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Literature Review and Global Consensus on Management of Acute Radiation Syndrome Affecting Nonhematopoietic Organ Systems

Published online by Cambridge University Press:  08 April 2013

Nicholas Dainiak ,
Robert Nicolas Gent ,
Zhanat Carr ,
Rita Schneider ,
Judith Bader ,
Elena Buglova ,
Nelson Chao ,
C. Norman Coleman ,
Arnold Ganser  and
Claude Gorin
...Show all authors
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Abstract

Objectives: The World Health Organization convened a panel of experts to rank the evidence for medical countermeasures for management of acute radiation syndrome (ARS) in a hypothetical scenario involving the hospitalization of 100 to 200 victims. The goal of this panel was to achieve consensus on optimal management of ARS affecting nonhematopoietic organ systems based upon evidence in the published literature.

Methods: English-language articles were identified in MEDLINE and PubMed. Reference lists of retrieved articles were distributed to conferees in advance of and updated during the meeting. Published case series and case reports of ARS, publications of randomized controlled trials of relevant interventions used to treat nonirradiated individuals, reports of studies in irradiated animals, and prior recommendations of subject matter experts were selected. Studies were extracted using the Grading of Recommendations Assessment Development and Evaluation system. In cases in which data were limited or incomplete, a narrative review of the observations was made.

Results: No randomized controlled trials of medical countermeasures have been completed for individuals with ARS. Reports of countermeasures were often incompletely described, making it necessary to rely on data generated in nonirradiated humans and in experimental animals. A strong recommendation is made for the administration of a serotonin-receptor antagonist prophylactically when the suspected exposure is >2 Gy and topical steroids, antibiotics, and antihistamines for radiation burns, ulcers, or blisters; excision and grafting of radiation ulcers or necrosis with intractable pain; provision of supportive care to individuals with neurovascular syndrome; and administration of electrolyte replacement therapy and sedatives to individuals with significant burns, hypovolemia, and/or shock. A strong recommendation is made against the use of systemic steroids in the absence of a specific indication. A weak recommendation is made for the use of fluoroquinolones, bowel decontamination, loperamide, and enteral nutrition, and for selective oropharyngeal/digestive decontamination, blood glucose maintenance, and stress ulcer prophylaxis in critically ill patients.

Conclusions: High-quality studies of therapeutic interventions in humans exposed to nontherapeutic radiation are not available, and because of ethical concerns regarding the conduct of controlled studies in humans, such studies are unlikely to emerge in the near future.

(Disaster Med Public Health Preparedness. 2011;5:183–201)

Keywords

countermeasures for ARStreatment of ARSnarrative review of countermeasures for ARSacute radiation syndromereviewsradiation effectsgastrointestinal diseasesskin diseasesburnsneurologic manifestationsethics, medicalpalliative carediabetes mellitusinfection controlcritical care
Type
Review Article
Information
Disaster Medicine and Public Health Preparedness , Volume 5 , Issue 3 , October 2011 , pp. 183 - 201
Copyright
Copyright © Society for Disaster Medicine and Public Health, Inc. 2011

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References

REFERENCES

1.Becker, SMTerrorism survey, frequency questionnaire, March 8-April 21, 2006. http://www.americanprogress.org/kf/terrorsurveypoll.pdf. Accessed June 16, 2011.Google Scholar
2.Bunn, M, Wier, ASecuring the bomb: an agenda for action. http://www.nti.org/e_research/analysis_cnwmupdate_052404.pdf. Published May 2004. Accessed June 16, 2011.Google Scholar
3.International Action Plan for Strengthening the International Preparedness and Response System for Nuclear and Radiological Emergencies. Accessed June 16, 2011. http://www-ns.iaea.org/downloads/rw/action-plans/ers-action-plan.pdf.Google Scholar
4.Waselenko, JK, MacVittie, TJ, Blakely, WFStrategic National Stockpile Radiation Working Group. Medical management of the acute radiation syndrome: recommendations of the Strategic National Stockpile Radiation Working Group. Ann Intern Med. 2004;140 (12):1037–1051.CrossRefGoogle ScholarPubMed
5.Gorin, NC, Fliedner, TM, Gourmelon, P.Consensus conference on European preparedness for haematological and other medical management of mass radiation accidents. Ann Hematol. 2006;85 (10):671–679.CrossRefGoogle ScholarPubMed
6.World Health Organization handbook for guideline development. http://www.searo.who.int/LinkFiles/RPC_Handbook_Guideline_Development.pdf. Published March 2008. Accessed June 16, 2011.Google Scholar
7.Schünemann, HJ, Oxman, AD, Brozek, JGRADE Working Group. Grading quality of evidence and strength of recommendations for diagnostic tests and strategies. BMJ. 2008;336 (7653):1106–1110.CrossRefGoogle ScholarPubMed
