Keywords
Neutrophil Lymphocyte Ratio, SOFA, APACHE IV, critical ill patient, sepsis
This article is included in the Datta Meghe Institute of Higher Education and Research collection.
Sepsis poses a significant threat in the Medical Intensive Care Unit (MICU), with high morbidity and mortality rates. Accurate prognostic tools are essential for guiding patient management. This study aims to compare the effectiveness of Neutrophil–Lymphocyte Ratio with Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation IV (APACHE IV) in predicting sepsis outcomes. A prospective cross-sectional design will enrol septic MICU patients, collecting baseline data and scoring systems. Patient outcomes, including mortality and length of MICU stay, will be analyzed using correlation and ROC curve analyses. This study addresses the current gap in direct comparisons of these tools.
The results of this study are anticipated to reveal significant correlations between the Neutrophil Lymphocyte Ratio combined with SOFA and APACHE IV scores and patient outcomes. Specifically, we expected to observe strong associations between the combined scoring system and mortality rates, length of MICU stay, and the need for organ support. Furthermore, we anticipate that the Neutrophil Lymphocyte Ratio combined with SOFA will demonstrate higher predictive accuracy than APACHE IV to assess prognosis in sepsis patients admitted to the MICU.
Based on the results obtained from this prospective cross-sectional study, we can draw conclusions regarding the comparative effectiveness of NLR (Neutrophil Lymphocyte Ratio) combined with SOFA and APACHE IV in assessing the prognosis of sepsis in the MICU. We anticipate that the combined scoring system will provide a more accurate prognostic assessment and enable healthcare professionals to make well-informed choices regarding patient care and the distribution of resources. These findings will contribute to building evidence on sepsis and may have implications for improving patient outcomes in the MICU setting.
Neutrophil Lymphocyte Ratio, SOFA, APACHE IV, critical ill patient, sepsis
Sepsis, a potentially fatal illness, is a severe organic malfunction caused by an uncontrolled response to infection in the body. If ignored, it can develop into septic shock, which is characterized by serious metabolic and circulatory problems and is often fatal.1
Inflammation and immunological response are crucial factors in many chronic illnesses. An indicator of the balance between two components of the defense mechanism, including acute and chronic inflammation (expressed by means of neutrophil count) and adaptive immunity (expressed by means of lymphocyte count), is (theeutrophil-to-lymphocyte ratio NLR, a biomarker found in the blood (peripheral).
NLR, an inflammatory biomarker computed by dividing the total count of neutrophils by the total count of lymphocytes, is a marker of systemic inflammation. This measure does not increase the price of standard full blood count testing routinely conducted in hospital settings. NLR has been studied as a prognostic indicator in various conditions, including sepsis, community-acquired pneumonia, and various forms of cancer.2
NLR is a widely utilized marker to assess the severity of bacterial infection and to predict the prognosis of patients with tumor pneumonia.3 NLR serves as a straightforward parameter for evaluating an individual’s inflammatory status and has demonstrated its utility in predicting the mortality of significant cardiac diseases, as well as being a robust prognostic factor for various cancer types.4,5
The SOFA is a straightforward and objective scoring system that assesses the severity and number of multi-organ dysfunctions across six organ systems: respiratory, liver, urology, cardiovascular, coagulation, and neurological. This score gauges dysfunction in individual organs or provides an overall assessment of organ dysfunction.6 A higher SOFA score indicates a greater likelihood of mortality.
• To estimate the combined SOFA and Neutophil Lymphocyte Ratio score in sepsis patients
• To estimate APACHE IV Score in sepsis patients
• To compare the neutrophil lymphocyte ratio combined sofa with APACHE IV in predicting outcomes in terms of mortality, ICU (Intensive Care Unit) stay, and mechanical ventilation in patientswith sepsis
Research design: Prospective, Cross sectional study.
