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Correspondence: Taraneh Naghibi MD, FCCM, Department of Anesthesiology and Critical Care Medicine, Mosavi Educational Hospital, Zanjan University of Medical Science, Zanjan, Iran
Atelectasis and pneumonia are highly prevalent in patients under mechanical ventilation. Studies indicate that using ventilation with an open lung concept improves recovery, decreases ventilator-related pneumonia, decreases mortality and leads to faster weaning from the ventilator. Therefore, this study investigated the effect of higher airway pressure on ventilator-associated pneumonia.
Methods
This randomized clinical trial was conducted on 120 patients under mechanical ventilation. The patients were divided into two groups based on ventilator pressure: the control group (pressure level 20) and the intervention group (pressure level 30). Demographic data, disease severity, the incidence of ventilator-associated pneumonia, organ damage, days connected to the ventilator, length of hospitalization in ICU, and mortality were compared between the two groups.
Results
There was no significant difference in demographic data and disease severity between the two groups. The average Clinical Pulmonary Infection Score in the intervention group was significantly lower than the control group (P = 0.02). The intervention group's average Sequential Organ Failure Assessment score was significantly lower than the control group (p = 0.016).
Conclusions
High-pressure levels can decrease ventilator-associated pneumonia and organ failure. It is recommended that the study be repeated with a larger, more diverse population.
Ventilator-associated pneumonia (VAP) is one of the common nosocomial infections that occur in patients who require mechanical ventilation. This kind of infection develops more than 48 h after intubation and is not present at the time of intubation.
Prevention of early ventilation- acquired pneumonia (VAP) in comatose brain-injured patients by a single dose of ceftriaxone: PROPHY-VAP study protocol, a multicentre, randomized, double-blind, placebo-controlled trial.
Incidence, risk factors, and outcome of ventilator-associated Pneumonia in 18 hospitals of Iran. Running title: ventilator-associated pneumonia in Iran.
Recent investigations have estimated VAP-related hospital costs to be between $25,000 to $28,000 per patient in the United States and £6,000 to £22,000 per patient in the United Kingdom.
Atelectasis is known as a cause of pulmonary complications such as pneumonia. An increase in total lung capacity with high airway inflation pressure could reverse lung atelectasis.
Effects of positive end-expiratory pressure/recruitment maneuvers compared with zero end-expiratory pressure on atelectasis during open gynecological surgery as assessed by ultrasonography: a randomized controlled trial.
Therefore, it is ideal to find the best recruitment maneuver to reduce atelectasis to decrease VAP incidence. In the lungs having identical dynamics, higher inspiratory pressure could increase tidal volume which prevents atelectasis, and VAP. For this reason, this randomized, double-blind study was designed to assess the role of two different levels of pressure in the prevention of VAP.
Methods
Study design
This parallel, double-blinded, randomized clinical trial study was performed in a 21-bed surgical ICU at Mosavi Hospital, Zanjan, Iran. The study was approved by the ethics committee (Approval number: ZUMS.REC.1393.134). The trial was registered with the Iranian Registry of Clinical Trials (IRCT201512065363N6). Valid informed written consent was obtained from the patient's relatives.
Patient population
The sample size was calculated for 60 patients per group based on the below formula, with the error of α = 0.05 and β = 0.20.
Patients were included in the study based on inclusion and exclusion criteria after receiving ethics committee approval. Inclusion criteria were age between 20 and 60 years, intubated and under mechanical ventilation, and absence of pneumonia, heart failure, and lung disease. Exclusion criteria were lack of consent of the patients and their relatives, extubation of less than a week, death of less than a week, and abnormality in lung mechanics including resistance (more than 15 cmH2O/l/s) and compliances (less than 50 ml/cmH2O).
Randomization and blinding
A computer random number generator (Randomization.com; http://www.randomization.com) was used for simple randomization. According to the statistician randomization code list, the patients were allocated to one of the study groups. Both the participants and the investigator were masked to the ventilation strategy. One of the care providers adjusted the ventilator setting and another evaluated outcome.
Study protocol
After enrollment, all patients were ventilated with a closed-loop ventilator.
For all intubated patients a 7-element care bundle was performed, including elevation of the head of bed 30°–45°, sedation daily awakening trial and spontaneous breathing trial, prophylaxis for peptic ulcer, deep vein thrombosis prophylaxis, oral care with chlorhexidine mouth wash, endotracheal intubation with in-line and keep the endotracheal tube cuff pressure at 20–30 mmHg. All patients were ventilated with Hamilton Raphael ventilators.