8.Bunn, MRisk of nuclear terrorism and the next steps to reduce the danger: testimony for the Committee on Homeland Security and Government Affairs, United States Senate. http://belfercenter.ksg.harvard.edu/files/bunn-nuclear-terror-risk-test-08.pdf. Published April 2, 2008. Accessed June 16, 2011.Google Scholar
9.Maurer, DC.Nuclear detection: preliminary observations on the Domestic Nuclear Detection Office's efforts to develop a global nuclear detection architecture. Testimony before the Committee on Homeland Security and Governmental Affairs, US Senate. http://www.gao.gov/products/GAO-08-999T. Published July 16, 2008. Accessed June 10, 2011.Google Scholar
10.Mowatt-Larssen, R.Nuclear terrorism and the 21st century. Statement before the Homeland Security and Governmental Affairs Committee, United States Senate. hsgac.senate.gov/public/_files/040208MowattLarssen.pdf. Published April 2, 2008. Accessed June 10, 2011.Google Scholar
11.Mettler, FA Jr, Voelz, GL.Major radiation exposure—what to expect and how to respond. N Engl J Med. 2002;346 (20):1554–1561.Google Scholar
12.Mettler, FA, Upton, AC.Deterministic effects of ionizing radiation. In: Mettler FA, Upton AC, eds. Medical Effects of Radiation. 3rd ed. Philadelphia: Saunders Elsevier; 2008.Google Scholar
13.Armed Forces Radiobiology Research Institute. Medical Management of Radiological Casualties Handbook.2nd ed. Bethesda, MD: AFRRI. http://www.afrri.usuhs.mil/www/outreach/pdf/2edmmrchandbook.pdf. Published April 2003. Accessed June 16, 2011.Google Scholar
14.Meineke, V, Fliedner, TM.Radiation-induced multi-organ involvement and failure: challenges for radiation accident medical management and future research. BJR Suppl. 2005;27:196–200.Google Scholar
15.Gourmelon, P, Marquette, C, Agay, D, Mathieu, J, Clarençon, D.Involvement of the central nervous system in radiation-induced multi-organ dysfunction and/or failure. BJR Suppl. 2005;27:62–68.CrossRefGoogle Scholar
16.Jackson, WL Jr, Gallagher, C, Myhand, RC, Waselenko, JK.Medical management of patients with multiple organ dysfunction arising from acute radiation syndrome. BJR Suppl. 2005;27:161–168.Google Scholar
17.Warren, S, Bowers, JZ.The acute radiation syndrome in man. Ann Intern Med. 1950;32 (2):207–216.Google Scholar
18.Brooks, JW, Evans, EI, Ham, WT Jr, Reid, JD.The influence of external body radiation on mortality from thermal burns. Ann Surg. 1952;136 (3):533–545.Google Scholar
19.Ledney, GD, Elliot, TB, Moore, MM.Modulations of mortality by tissue trauma and sepsis in mice after radiation injury. In: Mossman KL, Mills WA, eds. The Biological Basis of Radiation Protection Practices. Baltimore, MD: Williams & Wilkins; 1992:202-217.Google Scholar
20.Alexander, GA, Swartz, HM, Amundson, SA.BiodosEPR-2006 Meeting: acute dosimetry consensus committee recommendations on biodosimetry applications in events involving uses of radiation by terrorists and accidents. Radiat Meas. 2007;42(Suppl)972–996.CrossRefGoogle Scholar
21.Dainiak, NResponse to and management of a radiological crisis. http://chip.med.nyu.edu/course/view.php?id=14. Accessed June 14, 2011.Google Scholar
22.Committee to Assess Health Risks From Exposure to Low Levels of Ionizing Radiation. Health Risks From Exposure to Low Levels of Ionizing Radiation, BEIR VII Phase 2.Washington, DC: National Academies Press; 2006:267-312.Google Scholar
23.Anno, GH, Young, RW, Bloom, RM, Mercier, JR.Dose response relationships for acute ionizing-radiation lethality. Health Phys. 2003;84 (5):565–575.Google Scholar
24.Bender, MA, Gooch, PC.Somatic chromosome aberrations induced by human whole-body irradiation: the “Recuplex” criticality accident. Radiat Res. 1966;29 (4):568–582.CrossRefGoogle ScholarPubMed
25.Goans, RE, Holloway, EC, Berger, ME, Ricks, RC.Early dose assessment in criticality accidents. Health Phys. 2001;81 (4):446–449.Google Scholar
26.Demidenko, E, Williams, BB, Swartz, HM.Radiation dose prediction using data on time to emesis in the case of nuclear terrorism. Radiat Res. 2009;171 (3):310–319.Google Scholar
27.Fliedner, TM, Friesecke, I, Beyrer, K.Medical Management of Radiation Accidents: Manual on Acute Radiation Syndrome. Oxford, UK: British Institute of Radiobiology; 2001.Google Scholar
28.Wilkins, RC, Romm, H, Kao, TC.Interlaboratory comparison of the dicentric chromosome assay for radiation biodosimetry in mass casualty events. Radiat Res. 2008;169 (5):551–560.Google Scholar
29.Lloyd, DC, Edwards, AA, Moquet, JE, Guerrero-Carbajal, YC.The role of cytogenetics in early triage of radiation casualties. Appl Radiat Isot. 2000;52 (5):1107–1112.Google Scholar
30.Wojcik, A, Lloyd, D, Romm, H, Roy, L.Biological dosimetry for triage of casualties in a large-scale radiological emergency:capacity of the EU member states. Radiat Prot Dosimetry. 2010;138 (4):397–401.Google Scholar
31.Parker, DD, Parker, JC.Estimating radiation dose from time to emesis and lymphocyte depletion. Health Phys. 2007;93 (6):701–704.Google Scholar
32.Flynn, DF, Goans, RE.Nuclear terrorism: triage and medical management of radiation and combined-injury casualties. Surg Clin North Am. 2006;86 (3):601–636.Google Scholar
