https://orcid.org/0000-0002-0109-3208
Abstract
Objective
We aimed to determine the clinical, radiological and laboratory findings that may indicate poor prognosis in severe community acquired pneumonia (CAP) requiring intensified care to reduce the risk of death.
Methods
The medical histories, demographic characteristics and laboratory values of over 65 years old patients admitted to the intensive care unit (ICU) and diagnosed with CAP were recorded.
Results
Total of 86 patients were included in the study. Among those patients 39 were discharged from the ICU with health but 47 were expired. Diastolic blood pressure was significantly lower in expired patients (p = 0.044). In multivariate analysis, older age (>78 years) (p = 0.004), at admission elevated blood glucose (>108 mg/dL) levels (p = 0.048), decreased serum albumin (<3.5 g/dL) levels (p = 0.043), elevated serum procalcitonin levels (>0.63 μg/L) (p = 0.034) and in blood gas analysis decreased pH (<7.35) (p = 0.042)and increased lactate (>2mmol/L) (p = 0.001) were the significant risk factors for in-ICU mortality.
Conclusions
At old age, blood glucose and procalcitonin levels increased at the time of admission, serum albumin levels decreased, pH decreased in blood gas analysis and lactate levels increased, and significant mortality determinants in CAP patients over 65 years of age who applied to the intensive care unit.
Introduction
Despite recent advances in antimicrobial treatment, community acquired pneumonia (CAP) is one of the leading infectious cause of intensive care unit (ICU) admissions and adult mortality in developed countries [Citation1,Citation2]. Moreover, this common disease also incurs a significant economic burden [Citation3]. Although there are some scores such as CURB-65 score including confusion, urea, respiratory rate, blood pressure, and age ≥ 65 years score and Pneumonia Severity Index, the data regarding the risk factors for mortality in patients admitted in ICU for CAP is conflicting [Citation4]. In this study we aimed to determine the clinical, radiological and laboratory findings that may indicate poor prognosis in severe community acquired pneumonia requiring intensified care to reduce the risk of death. We believe that, considering these parameters in the follow-up and treatment of patients will decrease the morbidity and mortality rates in CAP.
Materials and methods
In this retrospective study, a total of 86 patients over 65 years old who were admitted to Izmir Esrefpaşa Municipal Hospital Intensive Care Unit with a diagnosis of community-acquired pneumonia between December 2015 and January 2018 were examined. The medical histories and demographic characteristics of the patients were recorded. Vital signs of the patients, the results of complete blood counts, bloodglucose levels, liver and kidney function tests, and arterial blood gas analyses at admission were recorded. Whether there was confusion or not was evaluated with a Glasgow coma scale. The results of chest X-ray and thorax computed tomography recorded. During ICU follow–up, intubation and mechanical ventilator necessity, requirements for tracheostomy, closed underwater drainage and/orcentral venous catheter (CVP) interventions, empirical antibiotic selection, length of hospital stay, comorbid diseases and mortality rates were recorded. Patients younger than 65 years of age, diagnosed with nosocomial pneumonia or healthcare-associated pneumonia, patients admitted to the ICU due to another causes than CAP, patients under any type of immunosuppressive treatments were excluded from the study. Pneumonia was clinically diagnosed in patients who had new pulmonary infiltrates on their chest radiographs and who had at least two of the followingsymptoms or findings: fever (>38 °C) or hypothermia (<36 °C), leukocytosis (>12 × 103/μL) or leukopenia (<4 × 103/μL), presence of purulent tracheal secretions, and a decline in oxygenation.
Statistical analyses
The statistical analysis was performed with the SPSS Statistics software package, version 21.0 (IBM Corporation, Armonk, NY, USA). For group comparisons, normal distribution of the data was assessed with the Shapiro–Wilk test, continuous variables were assessed with Student’s t-tests, and categorical variables were assessed with chi-square tests. Univariate and multivariate logistic regression analyses were performed for age, drinking alcohol, at admission blood glucose, blood urea nitrogen, serum creatinine and serum albumin levels, and in blood gas analysis pH, elevated PaCO2 and oxygen saturation. Values of p < 0.05 were considered statistically significant.