The first group underwent mechanical ventilation with the following settings:
The severity of the disease was assessed on the first day of the study, according to the Acute Physiology and Chronic Health Evaluation II (APACHE II) score (Evaluation II Acute Physiology and Chronic Health). Patients were monitored for a maximum period of 12 days during mechanical ventilation. The incidence of VAP was assessed by the CPIS (Clinical Pulmonary Infection Score), which was measured every three days, then the effect on reducing the rate of VAP was compared between the two different levels of pressure.
VAP occurrence was recorded until extubation within a maximum period of 12 days. Pneumonia was considered as early and late-onset: beginning on day six or later after admission, it was defined as late onset.
To assess organ injuries during ICU admission SOFA (Sequential Organ Failure Assessment) score was used daily. The information was collected in a specially designed form.
Outcome
Incidence of VAP up to 12 days was the primary outcome. Secondary outcomes were mortality during admission, the number of days in which the patient was separated from the ventilator, and the length of ICU stay.
Statistical analysis
All data were analyzed with the SPSS-16 software program (SPSS, Chicago, IL, USA). Significance has been defined as a P-value of less than 0.05. For evaluating the distribution of quantitative variables, the Kolmogorov-Smirnov test was used. Values were expressed as numbers (percentage) and mean ± standard deviation. Comparisons were performed by chi-square test for categorical variables, independent T-test for normally distributed, and Mann– Whitney test for non-normally distributed.
Results
Patient characteristics
In total, 120 patients were enrolled in the randomized trial, three patients were not included in the study due to pneumonia. Of the 117 patients, 60 cases were in the control group (with a pressure level of 20 cmH2O) and 57 cases were in the intervention group (with a pressure level of 30 cmH2O) (Fig. 1).
Fig. 1Flowchart of inclusion and exclusion of patients in the study.
Of the 117 participants, the median age was 45 years, 80.3% were men, and the mean APACHE II score was 25. 35.8% of participants were treated with antibiotics before the identification of VAP. 63.2% of patients were admitted for surgical reasons and other admissions had medical causes. The patient's main diagnosis on admission to the ICU was as follows:
20 patients (17%) respiratory, 31 (26.4%) neurologic, 34 (29%) trauma, 14 (11.9%) sepsis, 6 (5.1%) cardiovascular and 12 (10.2%) other medical and surgical reason. As shown in Table 1, patient characteristics between the two groups were not statistically different in age, sex, APACHE II score, the admitting diagnostic category, and antibiotic exposure (P > 0.05) (Table 1).
Within a maximum period of 12 days, the statistical analysis showed significant differences in the incidence of VAP between groups (Table 2). Incidence of VAP was significantly different in the third (P = 0.01) and sixth (P = 0.02) days between groups. It was not significantly different on the ninth (P = 0.25) and twelfth (P = 0.48) days (Table 2).
Table 2Incidence of ventilator-associated pneumonia (VAP).
SOFA score was significantly higher in the control group compared to the intervention group for all days of the study (Table 3). There was no significant difference in the mechanical ventilation, the length of ICU stays days, and ICU mortality between groups (Table 3).
On the other hand, focusing on surgical and medical subgroups, there was no statistically significant difference according to age, sex, SOFA score, APACHE II score, the incidence of VAP, mechanical ventilation days, the length of ICU stays and ICU mortality between two groups (p > 0.05).
Complications
No unexpected serious adverse reactions occurred during the study.
Discussion
This present randomized trial shows that a higher-pressure level of PCV mode can decrease VAP in patients under mechanical ventilation. This study compared two different inspiratory pressures for the prevention of VAP. To the best of our knoweldge, this is the first clinical trial to examine the role of inspiratory pressure in the prevention of VAP, so comparing our results with previous studies is not possible.
Atelectasis is caused by an incomplete expansion of lung tissue. It occurs when the alveoli become collapsed.
According to these reasons, the purpose of the present study was to determine the effect of increased inspiratory pressure on the incidence of VAP.
We included 117 patients in this study. There were 60 cases in the low inspiratory pressure group (compression level 20 cmH2O) and 57 cases in the high inspiratory pressure group (compression level 30 cmH2O). At the beginning of the study, the compressive levels in the ventilator settings were 25 cmH2O for low pressure and 35 cmH2O for high-pressure levels. During the investigation and after obtaining arterial blood gas samples, in some patients, the pressure decreased to 20 cmH2O and 30 cmH2O for low- and high-pressure groups, due tolosis in some patients.
