ACUTE RADIATION SYNDROME CLINICAL PICTURE, DIAGNOSIS AND TREATMENT Module XI Lecture organization Introduction ARS manifestations Haematological syndrome Gastrointestinal syndrome Neurovascular syndrome Triage of injured persons Medical management Summary Module Medical XI. 2 Introduction 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 ARS threat Discharged medical irradiators Industrial radiography units Commercial irradiators Terrorist detonation Nuclear fuel processing Nuclear reactors Module Medical XI. 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 Module Medical XI. 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). Module Medical XI. 5 Factors decreasing LD50/60 Coexisting trauma combined injury Chronic nutritional deficit Coexisting infection Contribution of high LET radiation Module Medical XI. 6 Phases of ARS Initial or prodromal phase Latent phase Manifest illness phase Recovery phase Module Medical XI. 7 Manifestations of ARS Haematopoietic syndrome (HPS) Gastrointestinal syndrome (GIS) Neurovascular syndrome (NVS) Module Medical XI. 8 Haematopoietic syndrome Normal bone marrow cells Module Medical XI. 9 Survival potential Bone marrow damaged by radiation injury Module Medical XI. 10 Haematological response to 1 Gy, whole body exposure to ionizing radiation Module Medical XI. 11 Haematological response to 3 Gy, whole body exposure Module Medical XI. 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 Module Medical XI. 13 Gastrointestinal (GI) syndrome (8-30 Gy) Pathophysiology of the GI Syndrome Depletion of the epithelial cells lining lumen of gastrointestinal tract Irradiated GI Mucosa Intestinal bacteria gain free access to body Haemorrhage through denuded areas Loss of absorptive capacity Module Medical XI. 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 Module Medical XI. 15 Systemic effects of GI syndrome Malabsorptionmalnutrition Fluid and electrolyte shiftsdehydration, acute renal failure, cardiovascular collapse GI bleedinganaemia Sepsis Paralytic ileusvomiting, abdominal distention Module Medical XI. 16 Pulmonary effects Irradiated lung tissue Pulmonary fibrosis Module Medical XI. 17 Neurovascular syndrome (NVS) At 30 Gy and above Endothelial cell damage Module Medical XI. 18 NVS prodromal perıod Burning sensation within minutes of exposure Nausea and vomiting within first hour Loss of balance, confusion with prostration Hypotension, hyperpyrexia Module Medical XI. 19 NVS latent period Apparent improvement lasting several hours –Maybelucidandin no pain but weak Module Medical XI. 20 NVS overt clinical picture Rapid onset Watery diarrhoea Respiratory distress Gross CNS signs Wide pulse pressure Hypotension Module Medical XI. 21 ARS Neurovascular Syndrome Life threatening Death of Radiation Symptoms injuries patients dose (Gy) 16 Loss of consciousness 5-12 days 20 25 Neurovascular 30 damage 2-5 days Module Medical XI. 22 Trıage of ınjured persons Module Medical XI. 23 Measurement of severity Prodromal effects Time of onset Degree of symptoms Haematological changes Lymphocyte counts Biological dosimetry Physical dosimetry Attendant readable Module Medical XI. 24 Radiation dose under 5 Gy No immediate life-threatening hazard exists Prodromal symptoms of moderate severity Onset > 1 hour Duration < 24 hours Module Medical XI. 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 Module Medical XI. 26 Triage categories of radiation injuries according to early symptoms Module Medical XI. 27 Guide for management of radiation injuries on the basis of early symptoms No vomiting < 1 Gy Outpatient with 5-week surveillance Vomiting 2-3 h 1-2 Gy Surveillance in a general hospital (or after exposure outpatient for 3 weeks) followed by hospitalization Vomiting 1-2 h 2-4 Gy Hospitalization in a haematological after exposure department Vomiting > 4 Gy Hospitalization in a well equipped earlier than 1 h, haematological or surgical department other severe with transfer to a specialized centre symptoms, like hypotension for radiopathology hyperthermia, diarrhoea, oedema, erythema, CNS Modulesymptoms Medical XI. 28 Lymphocytes 3Gy 4-5Gy Module Medical XI. 29 Change of lymphocyte counts in initial days of ARS depending on dose of acute WB exposure Degree of Dose Lymphocyte counts ARS (Gy) (cells/L) 6 days after first exposure Preclinical phase 0.1-1.0 1500-2500 Mild 1.0-2.0 700-1500 Moderate 2.0-4.0 500-800 Severe 4.0-6.0 300-500 Very severe 6.0-8.0 100-300 Lethal >8.0 0-50 Module Medical XI. 30 Granulocyte counts and dose relationship after irradiation Module Medical XI. 31 Medical management of acute radiation syndrome Module Medical XI. 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 Module Medical XI. 33 Infection managment General principles Prophylaxis Direct therapy for infections Barrier/isolation Culture specific Gut decontamination antibiotics Antiviral agents Therapy for Antifungal agents leukopenia Pneumocystis prophylaxis Cytokine administration Early cytokine therapy Close wounds Avoid invasive procedures Module Medical XI. 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 Module Medical XI. 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) Module Medical XI. 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 Module Medical XI. 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) Module Medical XI. 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 Module Medical XI. 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 Module Medical XI. 40 Management of infection If there is evidence