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TMT Handbook: guidelines for treatment and long-term follow up of people exposed to radiation after a malevolent act
Maria del Rosario Pérez*1, Zhanat Carr1, Makoto Akashi2, Robert N. Gent3, Patrick Gourmelon4, Siegfried Joussineau5, Volker List6, David Lloyd3, Nelson Valverde7, Albert Wiley8, Carlos Rojas-Palma9, Phil Kruse10 George Etherington3,Tua Rahola11, Maarit Muikku11, Astrid Liland12, Alicja Jaworska12, Ane Jerstad12 and Genowefa Smagala13
1World Health Organization 2National Institute of Radiological Sciences (NIRS), Japan 3Health Protection Agency, United Kingdom 4Institute of Radioprotection and Nuclear Safety (IRSN), France 5Karolinska University Hospital, Sweden 6Karlsruhe Nuclear Research Centre , Germany 7Laboratory of Radiological Sciences (LCR), Brazil 8Radiation Emergency Assistance Center/Training Site (REAC/TS), United States 9Belgian Nuclear Research Centre (SCK•CEN) 10Enviros Consulting, United Kingdom 11Radiation and Nuclear Safety Authority (STUK), Finland 12Norwegian Radiation Protection Authority (NRPA) 13Central Laboratory for Radiation Protection, Poland Abstract. Public health emergencies may be triggered in diverse scenarios including malevolent use of radioactive material. The change in global security has shifted the focus of emergency preparedness from nuclear accidents towards radiological terrorism scenarios. In such emergencies, members of the general public will most likely suffer most casualties with the numbers ranging widely depending on the scenario. Radiation doses can also range from very low to substantial life-threatening doses, and possibly combined with conventional injuries. Despite considerable efforts made in this area, there are still some gaps in terms of providing user- friendly tools for effective medical and public health response to such emergencies. The World Health Organization (WHO) participates in the collaborative research project “Triage, Monitoring and Treatment (TMT) - handbook for management of the public in the event of malevolent use of radiation” under the European FP6 programme. WHO coordinates development of the chapter on hospital phase of response and long-term follow- up. The chapter addresses diagnosis, treatment and follow-up of acute radiation syndrome, local radiation injuries, internal contamination, combined injuries, as well as psychological impact management. Although this chapter is focused on actions conducted at hospital level, critical links between pre-hospital and hospital responses are also addressed. The chapter is based on best available international guidance on health interventions in radiation emergencies, current European consensus and relevant IAEA and WHO publications. A wide distribution of the TMT handbook is envisaged and its incorporation into national exercise and training programmes will be encouraged. KEYWORDS: radiation emergency, medical and public health response, malevolent use of radioactive material .
Actual or potential major health emergencies are objects of intense public attention and debate. Health crises may be triggered by sudden, catastrophic events as well as by complex continuing emergencies and slow onset disasters, in many diverse scenarios e.g. natural disasters, technological disasters and deliberate events. In many countries, national radiation emergency response plans have long been mainly focused on nuclear accidents. More recently, the risk of malicious use of radioactive material has shifted the
focus demanding authorities being prepared also to respond to malevolent uses of ionizing radiation, including the probability of mass casualty events. The casualties will most likely be members of the public where the number of affected people can widely vary according to the scenario and radiation doses can range from very low to potentially letal, combined with conventional injuries. Radiological attacks are mainly aimed at creating disruption and panic in society. They are more likely to give rise to psychological consequences among public, and even among responders, if compared to other malicious acts. The European Commission is sponsoring a research project under the 6th EURATOM framework called “Triage, Monitoring and Treatment - handbook for management of the public in the event of malevolent use of radiation” (TMT project). Under the TMT project several tasks were undertaken in six work packages aimed to develop guidance for triage, monitoring, treatment and follow-up. 2. Objectives of Work Package 4
The objectives of work package 4 (WP4), led by WHO, were to develop evidence-based practical guidelines on:
o Treatment, health care management and long-term health surveillance of persons affected by
events involving the malevolent use of ionizing radiation including acute radiation syndrome, local radiation injuries, radiological contamination and combined injuries;
o Management of "worried well" persons not actually exposed to radiation or affected to an
extent not requiring specific medical assistance;
o Prevention and management of psychological effects.
