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ORIGINAL ARTICLE
Year : 2015  |  Volume : 28  |  Issue : 1  |  Page : 254-258

Biomarker predictors of survival in patients with ventilator-associated pneumonia


1 Department of Anaesthesia and Critical Care, Menoufia University, Menoufia Governorate, Egypt
2 Department of Clinical Pathology, Faculty of Medicine, Menoufia University, Menoufia Governorate, Egypt

Date of Submission23-Jul-2014
Date of Acceptance28-Nov-2014
Date of Web Publication29-Apr-2015

Correspondence Address:
Asmaa E Salama
Department of Anaesthesia and Critical Care, Faculty of Medicine, Menoufia University, Kamshish, Tala, Menoufia Governorate
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1110-2098.156004

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  Abstract 

Objective
The aim of this study was to determine the role of procalcitonin (PCT) and C-reactive protein (CRP) as predictors of survival in ventilator-associated pneumonia (VAP) and determine the most common micro-organisms involved in VAP in the Menofiya University Hospital ICU.
Background
The prediction of survival in VAP remains a major challenge. We evaluated the performance of clinical score [Sequential Organ Failure Assessment (SOFA)], PCT, and CRP threshold values and kinetics as predictors of VAP survival.
Materials and methods
A total of 50 patients with VAP were studied at the Menofiya University Hospital ICU. Acute Physiology And Chronic Health Evaluation II (APACHE II) score was assessed during first 24 h of admission; clinical pulmonary infection score was followed up in mechanically ventilated patients for diagnosis of VAP. SOFA score, serum CRP, and serum PCT were assessed on day 1, day 4, and day 7 of VAP diagnosis and were correlated with the 28-day survival/mortality. Patients who survived were considered survivors (group A), and patients who died before 28 days were considered nonsurvivors (group B).
Results
The 28-day mortality rate was 40%. The APACHE II score was significantly lower in survivors than nonsurvivors (P < 0.001). Serum PCT was significantly lower on days 4 and 7 in the survivor group (504.87 ± 267.28, 164.30 ± 98.56 pg/l, respectively) in comparison with the nonsurvivor group (930.30 ± 177.54, 897.35 ± 200.99 pg/l) with a P-value of less than 0.001. The SOFA score was significantly lower on days 1, 4, and 7 in the survivor group (5.73 ± 1.80, 4.57 ± 1.22, 3.63 ± 1.16) compared with the nonsurvivor group (7.95 ± 1.39, 8.60 ± 1.53, 9.85 ± 1.90, respectively), with a P-value of less than 0.001. Serum CRP was comparable on days 1, 4, and 7 days in the survivor (108.0 ± 55.93, 103.60 ± 43.69, 85.6 ± 58.68 mg/dl) and the nonsurvivor group (108.0 ± 46.39, 100.80 ± 51.41, 100.80 ± 58.06 mg/dl), respectively. Age was significantly higher in the nonsurvivors than the survivors (61.30 ± 15.60, 46.93 ± 18.25, respectively) (P = 0.002).
Conclusion
The SOFA score can predict survival in VAP. The serum level of PCT can be used for diagnosis of VAP. PCT kinetics can be used to assess prognosis in VAP patients. CRP is useful as a diagnostic but not as a prognostic biomarker in VAP.

Keywords: Acute Physiology And Chronic Health Evaluation II score, C-reactive protein, procalcitonin, Sequential Organ Failure Assessment score, ventilator-associated pneumonia


How to cite this article:
Afifi MH, Elhendy AA, Eltaweel MM, Soliman NM, Elfeky EM, Salama AE. Biomarker predictors of survival in patients with ventilator-associated pneumonia. Menoufia Med J 2015;28:254-8

How to cite this URL:
Afifi MH, Elhendy AA, Eltaweel MM, Soliman NM, Elfeky EM, Salama AE. Biomarker predictors of survival in patients with ventilator-associated pneumonia. Menoufia Med J [serial online] 2015 [cited 2019 Jun 17];28:254-8. Available from: http://www.mmj.eg.net/text.asp?2015/28/1/254/156004


  Introduction Top


Ventilator-associated pneumonia (VAP) is a subtype of hospital-acquired pneumonia that occurs 48 h after intubation and mechanical ventilation (MV) [1].