Results
In a total of 86 patients (24 males, 62 females) were included in the study. Among those patients 39 were discharged from the ICU with health but 47 were expired. Comparison of demographic features among discharged and expired patients is summarized in . Expired patients were significantly older (68.15 ± 18.97 vs. 77.61 ± 18.68, p = 0.002) and drinking alcohol more commonly (7.7% vs. 23.4%, p = 0.001) compared with the discharged patients. Pleural fluid was present in 7 patients; four (3 exudates,1 empyema) were in discharged group and 3 (2 exudates, 1 transudate) were in expired group. Among patients, intubation and mechanical ventilator was required in 7 (17.9%) patients in discharged group, but in 43 (91.5%) patients in expired group (p = 0.001). Tracheostomy was required in one patient in discharged group. Closed underwater drainage was required in one patient in each group. CVP catheter was inserted in 4 patients in expired group. Vital signs of patients at admission to the ICU were compared among discharged and expired patients (). Systolic blood pressure, heart rate, body temperature and respiratory rate were not different between two groups of patients, however, diastolic blood pressure was significantly lower in expired patients (69.35 ± 12.25 vs. 63.40 ± 14.78, p = 0.044). In expired patients, confusion at admission to the ICU was more prominent (p = 0.001).
Table 1. Comparison of demographic features among discharged and expired patients.
Table 2. Comparison of vital signs at admission to the ICU among discharged and expired patients.
Laboratory data of patients at admission to the ICU were compared among discharged and expired patients (). At admission to the ICU blood glucose (109.33 ± 37.31 vs. 132.87 ± 32.56, p = 0.02), blood urea nitrogen (20.8718 ± 15.58 vs. 46.97 ± 13.22, p = 0.001), serum creatinine (0.97 ± 0.27 vs. 2.05 ± 1.71, p = 0.001), albumin (3.72 ± 0.68 vs. 3.30 ± 0.57, p = 0.003) and C-reactive protein (CRP) (88.91 ± 30.52 vs. 137.23 ± 32.73, p = 0.001) and procalcitonin (0.47 ± 0.21 vs. 1.28 ± 0.59, p = 0.001) levels were significantly different between groups.
Table 3. Comparison of laboratory data at admission to the ICU among discharged and expired patients.
The results of blood gas analyses at admission to the ICU were compared among discharged and expired patients (). pH (7.37 ± 0.10 vs. 7.27 ± 0.12, p = 0.001), PaO2 (54.11 ± 14.02 vs.44.32 ± 11.98, p = 0.001) and oxygen saturation (81.23 ± 9.55 vs. 70.26 ± 11.10, p = 0.001) were significantly lower in expired patients compared with the discharged patients, while PaCO2 (41.87 ± 14.51 vs. 50.65 ± 13.27, p = 0.022) and lactate (1.58 ± 0.38 vs 2.06 ± 0.53) were significantly higher (p = 0.001).
Table 4. Comparison of the results of blood gas analyses at admission to the ICU among discharged and expired patients.
The findings of postero-anterior lung graph were also analyzed. Lobar pneumonia was present in 18 patients (6 in discharged group and 12 in expired group) while bronchopneumonia was present in 44 patients (21 in discharged group and 23 in expired group). There was not any significant difference between groups regarding the postero-anterior lung graph findings (p = 0.271). Thorax computed tomography was present in all patients and multi-lobular pneumonia was determined in 13 patients in discharged group and 21 patients in expired group. There was not any significant difference between groups concerning the presence of multi-lobular pneumonia in thorax computed tomography (p = 0.376).
The results of sputum cultures obtained from the patients are summarized in . However, since the number of patients with positive culture results was very low, any statistical analyses could not be performed.
Table 5. The results of sputum cultures obtained from the patients.
Concomitant diseases in study participants are also recorded. In discharged group, chronic neurological disease was present in 2 patients, chronic lung disease in was present 5 patients, diabetes mellitus was present in 4 patients, hypertension was present in 11 patients and congestive heart failure was determined in 2 patients. In expired group, chronic kidney disease was observed in 1 patient, chronic neurological disease was present in 4 patients, chronic lung disease in was present 9 patients, diabetes mellitus was present in 6 patients, hypertension was present in 15 patients and congestive heart failure was determined in 8 patients.
Total hospitalization period in ICU was 19.05 ± 9.48 days in discharged group and it was 8.95 ± 8.65 in expired group (p = 0.001).
Regarding these results, we estimated the risk factors for expiration in ICU. We analyzed the estimated risks for the factors which were significantly different between discharged and expired patients. In order to determine the cut-off values which will be analyzed in this study, we used the median points. In that aspect, risk ratios were calculated for the parameters age >78 years, drinking alcohol, presence of confusion, at admission diastolic blood pressure <60 mm-Hg, blood glucose > 108 mg/dL, serum creatinine> 1.1 mg/dL, serum albumin <3.5 g/dL, serum CRP >89 mg/L and procalcitonin >0.63 μg/L and in blood gas analysis pH < 7.35, PaO2 < 47 mmHg, PaCO2 > 41 mmHg, oxygen saturation <75% and lactate levels >2 mmol/L. Among those parameters, age > 78 years, drinking alcohol, at admission blood glucose >108 mg/dL, blood urea nitrogen >21 mg/dL, serum creatinine> 1.1 mg/dL, serum albumin <3.5 g/dL, serum CRP >89mg/L and procalcitonin >0.63 μg/L and in blood gas analysis pH < 7.35, paCO2 > 41 mmHg, lactate >2 mmol/L and oxygen saturation <75% were significantly increasing the risk of expiration in ICU patients admitted with community acquired pneumonia ( and ).
