Neutropenic Fever in the ICU

Neutropenic Patients with Fever in the MICU

Neutropenia can be defined as a reduction in the total blood neutrophil count. It is frequently the cause of greater susceptibility to infections with fungal or bacterial pathogens and is often a cause of iatrogenic disease, morbidity and mortality within the Medical Intensive Care Unit (MICU). Neutropenia us generally classified based upon the relative granulocyte count. (Total white blood cell [WBC} count multiplied by the percent of granulocytes) as well as the individual patient's relative risk of infection, based upon intrinsic and extrinsic factors. Neutropenia may be classified as mild (1000 to 2000/microliter), moderate (500 to 1000/microliter) and severe (

Neutropenia is often secondary to impaired cell production and myelogenous failure. This is most often secondary to the effect of drugs. Neutropenia is often seen with chemotherapeutic agents, anti-thyroid drugs, some phenothiazines and their derivatives, anticonvulsant medications, antibiotics such as penicillin, sulfonamides and other anti-neoplastic drugs. The decrease in the neutrophil count is compounded by increased cell margination and a significant element of redistribution of all cell types in the blood and acceleration in the rate of cellular utilization and turnover. It is classified as chronic (lasting months to years) or acute (occurring over the course of a few days) and may be the sole presenting hematological abnormality in the intensive care patient presenting with fever, as is seen in the case of chronic idiopathic neutropenia with acute infection, or as part of a broader hematological abnormality such as aplastic anemia. It should also be noted that the effect of anti-neoplastic drugs usually effect the neutrophil count in a predictable way. Other drugs can cause an idiosyncratic drug reaction, which would be neither dose nor duration related. For this reason, when using a drug which may have the side effect of neutropenia, cell counts should be checked regularly, especially at the initiation of therapy.

It should be noted there may also be a diminished neutrophil count in patients who have rare hereditary or congenital disease, such as familial neutropenia, patients who suffer from pancreatic insufficiency and immune disorders. In these cases, the reduced production of neutrophils may be compounded by the addition of drugs which exert a negative effect on neutrophil production and should be considered before the initiation of such drugs. Other diseases such a malignancies, granulomatous diseases, b12 deficiencies and folate deficiencies (as are often seen in patients which chronic alcoholism) can also exert an effect on neutrophil count. Patients who undergo hemodyalis may experience neutropenia secondary to complement activation from the exposure of the blood to the foreign surface. All these issues should be considered when evaluating the cause of neutropenic fever in the MICU patient.

Like other blood cells, neutrophils arise from the hemtopoietic stem cells which exhibit pluripotential. Some of the drugs already mentioned actually effect the cells within the marrow. This may occur at any point during the cellular maturation process or after the cell is released into circulation. Europhiles also have distinctive surface antigens which may make the susceptible to immune mediated cytolysis somewhat similar to that which is seen in an auto-immune related hemolysis. The cells then begin increased margination and become excessively adhesive to the vascular endothelium or trapped within the lungs and the spleen. Sequestration of the neutrophils within the spleen in such a case may lead to splenic enlargement. This in turn can lead to an activation of the complement cascade, resulting in increased margination, increased vascular adhesiveness.

There may be no specific sign of neutropenic fever in a MICU patient other than manifestation of those causative infections which may be present. Any other associated symptoms are likely associated with the severity of the condition, the duration of the neutropenia and of course the cause. Patients should be monitored with serial complete blood counts to include a differential count as well as blood cultures for bacterial and fungal pathogens. Bone marrow biopsy is most likely the most effective and useful laboratory evaluation in the patient with neutropenic fever, and may help discern leukemia, infiltrative or myeloproliferative disorders. The exact cause of the neutropenia may be difficult to determine. A neutrophilic antibody count may be helpful when no other obvious cause may be determined.

Treatment will be directed toward causative organisms as well as supportive therapy, and the duration and nature of the neutropenia. Acute and severe neutropenia with infection and fever always requires intensive treatment with a broad spectrum antibiotic until specific etiology can be determined. Should there be any suspicion that the neutropenia is secondary to a drug side effect, then obviously the effecting agents should be discontinued immediately. Antibiotics should be continued, even when cultures are negative, until the patient is afebrile for 24 to 48 hours, or until an alternative diagnosis and prognosis are clearly defined.