Setting: All patients visiting the Department of General Medicine (Acharya VinobhaBhave Rural Hospital, Datta Meghe Institute of Medical Sciences, Sawangi (Meghe), Wardha) who met the criteria for sepsis.
After obtaining written informed consent, all patients who satisfied the inclusion and exclusion criteria were included in the study.
Duration for study: 2022 to 2024.
Inclusion criteria:
• Patients older than 18 years of age
• The patient satisfied diagnosis and diagnostic criteria of sepsis on the SOFA, and their survival time after admission is ≥24 hours.
The following exclusion criteria must be met:
Cardiac or Respiratory Arrest
Outcomes:
1. Mortality (within a specified time frame): The primary outcome measure indicated whether the patient died within a specified time period.
2. Length of MICU stay - The duration will be measured in hours or days.
3. Requirement for organ support: The need for specific interventions or therapies to support organ function, such as mechanical ventilation or vasopressors.
Exposures:
1. Neutrophil Lymphocyte Ratio - A calculated by dividing the neutrophil count by the lymphocyte count from a patient’s blood sample, reflecting the balance between anti-inflammatory neutrophils and pro-inflammatory lymphocytes.
2. SOFA score: A scoring system that evaluates the degree of organ malfunction in six major organ systems: circulatory, neurological, hepatic, renal, respiratory, and coagulation.
3. APACHE IV score: A comprehensive scoring system that evaluates the severity of acute conditions, incorporating physiological parameters, chronic illness, and age.
Predictors:
1. Comorbidities: pre-existing illnesses that could affect the patient’s prognosis, such as diabetes, hypertension, or chronic kidney disease.
2. Source of infection: The primary site or origin of the infection causing sepsis (e.g., respiratory, urinary, and abdominal).
3. Microbiological culture results: Laboratory results identifying the specific causative organism responsible for the infection.
4. Laboratory parameters: Results of blood tests, including white blood cell count and lactate levels, may indicate the severity of infection and organ dysfunction.
Potential confounders:
1. Presence of septic shock: The occurrence of sepsis-induced circulatory and cellular/metabolic abnormalities results in a higher risk of mortality.
2. Severity of illness: The overall severity and complexity of the patient’s acute illness, which may affect prognosis.
3. Use of specific treatments or interventions: The administration of specific therapies or interventions such as antibiotics or fluid resuscitation can influence patient outcomes.
Effect modifiers:
1. Age: Patient age may modify the relationship between exposure and outcomes.
2. Sex: The biological sex of the patient may interact with exposure to influence outcomes.
3. Presence of comorbidities: Pre-existing medical conditions may modify the effects of exposure on outcomes.
4. Source of infection: The specific site or origin of the infection may interact with the exposure to affect outcomes.
5. Specific type of organ dysfunction: The presence of specific organ dysfunction may modify the effects of exposure on outcomes.
Collection of Blood Sample
To begin the blood collection process, the skin above the median cubital vein was prepared by applying spirit to the cubital fossa area. Additionally, a tourniquet was placed proximal to the fossa. Subsequently, a sterile venipuncture needle, the standard in its design, was used to collect the blood. blood was drawn into a bulb containing potassium ethylenediamine tetra acetate for sample collection and complete blood cell count analysis. Importantly, blood sample analysis was carried out within a 15-minute timeframe from the time of collection.
Confidentiality
The collected data will be kept confidential. The data were coded and entered into a password-protected digital form. The names and other personal details of the patients will not be revealed.
Procedure
Blood samples will be taken under strict aseptic precautions.
Measurement of Blood Pressure
According to the guidelines set forth by the American Heart Association (AHA), readings of 130 mmHg or higher for systolic blood pressure (SBP) or 80 mmHg or higher for diastolic blood pressure (DBP) are indicative of elevated blood pressure. The blood pressure of each patient was measured according to the protocol recommended by the AHA.
