Identification of diagnostic criteria of septic complications in children with neutropenia

Introduction

Septic complications in neutropenic patients after chemotherapy lead to high morbidity and mortality in the pediatric oncology ward. There are no clear criteria of systemic inflammatory response syndrome (SIRS) and sepsis for neutropenic patients. It is usual that patients after chemotherapy have altered WBC, and the majority of them demonstrate tachycardia and mild to moderate fever (signs of SIRS) without infection. There is no clear differentiation between definitions of febrile neutropenia and sepsis for this group of patients.

Objective

To define additional diagnostic criteria of SIRS in children with febrile neutropenia after chemotherapy.

Study design

Monocentric, retrospective, case–control (equilibration of age, sex, diagnose) study, cases of severe sepsis and septic shock compared with control patients with febrile neutropenia.

Methods

Ninety-two patients were investigated (48 cases and 44 controls), aged 12 ± 4.5, and included 52 males and 40 females. The majority of patients had lymphoproliferative and myeloproliferative disorders, acute lymphoblastic leukemia 27%, acute myeloblastic leukemia 26%, non-Hodgkin lymphoma 13%, CNS tumors 17%, solid tumors (oseosarcoma, Ewing sarcoma, neuroblastoma, rhabdomyosarcoma) 14%. All patients had fever and neutropenia. We compared data of vital signs, levels of C-reactive protein, fibrinogen, urea and creatinin during 72 hours before a febrile episode or ICU admission. For the statistical analysis the Mann–Whitney U test was used; P < 0.05 was considered significant.

Results

Forty-eight patients (case group) (52%) developed severe sepsis or septic shock and required ICU admission (27 and 21 patients, respectively); all of these patients had clinical signs of sepsis, but only 76% had positive blood cultures. The mortality rate in the case group was 65%. In the control group only eight patients out of 44 had ICU admission, and in the control group we observed recovering in 24–32 hours after start of treatment with antibiotics in all patients. There was no mortality in the control group. Heart rate higher than 140% to normal, fever higher than 38 more than three times daily, and CRP level higher than 7.5 mg/dl was found in 92% patients of the case group 48 hours before ICU admissions. In the control group the level of CRP was significantly lower (2.6 ± 1.1 mg/dl), the heart rate was in a range between 110 and 122% to normal, fever higher than 38 was observed one or two times daily and discontinued in 24–48 hours. There were no significant difference in levels of fibrinogen, urea, and creatinin in the two groups as well as the presence of tachypnea, blood pressure and other signs during the period of observation.

Conclusion

The presence of high levels of CRP, tachycardia, and severe fever in children with neutropenia are predictors of transformation febrile neutropenia to sepsis, severe sepsis and septic shock. The use of these factors as diagnostic criteria should allow preventing severe complication in patients after chemotherapy.