VAP is a common problem in the ICU and it occurs in up to 25% of patients who receive MV. VAP can occur at any time during MV, but occurs more often within the first few days after endotracheal intubation [1],[2].

VAP prolongs the length of ICU stay and is associated with 20-30% increase in the risk of death. The mortality rate of VAP ranges from 20 to 50%, and can reach up to 76% in specific setting or when the lung infection is caused by multidrug resistant pathogens [1],[3].

The clinical assessment of VAP is based on the presence of fever (core temperature of >38.3°C), leukocytosis (leukocytic count >11 000/mm 3 ), or leukopenia (leukocytic count <4000/mm 3 ), purulent tracheal secretion, and the presence of a new or persistent lung infiltrate [4],[5].

The evaluation of the response of VAP to treatment with antibiotics and the prognosis of the patients cannot rely on a single parameter; however, many scores and markers have been proposed to be the most promising candidate, such as Acute Physiology And Chronic Health Evaluation (APACHE II) score, Sequential Organ Failure Assessment (SOFA) score, clinical pulmonary infection score (CPIS), leukocytic count, C-reactive protein (CRP), and procalcitonin (PCT) [6],[7].

CRP is an acute-phase protein produced by the liver. PCT is the prehormone of calcitonin that is normally secreted by the parafollicular C-cells of the thyroid gland in response to hypercalcemia. Under normal conditions, negligible levels of PCT are detected. In systemic infection, sepsis, and sepsis-like conditions, the serum level of PCT is markedly elevated, although its origin is a matter of discussion. The level of serum PCT correlates positively with the severity of illness and mortality [8],[9].

The predictive performance of PCT, CRP, and SOFA score is dependent on their kinetics between onset of VAP (day 1), day 4, and day 7 of VAP treatment [10].


  Aim of the work Top


The aim of this study was to determine the role of PCT and CRP as predictors of survival in VAP and determine the most common micro-organisms involved in VAP in the Menofiya University Hospital ICU.


  Materials and methods Top


The study was conducted at the Menofiya University Hospital ICU from January 2013 to December 2013. A total of 50 patients above 18 years old, mechanically ventilated, and developed VAP diagnosed by the CPIS were studied. Patient consent and approval from the ethical committee were obtained. APACHE II score was assessed on the first 24 h of ICU admission. Total leukocytic count, chest radiography, culture, and sensitivity of tracheal aspirate were carried out for VAP diagnosis. SOFA score, serum PCT, and serum CRP were evaluated on day 1, day 4, and day 7 of VAP diagnosis. Patients were followed up for 28 days. Patients survived were considered survivors (group A), and patients who died before 28 days were considered nonsurvivors (group B).

Statistical analysis

Values were expressed as mean ± SD. Comparisons between groups were made using t-test. Categorical variables were compared with the c2 -test. P-value less than 0.05 was considered significant.


  Results Top


The mortality rate from VAP was 40% in our ICU. Baseline characteristics of VAP patients stratified as survivors or nonsurvivors, including age, cause of ICU admission, duration of MV before onset of VAP, chest radiographic finding, APACHE II score, and CPIS, are given in [Table 1]. Age was significantly higher in nonsurvivors than in survivors; duration of MV before onset of VAP was significantly shorter in survivors than in nonsurvivors. APACHE II score was significantly lower in survivors than in nonsurvivors (P < 0.001).
Table 1: Characteristics of 50 patients who developed ventilator-associated pneumonia

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SOFA score was significantly lower on days 1, 4, and 7 in the survivor group (5.73 ± 1.80, 4.57 ± 1.22, 3.63 ± 1.16, respectively) versus the nonsurvivor group (7.95 ± 1.39, 8.60 ± 1.53, 9.85 ± 1.90), with a P-value of less than 0.001. SOFA score was significantly lower in survivors on days 4 and 7 in comparison with day 1, whereas in nonsurvivors it was significantly higher on days 4 and 7 when compared with day 1 [Figure 1].

