Australian Clinical Guidelines for Radiological Emergencies - September 2012

Appendix E: Treatment of Acute Radiation Syndrome

Page last updated: 07 December 2012

Acute Radiation Syndrome (ARS) is classically described as having three sub-syndromes: the haemopoietic (>1 Gy), the gastro-intestinal (>3 Gy) and the neurological (>15 Gy). Case studies over the last twenty years, however, show that ARS is much a more complex condition, with appreciable damage occurring to the cardiovascular system and all internal organs at levels over 3 Gy.

Several cases of acute and sub-acute exposure to very high doses of radiation have demonstrated that, given optimal treatment, the haemopoietic syndrome can be survived, even when the dose is very high. Damage to the cardiovascular system and internal organs, however, is much more difficult to overcome, and most deaths in this group have come from Radiation-induced Multi-Organ Dysfunction (RiMOD).

Various publications give post-exposure outcomes in terms of LD50/60, and with modern treatment, this limit is approaching 8 Gy. However, longer-term survival figures are much less impressive. In spite of optimal treatment, the twelve-month survival rate from acute whole-body doses greater than 6 Gy appears to be zero. [Note that final whole-body dose assessments are generally lower than initial assessments, so it is proper to provide cytokines and supportive treatment to those where the initial estimate is up to 10 Gy].

For partial-body, fractionated or chronic doses, it is much harder to predict outcomes, for several reasons:

  • it is much more difficult to calculate equivalent whole-body doses;
  • damage is much more variable among organ systems; and
  • the body's self-repair mechanisms can mitigate against much of the impact.
ARS is much more likely following a criticality accident or nuclear detonation than a radiation dispersal device. In accident or terrorist scenarios exposure will rarely be even, and most patients will have sustained other injuries, such as burns or blast. These injuries should be given priority, as specific intervention for radiation injury (apart from an initial dose of cytokines) is not required for the first 48 hours.

Initial Emergency Management

If trauma is present, treat. If external contaminants are present, decontaminate.
Modalities for treating Acute Radiation Syndrome include:
  • Symptomatic relief (analgesia, anti-emetics)
  • Reverse isolation in a positive-pressure room
  • Enteral feeding with well-cooked, low-residue food
  • Anti-microbials
  • Blood products (irradiated whole blood, red cells and platelets)
  • Colony stimulating factors (G-CSF, GM-CSF, epoietin)
  • Stem cell transplants (including umbilical cord blood and bone marrow transplants)
It is difficult to ascertain in advance which patients will require the higher levels of treatment; but these modalities are not often required in the first 24-28 hours, allowing for preliminary biodosimetry and a more thorough secondary triage.

The following guidelines illustrate which treatments are available for components of ARS. They are general guidelines only, and treatment for individual patients should be based on the best available dose assessment and their clinical and haematological status. In a mass casualty event, it may be necessary to withhold intensive treatment from some of the more highly-exposed patients who have little chance of survival, which roughly corresponds to those who vomit within the first hour after an acute exposure (see triage chapter).

Symptomatic relief

Patients with ARS may experience severe pain from irradiated skin, even if they do not exhibit the classic "cutaneous" syndrome. Pain is often fleeting and not easily controlled - high doses of opioids may be required.

Nausea and vomiting may be amenable to common anti-emetics if the dose was low (< 3Gy), but most patients will require ondansetron or granisitron to control their symptoms. Note that another serotonin receptor antagonist, alosetron, is contra-indicated in ARS due to the risks of constipation and ischaemic colitis.

Reverse isolation

Ideally, patients who have been exposed to high doses should be placed in reverse (positive-pressure) isolation and started on cytokines and prophylactic antibiotics as soon as feasible. Realistically, there is no imperative for isolation to be imposed immediately, as the immune system will remain functional for a few days or weeks post-exposure.

The same precautions are required as for immuno-suppressed patients on chemo- or radiotherapy. Measures are taken to protect the patient from infectious organisms carried by people and the environment.

Fluids

Where the gut or kidneys have been affected, patients may experience difficulty in maintaining fluid balance. However, care should be taken not to over-hydrate patients, as radiation burns do not require the same level of fluid support as thermal burns per unit surface area.

Enteral feeding

Enteral feeding is an important modality for maintaining gut function and stimulating the crypt cells. Food must, however, be as free as possible from any source of infection. All foods must be well-cooked and no fresh food (for example, fruit or cheese) is allowed. High-calorie preparations, such as Sustagen, may be useful, but it is important to include some solid foods as well. A good multi-vitamin and mineral preparation may be required.

Anti-microbials

Anti-virals

For patients with a known history of Herpes simplex, Herpes/Varicella zoster, or Cytomegalovirus, recrudescence can be expected as the immune system fails. These patients will require prophylactic or therapeutic anti-viral treatment. Carriers of Human Immunodeficiency virus (HIV), hepatitis B (HBV) or hepatitis C (HCV) may also experience a resurgence of their disease.

