral and pharyngeal mucositis and
oesophagitis suggest herpes simplex
infection or candidiasis. Empiric acyclovir or
antifungal therapy should be considered
Management of infection

41. 41
Total parenteral nutrition vs enteral
feeding
Premise for early enteral feeding
Early enteral feeding Parenteral feeding
Nutrients stimulate villi growth Villi atrophy from enteral
starvation
Gut mucosal barrier remains
intact
Gut mucosal barrier breaks down
Healthy mucosa limits
translocation of bacteria
Unhealthy mucosal allows
translocation of
bacterial/endotoxin
Immune system clears limited
volume of translocated bacteria
Complementary activation occurs
Results: lowered stress response
and risk of sepsis
Results: increased stress
response and risk of sepsis

42. 42
Cytokines

43. 43
Cytokines
 Granulocyte-macrophage stimulating
factor (GM-CSF) - Sargramostim
(Leukine(R))
 Macrophage colony stimulating factor
(M-CSF)
 Granulocyte colony stimulating factor
(G-CSF) - Filgastrim (Neupogen(R))
 Stem cell factor (SCF)
 Interleukin series (IL 1-16)

44. 44
Selected cytokines
 G-CSF and GM-CSF are potent stimulators of
haematopoiesis and effective in reducing
duration and degree of neutropenia
 Additional benefit of CSFs ability to increase
functional capacity of neutrophil and thereby
contribute to prevention of infection as
active part of cellular host defence

45. 45
Advantages of cytokine
therapy
 Bone marrow
 increase production of white cells
 stimulate production of colony forming units
 decrease maturation time
 Mature cells
 increase viability
 prime neutrophils/macrophages
 stimulate additional cytokine release
 Many act in synergy to increase haematopoiesis

46. 46
Results of cytokine therapy
GM-CSF Sargramostim (LeukineR)
 Proven efficacy for decreasing duration
of absolute neutropenia
 Decreased length of hospital stay
 Decreased need for antibiotics
 Fewer fever days

47. 47
Use of cytokines for treatment
of ARS
 G-CSF and GM-CSF increase rate of
hemopoietic recovery in patients after
radiation exposure and may obviate need for
BMT, when stem cells are still viable.
Interleukins (IL-1 and IL-3) act in synergism
with GM-CSF
 Successfully used for radiation victims
after Goiânia, San Salvador, and Belarus and
Istanbul accidents

48. 48
Initiation and duration of
cytokine administration
 Benchmark absolute lymphocyte count
less than 500/l threshold for beginning
cytokine therapy in first 2 days
 Continue cytokine administration with
daily injections to reach ANC of 1000/l

49. 49
Cytokine dosage
 G-CSF Filgrastim (NeupogenR)
 2.5-5.0 µg/kg/day (100-200
µg/m2/day)
 GM-CSF Sagramostim (LeukineR)
 5.0-10.0 µg/kg/day (200-400
µg/m2/day)
 Begin therapy as early as practical
for maximum effect

50. 50
Comparative toxicity of
CSFs
 Predominant side effect of G-CSF - medullary
bone pain, observed shortly after initiation of
G-CSF treatment and again just before onset
of neutrophil recovery from nadir
 G-CSF may exacerbate preexisting
inflammatory conditions
 Main side effects of GM-CSF - fever, nausea,
fatigue, headache, bone pain, myalgia

51. 51
Contraindication for
cytokine treatment
Possibly in cases where
radiation exposure is continuing
(e.g. via internally deposited
radionuclides, chronic external
irradiation)

52. 52
Conventional therapy for
thrombocytopenia
 Transfusion of platelets remains primary
therapy to maintain adequate platelet counts
 Requirement for platelet support depends on
patient's condition. In irradiated patients
with or without other major medical
problems, platelets should be maintained at
greater than 20 000/L. If surgery is needed,
platelet count should be greater than
75 000/L

53. 53
Conventional therapy for
thrombocytopenia
 All blood products should receive 15-20 Gy
of radiation before infusion to prevent
graft-vs-host disease through infusion of
present mononuclear cells
 If transplant performed, avoid use of
platelets from related donors

54. 54
Growth factor therapy for
thrombocytopenia
 Use of thrombopoietic agents immediately after
radiation injury is not currently recommended
 Consider use of thrombopoietic agents
megakaryocyte growth and development
factor/thrombopoietin (MGDF/Tpo) or synthetic
IL-3 receptor agonist Synthokine in patient with
neutrophil recovery but still platelet transfusion
dependent after accidental irradiation