33.Andrews, GA.Medical management of accidental total-body irradiation. In: Hubner K, Fry S, eds. Medical Basis for Radiation Accident Preparedness. New York: Elsevier Press; 1980.Google Scholar
34.Blakely, WF, Ossetrova, NI, Manglapus, GL.Amylase and blood cell-count hematological radiation-injury biomarkers in a rhesus monkey radiation model-use of multiparameter and integrated biological dosimetry. Radiat Meas. 2007;42(Suppl)1164–1170.Google Scholar
35.Dainiak, N, Berger, P, Albanese, J.Relevance and feasibility of multi-parameter assessment for management of mass casualties from a radiological event. Exp Hematol. 2007;35 4(Suppl 1)17–23.Google Scholar
36.Monti, P, Wysocki, J, van der Meeren, A, Griffiths, NM.The contribution of radiation-induced injury to the gastrointestinal tract in the development of multi-organ dysfunction syndrome or failure. BJR Suppl. 2005;27(Suppl)89–94.Google Scholar
37.Hauer-Jensen, M, Kumar, KS, Wang, J.Intestinal toxicity in radiation- and combined injury: significance, mechanisms, and countermeasures. In: Larche RA, ed. Global Terrorism Issues and Developments. Hauppauge, NY: Nova Science Publishers; 2008.Google Scholar
38.Pizzarello, DJ, Witcofski, TL.Medical Radiation Biology. Philadelphia: Lea & Febiger.; 1982.Google Scholar
39.Lushbaugh, CC.The impact of estimates on radiation emergency management. Proceedings of a Symposium on the Control of Exposure of Public to Ionizing Radiation in the Event of Accident or Attack. National Council on Radiation Protection and Measurement, held on April 27-28, 1981, in Bethesda, Md; 1982; pp 46-47.Google Scholar
40.Dainiak, N, Waselenko, JK, Armitage, JO.The hematologist and radiation casualties. Hematology Am Soc Hematol Educ Progr; 2003:473-496.Google Scholar
41.Sigsgaard, T, Herrstedt, J, Handberg, J, Kjaer, M, Dombernowsky, P.Ondansetron plus metopimazine compared with ondansetron plus metopimazine plus prednisolone as antiemetic prophylaxis in patients receiving multiple cycles of moderately emetogenic chemotherapy. J Clin Oncol. 2001;19 (7):2091–2097.Google Scholar
42.Schmoll, HJ, Aapro, MS, Poli-Bigelli, S.Comparison of an aprepitant regimen with a multiple-day ondansetron regimen, both with dexamethasone, for antiemetic efficacy in high-dose cisplatin treatment. Ann Oncol. 2006;17 (6):1000–1006.Google Scholar
43.Walsh, T, Morris, AK, Holle, LM.Granisetron vs ondansetron for prevention of nausea and vomiting in hematopoietic stem cell transplant patients: results of a prospective, double-blind, randomized trial. Bone Marrow Transplant. 2004;34 (11):963–968.Google Scholar
44.Abdelsayed, GG.Management of radiation-induced nausea and vomiting. Exp Hematol. 2007;35 4(Suppl 1)34–36.Google Scholar
45.Roila, F, Hesketh, PJ, Herrstedt, JAntiemetic Subcommitte of the Multinational Association of Supportive Care in Cancer. Prevention of chemotherapy- and radiotherapy-induced emesis: results of the 2004 Perugia International Antiemetic Consensus Conference. Ann Oncol. 2006;17 (1):20–28.Google Scholar
46.Kris, MG, Hesketh, PJ, Somerfield, MRAmerican Society of Clinical Oncology. American Society of Clinical Oncology guideline for antiemetics in oncology: update 2006. J Clin Oncol. 2006;24 (18):2932–2947.Google Scholar
47.Harris, AG, O’Dorisio, TM, Woltering, EADiarrhea Management Consensus Development Panel. Consensus statement: octreotide dose titration in secretory diarrhea. Dig Dis Sci. 1995;40 (7):1464–1473.Google Scholar
48.Wadler, S, Benson, AB III, Engelking, C.Recommended guidelines for the treatment of chemotherapy-induced diarrhea. J Clin Oncol. 1998;16 (9):3169–3178.CrossRefGoogle ScholarPubMed
49.Ippoliti, C.Antidiarrheal agents for the management of treatment-related diarrhea in cancer patients. Am J Health Syst Pharm. 1998;55 (15):1573–1580.CrossRefGoogle ScholarPubMed
50.Szilagyi, A, Shrier, I.Systematic review: the use of somatostatin or octreotide in refractory diarrhoea. Aliment Pharmacol Ther. 2001;15 (12):1889–1897.CrossRefGoogle ScholarPubMed
51.Yavuz, MN, Yavuz, AA, Aydin, F, Can, G, Kavgaci, H.The efficacy of octreotide in the therapy of acute radiation-induced diarrhea: a randomized controlled study. Int J Radiat Oncol Biol Phys. 2002;54 (1):195–202.CrossRefGoogle ScholarPubMed
52.Hermsen, JL, Sano, Y, Kudsk, KA.Food fight! Parenteral nutrition, enteral stimulation and gut-derived mucosal immunity. Langenbecks Arch Surg. 2009;394 (1):17–30.CrossRefGoogle ScholarPubMed
53. McClave, SA, Martindale, RG, Vanek, VWA.S.P.E.N. Board of Directors; American College of Critical Care Medicine; Society of Critical Care Medicine. Guidelines for the Provision and Assessment of Nutrition Support Therapy in the Adult Critically Ill Patient: Society of Critical Care Medicine (SCCM) and American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.). JPEN J Parenter Enteral Nutr. 2009;33 (3):277–316.Google Scholar
54.Worthington, P, Gilbert, KA, Wagner, BA.Parenteral nutrition for the acutely ill. AACN Clin Issues. 2000;11 (4):559–579, quiz 634-636.Google Scholar
55.International Atomic Energy Agency. IAEA reports on Tokaimura accident. Health Phys. 2000;78 (2):231.Google Scholar