Anti-bacterials


Antibiotics should be administered to all patients with a neutrophil count of less than 0.5 x 109 cells/L. Gram-negative gut disinfection using an absorbable fluoroquinolone (such as norfloxacin or ciprofloxacin) is recommended for all patients, but other antibacterials should be administered only as required on clinical grounds.

Anti-fungals


Fungi and parasites are a significant hazard, and a high index of suspicion must be maintained for the duration of the patient's stay. Confirmation of infection is very difficult, but a persistent fever in the presence of adequate antibiotic cover is generally in an indication of candida, aspergillus or pneumocystis infection. Amphotericin B is the drug of choice.

Blood products

Blood products should be administered as required. Most patients who have suffered a high enough exposure to cause vomiting in the first two hours will experience severe marrow dysplasia and will require platelets (to prevent haemorrhage) and red cells (to combat anaemia). All blood products must be irradiated to 25 Gy to inactivate white cells and prevent GvHD. If it is possible, apheretic products are preferred to pooled products, but this is unlikely to be practical for mass casualty situations.

Colony-stimulating factors

There are several colony-stimulating factors available in Australia which may be helpful in treating irradiated patients. All are "authority" drugs and are not currently licensed for use in acute radiation syndrome; however, obtaining permission for off-license use in ARS is not expected to be difficult.

White cells: Both G-CSF (filgrastim, pegfilgrastim) and GM-CSF (sargramostim) are available, and may reduce the level and duration of neutropaenia. Pegfilgrastim has the advantage of being given once every 3-5 days rather than daily, making it more suitable for mass casualty use. Note that G-CSF may be inhibitory to megakaryocytes and can prolong thrombocytopaenia.

Red cells: Epoietin and darbepoietin act on erythrocyte precursors and may reduce the requirement for packed red cell transfusions. They can cause rapid splenic enlargement and even rupture, and can exhaust the body's iron stores.

Platelets: A megakaryocyte-stimulating factor (PEG-rHuMGDF) is available in the US.

The most important point to make for all the colony-stimulating factors is that they work best when given early - prior to the development of the manifest illness. If it is clear that a patient has received a potentially lethal dose (3-10 Gy) on symptomatology, then CSFs should be administered as soon as possible. For this purpose, pegylated preparations are preferred, as they do not need to be given daily.

If sufficient supplies are available, cytokines should be provided to ambulant patients in the 1-3 Gy exposure group as well, as they will reduce the need for intensive supportive care.

The provision of cytokines does not remove the need for optimal supportive care, as the cytokines will not produce adequate levels of circulating cells for some days or weeks.

Stem cell transplants

Stem cell transplants may be required when the whole-body dose has been high enough to ablate all the stem cells in the bone marrow (where the patient is classed as H4). At doses this high, however, there will be considerable damage to other tissues, and the chance of long-term survival is not high. Further complications arise from the fact that these patients require additional immunosuppression to ensure that the graft will "take", since bone marrow ablation is rarely as complete as in radiotherapy.

Stem cells from adults can be obtained through apheresis of peripheral blood following stimulation by G-CSF, but this procedure requires at least five days' preparation and is painful. There is also a theoretical risk of leukaemia for the donor due to the effects of G-CSF on the marrow.

Umbilical cord blood cells are a good source of stem cells with a low risk of graft versus host disease (GvHD), but the small quantities obtained from each cord, and the small number of samples stored, mean that the supply is limited, and a match may not be obtained.

Bone marrow cells can be obtained from adults more easily than apheretic stem cells, but the uptake is variable, and the risk of GvHD is high.

Table 1: Summary of treatment options
ScenarioPresentation
Dose range for treatment (Gy)
Antibiotics
Dose range for treatment (Gy)
Cytokines
Dose range for treatment (Gy)
Stem Cells
Small numbersHealthy, no other injuries
2-10
3-10
7-10*
Small numbersMultiple injuries or burns
2-6
2-6
N/A
Mass CasualtiesHealthy, no other injuries
2-7
3-7
7-10*
Mass CasualtiesMultiple injuries or burns
2-6
2-6
N/A
* 4-10 Gy if there is prior autologous marrow stored, or the patient has a syngeneic donor

Reference: Wasalenko JK, et al. Medical management of the acute radiation syndrome: recommendations of the strategic national stockpile radiation working group. Ann Int Med. 2004; 140: 1037-1051

Follow-up and counselling

Because of the diffuse radiation damage to body tissues, patients who have suffered ARS are at a higher risk of developing cardiovascular or respiratory complaints later in life. There is also a risk of cancer in general and haemopoietic cancer in particular. These risks are stochastic and cannot be predicted with any accuracy on an individual level.

Patients who have suffered supralethal exposures (> 6 Gy acute whole body) should be given the opportunity to discuss end-of-life matters with their families and appropriate counsellors.

References:
Waselenko et al. Medical Management of the Acute Radiation Syndrome: Recommendations from the Strategic National Stockpile Radiation Working Group. Ann Intern Med 2004; 140:1037-1051.