Febrile neutropenia

Description:

The febrile neutropenia differently called by "neytropenichesky fever" (English neutropenic fever) — a life-threatening state, suddenly and sharply developing at patients with decrease in number of the neutrophils circulating in blood lower than 500.

Symptoms of the Fibrilny neutropenia:

The febrile neutropenia is defined as sudden (within several hours, and sometimes even several tens minutes) temperature increase of the patient is above 38 °C, against the background of decrease in absolute number of the circulating neutrophils it is lower than 500 or absolute numbers of the circulating granulocytes lower than 1000. At the same time the sharpest general weakness, a fever, a serious general condition is characteristic. Pouring sweat, a tremor (as a result of a fever), tachycardia, hypotension is possible up to symptoms of a cardiovascular collapse or shock.

At the same time, as at such critical decrease in number of neutrophils inflammatory reaction of an organism to an infection is sharply oppressed, to quickly find the infection center, the temperature increase reason, it is not possible. The patient's lungs "pure" (rattles are absent), are not present symptoms and from a throat, the nasal courses, an urethral path or a GIT, abscesses of soft tissues or pustulous damages of skin are not found. These defeats can be shown much later, sometimes shortly before the death of the patient when intensity of an infection becomes so big that even in a situation of deep oppression of immunity inflammatory reaction will be shown.

Thus, the diagnosis "a febrile neutropenia" is "the diagnosis of an exception", the diagnosis which is made at impossibility quickly to establish the temperature increase reason at the patient with a neutropenia, to find the inflammation center. In case of detection of the specific reason of temperature increase the diagnosis changes on more exact (for example, can there be a speech about pneumonia or bacterial sepsis against the background of a neutropenia).

Reasons of the Fibrilny neutropenia:

The febrile neutropenia most often develops against the background of or soon after cytostatic chemotherapy concerning leukoses, is more rare after the intensive modes of cytostatic chemotherapy concerning other malignant new growths and is even more rare against the background of a neutropenia of other etiology, after radiation therapy, etc.

The febrile neutropenia can represent only giperergichesky reaction of an organism to toxic influence of cytostatic himiopreparat, products of destruction of tumor and healthy cells or to sharp decrease in quantity in itself of the circulating neutrophils and disturbance of products of cytokines and immunoglobulins. However, most often the febrile neutropenia is display of an infection which center timely does not manage to be established owing to suppression of the inflammatory answer of an organism to an infection. The infection at the same time proceeds extremely hard, quickly extends from primary center to other bodies and systems and quickly leads to the death of the patient, even when the infecting microorganism belongs to saprophytic or low-virulent for patients with normal immunity and normal quantity of the neutrophils circulating in blood, or localization of primary center of an infection does not belong to especially dangerous to patients with normal immunity (as, for example, an acute urethritis or pharyngitis).

The most frequent causative agents of infections at a febrile neutropenia are pathogenic strepto-and staphylococcus, Pseudomonas aeruginosa or Bacillus fragilis, clostridiums, etc. is frequent in association with anaerobic microorganisms, for example. More rare, but also it is rather frequent, fungi, in particular Candida spp are activators. and even less often the symptomatology is caused by reactivation of a virus of herpes or a cytomegalovirus.

Treatment of the Fibrilny neutropenia:

Empirical treatment by antibiotics at a febrile neutropenia has to be begun immediately, even before establishment of the exact etiological diagnosis and identification of the activator, at once after sampling of blood and biological liquids of the patient on analyses (but not before sampling as treatment by antibiotics can interfere with allocation of the activator and its identification).

At the same time it is necessary to give preference to combinations of powerful bactericidal antibiotics of a broad spectrum of activity (the standard of maintaining such patients purpose of 3 antibiotics plus antifungal drug is), paying special attention to that empirical therapy effectively covered all range of the most probable causative agents of heavy infections, in particular, affected both on stafilokokk and streptococci, and anaerobe bacterias.

The most rational mode of a starting antibioticotherapia, before establishment of the activator and definition of its sensitivity to antibiotics, the following combination is:

    * ingibitorozashchishchenny aminopenicillin, for example, amoxicillin-clavulanate of potassium or ampicillin-sulbaktam;
    * generation cephalosporin III (for example, цефтриаксон or ceftazidime) or karbapeny (imipeny or meropeny);
    * generation aminoglycoside II or III, for example, gentamycin or amikacin.

Other rational and often applied mode of a starting antibioticotherapia is following:

    * one (but not two, as in the combination described above) powerful beta лактамный an antibiotic (from subgroup of ingibitorozashchishchenny aminopenicillin, cephalosporins III of generation or karbapenem);
    * фторхинолон III—IV generations, for example moxifloxacin or спарфлоксацин;
    * generation aminoglycoside II or III, as in a case above.

Also purpose of powerful antifungal drug from group of azoles is obligatory, at the same time fluconazole is most often applied, is more rare кетоконазол. Reasonablly additional purpose of metronidazole for the purpose of strengthening of impact on pathogenic anaerobe bacterias.

If there are reasonable suspicions on the fact that the infection is polivalentno caused in the patient by steady stafilokokka (MRSA) or enterococci, it is reasonable to appoint at once as one of components of starting therapy Vancomycinum instead of aminoglycosides. Vancomycinum combination to aminoglycosides is undesirable in view of considerable mutual strengthening of nephrotoxicity. If there are reasonable suspicions on participation in a pathogeny of a disease of microbes of the sort Pseudomonas, it is reasonable to appoint instead of aminopenicillin "antipsevdomonadny" ureidopenicillin, for example, тикарциллин.

On receipt of results of bacteriological analyses, identifications of activators and definition of their sensitivity to antibiotics empirical therapy should be corrected according to datas of laboratory.

If within 3 days, despite an adequate antibioticotherapia, body temperature at the patient is not normalized and the clinical state does not improve, it is necessary to assume a possibility of initially fungal infection or accession of fungal superinfection against the background of treatment by antibiotics and to appoint treatment B Amphotericinum. At the same time in order to avoid nephrotoxicity it is undesirable to give aminoglycosides at the same time.

Use of recombinant growth factors of neutrophils (G-CSF and/or GM-CSF), repeated transfusions of granulotsitny weight, intravenous administration of the purified drugs of human gamma-globulin or hyperimmune plasma belongs to the additional methods of treatment reducing duration of the period of a febrile neutropenia and increasing survival of patients (reducing a lethality).

A specific place in therapy of a febrile neutropenia is held by a maintenance therapy: treatment and prevention of septic shock or a collapse (massive injection of infusion solutions of crystalloids, if necessary introduction of glucocorticoids, cardiovascular means like a dopamine), adequate food of the patient (if necessary intravenous), treatment of acute respiratory insufficiency (if necessary up to artificial ventilation of the lungs), topical treatment of cankers of skin and mucous etc.

It is not necessary to give to the patient with a febrile neutropenia at all febrifugal drugs as they can complicate assessment of a clinical condition of the patient and efficiency of antibiotics. As inflammatory reaction is suppressed owing to a neutropenia and there is no opportunity to estimate dynamics of a condition of the patient on symptoms from the inflammation center, body temperature can be almost only indicator of a condition of the patient and the only measure of adequacy of an antibioticotherapia.