There was no statistically significant difference between the two groups in demographic variables. In the present study, the average age of patients was 45 years, which is low compared to other ICU studies. There are two reasons for this difference. In the present study, one of the inclusion criteria was age between 20 and 60 years. The reason for choosing this criterion was fewer comorbidities which impact the variables of the study. On the other hand, in the present study, the most main diagnosis for admission to the ICU was trauma which usually occurs in young patients. These reasons could explain the difference in age between studies.
APACHE II score was not different between the two groups. This score was used to calculate the severity of the illness. It is used to assess patients who are newly admitted to the ICU. The system consists of several parts, with a score between 0 and 71, in which a higher score indicates a worsening illness and a higher risk of death.
In the present study, the results of the APACHE II score showed that there was no significant difference in the severity of illness between the two groups.
One of the most common interventions in ICU wards is advanced respiratory support. PCV is a mode of ventilation in which the operator selects a target pressure to control peak pressures. PCV is cycled by time mode with an inspiratory flow pattern. During inspiration, the ventilator delivers a preset target pressure to the airway; so, the tidal volume which is delivered to the patients is determined by the lung compliance and the airway resistance.
Mechanical ventilation is the most important factor which causes nosocomial pneumonia. VAP is an inflammation of the lung parenchyma caused by a bacterial infection that incubates in patients under mechanical ventilation. It is defined as pneumonia which appears more than 48 h after initiation of mechanical ventilation.
The current epidemiological landscape of ventilator-associated pneumonia in the intensive care unit: a multicenter prospective observational study in China.
In the present study, the clinical pulmonary infection score (CPIS) was used to diagnose VAP objectively, which was measured every three days. This tool's accuracy is moderate to good in the detection of VAP. Pneumonia was diagnosed when the CPIS score was higher than 6.
Trauma and antimicrobial resistance are independent predictors of inadequate empirical antimicrobial treatment of ventilator-associated pneumonia in critically ill patients.
Incidence, risk factors, and outcome of ventilator-associated Pneumonia in 18 hospitals of Iran. Running title: ventilator-associated pneumonia in Iran.
In this study, the incidence of VAP was 29%, which was similar to earlier studies. However, it is important to note that the incidence of VAP was significantly different between the two groups (p = 0.02). One of the main causative mechanisms of VAP is the microaspiration of oropharyngeal and gastric secretions. Nseir et al. have shown that low peak inspiratory pressure could increase the risk of microaspiration in intubated patients.
This is consistent with the present study in which VAP was higher in the low-pressure group. Based on the previous investigation, VAP has been divided into early and late-onset. Early-onset appears within the first 4 days of mechanical ventilation and late-onset occurs more than 5 days after mechanical ventilation.
Trauma and antimicrobial resistance are independent predictors of inadequate empirical antimicrobial treatment of ventilator-associated pneumonia in critically ill patients.
Our results showed that the incidence of pneumonia in the intervention group was significantly lower than in the control group on the third and sixth days after admission. However, this difference was not significant on other days. The pathogenesis of early VAP is different from that of late VAP. Multidrug-resistant microorganisms were found to be more frequent in late-VAP.
Microorganisms and clinical outcomes of early-and late-onset ventilator-associated pneumonia at Srinagarind Hospital, a tertiary center in Northeastern Thailand.
This could explain the difference in our intervention effect on different days. In this study, the mean CPIS score in the intervention group was significantly lower than the control group (P = 0.02). This indicates that high inspiratory pressure was effective in reducing the incidence of ventilator-associated pneumonia.
Driving pressure is calculated by plateau pressure minus positive end-expiratory pressure. In pressure-controlled ventilation, plateau pressure is measured at the end of inspiration which is set by the operator.
In the present study, driving pressure was higher in the intervention group. Park et al. have shown that in thoracic surgery, lower driving pressure could affect the incidence of postoperative pulmonary complications. The incidence of the pneumonia in pressure-guided ventilation group was reduced compared with conventional protective ventilation, during one-lung ventilation in thoracic surgery.
It is opposing to our study, in which the incidence of pneumonia was lower in the higher driving pressure group. Underlying disease, duration of ventilation, differences in ventilation methods, and differences in the microorganism that causes pneumonia between two groups could explain the reason for the difference.
