About this trial
Ventilator associated pneumonia is the most common manifestation of hospital acquired infections in ICU. The incidence of ventilator-associated pneumonia in patients receiving mechanical ventilation is as high as 20% -71%, which can lead to increased systemic antibiotic use, prolonged mechanical ventilation time and ICU stay, and increased treatment costs. In addition, ventilator-associated pneumonia is also the main cause of hospital infection related deaths in critically ill patients.
However, there is a certain buffer time for patients to develop ventilator-associated pneumonia after receiving endotracheal intubation. Previous studies have found that the peak incidence occurs after 7 days of mechanical ventilation, so there is an opportunity for early treatment to prevent infection. Despite the implementation of numerous preventive measures for ventilator-associated pneumonia over the decades, such as reducing sedation and withdrawal protocols, patient positioning, oral care, prophylactic probiotics, prophylactic antibiotics, and the use of silver plated endotracheal tubes. Among them, the research on the preventive use of antibiotics has a history of over 30 years and is a topic of substantial debate. Prophylactic use of antibiotics includes systemic application and local nebulization inhalation, and inhaled antibiotics may be an effective measure for preventing ventilator-associated pneumonia. Potential extensively drug-resistant Gram negative (XDR-GN) bacteria, such as Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii, are common pathogens causing VAP in ICU. The mortality rate of VAP caused by XDR-GN pathogen may be higher than 70%. With the increasing incidence of multidrug-resistant microorganisms, nebulized or inhaled aminoglycoside antibiotics are often used as empirical or definitive treatment for VAP in ICU patients. The previous group of antibiotics, polymyxin, has returned to the view of medical staff. Sodium polymyxin E methanesulfonate has been used as a salvage therapy for XDR-GN bacteria causing pneumonia, demonstrating its activity against XDR-GN causing VAP in critically ill patients. The guidelines of the Infectious Diseases Society of America (IDSA) on hospital acquired pneumonia also indicate that patients with Gram negative pneumonia caused by drug-resistant bacteria are sensitive to polymyxins. In this randomized controlled study, we aim to investigate the effect of prophylactic use of polymyxin E nebulized inhalation on the incidence of VAP.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Age >18 years old
Patients with brain injury admitted to ICU (including brain injury caused by trauma, cerebral hemorrhage, cerebral infarction, and cardiac arrest)
GCS score<12 points
Mechanical ventilation time ≥ 48 hours
Disqualifiers
Existing lung diseases that require long-term inhaled medication treatment.
Lower respiratory tract infection at admission.
New or persistent infiltration on chest imaging within 48 hours after admission.
Expected removal of endotracheal tube within the next 24 hours.
Trial design
Parallel
Treatments tested in this trial
Inhaled Placebo
DrugInhalation of drugs was started within 24 hours after the screening of patients. Both groups inhaled with vibrating mesh spray twice a day for 3 days. The NS group inhaled with normal saline .
inhaled corticosteroids and other asthma drugs
DrugInhalation of drugs was started within 24 hours after the screening of patients. Both groups used vibrating mesh spray twice a day for 3 days. The Polymyxin E group inhaled polymyxin, 75 mg bid.
Treatment groups
Trial outcomes
Primary outcomes
Prevention of VAP
The incidence of VAP from randomization to day 7.
Secondary outcomes
VAP incidence within 28 days
Incidence of VAP from randomization to day 28
Changes of CPIS within day 28
Changes of clinical pulmonary infection scores after randomization(CPIS)
Use of systemic antibiotic
The number of days of systemic antibiotic use and the daily dose of antibiotics administered within 28 days after randomization.
Success of SBT
The number of days from randomization to the first successful spontaneous breathing test(SBT)
Locations
Sponsors and contacts
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