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ORIGINAL ARTICLE
Year : 2021  |  Volume : 24  |  Issue : 5  |  Page : 680-684

The prognostic value of ischemia-modified albumin in patients with sepsis


1 Vocational School of Health Services, First Aid and Emergency Department, Izmir Tınaztepe University, Izmir, Turkey
2 Faculty of Medicine, Department of Emergency Medicine, Dokuz Eylul University, Izmir, Turkey
3 Faculty of Medicine, Department of Medical Biochemistry, Dokuz Eylul University, Izmir, Turkey

Date of Submission26-Apr-2020
Date of Acceptance28-Aug-2020
Date of Web Publication20-May-2021

Correspondence Address:
Dr. M Cetin
Izmir Tınaztepe University, Vocational School of Health Services 35400, Buca/İzmir, Turkey.
Turkey
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/njcp.njcp_211_20

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   Abstract 


Background: Sepsis is a significant contributor of mortality all over the world. Emergency departments have a critical role for diagnosing a suspected sepsis in a patient, since early and proper administration of antibiotics may decrease mortality significantly. But, the unavailability of an objective and reliable diagnostic test is the major challenge of this critical issue. Aims: The aim of this study is to evaluate the prognostic value of a novel biomarker, the ischemia-modified albumin (IMA) in patients with sepsis and septic shock in emergency department. Subjects and Methods: This prospective, observational study included 81 patients with sepsis or septic shock and 75 controls. Sociodemographic characteristics of the patients, site of infection, IMA levels, other biomarkers (procalcitonin, pH, lactate), mortality at 24-h and 28-day were evaluated. Results: The serum IMA levels in patient and control groups were 117.8 ± 85 IU/g and 115.8 ± 134.0 IU/g, respectively (P = 0.072). There was a weak but statistically significant positive correlation between IMA and lactate levels (P = 0.009). The mortality rates of patient group at 24-h and 28 days were 21% and 79%, respectively, but serum IMA levels were not found to be a prognostic marker to predict mortality. Conclusion: The main reason for the similarity between groups regarding IMA levels was thought to be associated with the distribution of the acute and chronic health problems other than sepsis in the control group. Emergency department physicians should not only depend on serum IMA levels for predicting the prognosis of patients with sepsis or septic shock.

Keywords: Emergency department, ischemia-modified albumin, sepsis, septic shock


How to cite this article:
Cetin M, Oray N C, Bayram B, Calan O G. The prognostic value of ischemia-modified albumin in patients with sepsis. Niger J Clin Pract 2021;24:680-4

How to cite this URL:
Cetin M, Oray N C, Bayram B, Calan O G. The prognostic value of ischemia-modified albumin in patients with sepsis. Niger J Clin Pract [serial online] 2021 [cited 2022 Dec 3];24:680-4. Available from: https://www.njcponline.com/text.asp?2021/24/5/680/316460




   Introduction Top


Sepsis and septic shock were comprehensively defined by the Third International Consensus Definition for Sepsis and Septic Shock (Sepsis-3) as a life-threatening organ dysfunction resulting from dysregulated host responses to infection, and a subset of sepsis in which underlying circulatory, cellular, and metabolic abnormalities are profound enough to substantially increase the risk of mortality, respectively.[1] This serious health problem is a primary contributor to morbidity and mortality,[2],[3] and early diagnosis and aggressive treatment is essential in every step of patient management. But, despite the intensive efforts and care for the treatment of sepsis, in-hospital mortality due to this disease ranges between 14.7 and 29.9%.[4] Nevertheless, currently available evidence shows that early and proper management and treatment for patients with sepsis significantly improves outcomes.[5],[6]

For achieving a timely diagnosis of sepsis, various biochemical markers are being used, and many others are being evaluated in laboratory and clinical studies. One of these novel indicators is the ischemia-modified albumin (IMA), which has been originally evaluated as an indicator of myocardial ischemia.[7] Basically, free radicals from the ischemic tissues modifies the N-terminus cobalt-binding site of the albumin molecule and forms the IMA. Several mechanisms including but not limited to hypoxia due to reduced blood flow, acidosis, superoxide-radical injury, exposure to free iron, and copper were proposed to play a role each in this modification.[8]

The global tissue hypo-perfusion and oxidative damage are the major causes of poor-prognosis in patients with sepsis.[9],[10] These mechanisms cause multi-organ failure, and this metabolic consequence eventually proceeds to death.[11] Thus, it is rational to presume that early identification of this cascade should include determination of the ischemia. From this aspect, IMA is a novel biomarker that has been assessed for its value in oxidative stress and ischemia-reperfusion in different clinical conditions including hemodialysis, hypercholesterolemia, end-stage renal disease, and acute coronary syndromes.[12],[13],[14],[15] Nevertheless, only a very limited number of studies have been evaluated its prognostic value in patients with sepsis.[16],[17],[18]

Diagnosing a patient with sepsis in emergency department and transferring him/her to an inpatient service or intensive care unit is a challenge against time, particularly in overcrowded settings. Thus, reliable assessment tools including clinical evaluation scales and biochemical markers have critical importance in the management of these patients. Based on this background, the aim of this study is to evaluate the prognostic value of IMA in patients that are diagnosed with sepsis and septic shock in emergency department.


