Association of neutrophil-to-lymphocyte ratio with age and 180-day mortality after emergency surgery

The inflammatory and immune response statuses before emergency surgery are not a component of any preoperative algorithm. Here, we identified an association between preoperative NLR and mortality. We observed that deceased patients at 30 and 180 days after surgery had a higher NLR upon admission for surgery than those who remained alive at these time points. Additionally, patients with an NLR > 3 exhibited decreased survival rates after 180 days. Through receiver characteristic curve analysis, we noted that NLR demonstrated acceptable discriminatory capacity. Predictive efficacy was higher in the age group < 65 years. Accordingly, the results of the multivariate logistic regression indicated that incorporating age into the model enhanced the predictive capacity of NLR for 180 days mortality.

Immune response is crucial in tissue repair and healing [17]. The assessment of the inflammatory status is often omitted in preoperative non-cardiac surgery evaluation algorithms, although the system response manifesting as sepsis is part of The American College of Surgery National Surgical Quality Improvement Program risk calculator [18]. In patients without sepsis, the inflammatory status or immune cellular response is not considered in the categorization or management algorithms of surgical patients.

Surgery involves controlled tissue damage, and its outcomes are related to the regenerative capacity of the tissue [19]. Activation of macrophages and neutrophils is required at the site of surgical damage [20, 21]. Neutrophils are the predominant immune cells in human blood and protect against pathogens and other harmful agents [22]. During injury, neutrophils are readily available after damage-associated molecular patterns are released from the damaged cells [23]. Upon recruitment, these cells undergo phenotypic changes, giving rise to distinct subpopulations aimed at various functions, such as clearing debris, releasing effectors such as growth factors and metalloproteinases, and engaging in processes related to angiogenesis, regeneration, anti-inflammatory responses, and secretion of reparative cytokines, all of which contribute to the resolution of injury [24, 25]. Despite their role in tissue repair, neutrophil-associated tissue injury is observed due to the amplification of the inflammatory response and the direct release of reactive oxygen species and proteolytic enzymes [26].

Additionally, a novel mechanism known as neutrophil extracellular trap-induced tissue damage has been proposed as an additional tissue injury factor [23, 27, 28]. This finding emphasizes the significance of neutrophils and their role in maintaining tissue homeostasis. Hence, understanding and integrating NLR as a preoperative factor could incorporate the balance in cellular immune status using preoperative algorithms.

The NLR has been studied in acute kidney injury [4], ischemic stroke [6], cardiovascular mortality [7], and chemotherapy outcomes in cancer [10]. Although preoperative evaluation is simple and available in most preoperative emergency and non-emergency settings at a low cost, it has not been implemented. Age-related differences appear to be important factors. We found that NLR may predict mortality more effectively in younger patients. Chronological age is not always correlated with biological age and is more difficult to assess using common algorithms. Although 65 years is a frequently recommended threshold to differentiate between young and older patients, it has been reported that older patients are more prone to complications after non-cardiac surgery [18]. Variations in the NLR values across different life stages have been described previously. In a healthy adult population, excluding geriatric individuals, NLR values are lower than 3.5 [2, 29]. The exact cutoff value remains elusive, and an NLR < 3 is considered to be within the normal range [30]. The cutoff value in older individuals may be affected by immune senescence, which could complicate utilizing the NLR in preoperative settings [31].

Our study has a few limitations. In addition to its retrospective design, our study was a single-center analysis over a one-year period, thereby limiting the external validity of our findings. Second, we found differences in the use of the NLR across different ages. After analyzing the values from our entire sample, we used 65 years as the cutoff to define age differences. This value, employed by preoperative evaluation guidelines owing to its association with cardiovascular complications, may not necessarily define the function and utility of NLR in predicting outcomes, as chronological and biological ages are not always related. Further studies are necessary to define this variable. Finally, owing to the small sample size, we did not obtain a clear cutoff value in our receiver operating curve analysis, and an NLR value of 3 was used according to the literature. Our analysis suggests that patients with an NLR greater than 8.5 are at increased risk of mortality at both 30 and 180 days. However, larger cohorts are necessary to elucidate this further. Confounding factors, such as the number of patients who developed sepsis, shock, or other inflammatory states related to the surgical intervention, were not analyzed in this retrospective study. This introduces an analysis bias that should be addressed in prospective studies.

Here, we found differences between patients who survived for 30 and 180 days regarding the preoperative NLR. When combined with age, it enhances the prediction of mortality; however, in older patients, NLR alone may not reflect postsurgical outcomes, as immune senescence may be a contributing factor.

It is also noteworthy that our NLR analysis was conducted among patients with no differences in total white blood cells count between those with higher or lower mortality. Introducing the component of innate and cellular immune response, as implied by the NLR, distinguishes mortality in patients undergoing emergency surgery and may be useful for clinicians as an accessible additional parameter beyond solely using leukocyte count as a marker of inflammation. This suggests that the NLR could enhance preoperative evaluation algorithms.

In conclusion, our study observed differences in preoperative NLR between patients who survived and those who died after emergency surgery. Patients with an NLR greater than 3 had lower survival rates at 180 days. Differences in NLR values in the younger and older than 65 years groups impacted the use of the NLR as a mortality risk factor. Further studies are necessary to validate the use of NLR in the preoperative evaluation of patients undergoing emergency surgery.

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