A comprehensive clinical examination will be conducted and all observed findings will be recorded. A thorough patient history and examinations will be performed. Relevant historical information, including smoking and alcohol consumption as well as medication use, will be documented. We will also assess any pre-existing medical conditions in the patients, inquiring about a history of hypertension, diabetes, malignancy, and chronic kidney and liver disease. Physical examination will include pulse rate, blood pressure, Glassgow coma scale score, and complete blood count.
The SOFA score, referred to as the sepsis-related organ failure assessment score previously, is employed to monitor an individual’s condition during their ICU stay. It is used to assess the degree of organ function or rate of organ failure in a person (Table 1)
The parameters for assessment include:
1. Age (years)
2. Body Temperature (°C)
3. Mean Arterial Pressure (MAP, mmHg)
4. Heart Rate (HR, beats per minute)
5. Respiratory Rate (RR, breaths per minute)
6. Mechanical Ventilation (Yes/No)
7. Fraction of Inspired Oxygen (FiO2, %)
8. Partial Pressure of Oxygen (pO2, mmHg)
9. Partial Pressure of Carbon Dioxide (pCO2, mmHg)
10. Arterial pH
11. Sodium (Na+, mEq/L)
12. Urine Output (mL per 24 hours)
13. Creatinine (mg/dL)
14. Urea (mEq/L)
15. Blood Sugar Level (BSL, mg/dL)
16. Albumin (g/L)
17. Bilirubin (mg/dL)
18. Hematocrit (Ht, %)
19. White Blood Cell Count (x1000/mm3)
20. Glasgow Coma Scale (GCS) with subcomponents:
21. Chronic Health Conditions:
Continuous variables will be expressed as mean ± Standard Deviation and compared across groups using unpaired t-test or ANOVA.
Categorical variables will be expressed as the number and percentage of patients and compared across groups. All the data will be entered in Microsoft Excel 2013, and the statistical software R studio Version 4.3.1 will be used for the analysis. An alpha level of 5% will be considered, that is, if any p-value is less than 0.05, it will be considered significant. Means between two different groups will be assessed using an unpaired t-test. Correlations will be done using Spearman’s or Pearson’s correlations.
1. Selection Bias: Non-random or non-representative participant selection.
2. Information Bias: Errors or inconsistencies in measurement or data recording.
3. Confounding Bias: Distortion of association due to an extraneous variable.
4. Reporting Bias: Publication bias favoring significant or positive results.
5. Observer Bias: Biased interpretation or reporting by researchers or clinicians.
6. Lead-time Bias: Differences in outcome assessment timing affecting results.
Applying Krejcie and Morgan Formula for the estimation of the sample size
is the chisquare tabulated value for 1 Degree of Freedom at 95% confidence interval
N is the total number of patients
P is the 50% proportion
c is the Error of Margin at 5%
Substituting the appropriate values for the statistical estimation in equation 1 leads to
This study aimed to assess the prognosis of sepsis patients in the MICU by comparing the neutrophil-lymphocyte ratio combined with the SOFA score versus the APACHE IV score. The expected outcomes included a comparative analysis of the predictive performance of these scoring systems in predicting mortality, length of MICU stay, and requirement for organ support. Additionally, the association between Neutrophil Lymphocyte Ratio, SOFA score, APACHE IV score, and outcomes will be examined. This study will evaluate the accuracy and discriminatory power of the scoring systems, identify potential effect modifiers, and explore the clinical implications of using these tools in assessing sepsis prognosis. These findings will contribute to the understanding of prognostic assessment in sepsis and may have implications for patient management and decision-making in the MICU.