Serum CRP was comparable on days 1, 4, and 7 in survivors (108.0 ± 55.93, 103.60 ± 43.69, 85.6 ± 58.68 mg/dl, respectively) and in nonsurvivors (108.0 ± 46.39, 100.80 ± 51.41, 100.80 ± 58.06 mg/dl, respectively). In each group, CRP was comparable on day 4 and day 7 in comparison with day 1 [Figure 2].
Figure 1: Sequential Organ Failure Assessment (SOFA) score between survivors and nonsurvivors.

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Figure 2: C-reactive protein (CRP) between survivors and nonsurvivors.

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PCT was significantly lower on day 4 and day 7 in the survivor group (504.87 ± 267.28, 164.30 ± 98.56 pg/l, respectively) in comparison with the nonsurvivor group (930.30 ± 177.54, 897.35 ± 200.99 pg/l), with a P-value of less than 0.100. In each group, PCT was significantly lower in survivors on day 4 and day 7 in comparison with day 1, whereas in nonsurvivors the results of day 4 and day 7 were comparable when compared with day 1 [Figure 3].
Figure 3: Procalcitonin (PCT) between survivors and nonsurvivors.

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Klebsiella pneumoniae infection was significantly higher in the survivor group (53.3%) in comparison with the nonsurvivor group (25%). Methicillin-resistant Staphylococcus aureus (MRSA) was significantly higher in the nonsurvivor group (15%) in comparison with the survivor group (0%). The other types of micro-organisms were comparable in both groups [Table 2].
Table 2: Microbiological examination of endotracheal aspirate

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  Discussion Top


In our study, the 28-day mortality was 40%. Age was significantly higher in nonsurvivors than in survivors; APACHE II score was significantly higher in nonsurvivors than in survivors. Other demographic data and CIPS were comparable.

Gram-negative organisms were predominant as a causative organism of VAP. K. pneumoniae was predominant in survivors, whereas MRSA was predominant in nonsurvivors.

SOFA score was significantly higher in nonsurvivors than in survivors at the day of VAP diagnosis; SOFA score was significantly lower in survivors at day 7, whereas it was significantly higher on day 7 in nonsurvivors when compared with day 1.

PCT was significantly higher in nonsurvivors than in survivors on day 1 of VAP diagnosis. Serum PCT level was significantly lower in survivors on day 4 and day 7, whereas in nonsurvivors it was significantly higher on day 4 and day 7. CRP results were comparable between the two groups.

Age was significantly higher in nonsurvivors than in survivors. Other demographic data and CIPS were comparable.

Kollef [11] quoted the crude mortality rate for VAP as 30%. Craven [12] listed the mortality to be between 27 and 43%, with surgical ICU being higher than medical ICU.

The age of studied groups was significantly higher (P < 0.05) in nonsurvivors than in survivors. Blot et al. [13] and Rakshit et al. [14] concluded that mortality from VAP was higher in older age patients.

Boeck et al. [15] studied the biomarkers of VAP between the survivor and nonsurvivor groups and found that age was significantly higher in the nonsurvivor group (55 in survivor vs. 67 in nonsurvivor).

In contrast to our study, Seligman et al. [16] studied a copeptin as a biomarker for VAP and found that age was insignificant in differentiating survivors and nonsurvivors; however, the age was older in the nonsurvivor group (64 years) than 58 years in the survivor group.

With regard to APACHE II score at the time of admission, it was significantly lower in survivors than in nonsurvivors.

Seligman et al. [16] and Huang et al. [17] found that APACHE II score was significantly higher in the nonsurvivor group.

Hillas et al. [18] studied the PCT and CRP in the VAP between survivors and nonsurvivors and found that APACHE II was slightly higher in the nonsurvivor group but not to a significant degree.

With regard to the duration of MV before onset of VAP, it was significantly lower in survivors than in nonsurvivors.

