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 Table of Contents  
ORIGINAL ARTICLE
Year : 2019  |  Volume : 6  |  Issue : 4  |  Page : 461-469

Midregional proadrenomedullin in correlation with Sequential Organ Failure Assessment score and Acute Physiology and Chronic Health Evaluation II score in sepsis


1 Lecturer of Critical Care Medicine, Critical Care Medicine department, Faculty of Medicine, Cairo University, Egypt
2 Professor of Critical Care Medicine, Critical Care Medicine department, Faculty of Medicine, Cairo University, Egypt
3 Consultant of Clinical Pathology, Critical Care Medicine department, Cairo University, Cairo, Egypt
4 Resident of Critical Care Medicine, Critical Care Medicine department, Faculty of Medicine, Cairo University, Cairo, Egypt

Date of Submission04-Apr-2018
Date of Acceptance17-Dec-2018
Date of Web Publication06-Jan-2020

Correspondence Address:
MBBCh Sayed Gaber
Faculty of Medicine, Cairo University, Master degree, Faculty of Medicine, Cairo University, Medical Doctorate degree, Faculty of Medicine, Cairo University
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/roaic.roaic_29_18

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  Abstract 

Introduction The early diagnosis of sepsis plays a central role in patient management. Many mediators have been proposed to be the cause of sepsis. In the present study, we investigate the role of plasma proadrenomedullin (proADM) levels in the diagnosis of sepsis, and to estimate its value as a prognostic marker of mortality. Also, the prognostic value of proADM was compared with those of C-reactive protein, serum lactate, Sequential Organ Failure Assessment, and Acute Physiology and Chronic Health Evaluation II scores.
Patients and methods This is a prospective cohort study done between March 2015 and January 2016 on 10 healthy individuals and 30 patients admitted with a new diagnosis of sepsis or developed septic shock during their ICU stay in Cairo University Hospitals. All included patients were followed until hospital discharge or death. Our patients were divided into two groups (survivors and nonsurvivors).
Results In the analyzed cohort, a total of 30 septic patients were enrolled. The mean age was 57.1±15.9 years; the overall nonsurvivors were 19 (63.3%) patients. ProADM showed the highest area under the curve (0.89) as compared with the rest of the biomarkers (P<0.0001). ProADM levels were directly proportional to Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment score (r=0.547; P=0.002 and r=0.549; P=0.002, respectively). ProADM levels were negatively correlated with mean arterial pressure on admission (r=−0.472; P=0.009) with also a strong association with vasopressor therapy (P<0.0001). ProADM levels at days 3 and 4 in patients required mechanical ventilation (MV) were significantly higher than patients without MV (141.1±32.4 and 154.4±33.5 pmol/l compared with 100.8±18.3 and 94±16.6 pmol/l, respectively) (P<0.0001).
Conclusion In patients admitted with sepsis or septic shock plasma proADM is strongly associated with the severity of disease, vasopressor requirement, and short-term mortality. Our prediction model for mortality, based on the best 4 predictors, had high sensitivity (94.7%) for nonsurvivors and high specificity (90.9%) for survivors. The best 4 predictors were proADM levels on day 4, C-reactive protein levels on day 4, MV duration, and type of sepsis (patients with severe sepsis or septic shock).

Keywords: Acute Physiology and Chronic Health Evaluation, mechanical ventilation, proadrenomedullin, sepsis-related organ failure assessment, septic shock


How to cite this article:
Wadie A, Gaber S, Rizk A, Safaan Z. Midregional proadrenomedullin in correlation with Sequential Organ Failure Assessment score and Acute Physiology and Chronic Health Evaluation II score in sepsis. Res Opin Anesth Intensive Care 2019;6:461-9

How to cite this URL:
Wadie A, Gaber S, Rizk A, Safaan Z. Midregional proadrenomedullin in correlation with Sequential Organ Failure Assessment score and Acute Physiology and Chronic Health Evaluation II score in sepsis. Res Opin Anesth Intensive Care [serial online] 2019 [cited 2020 Apr 6];6:461-9. Available from: http://www.roaic.eg.net/text.asp?2019/6/4/461/275137


  Introduction Top


Sepsis is a systemic illness that is diagnosed when there is a systemic inflammatory response syndrome (SIRS) and microbial invasion of normally sterile parts of the body. It is defined as severe when associated with hypoperfusion or dysfunction of at least one organ system and progress to septic shock when severe sepsis is accompanied by hypotension or need for vasopressors. SIRS may be triggered by both infectious and noninfectious causes [1].