A critical clinical state known as sepsis is characterised by dysregulated response of host to infections & frequently develops as consequence of severe infection.8 Cardinal symptoms of inflammation, such as vasodilation, leukocyte buildup, and increased vascular permeability, are part of this response and can manifest in tissues far from the infection site. High death rates are associated with sepsis, especially in patients who require treatment in the ICU. Early and precise diagnosis is essential to improve the prognosis of patients with sepsis.9
In critically ill patients, sepsis diagnosis is a formidable challenge, necessitating a multifaceted approach. In addition to obtaining a comprehensive medical history and conducting thorough physical examination, laboratory markers of infection and inflammation are vital components of the diagnostic process. These markers include White Blood Cell (WBC), C-reactive protein (CRP), procalcitonin (PCT), neutrophil, and lymphocyte counts. Among these indicators, neutrophil-to-lymphocyte ratio (NLR) has emerged as a valuable biomarker for sepsis diagnosis.
NLR is a straightforward and cost-effective parameter derived from complete blood count (CBC). It offers insights into the balance between neutrophils, which are indicative of inflammation, and lymphocytes, which reflects the immune response. Significantly, in sepsis, a higher NLR is associated with a worse outcome. The natural reaction of the immune system to infection and other stressful situations is an increase in neutrophil counts and a decrease in lymphocyte counts. While lymphocyte numbers decrease when activated cells travel to inflammatory tissues and incur greater apoptosis, neutrophil counts increase as a result of reduced apoptosis and rapid mobilization of neutrophils from the bone marrow.8
The neutrophil-lymphocyte count ratio (NLCR), first described in 2001, is a simple, quick, and economical metric for evaluating stress and inflammation in critically ill patients. Zahorec et al. conducted a prospective study. involving ninty patients in the ICU, revealing that NLR had the capability to forecast the severity and future outcomes in patients with sepsis.10 Recent research has demonstrated the predictive utility of NLCR in patients presenting to the Emergency Department (ED) with suspected bacteremia, as well as its correlation with the short- and long-term outcomes of patients in critical conditions.11
Heffernan et al. observed that trauma patients and those meeting the criteria for systemic inflammatory response syndrome (SIRS) exhibited a concurrent condition characterized by both low lymphocyte counts and high neutrophil counts.12 In contrast, Bermejo-Martín et al. found a link between reduced circulating neutrophil counts and an increased risk of mortality.13 This raises the possibility that sepsis patients with low circulating neutrophil counts may find it difficult to generate a potent innate immune response. Furthermore, sepsis syndrome may cause neutrophils to adhere to the vascular endothelium more strongly, which would lower the number of circulating neutrophils. Endothelial injury is a common consequence of sepsis.12
The SOFA scoring system is a widely utilized tool for gauging the severity of organ dysfunction in critically ill patients, including those with sepsis. The SOFA examines the condition in six distinct organ systems: cardiovascular, neurological, hepatic, renal, respiratory, and coagulation. Each system was assigned a score ranging from zero, representing normal function, to four, denoting severe dysfunction or failure). A score of 3 or 4 in any particular system indicated a high likelihood of organ failure within that specific system. The SOFA assigns a numerical value to each system, providing healthcare providers with a measurable indicator of dysfunction across various organs.13
In a study conducted by Shimoyama et al., it was noted that SOFA scores were correlated with higher estimated risk levels than NLR. Furthermore, this study disclosed that the likelihood of mortality increased by 13 % %with every increase of 1 unit in the SOFA scores. This phenomenon can be explained by the fact that SOFA scores are confined to a limited numerical range between 0 and 20, whereas the NLR lacks an upper numerical limit, permitting a wider spectrum of values.13,14
Both NLR and platelet-to-lymphocyte ratio (PLR) were identified as straightforward, cost-efficient, and expeditious indicators of mortality when juxtaposed with more intricate scoring systems, such as APACHE II and SOFA scores. The amalgamation of these biomarkers, such as SOFA scores and NLR, has the potential to increase the accuracy of mortality predictions. This unified approach capitalizes on the strengths of both systems and offers a more comprehensive evaluation of a patient’s condition. Consequently, the integration of SOFA scores and NLR can empower healthcare providers to make better informed decisions regarding the prognosis and treatment of critically ill patients, particularly those with sepsis in the intensive care unit (ICU).13
Notably, when measuring the neutrophil-to-lymphocyte ratio (NLR) upon admission to the Intensive Care Unit (ICU), researchers have found associations with both short-term and long-term mortality in critically ill adult patients. This suggests that NLR could serve as a valuable indicator of the inflammatory response in critically ill adults. In the context of sepsis management in the ICU, the NLR and NLCR can serve as valuable tools for risk stratification and prognostication. These biomarkers provide clinicians with additional insights into patients’ inflammatory and immune responses, helping to guide early intervention and treatment decisions. The APACHE IV is an enhanced and modernized model designed to forecast the mortality rate of groups of critically ill patients, while the previously revised equation is used to predict mortality rates in hospitals following coronary artery bypass graft (CABG) surgery.
