Prophylactic antibiotics to prevent ventilator associated pneumonia in adults with acute brain injury who are invasively ventilated in the ICU: A protocol for a systematic review and meta-analysis

Background Acute brain injury due to conditions such as trauma, subarachnoid haemorrhage, stroke or hypoxic-ischaemic encephalopathy, is a major public health issue. Lower respiratory tract infections and ventilator associated pneumonia (VAP), are common in patients who require invasive mechanical ventilation after suffering an acute brain injury, and may have potentially deleterious consequences such as fever, hypoxaemia, and hypotension, excessive pulmonary secretions and sputum plugging. These physiological disturbances may contribute to secondary brain injury and potentially to adverse clinical outcomes. Parenteral antibiotics given soon after the commencement of invasive mechanical ventilation may prevent the development of VAP and potentially reduce the associated adverse consequences, although there is conflicting evidence from randomised clinical trials (RCTs). Therefore, we plan to conduct a systematic review and meta-analysis to test the hypothesis that, in adults with acute brain injury who are invasively ventilated in the Intensive Care Unit (ICU), administration of prophylactic parenteral antibiotics, compared with a matched placebo or usual care, reduces the occurrence of mortality as well as ventilator associated pneumonia and other secondary outcomes. Methods and analysis We will undertake a systematic review and meta-analysis. We will include RCTs that compare the administration of prophylactic antibiotics to placebo or usual care on hospital mortality and other patient-centred outcomes in patients with acute brain injury receiving mechanical ventilation in the ICU. We will perform a search that includes the electronic databases MEDLINE and EMBASE and clinical trial registries. Two reviewers will independently screen titles and abstracts, perform full article reviews and extract study data, with discrepancies resolved by a third reviewer. We will report study characteristics and quantify risk of bias. We will perform random effects meta-analyses to provide pooled estimates that the administration of prophylactic antibiotics is associated with reduced hospital mortality and a reduced incidence of ventilator associated pneumonia, as well as other outcomes. We will evaluate overall certainty of evidence using the Grading of Recommendations Assessment, Development, and Evaluation framework. Conclusion This systematic review and prospective meta-analysis will provide clinicians with an overview of current evidence regarding the association between the administration of prophylactic antibiotics in patients with acute brain injury receiving invasive mechanical ventilation and mortality, the incidence of ventilator associated pneumonia and other clinical outcomes. PROSPERO registration CRD 42023424732