   Material and Method Top


Design and inclusion/exclusion criteria

This prospective, observational study was conducted between Jan 1, 2015 and June 30, 2015 in the Emergency Department of the Dokuz Eylul University Hospital. The study included a total of 90 patients with severe sepsis and septic shock based on the sample size estimation calculations with the assumption of 6.4% of sepsis prevalence in the emergency department and 75 patients without sepsis and septic shock serve as controls. Local ethical committee approved the study protocol (protocol number: 1770-GOA, approval number: 2014/34-19).

The diagnosis of sepsis was evaluated within the first hour of admission according the Sepsis Guideline.[19] Patients with suspected severe sepsis and septic shock were included in the study. Patients with a serum albumin level that is below 2 g/dl and above 5.5 g/dl (which may interfere with the IMA measurements), or with any acute or chronic condition that may affect IMA levels (trauma, acute ischemic heart disease, myocardial infarction, peripheral vascular disease, mesenteric ischemia, acute ischemic cerebrovascular disease, pulmonary embolism, muscle disease, liver disease, seizures), and patients who disagreed to participate in the study were excluded from the study. Sex and age (±2 years) matched patients with a diagnosis other than sepsis and without exclusion criteria were included as the control group.

The criteria of septic shock were considered as a systolic blood pressure which is lower or equal to 90 mmHg, or a mean arterial pressure that is lower than 60 mmHg or a decrease of 40 mmHg and more than the initial levels, despite the adequate fluid resuscitation.

The infections were classified in the following groups: respiratory system, urinary tract infection, intraabdominal infection, central nervous system infection, soft-tissue infection, and unknown site of infection [Figure 1].
Figure 1: IMA levels by sites of infection

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Laboratory analyses

Blood samples obtained from the patients during initial assessment in the emergency department were centrifuged for 15 min at 3000 rpm to separate the sera and the serum samples were kept at -80°C. Mybiosource Human ischemia-modified albumin ELISA® kit (USA) was used for the analyses, and IMA levels were determined by the double-antibody sandwich enzyme-linked immunosorbent assay (ELISA). Procalcitonin was studied in Advia Centaur. Lactate, base deficit, pH, and pCO2 were also performed at Radiometer ABL800.

Data collection and analysis

The data collected from the patients were sociodemographic characteristics, site of infection, IMA levels, other sepsis related biomarkers (procalcitonin, pH, lactate) and mortality at 24-h and 28-day.

All statistical analyses were performed with SPSS 22 (IBM Inc., Armonk, NY, USA). Independent and dependent group comparisons were done with independent-samples t test, and Mann-Whitney U test, respectively. Categorical data were compared using Chi-square test. Spearman correlation analysis was performed to correlate IMA and other biomarkers. Sensitivity and specificity samples were done with ROC analyses. The statistical significance was considered as a P value lower than 0.05 in all analyses.


   Results Top


After excluding 9 patients for low albumin levels (n = 6) and retraction of consent (n = 3), remaining 81 patients and 75 controls were included in the final analyses. Mean age of the patient and control groups were 71.5 ± 1.5and 70 ± 1.6 years, respectively. Male/Female distribution of the groups was similar [Table 1].
Table 1: Demographic characteristics of the groups

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The IMA levels in patient and control groups were 84.8 ± 85 IU/g and 71.7 ± 134.0 IU/g, respectively (P = 0.072). Nevertheless, IMA levels were significantly different between with site of infections in patients group [P = 0.005, [Table 2]]. In our study we found the highest levels of IMA in patients who have central nervous system infections.
Table 2: IMA levels of according the site of infections

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The correlations between sepsis-associated biomarkers (IMA, lactate, procalcitonin, and pH) are shown in [Figure 2]. Accordingly, there was only a statistically significant and weak positive correlation between IMA and lactate levels (r = 0.289; P = 0.009). IMA levels were not found to be correlated with procalcitonin and pH levels.
Figure 2: Correlations between sepsis-associated markers

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The mortality rates of patient group in this study at 24-h and 28-day were 21% and 79%, respectively. The comparisons of laboratory parameters between survivors and non-survivors patients at 24-hour revealed that IMA (P = 0.09), procalcitonin (P = 0.038), and lactate (P = 0.002) were significantly higher, and pH levels were lower (P = 0.001). Among these parameters, only lactate levels (P = 0.01) were found to be significantly higher in patients with 28-day mortality [Table 3].
Table 3: Laboratory parameters of survivor and non-survivor patients in the study group