The APACHE IV is a scoring system and predictive model utilized in medical settings to assess the severity of illness and predict the risk of mortality.15 It includes the following components:
1. Acute Physiology Score (APS): This component assesses the physiological status of a patient upon admission to the ICU. It considers vital signs, laboratory values, and other clinical parameters to measure the severity of an acute illness.
2. Age: The patient’s age is a factor in the APACHE IV model, as older age can be associated with increased mortality risk.
3. Chronic Health Points (CHP): This component considers a patient’s pre-existing health conditions and comorbidities. It assigns points based on the presence and severity of chronic illness.
4. Glasgow Coma Scale (GCS): The patient’s degree of consciousness and neurological function are evaluated using the GCS.
5. Admission Source: This component considers where the patient was admitted, such as the emergency department, operating room, or other locations within the hospital.
6. Admission Type: It categorizes the patient’s admission as either scheduled (elective) or unscheduled (emergency).
7. Diagnostic Category: This component classifies the patient into one of several diagnostic categories, which helps to group patients with similar conditions for risk prediction.
8. Chronic Health Conditions: APACHE IV includes specific chronic health conditions and comorbidities as risk factors.
9. Organ Support: It considers whether the patient requires mechanical ventilation, renal replacement therapy, or other forms of organ support.
10. Surgical Status: APACHE IV accounts for surgical patients and their post-operative status, including elective or emergency surgery.
These components were used to calculate the predicted risk of mortality for each ICU patient. The APACHE IV score provides valuable information for clinicians and researchers to assess illness severity and make informed decisions regarding patient care. It is a widely used tool in critical care medicine for risk stratification and quality improvement. Keep in mind that The specific details and components of the APACHE IV may evolve over time as new versions or updates are developed.15
This study aimed to assess the combined SOFA and NLR scores as predictors of outcomes in patients with sepsis and to estimate the APACHE IV Score for the same patient population. This study aimed to compare the predictive capabilities of the combined NLR-SOFA score with the APACHE IV score in terms of mortality risk, length of stay in the intensive care unit (ICU), and need for mechanical ventilation among sepsis patients. This analysis aimed to provide valuable insights into the effectiveness of these scoring systems in guiding clinical decisions and improving patient care for individuals with sepsis.
Written consent will be taken from all the participants in the study.
Ethical committee: Datta Meghe Institute of Medical Sciences (Deemed to be University) IEC NO- DMIMS (DU)/IEC/2022/1091 aprooved on 27/06/2022.
Study status: Not yet started.
All authors mentioned for the study have contributed equally to the study design, data curation, data availability, conceptuality, writing, and drafting.
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Is the rationale for, and objectives of, the study clearly described?
Yes
Is the study design appropriate for the research question?
Partly
Are sufficient details of the methods provided to allow replication by others?
Partly
Are the datasets clearly presented in a useable and accessible format?
Not applicable
Competing Interests: No competing interests were disclosed.
Reviewer Expertise: Scoring systems in sepsis
Alongside their report, reviewers assign a status to the article:
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Version 1 26 Apr 24 |
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