Table 6. Risks factors for expiration in ICU hospitalizations due to community acquired pneumonia determined with univariate logistic regression analysis.
Table 7. Risks factors for expiration in ICU hospitalizations due to community acquired pneumonia determined with multivariate logistic regression analysis.
Discussion
In this study, we analyzed the general clinical, laboratory and radiological factors associated with death in ICU in patients over 65 years of age who presented with CAP. We determined that older age (>78 years), at admission, elevated blood glucose (>108 mg/dL) levels, elevated procalcitonin (>0.63 μg/L) and decreased serum albümin (<3.5 g/dL) levels, and in blood gas analysis, decreased pH (<7.35) and increased lactate (>2mmol/L) were significantly increasing the risk of expiration in ICU patients admitted with community acquired pneumonia.
Aging is associated with an increased prevalence of chronic co-morbidities and alterations in immune system resulting in an augmented susceptibility to infections. We determined that patients older than 78 years of age were having a 7.20 times increased risk for expiration compared with the younger patients. Recently, Cillóniz et al. [Citation5] reported that in patients ≥80 years in-hospital and 1-year mortality rates were increased if they developed sepsis. In especially very old patients, uncommon presentation of pneumonia, causing delays in diagnosis and treatment may also be some of the reasons of increased mortality in that age group [Citation6]. Although recently, due to the ageing in populations with increased longevity, approximately 70% of patients with CAP were reported to be older than 65 years of age [Citation7]. Mortality rates in different age groups, in patients admitted to the ICU with CAP should be studied in further studies to determine the direct effects of old age in mortality.
In this study, we determined that, current alcohol consumption was associated with an increased risk of in ICU-mortality in univariate analysis but not in multivariate analysis. In previous literature, alcohol consumption was associated with more severe clinical presentations and poorer outcomes in patients with pneumonia [Citation8–10]. This increased risk of CAP was attributed to the malnutrition and adversely altered immune functions in patients consuming alcohol [Citation11]. Similar with our results, Mahendra et al. [Citation12] also reported that alcoholism, and old age (>60 years) were observed to be important risk factors for severe CAP. Moreover, Montull et al. [Citation13] also reported that CAP patients with renal disease and alcohol abuse, were more likely to present to the hospital with severe sepsis. However, recently Gupta et al. [Citation14] reported that alcohol use disorder was not associated with increased mortality in a retrospective cohort study. We suggest that, alcohol consumption and associated conditions should be studied in patients admitted to the ICU with CAP.
Confusion is one of the criteria included in CURB-65 which is an effective clinical prediction scale intended to stratify patients with pneumonia by expected mortality [Citation15]. In multivariate regression analysis, we did not determine confusion as a significant marker in predicting in-ICU mortality.
Blood glucose levels at admission to the ICU, higher than 108 mg/dL was associated with increased mortality in this study. Diabetic patients were not excluded in this study, and diabetes mellitus was present in one patient in discharged group and in four patients in expired group. The negative effects of hyperglycemia on immune system are clearly known. increase in admission blood glucose (blood glucose ≥11.1 mg/dL) was associated with risk for ICU admittance, but not significantly associated with in-hospital mortality Postma et al. [Citation16] reported that the predicted risk on mortality was increasing with increasing admission blood glucose levels (glucose levels >7 mg/dL) in 1549 patients with CAP. Jensen et al. [Citation17] reported that in patients without diabetes anwhile in patients with diabetes an increase in admission blood glucose was not associated with ICU admittance or in-hospital mortality. Lepper et al. [Citation18] also reported that serum glucose levels on admission to hospital can predict death in patients with CAP without pre-existing diabetes. We believe that, blood glucose levels at admission may be suggested as an independent risk factor in predicting mortality associated with CAP in ICU.
We determined that serum creatinine levels above the 1.1 mg/dL and blood urea nitrogen levels above 21 mg/dL were associated with an increased risk of mortality in univariate analysis but not in multivariate analysis. Similarly, Wang et al. [Citation19] described a new scoring system including serum creatinine, C-reactive protein (CRP), bicarbonate, and Glasgow coma scale. Cilloniz et al. [Citation20] reported that elevated creatinine (>1.5 mg/dL) levels at admission were not a risk factor for early mortality but a risk factor for pulmonary complications. Alterations in renal function tests at admission in ICU should be evaluated in further studies.