The SOFA score was initially designed to assess the evolution of organ failure in sepsis patients. On the other hand, this tool was used to evaluate the effects of treatments like mechanical ventilation and vasopressors on organ dysfunction. Six systems were evaluated with SOFA score, including cardiovascular, respiratory, renal, neurological, coagulation, and hepatic. The SOFA score is between 0 to 24 and the higher score indicates more multi-organ dysfunction.
Validation of prognostic accuracy of the SOFA score, SIRS criteria, and qSOFA score for in-hospital mortality among cardiac-, thoracic-, and vascular- surgery patients admitted to a cardiothoracic intensive care unit.
This is consistent with the present study in which a higher sofa score was observed in the group with a higher incidence of VAP (lower inspiratory pressure group). In the present study, the SOFA score in the control group is significantly higher than in the intervention group (P = 0.016). This finding suggests that the positive effect of this intervention could reduce organ failure and relative improvement in patients.
The results of the chi-square test in the present study have shown that there is no significant difference in mortality between the intervention and control groups. Wu et al. have reported that higher driving pressure is associated with higher incidences of mortality in patients with pneumonia who have no ARDS (acute respiratory distress syndrome), which is opposite to our finding.
In the present study, patients have been excluded if they have any kind of lung disease such as ARDS. This reason could be explained by the difference between the results of the two investigations. Schmidt et al have demonstrated that in patients without ARDS, the driving pressure on the first day of mechanical ventilation is not independently associated with mortality, which is consistent with our study.
Several limitations of this study should be mentioned. First, it was a small study in a single center. Second, the causes of hospitalization were different for critically ill patients, which may have influenced the outcome of the investigation. Third, a short period for evaluation of VAP was performed, only 12 days during mechanical ventilation, to simplify the collection of data.
The strength of the present study was that, to our knowledge, this is the first study that determines the effect of two different inspiratory pressure in the prevention of the VAP rate. On the other hand, the study was well-designed regarding its limitations. There are two other main strengths in this investigation. First, this is a clinical trial study with a good design. Second, serial data was presented throughout the study with good randomization and blinding.
Conclusions
Our findings imply that the level of pressure in patients who are under mechanical ventilation may be the key factor in the prevention of Ventilator-associated pneumonia.
Funding
The research council of Zanjan University of Medical Sciences, ZUMS.REC.1393.134
CRediT authorship contribution statement
Taraneh Naghibi: Conceptualization, Writing – original draft. Hamideh Karimi: Data curation, Formal analysis.
Declaration of Competing Interest
There is no conflict of interest in this article.
Acknowledgments
For the financial support, the authors gratefully acknowledged the research council of Zanjan University of Medical Sciences (approval number: ZUMS.REC.1393.134). The authors thank all the personnel of the Mosavie Hospital ICU for providing clinical assistance in this research.
References
Bearman G.
Doll M.
Cooper K.
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Hospital infection prevention: how much can we prevent and how hard should we try?.
Prevention of early ventilation- acquired pneumonia (VAP) in comatose brain-injured patients by a single dose of ceftriaxone: PROPHY-VAP study protocol, a multicentre, randomized, double-blind, placebo-controlled trial.
Incidence, risk factors, and outcome of ventilator-associated Pneumonia in 18 hospitals of Iran. Running title: ventilator-associated pneumonia in Iran.
Effects of positive end-expiratory pressure/recruitment maneuvers compared with zero end-expiratory pressure on atelectasis during open gynecological surgery as assessed by ultrasonography: a randomized controlled trial.
The current epidemiological landscape of ventilator-associated pneumonia in the intensive care unit: a multicenter prospective observational study in China.
Trauma and antimicrobial resistance are independent predictors of inadequate empirical antimicrobial treatment of ventilator-associated pneumonia in critically ill patients.
Microorganisms and clinical outcomes of early-and late-onset ventilator-associated pneumonia at Srinagarind Hospital, a tertiary center in Northeastern Thailand.
Validation of prognostic accuracy of the SOFA score, SIRS criteria, and qSOFA score for in-hospital mortality among cardiac-, thoracic-, and vascular- surgery patients admitted to a cardiothoracic intensive care unit.
Statistically significant difference between groups (P < 0.05). Data are shown as mean ± SD or No (%)ICU: Intensive Care Unit.
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