3. Working procedure
To obtain consensus on best practice, WHO convened an expert panel which brought together the expertise of professionals from the WHO/REMPAN network. The consultancy meeting on TMT WP4 was held with a dual purpose:
to reach consensus on medical and public health issues involved in preparedness and response to radiation emergencies resulting from malevolent acts; and
to develop as far as possible an outline of that particular chapter of the TMT Handbook.
The output of the consultancy was a meeting report that constituted the basis for the development of the draft chapter. The meeting report included:
o A summary of the discussions conducted during working sessions on diagnosis, treatment and
follow-up of victims of radiation emergencies resulting from malevolent acts.
o Identified areas where consensus existed and more controversial areas requiring further
o Conclusions and consensus-based generic recommendations for health interventions in
radiation emergencies resulting from malevolent acts.
o General recommendations on the outline of the respective chapter of the TMT Handbook. o List of relevant terms requiring harmonization and core definitions to be further included in a
o List of relevant publications to be referenced and used for the Handbook development.
The expert panel identified some overlapping issues bridging pre-hospital and hospital responses and recommended further interaction between WHO and the consortium members involved in the TMT work package 3 (WP3), which addressed pre-hospital response. Based on that recommendation, a joint meeting WP3/WP4 was convened to ensure harmonization and consistency between the respective chapters. To develop the chapter, a comprehensive literature review was conducted and existing European guidance for health interventions, as well as related past or current European initiatives/projects (e.g.
TIARA 1 , METREPOL 2 , EBMT 3 consensus) were taken into account. Relevant international documents on health interventions in radiation emergencies (e.g. IAEA/ WHO publications) were referenced.
The guidelines were developed assuming that the end users for health interventions included in the TMT Handbook may include advisory agencies with competence in emergency response, local and national health authorities, emergency responders, general practitioners, medical and paramedical emergency department staff. 4. Results
As part of the TMT Handbook (Chapter F) these guidelines are addressed to physicians, nurses and other health workers who might be responsible for actions to be taken at the first referral level (i.e. hospital response) since pre-hospital response, triage and monitoring on scene was developed under WP3. However, some critical links between pre-hospital and hospital responses are pointed out. Some assumptions about possible scenarios are made, for scaling-up the response as necessary. The topic "public information and risk communication" is specifically addressed in another chapter of the Handbook. However, the relevance of this topic in medical and public health interventions during emergency and recovery as well as its importance for preventing/reducing psychological consequences were particularly addressed. The guidelines are conceived for use in hospitals with basic laboratory facilities and availability of essential drugs and medicines. An individual (patient-based) approach is used for recommending clinical procedures and, where appropriate, a public health (population-based) approach is also presented. The guidelines express an harmonized approach across the European Union and are consistent with currently existing international guidance. Actions recommended in the chapter are evidence-based statements to assist decisions about appropriate health interventions. In areas where clinical evidence is limited, recommendations were based on expert criteria according with lessons identified in recent radiation accidents. The guidelines were structured under twelve different sections providing guidance on:
1. Notification of the incident and collection of relevant information from the field; 2. How to prepare the hospital to receive victims in radiation emergencies; 3. Arrival of victims at the hospital (transfer and admission); 4. Performing a second triage at the hospital; 5. Diagnosis and treatment of acute radiation syndrome ; 6. Management of combined injuries; 7. Diagnosis and treatment of local radiation injuries 8. Dealing with externally contaminated patients and management of radionuclide incorporation 9. Dealing with deceased victims at the hospital 10. Biodosimetry 11. Public health response 12. Prevention and management of psychological impact
Guidance on the sequence of steps to sort victims of radiation emergencies is provided, including clear instructions to deal with contaminated victims in the emergency department. It is emphasized that the triage performed at the hospital should start with a conventional triage based on clinical conditions,
1 TIARA: Treatment Initiatives After Radiological Accidents 2 METREPOL: Medical Treatment Protocols for radiation accident victims 3 EBMT: European Bone Marrow Transplantation