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The prognostic value of these parameters for 24-h and 28-day mortality were assessed in logistic regression models. Accordingly, decreased pH levels (OR: 0.003; P = 0.01) and increased procalcitonin levels (OR: 1.02; P = 0.08) were found to be associated with 24-hour mortality, and increased lactate levels (OR: 1.23; P = 0.09) was found to be associated with 28-day mortality. IMA was not found to have prognostic value to predict neither 24-h nor 28-day mortality in this patient group [Table 4].
Table 4: Regression analysis of laboratory parameters for 24-h and 28-day mortality

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   Discussion Top


In this study, we have primarily assessed the prognostic value of IMA in patients with sepsis and septic shock in an emergency department setting. Our results showed that IMA could not reach adequate prognostic value in this patient group neither in short nor long term. But, these results should be considered carefully, since only severe sepsis and septic shock patients have been included in this study.

Nevertheless, our results are contradictory with the currently available limited data in the literature. A recent study by Yin et al.[16]which evaluated the predictive value of IMA for short term mortality in patients with severe sepsis reported that it was found to be a useful predictor for 28-day mortality and independent risk factor for death. Particularly, authors stated that IMA levels above 110 U/mL should be a critical sign for physicians about the increased death risk of the patient. Another study by Prashanth and Anand[17] reported that the levels of this IMA significantly increases in these patients, which can be used to identify oxidative stress and to avoid ischemic damage to the organism. A study by Khashana et al.[20] also reported that neonates with infection had increased IMA levels, and this biomarker could be an early indicator of neonatal sepsis to initiate antibiotics for better patient outcomes. Similar results have also been observed in other studies.[21],[22]

We have hypothesized in this study that IMA levels should increase in case of sepsis in the organism, based on the common mechanisms that are shared by septic and ischemic conditions. One of the main features of sepsis is the cardiac and vascular insufficiency that results in global tissue hypoxia.[9],[10] Recent studies have revealed that IMA was associated with increased oxidative stress and increased levels of IMA were shown in patients with sepsis. The reason that our study did not reveal a significant difference regarding IMA between patients with and without sepsis might be associated with the general characteristics of patient population at our study site. Patients with chronic respiratory system diseases, chronic cardiac problems, vascular diseases, etc., may have increased IMA levels due to chronic hypoxia, which should bias our expected difference between patients with and without sepsis toward null. This is consistent with the results of Yin et al.,[16]who reported a critical value of 110 U/mL for IMA to create a signal for the risk of death. We found that levels of IMA were higher than this cut-off in both patient and control groups, which may be indicative of ischemic conditions in both study groups. A comparison between patients with sepsis and healthy control subjects may provide clearer results to make more reliable comments about the prognostic value of IMA in sepsis as has been shown by the Ashok Kumar and Anand's study,[18] which reported that critically ill patients with sepsis had significantly higher IMA levels compared to the control group with apparently healthy subjects.

In this study, we have also assessed the correlations between sepsis-associated biomarkers. Lactate is a widely used biomarker that has a clear role for risk stratification in suspected sepsis patient in the emergency department.[23],[24] Nevertheless, previous studies showed that it was not sensitive or specific for sepsis.[25]Another biomarker is procalcitonin, which is produced by thyroid C-cells as a precursor of calcitonin, an acute phase protein. Previous studies showed that it has a modest sensitivity/specificity for bacterial sepsis, and superior to CRP in bacterial infections.[26],[27]Serum pH level is another surrogate marker in sepsis, which reflects the acidotic state in the organism. But, it may also be associated with the management of the critically ill patient as well as it is associated with the disease itself.[28] Our results revealed that there was a significant but modest positive correlation between IMA and lactate levels, but not with procalcitonin or serum pH levels. The heterogeneity of the etiologies of sepsis and septic shock in our patient group might be associated with this result. We observed that the highest IMA levels were present in patients with central nervous system infections, and infections of unknown primary sites. But, the number of the patients in these groups were very low compared to other infection sites. The patients with infections at other sites have IMA levels approximately between 100 and 120 IU/g, a value that can be considered as a significantly increased IMA level according to the literature data. More homogenous subsets of patient populations may provide more reliable results regarding the associations of sepsis-associated biomarkers.

Limitations

The control group was selected from patients who were referred to emergency hospitals with other complaints other than sepsis. Although conditions that affect the level of IMA are considered exclusion criteria and have been used in the control group, there may be additional untested or overlooked conditions in these patients that increase the IMA level.


   Conclusion Top


Our study has provided contradictory results to the literature data about the prognostic value of IMA in patients with sepsis. Emergency department physicians should not only depend on serum IMA levels for predicting the prognosis of patients with sepsis or septic shock.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

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    Figures

  [Figure 1], [Figure 2]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

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