The inflammatory response, as well as clinical signs and symptoms, can be highly variable in both sepsis and SIRS [2]. This often creates difficulties in the differentiation of sepsis from noninfectious SIRS [3].

Early diagnosis and stratification of sepsis severity plays a central role in patient management by increasing the possibility of starting timely and specific treatment. If antimicrobial treatment is delayed, sepsis dysfunction can lead to global tissue hypoxia, direct tissue damage, and ultimately to multiple organ failure [4].

During sepsis, there is a wide array of many mediators released into the circulation. The most used biomarkers in clinical settings are the acute-phase proteins C-reactive protein (CRP) and procalcitonin (PCT) [5].

Other prohormones such as midregional (MR) proatrial natriuretic peptide and MR proadrenomedullin (proADM) have been proposed as useful biomarkers to predict the severity and outcome in sepsis [6].

Increased MR-proADM is associated with sepsis severity and plays a role in host defense against systemic bacterial infections. Its expression is enhanced after polymicrobial insult and its mucosal levels reach an appropriate concentration to be effective as an antimicrobial peptide [7].

So far, the potential utility of MR-proADM to predict the outcome of sepsis is controversially discussed in a number of trials. Single MR-proADM assessment on admission to the ICU may be useful to predict in-hospital mortality, although the statistic performance is not outstanding [8].


  Patients and methods Top


This current study was conducted on 30 adult patients (16 men and 14 women with their ages ranging from 19 to 93 years with a mean±SD of 57.1±15.9 years) with a proven diagnosis of sepsis or developed septic shock during their ICU stay in Cairo University Hospital. All doctors whose names are on the paper agree to publish the article.

Exclusion criteria for all participants selected for the study included: patients below 18 years old and patients who are suffering from terminal stage of disease (malignant cancer of any type, acquired immunodeficiency syndrome, and end-stage liver or renal disease). All patients were followed until hospital discharge or death.

All included patients were subjected to resuscitation for sepsis according to the approved guidelines, full clinical evaluation, and routine microbiological and laboratory investigations. The patients were followed up daily to assess their clinical course, length of ICU stay, duration of mechanical ventilation (MV), need for vasopressors, and the final outcome.
  1. Parameters include heart rate, mean arterial pressure (MAP), respiratory rate and temperature, and Glasgow coma scale.
  2. Routine laboratory tests (withdrawn on days 0, 3, and 4) include: complete blood count, coagulation profile, arterial blood gases, liver function tests, and kidney function tests.
  3. Specific laboratory tests for our study include: proADM, CRP, and lactate. CRP and proADM levels were withdrawn on days 0, 3, and 4. Serum lactate was measured on day 3. These biomarkers were assessed as prognostic markers for sepsis and their ability to predict mortality in sepsis.
  4. Acute Physiology and Chronic Health Evaluation (APACHE) II score was calculated on admission and Sequential Organ Failure Assessment (SOFA) score was calculated on admission and on day 3.


Statistical analysis

  1. The data was coded and entered using the Statistical Package for the Social Sciences, version 15 (Interactive, or batched, statistical analysis. Long produced by SPSS Inc., IBM in 2009, versions (2015), IBM SPSS 15 Statistics).
  2. All quantitative data were expressed as mean, SD, minimal, and maximum values.
  3. Qualitative data were expressed as frequencies.
  4. Statistical differences between groups were tested using χ2 test (Fisher’s exact test).
  5. Independent t test was used to compare two groups for all continuous normally distributed data.
  6. A P value of less than or equal to 0.05 was considered statistically significant.
  7. Spearman’s correlation coefficient test (r) was used to test a positive or negative relationship between two variables.
  8. Correlations were done to test for linear relations between variables.
  9. Sensitivity, specificity, positive, and negative predictive values together with odds ratio.
  10. Discrimination between hospital survivors and nonsurvivors was evaluated by the receiver operating characteristic (ROC) curve analysis.