identifying levels of priority (P1 to P3) according to the level of urgency for medical intervention. Then, the radiological triage is aimed to direct patients to the most appropriate level of medical assistance. A simple method for primary scoring of patients with acute radiation syndrome (ARS) is proposed, based on the evaluation of severity and chronology of some medical parameters (signs and symptoms) attributable to radiation exposure: erythema, asthenia, nausea, vomiting, diarrhea, abdominal pain, headaches, temperature, blood pressure, loss of consciousness and lymphocyte count. As a result of this second radiological triage, performed at the hospital, patients may be categorized according to their individual medical needs (Table 1) . A therapeutic strategy for ARS is proposed according to the clinical status of the patient (Table 2). Table 1: Radiological triage categories Score Condition 0
Bystanders who most probably were not exposed to radiation
Irradiated patients that can be followed on an outpatient basis or by a day care hospital structure
Patients needing maximum medical effort to be rescued
Patients predicted to develop multiple organ failure (MOF) beyond any curative perspective
Table 2: Therapeutic strategy
re-evaluation during the 1st week based on laboratory and clinical symptoms revealing (or not) irreversible organ damage or MOD/MOF
Criteria to transplant: severe bone marrow aplasia
persisting 14-21 days under cytokines, no residual haematopoiesis, no irreversible organ damage. Type of graft: bone marrow, peripheral stem cells, cord blood. Conditioning: fludarabine +/- antilymphocyte globulin. Don't use MTX for GVDH prevention
G-CSF: granulocyte colony stimulating factor GI: gastrointestinal MOD/MOF: multiorgan dysfunction/failure MTX: methotrexate GVHD: graft vs. host disease
The guidelines propose a comprehensive organ specific grading to be applied beyond the first 48h. This grading method is based on a semiquantitative categorization of patients (METREPOL) which rates the severity of signs and symptoms considering four critical organ systems: neurovascular, haematopoietic, cutaneous and gastrointestinal. The integration of elements of the four organ systems determines the response category (RC), which reflects the damage to critical organs. Based on the RC the patient may be discharged, admitted to a routine care medical/surgical floor, admitted to an intensive care unit or referred to other specialized hospital. The guidelines emphasizing that, since radiation does not cause immediate life-threatening risks, serious conventional combined injuries (e.g. burns, wounds, trauma) will take priority over concerns about irradiation and contamination. Instructions regarding surgical procedures, transfer of patients, treatment of thermal burns, stabilization of fractures and management of contaminated wounds are included. The clinical evolution of local radiation injuries4 (LRI) is described. Guidance on how to identify a skin lesion attributable to radiation exposure is provided. Main diagnostic tools are proposed and different therapeutic options are presented, including the novel approach of regenerative medicine combining dosimetry-guided surgery with autologous mesenchymal stem cell therapy. The guidelines emphasize that the treatment of severe LRI should be performed at specialized institutions. Practical guidance for general management of contaminated patients is associated with procedures for external decontamination using specific or non-specific washing solutions. Decontamination of normal skin, wounds and natural orifices is considered, with objective criteria for deciding when to stop external decontamination efforts. Principles of treating internal contamination are based on the criteria adopted by TIARA, in terms of committed effective dose assessed by bioassay. The guidelines point out that the clinical evidence about use of decorporating and blocking agents is limited. Detailed explanation is provided about the few agents that have been proven to be effective (e.g. potassium iodide, DTPA, Prussian blue) and additional information about other possible agents is provided in an annex. Blood sampling procedures for cytogenetic dosimetry are described, and recommendations about packaging and transport of blood samples are also provided. The section on public health response addresses the role of the health authorities during the emergency and provides guidance for scaling-up the response as the magnitude of the event unfolds. In emergencies with many victims it is particularly important to put into place a scheme to bring people into the health care system yet avoiding overwhelming the hospitals. This section includes instructions on how to establish and manage peripheral health care centres during radiation emergencies. Guidance on how to deal with an outbreak of an unusual disease attributable to radiation exposure is also provided. Criteria for long-term follow-up are presented in a dual approach:
1. individuals who developed deterministic effects (e.g. ARS, LRI); 2. population exposed to low radiation doses.
Guidance for prevention and management of the psychological impact is presented in an explanatory rather than prescriptive text, including:
How to deal with "worried well" people;
4 Cutaneous radiation syndrome (CRS) is also proposed to describe the inflammatory skin reaction associated with a particular cytokine profile observed after radiation exposure. However, following exposure to high doses of IR it is not only the skin which is involved, but also the subcutaneous tissue and even muscles and bones and for the purpose of the handbook this entity is termed as LRI.
