These analyses demonstrate that there is a correlation between neutrophil-lymphocyte-ratio and renal oxygen extraction. A neutrophil-lymphocyte-ratio greater than 2.95 had fair performance in identifying a renal oxygen extraction of greater than 35%.
The correlation between absolute neutrophil-lymphocyte-ratio and absolute renal oxygen extraction was not too strong but there was greater strength in the association of neutrophil-lymphocyte-ratio in identifying the binary endpoint of a renal oxygen extraction of greater than 35%.
In the pediatric population, the neutrophil-lymphocyte-ratio has been demonstrated to be associated with, and have prognostic implications in the setting of, several clinical occurrences such as pleural effusion after cardiac surgery, duration of mechanical ventilation after cardiac surgery, length of stay after cardiac surgery, low cardiac output after cardiac surgery, cardiac dysfunction, refractory Kawasaki disease, coronary artery lesions with Kawasaki disease, lymphatic anomalies after the Fontan procedure, carditis with Rheumatic fever, reactive airway disease, and necrotizing enterocolitis among others [1–17].
This phenomenon is likely an association and not causal although the current data do not prove this. Many of the clinical settings in which neutrophil-lymphocyte-ratio has been demonstrated to have clinical significance are settings in which there may be inflammation or regional hypoxia.
In the setting of inflammation, neutrophils help mediate the inflammatory state along with other inflammatory cells. Neutrophils remain in circulation for a short period of time and change their morphology over the course of this relatively short period of time. Various signaling mechanisms facilitate the exit of neutrophils from the bone marrow and into the circulation. One such impetus for exit of neutrophils from the bone marrow is inflammation and neutrophils are the predominant cell type in early inflammation. Once at sites of inflammation, neutrophils can change phenotype and generate various subpopulations, indirectly and directly influencing the immune and inflammatory response. Ultimately these neutrophiles are removed by macrophages [18, 19]. At sites of inflammation, often sites with regional hypoxia, neutrophils survive longer due to mechanisms that inhibit neutrophil apoptosis or phagocytosis [20]. Regional hypoxia due to other reasons, such as acute arterial occlusion, lead to similar neutrophil response.
The inflammatory response may be secondary to a process that is leading to an inadequacy of oxygen delivery or may be directly contributing to inadequacy of oxygen delivery due to increased oxygen consumption to sustain the inflammatory process. This is an important notion as it means that it is unclear whether the association of increasing neutrophil-lymphocyte-ratio with increasing renal oxygen extraction is the cause or the effect. It is plausible that decreased oxygen delivery may alter the differentiation and express of cells but it also plausible that increased oxygen consumption by the cells themselves as they perform their specific functions is leading to increased oxygen extraction. It is also very plausible that both are occurring simultaneously to some degree.
If inadequacy of oxygen delivery itself mediates an increase in neutrophil-lymphocyte-ratio, then the question is if this has clinical consequences in regard to immune and inflammatory response. Does this lead to increased susceptibility to infection? Does it alter the outcomes with infections that do occur? For adults who are already have a documented infection and sepsis, a higher neutrophil-lymphocyte ratio is associated with increased mortality. The current data do not explore these issues although they are logical considerations from such data and would be interesting questions to answer with future studies.
Regardless of whether or not increased neutrophil-lymphocyte-ratio is the result or cause of increasing oxygen extraction, it remains that neutrophil-lymphocyte-ratio is a relatively inexpensive, simple blood test that can help lend insight into underlying adverse processes that may be occurring or the prognosis of underlying adverse processes. The current data specifically pertain to the ability to use neutrophil-lymphocyte-ratio as a screen for increased renal oxygen extraction, concerning for inadequacy of oxygen delivery.
Monitoring the adequacy oxygen delivery is of utmost importance in all patients as organ function is dependent on this. Systemic oxygen delivery is the product of oxygen content and cardiac output. Out of these equations, the components that can be monitored clinically are hemoglobin, arterial saturation, venous saturation, and partial pressure of oxygen [21–23]. More routinely, continuously monitored indices such as hear rate, blood pressure, and respiratory rate are not included in these equations [24]. Monitoring the adequacy of systemic oxygen delivery requires both the arterial and venous saturations. The arterial saturation can be monitored by pulse oximetry or blood gas analysis while the venous saturation can be monitored by near infrared spectroscopy or blood gas analysis [25–27]. Such monitoring is important as monitoring of adequacy of oxygen delivery using a venous saturation, or an estimation of it, helps to determine the probability of adverse events including, but not limited to, developmental delay, acute kidney injury, hepatic insufficiency, extubation failure, cardiac arrest, and mortality [28–35].
This study utilizes high-fidelity data captured at five second intervals, enabling for trends and associations to be effectively characterized. It also explores a novel aspect of neutrophil-lymphocyte-ratio. Thus, it is additive to the current literature. However, this study is not without its limitations. First, this is a single-center study and there could be factors not captured here that may be mediating associations that are related to center-specific practices Second, this is retrospective in nature and so causality cannot be gauged. The absolute number of patients is low but the number of neutrophil-lymphocyte-ratio and renal oxygen extraction data pairs is quite high, and these are the "subjects" in the analyses. Thus, the analysis is adequately powered at this level. Although, patient specific factors which are accounted for in the regression cannot be confidently commented on due to the low number of patients.