  Results Top


Patient characteristics

  1. The study involved 30 adult patients with a proven diagnosis of sepsis or septic shock and admitted to the ICU. The age of the studied group ranged from 19 to 93 years with a mean±SD of 57.1±15.9 years. Sixteen (53.3%) patients were men and 14 (46.7%) patients were women. Nearly half of the patients (12 patients, 40%) patients were smokers.
  2. The control group was 10 adult volunteers (eight men and two women). The age of the control group ranged from 19 to 45 years with a mean±SD of 37.2±11.1 years.
  3. The most frequent comorbidity was hypertension (66.7%) followed by diabetes mellitus (53.3%) and ischemic heart disease (36.7%).
  4. The CRP levels were elevated on day 0 with a mean±SD of 180.3±102.4 mg/l and were shown to decline on day 3 (170.9±67.4 mg/l) and day 4 (144.5±79.3 mg/l). ProADM levels were elevated on day 0 with a mean±SD of 113.4±22.2 pmol/l and were shown to increase on day 3 (130.4±34.2 pmol/l) and day 4 (141±39.7 pmol/l).
  5. The control group (n=10) had proADM levels mean±SD of 8.7±4.3 pmol/l as compared with 113.4±22.2 pmol/l in the patients group (n=30) with P=0.0001.
  6. APACHE II score was elevated on day 0 (with a mean±SD of 21±7.2).
  7. SOFA score was elevated on days 0 and 3 (with a mean±SD of 8.1±3.8 and 8.9±5.3, respectively).
  8. According to the type of sepsis, we have 30 patients (13 patients with sepsis, 17 patients with severe sepsis and septic shock) on admission. In our study, chest infection was the most common cause of sepsis (80%, 24 cases), followed by urinary tract source (36.7%, 11 cases).
  9. Sputum culture was the most common site of positive culture (73.3%, 22 patients) followed by blood culture (60%, 18 cases). Also, Klebsiella pneumoniae and methicillin-resistant Staphylococcus aureus together followed by Acinetobacter baumannii were the most isolated organisms in the microbiological cultures in our study.
  10. Out of 30 patients (our study population), 22 (73.3%) patients required MV. The median period of MV duration in 22 patients was 10 days, ranging from 3 to 35 days, with a mean±SD of 9±8.8 days. Also, out of the 30 patients 20 (66.6%) patients required inotropic support as shown in [Figure 1].
    Figure 1 Frequency of mechanical ventilation (MV) and inotropic support in the studied group.

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  11. Regarding ICU stay, our results showed mean±SD of 16.4±9.7 days with a range of 5–47 days. Nineteen out of 30 (63.3%) patients did not survive, while 11 (36.7%) patients survived and were discharged. However, two of the latter group were discharged on demand and not for cure.


Comparison between survivors and nonsurvivors

  1. Regarding the age of the patients, there was no significant difference between nonsurvivors and survivors (58±16.2 vs. 55.4±15.9 years, respectively) (nonsignificant P value).
  2. Also, there was no significant correlation between comorbidities and outcome of the studied group as shown in [Table 1].
    Table 1 Relationship between outcome and associated comorbidities

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  3. Compared with the survivors, hematocrit value was significantly lower in the nonsurvivors (P=0.027). In contrast, the prothrombin time was significantly higher in the nonsurvivors (P=0.05).
  4. The nonsurvivors had significantly higher proADM levels on days 3 and 4 compared with the survivors (143.5 and 158.9 compared with 107.6 and 105, respectively) (P=0.001 and P<0.0001, respectively), whereas the CRP levels at day 4 were significantly higher in the nonsurvivors than the survivors (170.2±70.8 mg/l compared with 93.3±73.2 mg/l, respectively] (P=0.014). Also, compared with the survivor group, 13 out of 19 patients of the nonsurvivors had significantly higher lactate levels more than 2 mmol/l on day 3 with a significant P value of less than 0.0001.
  5. As shown in [Table 2] nonsurvivors have a significantly higher number of affected organs compared with the survivors as denoted by the:
    • Higher APACHE II score at day 0 (24.2±6.7 vs. 18±6.5) (P=0.020).
    • Higher SOFA score at day 0 (9.3±4.1 vs. 6.1±2.3) (P=0.027).
    • Higher SOFA score at day 3 (11.8±4.4 vs. 3.9±1.8) (P<0.0001).
    Table 2 Prognostic biomarkers and scoring systems in survivors and nonsurvivors

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  6. The 19 (100%) patients of the nonsurvivors needed MV compared with only three (27.2%) out of 11 patients of the survivor group (P<0.0001). Also, the duration of MV was compared between nonsurvivors and survivors with a mean±SD of 12.4±8.3 days compared with 3.2±6.5 days, respectively (P=0.004).
  7. Seventeen out of 19 (89.4%) patients of the nonsurvivor group received inotropic support compared with only three (27.3%) out of 11 patients from the survivors (P=0.001).


