Inha'le'd, Ventilator-Associated Pneumonia (VAP)
Conditions
Brief summary
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.
Interventions
DRUGInhaled colistin
Colistin powder will be solubilised in 0.9% Nacl (75mg per 5 mL)， and used for nebulisation twice a day at a dose of 75mg for 3 days
DRUGInhaled 0.9% sodium chloride
Saline solution of 0.9% sodium chloride (NaCl) will be used as placebo. The equivalent volume of 0.9% NaCl will be placed in the nebuliser and delivered twice a day for 3 days.
Sponsors
Southeast University, China
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Patients aged more than or equal to 18 years and less than 80 years 2. ABI patients admitted to the ICU, including TBI, intracranial haemorrhage, ischaemic stroke, post-cardiac arrest hypoxic-ischaemic encephalopathy or other acute neurological insults 3. Glasgow Coma Scale (GCS) score ≤12 4. Duration of mechanical ventilation more than or equal to 48 hours at enrolment 5. Written informed consent provided by the participant's legally authorised representative.
Exclusion criteria
1. patients with suspected or confirmed VAP on the day of enrolment 2. Anticipated extubation within the next 24 hours. 3. Duration of mechanical ventilation exceeding 96 hours prior to enrolment. 4. Patients currently receiving or having recently received (within the preceding 24 hours) polymyxin (administered intravenously and/or via nebulization). 5. Known hypersensitivity to polymyxin. 6. Pregnant or breastfeeding women. 7. Myasthenia gravis. 8. Patient with high risk of death within the first 48h after ICU admission. 9. Advanced-stage solid organ malignancy or hematological malignancy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Prevention of early VAP | From randomization to 7 days | the incidence of VAP within 7 days after randomisation |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| VAP incidence within 28 days | From randomization to 28 days | The incidence of VAP within 28 days after randomisation |
| Use of systemic antibiotic | From randomization to day 28 | The number of days of systemic antibiotic use and the daily dose of antibiotics administered within 28 days after randomization. |
| Success of SBT | From randomization to first success of SBT | The number of days from randomization to the first successful spontaneous breathing test (SBT). |
| Invasive ventilator-free days at 28 days | From randomization to 28 days | Days alive without endotracheal intubation and invasive mechanical ventilation |
| Successful weaning from mechanical ventilation | From randomization to 28 days | The proportion of patients who were successfully weaned from mechanical ventilation within 28 days after randomisation. |
| ICU days at day 28 | From randomization to 28 days | The number of ICU days within 28 days after randomization |
| Hospital days at day 28 | From randomization to 28 days | The number of Hospital days within 28 days after randomization |
| 28-day mortality | From randomization to 28 days | The proportion of patients who died within 28 days |
| Incidence of AKI | From randomization to day 28 | The proportion of patients who were newly diagnosed acute kidney injury (AKI) within 28 days after randomization, defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. |
Countries
China
Contacts
CONTACTLili Huang, Doctor
Outcome results
None listed