De Silva et al. [19] studied the epidemiology and microbiological analysis of VAP and concluded that risk factors for death included age, MV duration, and surgery. Rakshit et al. [14] concluded that the duration of MV in the survivors was significantly lower.

In terms of CPIS and cause of ICU admission, the two groups were comparable. Seligman et al. [16], found that CIPS and the cause of ICU admission were not significantly pronounced in both groups.

Su et al. [20] studied the diagnosis of VAP in critically ill patients and concluded that the CIPS was significantly lower in the survivor group.

The SOFA score in our study was significantly higher in the nonsurvivors at day 1 compared with the survivors. The SOFA score was significantly lower in survivors, whereas it was significantly higher in nonsurvivors starting from day 4. Boeck et al. [15] and Hillas et al. [18] concluded that the only predictor of septic shock development was the SOFA score. Although the SOFA score was significantly higher in VAP patients with septic shock on all days (day 1, day 4, day 7), only the SOFA score on day 1 was predictive of septic shock development. Ruiz-Alvarez et al. [21], studied PCT level in sepsis (103 patients) and concluded that SOFA score, age, and sex had a prediction in mortality rate.

Serum levels of CRP on day 1, day 4, and day 7 during the course of VAP did not discriminate survivors from nonsurvivors. CRP was not valuable in assessing prognosis in VAP patients. Hillas et al. [18], Su et al. [20], and Ruiz-Alvarez et al. [21], concluded that CRP did not change in either group.

Seligman et al. [16] suggested that decreasing CRP values between the onset and fourth day of VAP could predict survival. This difference may owing to a large number of patients (75 patients), measurement of the CRP every day, and calculation of the change in the CRP level. The duration of the study was 4 days only.

Póvoa et al. [22], concluded that CRP was a good tool in resolution from VAP not as a predictor of death.

At the time of VAP diagnosis (day 1), our study showed that there was no difference in the mean PCT plasma concentrations between survivors and nonsurvivors. However, after that, mean PCT plasma concentration in survivors declined toward the normal range compared with a steady increase, or slight nonsignificant decrease in nonsurvivors, with a significant difference (P < 0.05) between survivors and nonsurvivors starting from day 4 and day 7. Lower PCT level was predictive of survival in VAP patients, whereas higher PCT was associated with unfavorable outcome.

Bloos et al. [23] concluded that PCT is associated with the severity of illness in patients with severe pneumonia and appeared to be a prognostic marker of morbidity and mortality comparable to the APACHE II score.

Boeck et al. [15] concluded that the combination of midregional proatrial natriuretic peptide and PCT improves the diagnostic performance of simplified acute physiology score II and SOFA score in VAP survival by complementing, rather than replacing, clinical judgments. The combination of prognostic scores and biomarkers represents a new and promising approach for risk stratification in VAP.

Seligman et al. [16] concluded that measurement of PCT and CRP at onset and day 4 of treatment can predict survival in patients with VAP.

Luyt et al. [24] suggested that the serum PCT levels on day 1, day 3, and day 7 during the course of VAP are strong predictors of unfavorable outcome defined as death, recurrent VAP, or extrapulmonary infection.

Hillas et al. [18] found that CRP and PCT kinetics between day 1, day 4, and day 7 were not able to predict survival. They considered that the decrease in the CRP and PCT levels on day 7 compared with day 1 in most survivors lacks clinically useful prognostic significance, because this result is rather expected. Since 7 days after the initiation of antibiotic treatment, VAP has either responded to treatment and progresses toward resolution, or is refractory to it.


  Conclusion Top


The mortality rate of VAP was 40% in our ICU. APACHE II score and SOFA score can predict survival in VAP patients, whereas CIPS did not significantly change in either group. K. pneumoniae was predominant in survivors, whereas MRSA was predominant in nonsurvivors. The serum level of PCT can be used for diagnosis of VAP. PCT kinetics can be used to assess prognosis in VAP patients. CRP is useful as a diagnostic but not as a prognostic biomarker in VAP.


  Acknowledgements Top


Conflicts of interest

None declared.

 
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