Importance of the neutrophil-to-lymphocyte ratio as a marker for microbiological specimens in critically ill patients after liver or lung transplantation

Abstract

Purpose: The correct and early diagnosis of an infection is pivotal for patients, especially if the patients are immunocompromised. Various infection markers are used in clinics with different advantages and disadvantages. The neutrophil-to-lymphocyte ratio (NLR) is a cost effective parameter easily obtained without further investments. The aim of this study is to elucidate the value of the NLR in comparison to other established inflammation markers in patients in the intensive care unit who underwent liver or lung transplantation for the detection of bacterial and fungal specimens.

Methods: In this retrospective single centre study infection marker and microbiology data of 543 intensive care cases of liver or lung transplanted patients in the intensive care unit after transplantation were analysed.

Results: In total 5,072 lab work results and 1,104 positive microbiology results were analysed. Results of an area under curve analysis were better for the NLR (0.631; p < 0.001) than for CRP (0.522; p = 0.152) or IL-6 (0.579; p < 0.001). The NLR was independent of type of organ which was transplanted and gender of patients, whereas IL-6 values differed significantly between liver and lung transplanted patients and between male and female.

Conclusion: All analysed inflammation markers are far from being perfect. The NLR is a sensitive marker with reasonable threshold for the detection of microbiological specimens independent of gender or type of organ transplanted. The use allows a more differentiated approach to face the challenge of bacteria and fungus in patients who underwent liver or lung transplantation.

Keywords: IL-6; Infection; Intensive care medicine; Liver transplantation; Lung transplantation; Neutrophil-to-lymphocyte ratio.

Fig. 1

The NLR differs depending on the type of positive microbiology results. The NLR was highest in patients that were tested positive for the combination of Gram-positive and Gram-negative bacteria (v) (18.4; [14.1, 24.2]), but lowest in patients infected with Gram-negative bacteria (ii) (9.1; [8.5, 10.6]). The dotted line indicates the proposed threshold for NLR (6.2) for infection. (i: Gram-positive; ii: Gram-negative; iii: fungus; iv: combination of bacteria and fungus; v: combination of Gram-positive and Gram-negative)

Fig. 2

The NLR showed the highest sensitivity and specificity of inflammation markers in patients with multiple times positive microbial results. NLR showed highest sensitivity to specificity relationship in ROC analysis (AUC: 0.632; p < 0.001. The AUC for IL-6 was smaller (AUC: 0.580; p < 0.001). AUC of neutrophils and lymphocytes were 0.550 (p = 0.001) and 0.608 (p < 0.001). AUC of CRP was not significant and therefore not included in the figure

Fig. 3

Frequency of elevated NLR as an inflammation marker is increased, if leukocytes are elevated. The NLR was highest in patients with the combination of Gram-positive/Gram-negative bacteria (v) (24.2; [16.5, 38.9]), but lowest in patients infected with Gram-negative bacteria only (ii) (16.3; [13.8, 19.1]. The dotted line indicates the proposed threshold for NLR (6.2) for infection. (i: Gram-positive; ii: Gram-negative; iii: fungus; iv: combination of bacteria and fungus; v: combination of Gram-positive and Gram-negative)

Fig. 4

Concentration of the NLR is independent of type of organ transplant and patients gender in contrast to Interleukin-6. The NLR values were similar in patients who are (a) lung or liver recipients (11.7 [10.6, 12.6] vs. 13.4 [10.9, 16.5]; p = 0.156) and (b) female or male (10.9 [9.6, 13.1] vs. 12.2 [11.1, 14.2]; p = 0.178). IL-6 values were higher in (c) liver recipients (57.9 pg/mL [48.8, 69.4] vs. 28.2 pg/mL [26.0, 31.7]; p < 0.001) and in (d) male patients (41.1 pg/mL [35.6, 47.4] vs. 28.1 pg/mL [25.4, 32.0]; p < 0.001)