56.Meineke, V.Medical and Organization Challenges Resulting From a Radiological Nuclear Emergency. Acute Radiation Syndrome of the Skin: New Aspects in Pathophysiology and Treatments Following Radiation Exposure. Washington, DC: Radiation Injury Treatment Network; 2007.Google Scholar
57.Hoashi, T, Okochi, H, Kadono, T.A case of acute radiation syndrome from the dermatological aspect. Br J Dermatol. 2008;158 (3):597–602.Google Scholar
58.Peter, RU.Klinische Aspekte des kutanen Strahlensyndroms nach Strahlenunfallen—Erfahrungen von Goiania und Tschernobyl. Akuel Dermatol. 1993;19:364–367.Google Scholar
59.Peter, RU.The cutaneous radiation syndrome. In: MacVittie TJ, Weiss JF, Browne D, eds. Advances in the Treatment of Radiation Injuries. Oxford, UK: Elsevier; 1999.Google Scholar
60.Goldschmidt, H.Dermatologic roentgen therapy and radiocarcinogenesis. Hautarzt. 1982;33 (4):183–190.Google Scholar
61.Müller, K, Meineke, V.Radiation-induced alterations in cytokine production by skin cells. Exp Hematol. 2007;35 4(Suppl 1)96–104.Google Scholar
62.Meineke, V, van Beuningen, D, Sohns, T, Fliedner, TM.Medical management principles for radiation accidents. Mil Med. 2003;168 (3):219–222.Google Scholar
63.Meineke, V.The role of damage to the cutaneous system in radiation-induced multi-organ failure. BJR Suppl. 2005;27:85–99.Google Scholar
64.Roy, L, Bertho, JM, Souidi, M, Vozenin, MC, Voisin, P, Benderitter, M.Biochemical approach to prediction of multiple organ dysfunction syndrome. BJR Suppl. 2005;27:146–151.Google Scholar
65.Bertho, JM, Roy, L, Souidi, M.New biological indicators to evaluate and monitor radiation-induced damage: an accident case report. Radiat Res. 2008;169 (5):543–550.Google Scholar
66.Berger, ME, Christensen, DM, Lowry, PC, Jones, OW, Wiley, AL.Medical management of radiation injuries: current approaches. Occup Med (Lond). 2006;56 (3):162–172.Google Scholar
67.Chambers, JA, Purdue, GF.Radiation injury and the surgeon. J Am Coll Surg. 2007;204 (1):128–139.Google Scholar
68.Orgill, DP.Excision and skin grafting of thermal burns. N Engl J Med. 2009;360 (9):893–901.Google Scholar
69.Foster, K, Greenhalgh, D, Gamelli, RLFS 4IU VH S/D Clinical Study Group. Efficacy and safety of a fibrin sealant for adherence of autologous skin grafts to burn wounds: results of a phase 3 clinical study. J Burn Care Res. 2008;29 (2):293–303.Google Scholar
70.Brown, JB, McDOWELL, F, Fryer, MP.Surgical treatment of radiation burns. Surg Gynecol Obstet. 1949;88 (5):609–622.Google Scholar
71.Berger, ME, Hurtado, R, Dunlap, J.Accidental radiation injury to the hand: anatomical and physiological considerations. Health Phys. 1997;72 (3):343–348.CrossRefGoogle Scholar
72.Geraci, JP, Mariano, MS, Jackson, KL, Taylor, DA, Still, ER.Effects of dexamethasone on late radiation injury following partial-body and local organ exposures. Radiat Res. 1992;129 (1):61–70.Google Scholar
73.DiCarlo, AL, Hatchett, RJ, Kaminski, JM.Medical countermeasures for radiation combined injury: radiation with burn, blast, trauma and/or sepsis. report of an NIAID Workshop, March 26-27, 2007. Radiat Res. 2008;169 (6):712–721.Google Scholar
74.Peter, RU, Gottlöber, P.Management of cutaneous radiation injuries: diagnostic and therapeutic principles of the cutaneous radiation syndrome. Mil Med. 2002;167 2(Suppl)110–112.Google Scholar
75.Ashcroft, GS, Greenwell-Wild, T, Horan, MA, Wahl, SM, Ferguson, MW.Topical estrogen accelerates cutaneous wound healing in aged humans associated with an altered inflammatory response. Am J Pathol. 1999;155 (4):1137–1146.CrossRefGoogle ScholarPubMed
76.Tattini, C, Manchio, J, Zaporojan, V.Role of TGF-beta and FGF in the treatment of radiation-impaired wounds using a novel drug delivery system. Plast Reconstr Surg. 2008;122 (4):1036–1045.CrossRefGoogle ScholarPubMed
77.François, S, Bensidhoum, M, Mouiseddine, M.Local irradiation not only induces homing of human mesenchymal stem cells at exposed sites but promotes their widespread engraftment to multiple organs: a study of their quantitative distribution after irradiation damage. Stem Cells. 2006;24 (4):1020–1029.Google Scholar
78.Lataillade, JJ, Doucet, C, Bey, E.New approach to radiation burn treatment by dosimetry-guided surgery combined with autologous mesenchymal stem cell therapy. Regen Med. 2007;2 (5):785–794.Google Scholar
79.Chapel, A, Bertho, JM, Bensidhoum, M.Mesenchymal stem cells home to injured tissues when co-infused with hematopoietic cells to treat a radiation-induced multi-organ failure syndrome. J Gene Med. 2003;5 (12):1028–1038.Google Scholar
80.Miuram, M, Miura, Y, Padilla-Nash, HM.Accumulated chromosomal instability in murine bone marrow mesenchymal stem cells leads to malignant transformation. Stem Cells. 2006;24 (4):1095–1103.Google Scholar
81.Pittenger, MF, Mackay, AM, Beck, SC.Multilineage potential of adult human mesenchymal stem cells. Science. 1999;284 (5411):143–147.Google Scholar
82.Uccelli, A, Moretta, L, Pistoia, V.Mesenchymal stem cells in health and disease. Nat Rev Immunol. 2008;8 (9):726–736.Google Scholar
83.Nauta, AJ, Fibbe, WE.Immunomodulatory properties of mesenchymal stromal cells. Blood. 2007;110 (10):3499–3506.Google Scholar