55. 55
Therapy for anaemia
 Transfusion of peripheral red blood cells
(PRBCs) remains primary therapy to maintain
haemoglobin above 8 g/dl; PRBC transfusions
should be irradiated
 Erythropoietin (Epo) anaemia therapy: Use of
Epo after radiation injury is not recommended
even though probably safe as anaemia is not
generally life-threatening in this situation

56. 56
Granulocyte transfusions (GTX)
from CSF-stimulated donors
 G-CSF, when administered to normal individuals,
increases granulocytes collected, resulting in significant
circulating levels of granulocytes in neutropenic patients.
Use of HLA-compatible donors may avoid the problem of
alloimmunization
 G-CSF additional benefit, enhancing phagocytic and
microbicidal activity of stimulated PMNs
 GTX of G-CSF-stimulated PMNs could prove effective
therapy for severely neutropenic patients with sepsis
who have failed to respond to appropriate antibiotic
therapy

57. 57
Bone marrow
transplantation (BMT)
 Indication for BMT following
radiation accidents is probably
limited
 Following reversible BM injury BMT
may have a negative effect,
development of high risk graft
rejection

58. 58
Indications for BMT
Physicians should consider allo-BMT if:
 fully matched sibling donor available
 patient has absolute lymphocyte count
(ALC) <100/l
 radiation dose unknown or likely to be 8-12 Gy
 no other injuries preclude survival or
transplantation (e.g. severe burns)
 irradiation is not continuing from internal source

59. 59
Timing of grafting
 Timing is important - grafting in peak period of
immunosuppression may reduce chance of graft
rejection. Early marrow transplantation desirable, even
in first week after exposure
 Note importance of reliable clinical, biological and
dosimetric findings to assess dose level and
distribution in the body. Without reliable physical
dosimetry and haematological parameters, allogenic
bone marrow transplant unjustified

60. 60
Limitations of BMT
 Identification of histocompatible donors
 HLA typing in lymphogenic patients
 Need for additional immunosuppression
 Risk of graft versus host disease (GvHD)

61. 61
Peripheral blood stem cell
transplantation (PBSCT)
 Increasing evidence that PBSCT of cells mobilized
by growth factors enables reliable, rapid, and
durable autologous haematopoietic engraftment
 Autologous mobilized (primed) PBSCT offered
more rapid recovery of granulocytes and platelets
than BMTs derived from normal, resting marrow
 Cautious use of allogeneic PBSCT based on
unknown toxicities from cytokine administration in
donors and increased risk of GVHD from the large
number of t-cells infused

62. 62
Combination of allo-BMT and
allo-PBSCT
 Potential advantage of dual engraftment properties
available in PBSC grafts
1. Mobilized peripheral blood cells contain large quantities
of committed progenitors in addition to haematopoietic
stem cells. These committed progenitors would provide
for an earlier, although unsustained, phase of
engraftment
2. More primitive stem cells contained in both PB and BM
graft would then provide for later, durable, long-term
reconstitution

63. 63
Criteria for choice of
therapy-I
 Therapeutic recommendations:
If lymphocyte count during first week 200-
500 cells/µL, spontaneous recovery
possible
Therapy: Isolation, antibiotics, supportive
therapy including platelet infusion. Growth
factors (cytokines) can be used

64. 64
Criteria for choice of
therapy-II
If lymphocyte count in first week
below 200 cells/µL, stem cells
probably irreversibly damaged
Therapy: Isolation, antibiotics,
supportive therapy including platelet
infusion. Additional growth factor
therapy method of choice

65. 65
Criteria for choice of
therapy-III
If the lymphocyte count in first week below
100 cells/µL, consider treatment with
growth factors and BMT
Observe HLA compatibility at allogenic
BMT. This therapy may be recommended for
patients exposed to WB radiation doses
exceeding 9 Gy

66. 66
Therapeutic support for severely
irradiated patient: gastrointestinal
syndrome
 Nausea,vomiting and diarrhoea associated with
prodromal effects of radiation exposure most
likely related to neurohumoral factors. Nausea
and vomiting can be prevented/ameliorated by
new generation of 5-HT3-receptor antagonists
such as ondansetron and granisetron
 Diarrhoea associated with prodromal and
subacute phases of gastrointestinal injury most
likely affects gastrointestinal motility and
transport. Anticholinergics, metamucil,
amphogel, and loperamide can be used

67. 67
Therapeutic support for
severely irradiated patient:
gastrointestinal syndrome

68. 68
 Generally, exposure to dose range 8-30 Gy - causes
reproductive death of mucosal crypt stem cell
 In spite of considerable medical advances in
treatment of radiation injury,
no patient with full-scale gastrointestinal
syndrome has survived !
GI system and possibly lungs can limit survival
probability, assuming patient survives bone marrow
damage
Gastrointestinal syndrome