We reported that decreased serum albumin (<3.5 g/dL) levels were associated with increased mortality risk in ICU patients admitted with CAP. Peterson et al. [Citation21] reported that albumin < 3.2 g/dL at discharge was associated with increased risk of 30-day re-admission in patients hospitalized for CAP. Tokgoz Akyil et al. [Citation22] reported that advanced age and elevated blood urea nitrogen/ratios were the predictors of long-term mortality. Hu et al. [Citation23] reported that albumin < 3.0 g/dL, and age ≥ 80 years were independent prognostic factors for 30-day mortality in patients with CAP at low drug-resistant pathogen risk. Similar to our study, it shows that low serum albumin levels are an independent risk factor for increased mortality. We similarly determined that decreased serum albumin (<3.5 g/dL) levels were an independent risk factor for increased in-ICU mortality in patients admitted with CAP. Albumin is a negative acute phase reactant maintaining physiological hemostasis [Citation24] and may be suggested to have a role in predicting prognosis of CAP in ICU patients. Similarly, Okmen et al. [Citation25] have studies showing that homeostasis is balanced by supporting respiratory muscle functions, reduction of edema and lymphatic circulation. Determining that plasma albumin levels are associated with thiol/disulfide homeostasis, Sengoren et al. explained chronic obstructive pulmonary diseases and obstructive sleep diseases through this mechanism. Intrathoracic pressure changes and recurrent hypoxia attacks provide ground for oxidative stress, inflammation, metabolic disorder and endothelial dysfunction, especially in older cases [Citation26,Citation27]. Yazıcı et al. [Citation28] Found that the most common comorbidity among prognostic factors in their studies investigating atherosclerotic heart diseases and impaired cardiac functions developed with chronic recurrent hypoxia was low albumin level and high procalcitonin and lactate levels.
CRP and procalcitonin levels are clinically important tools in follow-up of ICU patients. In this study we determined procalcitonin as an important tool in predicting in-ICU mortality but not the CRP levels. Ge et al. [Citation29] reported that serum hs-CRP levels were improving the clinical usefulness of clinical indexes in predicting ICU admission and mortality in patients with community acquired pneumonia. Similar with our results Keramat et al. [Citation30] also reported a statistically significant association between the serum level of procalcitonin and the outcomes of the patients with community acquired pneumonia. Wang et al. [Citation19] suggested a new scoring system as an efficient, accurate and objective method to predict the early hospital mortality among patients community-acquired pneumonia; having a CRP value of >189.4 mg/L. Both CRP and procalcitonin are easily available blood tools in ICU patients. Further studies investigating the role of these parameters in ICU mortality are warranted.
Blood gas analysis is an important tool in maintaining treatment in ICU patients. We determined that in blood gas analysis decreased pH (<7.35) and elevated lactate levels (>2) were significantly increasing the risk of expiration in ICU patients admitted with CAP. Wang et al. [Citation31] reported that metabolic acidosis was a prognostic risk factor for fatality in children admitted with CAP. On the other hand, Laserna et al. [Citation32] reported that in 453 hospitalized patients with CAP, both hypocapnia and hypercapnia were associated with an increased need for ICU admission and higher 30-day mortality. We determined that acidosis but not alterations in oxygen or carbon dioxide pressure were independent risk factors for in-ICU mortality in patients admitted with CAP. Pereira et al. [Citation33] reported a new scoring system including elevated procalcitonin and lactate levels in serum in predicting treatment failure in patients admitted with severe CAP. Demirel [Citation34] reported that, at a cut-off point of 3.35 mmol/L, the lactate level was a good predictor for mortality. In another study, lactate was also reported to have important roles in predicting mortality, hospitalization and ICU admission in pneumonia patients admitted to the emergency department [Citation35]. Supporting these results, we also reported that lactate levels >2 mmol/Lwas significantly increasing the risk of in-ICU mortality.
There are some limitations of this study that should be mentioned. First is the low number of patients included in the study and second is the lack of long-term follow-up of patients.
In conclusion, in our study, older age, at admission, elevated blood glucose levels, elevated serum procalcitonin levels, decreased serum albumin levels, and in blood gas analysis, decreased pH and increased lactate levels were significant predictors of mortality in patients with CAP admitted to the ICU. The role of new prognostic criteria including these parameters should be investigated in prospective studies of CAP patients over 65 years old who are admitted to the intensive care unit.
Disclosure statement
The authors declare that they have no conflict of interest related to the publication of this manuscript. This research did not receive any specific grants from any funding agency in the public, commercial, or not-for-profit sector.
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