84.Le Blanc, K, Samuelsson, H, Gustafsson, B.Transplantation of mesenchymal stem cells to enhance engraftment of hematopoietic stem cells. Leukemia. 2007;21 (8):1733–1738.Google Scholar
85.Le Blanc, K, Frassoni, F, Ball, LDevelopmental Committee of the European Group for Blood and Marrow Transplantation. Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a phase II study. Lancet. 2008;371 (9624):1579–1586.Google Scholar
86.Ball, LM, Bernardo, ME, Roelofs, H.Cotransplantation of ex vivo expanded mesenchymal stem cells accelerates lymphocyte recovery and may reduce the risk of graft failure in haploidentical hematopoietic stem-cell transplantation. Blood. 2007;110 (7):2764–2767.CrossRefGoogle ScholarPubMed
87.Doucet, C, Ernou, I, Zhang, Y.Platelet lysates promote mesenchymal stem cell expansion: a safety substitute for animal serum in cell-based therapy applications. J Cell Physiol. 2005;205 (2):228–236.Google Scholar
88.Anno, GH, Baum, SJ, Withers, HR, Young, RW.Symptomatology of acute radiation effects in humans after exposure to doses of 0.5-30 Gy. Health Phys. 1989;56 (6):821–838.Google Scholar
89.Prasad, KN.Radiation damage to the nervous system. In: Prasad KN, ed. Handbook of Radiobiology. 2nd ed. Boca Raton, FL: CRC Press; 1995:161-170.Google Scholar
90.Walker, RI, Cerveny, RJ.Medical Consequences of Nuclear Warfare. Falls Church, VA: Office of the Surgeon General; 1989.Google Scholar
91.Cancer Pain Relief. 2nd ed. Geneva: World Health Organization; 1996.Google Scholar
92.TMT Handbook Consortium. Triage, monitoring and treatment of people exposed to ionizing radiation after a malevolent act. http://www.tmthandbook.org. Accessed July 2, 2009.Google Scholar
93.Collins, DL.Behavioral differences of irradiated persons associated with the Kyshtym, Chelyabinsk, and Chernobyl nuclear accidents. Mil Med. 1992;157 (10):548–552.Google Scholar
94.Cornely, OA, Maertens, J, Winston, DJ.Posaconazole vs. fluconazole or itraconazole prophylaxis in patients with neutropenia. N Engl J Med. 2007;356 (4):348–359.CrossRefGoogle ScholarPubMed
95.Maekawa, K.Overview of medical care for highly exposed victims in Tokaimura accident. In: Ricks RC, Berger ME, O’Hara FM, eds. The Medical Basis for Radiation-Accident Preparedness: The Clinical Care of Victims. Boca Raton, FL: Partheon Publishing Group; 2002:313-318.Google Scholar
96.Asano, S.Multi-organ involvement: lessons from the experience of one victim of the Tokai-mura criticality accident. BJR Suppl. 2005;27:9–12.Google Scholar
97.Dainiak, N.Hematologic consequences of exposure to ionizing radiation. Exp Hematol. 2002;30 (6):513–528.Google Scholar
98.Dellinger, RP, Levy, MM, Carlet, JMInternational Surviving Sepsis Campaign Guidelines Committee; American Association of Critical-Care Nurses; American College of Chest Physicians; American College of Emergency Physicians; Canadian Critical Care Society; European Society of Clinical Microbiology and Infectious Diseases; European Society of Intensive Care Medicine; European Respiratory Society; International Sepsis Forum; Japanese Association for Acute Medicine; Japanese Society of Intensive Care Medicine; Society of Critical Care Medicine; Society of Hospital Medicine; Surgical Infection Society; World Federation of Societies of Intensive and Critical Care Medicine. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med. 2008;36 (1):296–327.CrossRefGoogle ScholarPubMed
99.Akashi, M.Role of infection and bleeding in multiple organ involvement and failure. BJR Suppl. 2005;27:69–74.Google Scholar
100.Hirama, T, Tanosaki, S, Kandatsu, S.Initial medical management of patients severely irradiated in the Tokai-mura criticality accident. Br J Radiol. 2003;76 (904):246–253.Google Scholar
101.Crawford, SW.Diagnosis and management of pulmonary problems associated with radiation injury. In: Ricks RC, Berger ME, O’Hara FM, eds. The Medical Basis for Radiation Accident Preparedeness: The Clinical Care of Victims. Boca Raton, FL: Parthenon Publishing Group; 2002:131-138.Google Scholar
102.Ghafoori, P, Marks, LB, Vujaskovic, Z, Kelsey, CR.Radiation-induced lung injury. Assessment, management, and prevention. Oncology (Williston Park). 2008;22 (1):37–47, discussion 52-53.Google Scholar
103.Johnston, AM.Pulmonary effects of combined blast injury and radiation poisoning. J R Army Med Corps. 2004;150 3(Suppl 1)22–26.Google Scholar
104.Mefferd, JM, Donaldson, SS, Link, MP.Pediatric Hodgkin's disease: pulmonary, cardiac, and thyroid function following combined modality therapy. Int J Radiat Oncol Biol Phys. 1989;16 (3):679–685.Google Scholar
105.The Acute Respiratory Distress Syndrome Network. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med. 2000;342 (18):1301–1308.Google Scholar
106.Manthous, CA, Jackson, WL JrThe 9-11 Commission's invitation to imagine: a pathophysiology-based approach to critical care of nuclear explosion victims. Crit Care Med. 2007;35 (3):716–723.Google Scholar
107.Barrett, A, Depledge, MH, Powles, RL.Interstitial pneumonitis following bone marrow transplantation after low dose rate total body irradiation. Int J Radiat Oncol Biol Phys. 1983;9 (7):1029–1033.CrossRefGoogle ScholarPubMed
108.Depledge, MH, Barrett, A, Powles, RL.Lung function after bone marrow grafting. Int J Radiat Oncol Biol Phys. 1983;9 (2):145–151.Google Scholar
