Acurácia diagnóstica do leucograma, proteína C-reativa, interleucina-6 e fator de necrose tumoral-alfa na sepse neonatal tardia

Abstract

Objective

To evaluate the diagnostic value for late neonatal sepsis of white blood cell count (WBC) and assays for C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α), in isolation and in conjunction.

Methods

This was a diagnostic test validation study. Chemiluminescence was used to assay CRP, IL-6 and TNF-α at the time of clinical suspicion and again after 24 and 48 hours, whereas the WBC was performed only once, at the time of suspicion. Patients were classified into three groups based on clinical progress and culture results: confirmed sepsis (CS), probable sepsis (PS), and not infected (NI). Statistical analysis was performed using the Wilcoxon and chi-square tests and Friedman analysis of variance; cutoffs were defined by plotting receiver operator characteristic curves.

Results

The total study sample comprised 82 children, 42 of whom were classed as CS, 16 as PS and 24 as NI. At all three test times, the medians for CRP and IL-6 were significantly more elevated in the CS and PS groups, while the medians for TNF-α were abnormal only in the CS group. The CRP test had elevated indices of diagnostic utility at all three test times, better accuracy than the WBC and similar accuracy to the first IL-6 and TNF-α assays. There was no statistical difference between the cytokines, nor between them and the WBC. Combining tests did not increase diagnostic power, with the exception of the combination of WBC with CRP2 and when the sequential CRP assays were combined.

Conclusions

Both CRP and WBC were useful for the diagnosis of late neonatal sepsis and comparable with IL-6 and TNF-α. Accuracy increased when CRP and WBC were combined and when sequential CRP assay results were used.

Resumen

Objetivo

Avaliar o valor do leucograma, proteína C-reativa (PCR), interleucina-6 (IL-6) e do fator de necrose tumoral-alfa (TNF-α), isoladamente e em conjunto, na detecção da sepse neonatal tardia.

Métodos

Estudo de validação diagnóstica. A PCR, IL-6 e TNF-α foram dosados por quimioluminescência à suspeita clínica, 24 e 48 horas depois, e o leucograma unicamente à suspeita. De acordo com evolução clínica e resultados de culturas, três grupos foram definidos: sepse comprovada (SC), sepse provável (SP) e não infectados (NI). Os testes estatísticos utilizados foram os de Wilcoxon, qui-quadrado e análise de variância de Friedman e os limites de corte foram obtidos pela construção da curva ROC.

Resultados

Estudaram-se 82 crianças, sendo 42 no grupo SC, 16 no SP e 24 NI. Nos três momentos, as medianas da PCR e da IL-6 mostraram-se significativamente mais elevadas nos grupos SC e SP, e as do TNF-α alteraram-se apenas no grupo SC. Os índices diagnósticos da PCR foram elevados nos três momentos e com acurácia superior a do leucograma e semelhante a da IL-6 e a do TNF-α em suas primeiras medidas. Entre as citocinas, não houve diferença estatística entre elas, nem em relação ao leucograma. A associação dos testes não aumentou a capacidade diagnóstica, exceto na combinação entre leucograma e PCR2 e na dosagem seriada de PCR.

Conclusões

A PCR e o leucograma mostram-se úteis no diagnóstico de sepse neonatal tardia e comparáveis à IL-6 e ao TNF-α. A acurácia aumentou com a associação PCR-leucograma e a dosagem seriada da PCR.