Febrile Neutropenia

Sistemsko zdravljenje solidnih in hematoloških rakov s citostatiki predstavlja tveganje za različne neželene učinke. Febrilna nevtropenija (FN) je eno od urgentnih stanj v onkologiji, ker lahko pride do zapletov, kot sta septični šok ali sindrom dihalne stiske. O FN govorimo, če pri bolniku z absolutnim številom nevtrofilnih granulocitov pod 0,5 x 109 /l enkrat izmerimo temperaturo nad 38,3 0C ali če ima temperaturo nad 38 0C več kot eno uro. Tveganje za okužbe narašča s stopnjo in trajanjem nevtropenije. Možnost okužbe je večja tudi ob uporabi perifernih in centralnih venskih kanalov, zdravljenju z nekaterimi biološkimi zdravili za zdravljenje raka, pri bolnikih, hospitaliziranih zaradi spremljajočih bolezni, in pri bolnikih z napredovalo rakavo boleznijo. V 80 % je izvor okužbe bolnikova lastna endogena flora. Po natančni anamnezi, kliničnem pregledu bolnika in odvzemu kužnin nevtropenične bolnike zdravimo izkustveno s širokospektralnimi baktericidnimi antibiotiki, usmerjenimi proti najverjetnejšim povzročiteljem okužbe. O načinu zdravljenja se odločimo, ko pretehtamo dejavnike tveganja, na podlagi katerih bolnike razdelimo v tri rizične skupine. Bolnike, pri katerih je pričakovano obdobje nevtropenije krajše od 7 dni, so brez vnetja ustne in drugih sluznic, driske, spremljajočih bolezni in so hemodinamsko stabilni, lahko ob skrbnem nadzoru zdravimo ambulantno, in sicer peroralno, dvotirno, s ciprofloksacinom in amoksicilinom/klavulansko kislino. Bolnike, pri katerih je pričakovano obdobje nevtropenije daljše od 7 dni in so hemodinamsko nestabilni ali pa imajo vnetje sluznic ali drisko, zdravimo v bolnišnici s parenteralnimi antibiotiki v monoterapiji (npr. cefalosporin tretje ali četrte generacije ali karbapenem) ali s kombinacijo antibiotikov, najpogosteje s kombinacijo cefalosporina tretje generacije in aminoglikozidnega antibiotika. Skrbno spremljamo bolnikovo stanje in izsledke kultur in v skladu s tem prilagajamo antibiotično zdravljenje. Če je pričakovano trajanje nevtropenije daljše kot 5 do 7 dni in je bolnik še vedno febrilen brez jasnega izvora okužbe, dodamo še protiglivično zdravilo. Trajanje zdravljenja prilagodimo glede na izoliranega povzročitelja, trajanje vročine in trajanje nevtropenije. Rastne dejavnike za granulocite pri že razviti febrilni nevtropeniji uporabljamo le izjemoma pri zelo ogroženih bolnikih. Preventivno pa jih uporabljamo pri bolnikih, ki so že utrpeli FN, da bi preprečili febrilno nevtropenijo ob naslednjih ciklih citostatskega zdravljenja, pri starejših bolnikih in pri bolnikih, pri katerih smo ocenili, da ob citostatskem zdravljenju obstaja več kot 20-odstotno tveganje za FN.Systemic treatment of solid as well as haematologic tumors with cytostatics may pose a risk to cancer patients to develop various undesired effects of treatment. Febrile neutropenia (FN) is one of the emergency conditions in oncology because it may lead to further complications, e.g. septic shock or acute respiratory distress syndrome. Febrile neutropenia is considered to be present when the body temperature of a patient with the absolute count of neutrophyl granulocytes lower than 0.5 x 109 /l is higher than 38.3oC or when it persists at 38oC or more for more than one hour. The risk for infections increases with the grade and duration of neutropenia and is higher in the patients with an indwelling peripheral or central venous catheter, in those treated for cancer with some of biological drugs, in the patients hospitalized for accompanying diseases, and in cancer patients with the disease in an advanced stage. In 80% of cases, the infection stems from the patient’s endogenous flora. After obtaining accurate medical history, clinical examination of each patient and collection of samples for microbiology examination, neutropenic patients are treated with empirical broad-spectrum bactericidal antibiotics targeting the most likely causal agents of infection. The decision on the treatment regime is made only after a thorough consideration of risk factors according to which the patients are classified into three risk groups. The patients with the anticipated duration of neutropenia of less than 7 days, with no signs of oral mucositis or elsewhere in the digestive track, with no signs of diarrhoea or of accompanying diseases, and who are hemodynamically stable may be treated as outpatients with oral antibiotic combination therapy of ciprofloxacin and amoxicillin/ clavulanic acid. The patients with the anticipated duration of neutropenia of more than 7 days, who are hemodinamically unstable, and have signs of mucositis or of diarhhoea, are hospitalized and treated with parenteral antibiotics applied as monotherapy (e.g. cephalosporin - the third or fourth generation agents or carbapenems) or with the combination of antibiotics, most frequently with the combination of cephalosporin – the third generation agents and aminoglycoside antibiotics. The patients’ condition and culture test results should be most carefully followed and the antibiotic therapy adjusted to actual findings. If the duration of neutropenia is anticipated to exceed 5-7 days and the patient’s febrile condition persists, and if at the same time the source of infection remains unclear, antifungal agents should be added to antibiotic therapy. The duration of therapy should be attuned to the isolated causal agent, persistence of febrile condition and of neutropenia. Granulocyte growth factors in cases of already developed neutropenia can exclusively be used if the patients are at high risk for further complications. However, they may be used as prophylaxis in the patients who have been already treated for febrile neutropenia in order to prevent febrile neutropenic episodes during further cycles of cytostatic treatment, in elderly patients, and in the patients in whom the risk to develop febrile neutropenia has been assessed to be higher than 20%