Relationship between comorbidities and measured variables to proadrenomedullin

  1. There was no correlation between proADM levels on admission and age of the patients (r=−0.133; P=0.482). Also, there was no correlation between proADM levels, sex, smoking, and associated comorbidities.
  2. ProADM levels were directly proportional to APACHE II and SOFA score (r=0.547; P=0.002 and r=0.549; P=0.002, respectively). ProADM levels were negatively correlated with MAP on admission (r=−0.472; P=0.009) with also a strong association with vasopressor therapy (P<0.0001). ProADM levels at days 3 and 4 in patients required MV were significantly higher than patients without MV (141.1±32.4 and 154.4±33.5 pmol/l compared with 100.8±18.3 and 94±16.6 pmol/l, respectively) (P<0.0001).


Predictors of hospital outcome

Our prediction model based on the best 4 predictors for the outcome and the weight of each predictor is presented in [Table 3],[Table 4],[Table 5].
Table 3 Standardized canonical discriminant function coefficients

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Table 4 Functions at group centroids

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Table 5 Classification statistics

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Out of the different variables, our prediction model for mortality, based on the best 4 predictors, had high sensitivity of 94.7% for nonsurvivors and high specificity of 90.9% for survivors. The best 4 predictors were proADM levels on day 4, CRP levels on day 4, MV duration, and type of sepsis (patients with severe sepsis or septic shock).

Receiver operating characteristic curve

  1. The ROC curve compares sensitivity versus specificity across a range of values and is useful in assigning the best cutoffs for clinical use. The overall accuracy is expressed as area under the curve (AUC).


The ROC curve was calculated for the use of proADM and CRP levels on day 4 in addition to MV duration in patients with severe sepsis and septic shock as predictors of ICU mortality as shown in [Table 6] and [Figure 2],[Figure 3],[Figure 4],[Figure 5].
Table 6 Receiver operating characteristic curve for the best 4 predictors of ICU mortality in the studied group

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Figure 2 Assessment effect of proADM, CRP, MV duration, and type of sepsis on outcome through ROC curve. CRP, C-reactive protein; MV, mechanical ventilation; ProADM, proadrenomedullin; ROC, receiver operating characteristic.

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Figure 3 Assessment effect of proADM, CRP, MV duration, and type of sepsis on outcome through ROC curve. CRP, C-reactive protein; MV, mechanical ventilation; ProADM, proadrenomedullin; ROC, receiver operating characteristic.

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Figure 4 Assessment effect of proADM, CRP, MV duration, and type of sepsis on outcome through ROC curve. CRP, C-reactive protein; MV, mechanical ventilation; ProADM, proadrenomedullin; ROC, receiver operating characteristic.

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Figure 5 Assessment effect of proADM, CRP, MV duration, and type of sepsis on outcome through the ROC curve. CRP, C-reactive protein; MV, mechanical ventilation; ProADM, proadrenomedullin; ROC, receiver operating characteristic.

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  Discussion Top


Sepsis, a syndrome of physiologic, pathologic, and biochemical abnormalities induced by infection, is a major public health concern, accounting for more than $20 billion (5.2%) of total US hospital costs in 2011 [9]. Despite efforts to improve early recognition and clinical treatment, sepsis often evolves to septic shock and multiorgan failure, which are the most frequent causes of death in septic patients [10].

Over the last decade, biomarkers such as CRP and PCT are widely used in clinical practice. However, they lack sensitivity and specificity [11]. Several studies suggest that the prognostic accuracy of MR-proADM is probably better than other biomarkers such as CRP and PCT. Also, it is possibly as good as validated severity scores in detecting critically ill patients with sepsis [8].

ADM is a peptide isolated from human pheochromocytoma cells and has later been detected in other tissues, including heart, lungs, kidneys, and adrenal medulla [12]. It is a potent vasodilator, causes hypotension and has inotropic and natriuretic effects stimulated by cardiac pressure and volume overload [13]. ADM has also bactericidal activity, which is further enhanced by modulation of complement activity and regulation. As a consequence of these activities, the serum level of ADM increases in sepsis. Unfortunately, the accurate measurement of ADM is a challenging procedure due to its rapid blood clearance, which makes difficulty in its detection because of its half-life time of 22 min [14]. In addition, the circulating ADM is masked by a binding protein (complement factor H), making it inaccessible for immune metric analysis.