109.Mancebo, J, Fernández, R, Blanch, L.A multicenter trial of prolonged prone ventilation in severe acute respiratory distress syndrome. Am J Respir Crit Care Med. 2006;173 (11):1233–1239.Google Scholar
110.Villar, J, Pérez-Méndez, L, López, JHELP Network. An early PEEP/FIO2 trial identifies different degrees of lung injury in patients with acute respiratory distress syndrome. Am J Respir Crit Care Med. 2007;176 (8):795–804.Google Scholar
111.Annane, D, Sébille, V, Charpentier, C.Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA. 2002;288 (7):862–871.Google Scholar
112.Briegel, J, Forst, H, Haller, M.Stress doses of hydrocortisone reverse hyperdynamic septic shock: a prospective, randomized, double-blind, single-center study. Crit Care Med. 1999;27 (4):723–732.Google Scholar
113.Ishii, T, Futami, S, Nishida, M.Brief note and evaluation of acute-radiation syndrome and treatment of a Tokai-mura criticality accident patient. J Radiat Res (Tokyo). 2001;42(Suppl)S167–S182.Google Scholar
114.Akashi, M, Hirama, T, Tanosaki, S.Initial symptoms of acute radiation syndrome in the JCO criticality accident in Tokai-mura. J Radiat Res (Tokyo). 2001;42(Suppl)S157–S166.CrossRefGoogle ScholarPubMed
115.Brook, AD, Ahrens, TS, Schaiff, R.Effect of a nursing-implemented sedation protocol on the duration of mechanical ventilation. Crit Care Med. 1999;27 (12):2609–2615.Google Scholar
116.D’Amico, R, Pifferi, S, Leonetti, C, Torri, V, Tinazzi, A, Liberati, A.Effectiveness of antibiotic prophylaxis in critically ill adult patients: systematic review of randomised controlled trials. BMJ. 1998;316 (7140):1275–1285.Google Scholar
117.Bergmans, DC, Bonten, MJ, Gaillard, CA.Prevention of ventilator-associated pneumonia by oral decontamination: a prospective, randomized, double-blind, placebo-controlled study. Am J Respir Crit Care Med. 2001;164 (3):382–388.CrossRefGoogle ScholarPubMed
118.de Jonge, E, Schultz, MJ, Spanjaard, L.Effects of selective decontamination of digestive tract on mortality and acquisition of resistant bacteria in intensive care: a randomised controlled trial. Lancet. 2003;362 (9389):1011–1016.Google Scholar
119.de Smet, AM, Kluytmans, JA, Cooper, BS.Decontamination of the digestive tract and oropharynx in ICU patients. N Engl J Med. 2009;360 (1):20–31.CrossRefGoogle ScholarPubMed
120.Karas, JS, Stanbury, JB.Fatal radiation syndrome from an accidental nuclear excursion. N Engl J Med. 1965;272:755–761.Google Scholar
121.Gale, RP.Immediate medical consequences of nuclear accidents. Lessons from Chernobyl. JAMA. 1987;258 (5):625–628.Google Scholar
122.International Atomic Energy Agency. The Radiation Accident at the Irradiation Facility in Nesvizh. IAEA STI/PUB/1010. Vienna: International Atomic Energy Agency; 1996.Google Scholar
123.Coleman, CN, Blakely, WF, Fike, JR.Molecular and cellular biology of moderate-dose (1-10 Gy) radiation and potential mechanisms of radiation protection: report of a workshop at Bethesda, Maryland, December 17-18, 2001. Radiat Res. 2003;159 (6):812–834.Google Scholar
124.Moulder, JE, Cohen, EP.Radiation-induced multi-organ involvement and failure: the contribution of radiation effects on the renal system. BJR Suppl. 2005;27:82–88.Google Scholar
125.Moghissi, ES, Korytkowski, MT, DiNardo, MAmerican Association of Clinical Endocrinologists; American Diabetes Association. American Association of Clinical Endocrinologists and American Diabetes Association consensus statement on inpatient glycemic control. Diabetes Care. 2009;32 (6):1119–1131.Google Scholar
126.Bernard, GR, Vincent, JL, Laterre, PFRecombinant human protein C Worldwide Evaluation in Severe Sepsis (PROWESS) study group. Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med. 2001;344 (10):699–709.Google Scholar
127.Vinsonneau, C, Camus, C, Combes, A, Hemodiafe Study Group. Continuous venovenous haemodiafiltration versus intermittent haemodialysis for acute renal failure in patients with multiple-organ dysfunction syndrome: a multicentre randomised trial. Lancet. 2006;368 (9533):379–385.Google Scholar
128.Clement, S, Braithwaite, SS, Magee, MFAmerican Diabetes Association Diabetes in Hospitals Writing Committee. Management of diabetes and hyperglycemia in hospitals. Diabetes Care. 2004;27 (2):553–591.Google Scholar
129.Wiener, RS, Wiener, DC, Larson, RJ.Benefits and risks of tight glucose control in critically ill adults: a meta-analysis. JAMA. 2008;300 (8):933–944.Google Scholar
130.Comi, RJ.Glucose control in the intensive care unit: a roller coaster ride or a swinging pendulum? Ann Intern Med. 2009;150 (11):809–811.Google Scholar
131.Finfer, S, Chittock, DR, Su, SYNICE-SUGAR Study Investigators. Intensive versus conventional glucose control in critically ill patients. N Engl J Med. 2009;360 (13):1283–1297.Google Scholar
132.Inzucchi, SE, Siegel, MD.Glucose control in the ICU—how tight is too tight? N Engl J Med. 2009;360 (13):1346–1349.Google Scholar
133.Berger, ME, Sadoff, RL.Psychological support of radiation-accident patients, families, and staff. In: Ricks RC, Berger ME, O’Hara FM, eds. The Medical Basis for Radiation-Accident Preparedness: The Clinical Care of Victims. Boca Raton, FL: Pantheon Press; 2002:191-200.Google Scholar