How to identify people at higher risk of developing mental health problems (e.g. children, pregnant women, mothers with young children);
How to deal with acute stress reactions;
How to prevent, predict and treat post traumatic stress disorder
6. Current status and next steps
The draft TMT Handbook was distributed to a wide range of end-users (radiation emergency response organizations in the European Union and associated states), who were invited to evaluate and, if possible, to test the handbook in their national emergency response exercises. Comments on the draft handbook and possible experience from its use in exercises will be presented by end-users during a Feedback Workshop. A final version of the handbook will be produced after a peer-review process. A training course based on the TMT Handbook is scheduled for the first quarter of 2009. This course aims to strengthening of national capability for response to malevolent acts involving a use of radiation. The training will also offer an opportunity to identify common challenges and ways of better harmonization of response strategies. In addition, the participants will be encouraged and expected to promote the incorporation of the TMT Handbook into exercises and training programmes in their own countries and disseminate it widely among national and local emergency response institutions. 7. Acknowledgements This work was partially supported by the EC under the 6th EURATOM Contract Number FP6- 036497 8. References BIODOSEPR-2006 MEETING: Acute dosimetry consensus committee. Recommendations on biodosimetry applications in events involving uses of radiation by terrorists and radiation accidents http://www.remm.nlm.gov/NewDosimetryArticleInPress.pdf CARR Z. The role of the World Health Organization in strengthening capacity of the Member States for preparedness and response to radiation emergencies. Acta Med Nagasaki, 50: 37-40 (2006). GORIN NC, FLIEDNER TM, GOURMELON P. et al. Consensus conference on European preparedness for haematological and other medical management of mass radiation accidents. Ann Hematol 85:671-679 (2006). Guidebook for the Treatment of Accidental Internal Radionuclide Contamination of Workers. Radiat Prot Dosim 41 no. 1 (1992). INTERNATIONAL ATOMIC ENERGY AGENCY and WORLD HEALTH ORGANIZATION, EPR-medical Medical generic procedures for medical response during a nuclear or radiological emergency, IAEA, Vienna (2005). ICRP Publication 96: Protecting People Against Radiation Exposure in the Event of a Radiological Attack. Edited by Jack Valentin; and International Commission on Radiological Protection . ISBN 0080446256 · Elsevier (2005). LATAILLADE J, DOUCET C, BEY E et al. New approach to radiation burn treatment by dosimetry- guided surgery combined with autologous mesenchymal stem cell therapy. Regenerative Medicine 2/5):785-794 (2007). MENETRIER F., BERARD PH. JOUSSINEAU S. et al TIARA: Treatment Initiatives After Radiological Accidents. Rad Prot Dosimetry 127(1-4): 444-448 (2007).
MENETRIER F., BERARD PH. JOUSSINEAU S. et al Dose Assessment of Inhaled Radionuclides in Emergency Situations. Edited by Health Protection Agency (2007). METTLER F. , GUSKOVA A., GUSEV I (Eds) Medical Management of Radiation Accidents, 2nd Edition, University of New Mexico, Albuquerque, New Mexico (2001). METREPOL compendium of the manual "Medical management of radiation accidents: manual on the acute radiation syndrome"(2001). Radiation Event Medical Management: Guidance on Diagnosis & Treatment for Health Care Providers. U.S. Department of Health and Human Services; Office of the Assistant Secretary for Preparedness and Response. http://www.remm.nlm.gov RICKS, RC, BERGER, ME, O’HARA, FM. (Eds) The medical Basis for Radiation Accident Preparedness; Clinical Care of Victims. Eds. NY: Parthenon (2002). WHO
https://www.who.int/ionizing_radiation/a_e/emergencies/WHO_stockpile_report_2007.pdf. WOOD R. ET AL Decorporation Treatment - Medical Overview. In Decorporation of Radionuclides from the Human Body. Radiat Prot Dosim 87 no. 1, 51-57 (2000).
Prof. Dr. med. Michael Riedel Publikationen I. Originalarbeiten II. Fallberichte III. Übersichtsartikel IV. Buchkapitel I Originalarbeiten 1. Müller N, Dobmeier P, Empl M, Riedel M. , Schwarz MJ, Ackenheil M: Soluble IL-6 Receptors in the serum and cerebrospinal fluid of paranoid schizophrenic patients. In: European Psychiatry, 1997, 12, 294 - 299 2. Müller N, Empl M,
Survey of Plasmids Collected from Antibiotic Resistant Enteric Department of Biology, Carroll College, 100 N. East Ave., Waukesha, WI 53186 Abstract: Materials and Methods: Bacterial antibiotic resistance is becoming increasingly problematic. Antibiotics are being prescribed more and more frequently at doctors’ offices, vets, and even in the agricultural industries. The effe