Recently, the more stable MR fragment of proADM, comprising amino acids 45–92, which reflects the levels of the rapidly degraded active peptide ADM was identified in the plasma of patients with septic shock [15].

Our study was conducted prospectively to evaluate the prognostic value of proADM in sepsis in correlation to physiological ICU scoring systems and other sepsis biomarkers.

All patients had confirmed diagnosis of sepsis syndrome based on the 1991 ACCP/SCCM Sepsis Directory [16], and the diagnostic criteria advanced by the 2001 International Sepsis Definition Conference [17].

We intended in this study to assess the severity of the disease by using APACHE II score on admission and SOFA score on admission and on day 3. Also, plasma levels of MR-proADM on days 0, 3, and 4 are measured together with the serum level of CRP on the same days. Serum lactate on day 3 is also measured. These biomarkers are assessed as prognostic markers for sepsis and their ability to predict mortality in sepsis.

Part 1: patient characteristics

All patients had at least one comorbidity in addition to sepsis. The most frequent comorbidity was hypertension (66.7%) followed by diabetes mellitus (53.3%). In concordance with our study, Marino et al. [18] conducted a similar prospective cohort study on 101 patients. Numerous comorbidities such as hypertension and diabetes were present (47 and 35%, respectively) in patients who had sepsis or septic shock on admission.

In our study, the nonsurvivors had significantly higher proADM levels on days 3 and 4 compared with the survivors (143.5 and 158.9 compared with 107.6 and 105, respectively) (P=0.001 and P<0.0001, respectively), whereas CRP levels at day 4 were significantly higher in the nonsurvivors than the survivors (170.2±70.8 mg/l compared with 93.3±73.2 mg/l, respectively) (P=0.014). Also, compared with the survivor group, 13 out of 19 patients of the nonsurvivors had significantly higher lactate levels more than 2 mmol/l on day 3 with a significant P value of less than 0.0001.

Using the area under the ROC curve for proADM levels on day 4 to predict ICU mortality was 0.889 (P<0.0001). The cutoff value for proADM on day 4 to predict ICU mortality was a level more than or equal to 121 pmol/l or a level more than or equal to 53.8 ng/ml. This cutoff value gave a sensitivity of 83.3% and a specificity of 77.8% for ICU mortality.

In concordance with our study, Suberviola et al. [19] conducted a similar study on 49 septic patients. Their study showed that the ROC curve for proADM yielded an AUC of 0.72, better than the AUC for PCT and CRP (0.40 and 0.44, respectively). The cutoff value for proADM to predict ICU mortality was a level more than or equal to 4.86 nmol/l. This cutoff value gave a sensitivity of 53% and a specificity of 84% for ICU mortality.

Also, Helmy and Beshey [20] studied the prognostic role of ADM in sepsis. They demonstrated that serum ADM at day 5 with a cutoff value of 41 pg/ml gave a sensitivity of 100% and a specificity of 84.4% as an early predictor of mortality in septic patients. ADM AUC was significantly higher than SOFA (P=0.0005). When testing the validity of ADM, SOFA score, CRP, PCT, and lactate to predict mortality after 5 days of admission all tested parameters could predict mortality, but the difference between AUCs of these variables was not statistically significant.

In another study, Suberviola et al. [8] conducted a prospective cohort study on 137 septic patients. Those patients were studied using proADM and soluble urokinase plasminogen activator receptor, comparing them with CRP and PCT, and evaluating whether their addition to severity scores (APACHE II and SOFA) could improve their prognostic accuracy. Their study showed that a single determination of soluble urokinase plasminogen activator receptor and proADM were better tools predicting patients’ mortality with severe sepsis and septic shock than CRP and PCT. However, the prognostic accuracy was significantly better for APACHE II or SOFA scores (P=0.001) than for any of the analyzed biomarkers. The addition of all four biomarkers to these severity scores only slightly improved their prognostic accuracy.

In our study, using the area under the ROC curve for CRP levels on day 4 to predict ICU mortality was 0.806 (P=0.014). The cutoff value for CRP on day 4 to predict ICU mortality was a level more than or equal to 109 mg/l. This cutoff value gave a sensitivity of 72.2% and a specificity of 66.7% for ICU mortality.