134.Devereaux, AV, Dichter, JR, Christian, MDTask Force for Mass Critical Care. Definitive care for the critically ill during a disaster: a framework for allocation of scarce resources in mass critical care: from a Task Force for Mass Critical Care summit meeting, January 26-27, 2007, Chicago, IL. Chest. 2008;133 5(Suppl)51S–66S.Google Scholar
135.Gostin, L.Public health strategies for pandemic influenza: ethics and the law. JAMA. 2006;295 (14):1700–1704.Google Scholar
136.Persad, G, Wertheimer, A, Emanuel, EJ.Principles for allocation of scarce medical interventions. Lancet. 2009;373 (9661):423–431.CrossRefGoogle ScholarPubMed
137.Emanuel, EJ, Wertheimer, A.Public health. Who should get influenza vaccine when not all can? Science. 2006;312 (5775):854–855.Google Scholar
138.White, DB, Katz, MH, Luce, JM, Lo, B.Who should receive life support during a public health emergency? Using ethical principles to improve allocation decisions. Ann Intern Med. 2009;150 (2):132–138.Google Scholar
139.Tabery, J, Mackett, CW IIIUniversity of Pittsburgh Medical Center Pandemic Influenza Task Force's Triage Review Board. Ethics of triage in the event of an influenza pandemic. Disaster Med Public Health Prep. 2008;2 (2):114–118.Google Scholar
140.Sandel, M.Justice: What's the Right Thing to Do? New York: Farrar, Straus & Giroux; 2009.Google Scholar
141.Fink, SL.Worst case: rethinking tertiary triage protocols in pandemics and other health emergencies. Crit Care. 2010;14 (1):103.Google Scholar
142.Coleman, CN, Knebel, AR, Hick, JL.Scarce resources for nuclear detonation: project overview and challenges. Disaster Med Public Health Prep. 2011;5(Suppl 1)S13–S19.CrossRefGoogle ScholarPubMed
143.Qaseem, A, Snow, V, Shekelle, PClinical Efficacy Assessment Subcommittee of the American College of Physicians. Evidence-based interventions to improve the palliative care of pain, dyspnea, and depression at the end of life: a clinical practice guideline from the American College of Physicians. Ann Intern Med. 2008;148 (2):141–146.Google Scholar
144.Curado, MPSB, Neto, C, Helou, S.Psychological aspects of the radiation-accident in Goiania: a general overview on victims and population. In: Ricks RC, Berger ME, O’Hara M, eds. The Medical Basis for Radiation Accident Preparedness III: The Psychological Perspective. New York: Elsevier; 1991:143-154.Google Scholar
145.Havenaar, J, Rumyantzeva, G, Kasyanenko, A.Health effects of the Chernobyl disaster: illness or illness behavior? A comparative general health survey in two former Soviet regions. Environ Health Perspect. 1997;105(Suppl 6)1533–1537.Google Scholar
146.Pastel, RH.Radiophobia: long-term psychological consequences of Chernobyl. Mil Med. 2002;167 2(Suppl)134–136.Google Scholar
147.International Atomic Energy Agency, World Health Organization. Generic procedures for medical response during a nuclear or radiological emergency. http://www-pub.iaea.org/MTCD/publications/PDF/EPR-MEDICAL-2005_web.pdf. Published April 2005. Accessed June 11, 2011.Google Scholar
148.DiGiovanni, C JrDomestic terrorism with chemical or biological agents: psychiatric aspects. Am J Psychiatry. 1999;156 (10):1500–1505.Google Scholar
149.Pynoos, RS, Goenjian, AK, Steinberg, AM.A public mental health approach to the postdisaster treatment of children and adolescents. Child Adolesc Psychiatr Clin N Am. 1998;7 (1):195–210, x.Google Scholar
150.Upton, AC.Radiation injury. In: Goldman L, Ausiello D, eds. Goldman's Cecil Medicine. 23rd ed. Philadelphia: Saunders Elsevier.; 2008:90-96.Google Scholar
151.Tochner, ZA, Lehavi, O, Glatstein, E.Radiation bioterrorism. In: Kasper DL, Fauci AS, Longo D, eds, et al. Harrison's Principles of Internal Medicine. 16th ed. New York: McGraw-Hill; 2005:1294-1300.Google Scholar
152.Manual for first responders to a radiological emergency. http://www-pub.iaea.org/MTCD/publications/PDF/epr_Firstresponder_web.pdf. Accessed June 16, 2011.Google Scholar
153.Joint radiation emergency management plan of the international organizations. http://www-pub.iaea.org/MTCD/publications/PDF/epr-JPLAN_2010_web.pdf. Published January 1, 2010. Accessed June 16, 2011.Google Scholar
154.National response framework, US Department of Homeland Security. http://www.fema.gov/pdf/emergency/nrf/nrf-core.pdf. Published January 2008. Accessed June 11, 2011.Google Scholar
155.Planning guidance for protection and recovery following radiological dispersal device (RDD) and improvised nuclear device (IND) incidents, DHS/FEMA, Z-RIN 1660-za02. http://ogcms.energy.gov/73fr45029.pdf. Published August 1, 2008. Accessed June 16, 2011.Google Scholar
156.Biodosimetry assessment tool. http://www.afrri.usuhs.mil/outreach/biodostools.htm. Accessed June 16, 2011.Google Scholar
157.Radiation event medical management downloadable for mobile devices. http://remm.nlm.gov/downloadmremm.htm. Accessed June 16, 2011.Google Scholar
158.International Atomic Energy Agency portable digital assistant for first responders to a radiological emergency. http://www-pub.iaea.org/MTCD/publications/pdf/epr-First_res-pda/html/default.htm. Accessed June 14, 2011.Google Scholar