Gebhardt et al. [21] and Silvestre et al. [22] in their study concluded that CRP was not an adequate test for the prognosis of sepsis patients. On the other hand, Devran et al. [23] reported that elevated CRP of more than 100 mg/l on the 3rd day of ICU admission may be used as a good predictor of ICU mortality. So, measurement of CRP levels a few days after admission may be more helpful for physicians to make judgments on treatment response and sepsis outcome in the ICU. Also, Gülcher et al. [24] conducted a retrospective cohort study on 1239 ICU patients with elevated CRP (≥75 mg/l) at ICU discharge. They found that elevated CRP (≥75 mg/l) at ICU discharge was associated with adverse outcome (ICU readmission and/or death) in patients with a prolonged ICU stay (>48 h). However, CRP at discharge represents only a risk factor and may not be used for individual clinical decision making.

In our study, in the nonsurvivors, the APACHE II score was considerably predictive of patients’ mortality (24.2±6.7 vs. 18±6.5) on admission (P=0.020). Also, SOFA score at days 0 and 3 were correlated well with the short-term mortality (9.3±4.1 vs. 6.1±2.3) at day 0 and (11.8±4.4 vs. 3.9±1.8) at day 3 (P=0.027 and P<0.0001, respectively).Jones et al. [25] studied the role of SOFA score at days 0 and 3 for predicting patients’ mortality in 248 severe sepsis patients. They concluded that the SOFA score was a potentially valuable prognostic parameter in predicting in-hospital patient’s mortality.

Another study done by Bale et al. [26] evaluated the role of SOFA score as a prognostic marker in sepsis patients. The SOFA score was calculated twice (on admission and 48 h later) and was found to be a good predictor of mortality.

In our study, chest infection was the most common cause of sepsis (80%, 24 patients) followed by urinary tract infection (36.7%, 11 patients). Martin [27], Esper et al. [28], and Danai et al. [29] reported that respiratory infections are invariably the most common cause of sepsis, severe sepsis, and septic shock.

Part 2: relationship between comorbidities and measured variables to proadrenomedullin

ProADM levels were directly proportional to APACHE II and SOFA scores (r=0.547; P=0.002 and r=0.549; P=0.002, respectively). ProADM levels were negatively correlated with MAP on admission (r=−0.472; P=0.009) with also a strong association with vasopressor therapy (P<0.0001). ProADM levels at days 3 and 4 in patients who required MV were significantly higher than patients without MV (141.1±32.4 and 154.4±33.5 pmol/l compared with 100.8±18.3 and 94±16.6 pmol/l, respectively) (P<0.0001).

Marino et al. [18] supported this hypothesis as they found that admission ADM levels were negatively correlated with MAP (r=−0.39; P<0.0001). Also, patients who required vasopressors on admission had significantly (P<0.0001) higher ADM concentrations [129 (83–264) pg/ml] than those who did not require vasopressor support [48 (32–75) pg/ml]. Also, Cicuendez et al. [30] conducted a similar prospective cohort study. Their study showed that proADM was the biomarker showing better prognostic accuracy in any time points analyzed by area under ROC curve (P) for short-term mortality, better than SOFA score at first and seventh days of admission. Also, the correlation test showed that proADM presents the strongest association with SOFA in all time points analyzed.

Part 3: limitations of the study

  1. We tried to match the recruitment time to the time of the onset of sepsis. However, this is nearly an impossible task mainly due to delays in the presentation to the ICU, lead-time bias, ICU bed availability, referral patterns, the presentation of symptoms, and/or the reporting of the microbiology test results.
  2. We consider that our results are prospective but need to be validated in more patient numbers. The small sample size reduces the power of some analyses (comparisons).



  Conclusion Top


  1. MR-proADM can predict short-term outcome in septic patients, whatever the etiology and the comorbidity that coexist with sepsis.
  2. In comparison to other sepsis biomarkers, proADM is an important prognostic biomarker of survival when measured on the fourth day of admission of septic patients to the ICU.
  3. ProADM level is associated with the severity of disease, need for MV, requirement for vasopressor therapy, and 28-day mortality rate (independent from and additive to SOFA and APACHE II scores).
  4. Our prediction model for mortality, based on the best 4 predictors, had high sensitivity (94.7%) for nonsurvivors and high specificity (90.9%) for survivors. The best 4 predictors were: proADM levels on day 4, CRP levels on day 4, MV duration, and type of sepsis (patients with severe sepsis or septic shock).


Financial support and sponsorship

Nil.

Conflicts of interest

There is no conflict of interest disclosure.

 
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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]



 

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