159.Emergency Management Institute (DHS/FEMA). Radiological emergency management independent study course. http://training.fema.gov/emiweb/downloads/IS3_is3all.pdf. Accessed June 16, 2011.Google Scholar
160.International Atomic Energy Agency, World Health Organization. Training for radiation emergency preparedness and response. Medical preparedness and response. Educational material. http://www-pub.iaea.org/MTCD/publications/PDF/eprmedt/Start.pdf. Published 2002. Accessed June 16, 2011.Google Scholar
161.International Atomic Energy Agency. Training for radiation emergency preparedness and response. First response to a radiological emergency –training materials. http://www-pub.iaea.org/MTCD/publications/PDF/EPR-First_Res-T2009_web/start.pdf. Published 2009. Accessed June 14, 2011.Google Scholar
162.Section 10. Education and training opportunities. http://www.ama-assn.org/ama1/pub/upload/mm/415/10_education.pdf. Published 2005. Accessed June 16, 2011.Google Scholar
163.Waeckerle, JF, Seamans, S, Whiteside, MTask Force of Health Care and Emergency Services Professionals on Preparedness for Nuclear, Biologiccal, and Chemical Incidents. Executive summary: developing objectives, content, and competencies for the training of emergency medical technicians, emergency physicians, and emergency nurses to care for casualties resulting from nuclear, biological, or chemical incidents. Ann Emerg Med. 2001;37 (6):587–601.Google Scholar
164.Homeland Security Council Interagency Policy Coordination Subcommittee for Preparedness & Response to Radiological and Nuclear Threats. Planning guidance for response to a nuclear detonation. http://remm.nlm.gov/planning-guidance.pdf. Published January 16, 2009. Accessed June 16, 2011.Google Scholar
165.Becker, SM, Middleton, SA.Improving hospital preparedness for radiological terrorism: perspectives from emergency department physicians and nurses. Disaster Med Public Health Prep. 2008;2 (3):174–184.Google Scholar
166.Veenema, TG, Walden, B, Feinstein, N, Williams, JP.Factors affecting hospital-based nurses' willingness to respond to a radiation emergency. Disaster Med Public Health Prep. 2008;2 (4):224–229.Google Scholar
167.Clark, RC, Mayer, RE.e-Learning and the Science of Instruction: Proven Guidelines for Consumers and Designers of Multimedia Learning. San Francisco: Pfeiffer/John Wiley & Sons; 2008.Google Scholar
168.Oak Ridge Institute for Science and Education (ORISE)/Radiation Emergency Assistance Center/Training Site. (REACT/TS). http://orise.orau.gov/reacts. Accessed August 19, 2009.Google Scholar
169.Armed Forces Radiobiology Research Institute. Medical effects of ionizing radiation (MEIR) course. http://www.afrri.usuhs.mil/outreach/meir/meir.htm. Accessed June 9, 2011.Google Scholar
170.Health Protection Agency. Radiation training courses. http://www.hpa.org.uk/eventsprofessionaltraining/radiationtraining/radiationtrainingcourses/. Accessed August 29, 2011.Google Scholar
171.Mettler, FA, Guskova, AK, Gusev, IA.Medical Management of Radiation Accidents. 2nd ed. Albuquerque: University of New Mexico; 2001.Google Scholar
172.Waller, E, Millage, K, Blakely, WF.Overview of hazard assessment and emergency planning software of use to RN first responders. Health Phys. 2009;97 (2):145–156.Google Scholar
173.Radiation Event Medical Management (REMM). Guidance for health care providers. http://remm.nlm.gov. Accessed June 16, 2011.Google Scholar
174.Centers for Disease Control and Prevention. Radiation emergencies. http://www.bt.cdc.gov/radiation. Accessed June 16, 2011.Google Scholar
175.Armed Forces Radiobiology Research Institute. Accessed June 16, 2011. http://www.afrri.usuhs.mil.Google Scholar
176.International Atomic Energy Agency. E-learning Tools for First Response to a Radiological Emergency, EPR-First Responders/E-Learning, IAEA, Vienna (2009). http://www-pub.iaea.org/mtcd/publications/pdf/epr-fr-elearning/main.htm. Accessed June 16, 2011.Google Scholar
177.Johns Hopkins Bloomberg School of Public Health. Chemical, biological, radiological, nuclear, explosive-related trainings. http://www.jhsph.edu/preparedness/training/online/chem_trainings. Accessed August 29, 2011.Google Scholar
178.Fliedner, TM, Chao, NJ, Bader, JL.Stem cells, multiorgan failure in radiation emergency medical preparedness: a U.S./European Consultation Workshop. Stem Cells. 2009;27 (5):1205–1211.Google Scholar
179.ASCO University. Medical Responses to Mass Casualty Radiological and Nuclear Events (I). http://university.asco.org/MassCasualty. Accessed September 8, 2011.Google Scholar
180.American Society of Clinical Oncology. Train for Radiological and Nuclear Disaster Response on ASCO University. http://www.asco.org/ASCOv2/Meetings/Annual+Meeting/Past+Annual+Meetings/2009+Annual+Meeting/2009+ASCO+Daily+News/Saturday,+May+30,+2009/Train+for+Radiological+and+Nuclear+Disaster+Response+on+ASCO+University. Accessed September 8, 2011.Google Scholar
181.Coleman, CN, Hrdina, C, Bader, JL.Medical response to a radiologic/nuclear event: integrated plan from the Office of the Assistant Secretary for Preparedness and Response, Department of Health and Human Services. Ann Emerg Med. 2009;53 (2):213–222.Google Scholar