ABSTRACT
Introduction: Respiratory failure is the most common organ failure seen in the intensive care unit1 and is managed with non-invasive or invasive positive pressure ventilation (PPV). Negative pressure ventilation (NPV) could offer a safe and effective alternative, however existing devices, such as the iron lung, are heavy and access to the patient for ongoing care is a limitation. The COVID-19 pandemic necessitated intense focus on the rapid design and manufacture of new ventilators,2 most of which were positive pressure ventilators. However, new, light-weight negative pressure ventilators were also designed and appeared to be safe and effective in an early trial in healthy human volunteers.3 These devices have the potential to offer patients an alternative to PPV, without the limitations associated with the early negative pressure devices. They are cheaper to manufacture, and importantly, do not require a pressurised gas supply, which may be of particular benefit to countries with less well-resourced healthcare facilities in which acute and acute-onchronic respiratory failure continue to cause significant morbidity and mortality.4 Objectives: To address whether acute or acute-onchronic respiratory failure in hospitalised adults can be safely and effectively managed with NPV. Methods: This systematic review was registered with the international prospective register of systematic reviews (ID CRD420200220881). MEDLINE, EMBASE, CENTRAL, medRxiv, bioRxiv and Trip databases were searched (from inception to 22nd April 2021). Eligible studies included non-intubated hospitalised adults who received NPV in the management of acute or acute on chronic respiratory failure. We included randomised controlled trials, non-randomised studies of intervention and case series. Risk of bias was assessed using three separate tools due to differing study designs. Results: 575 unique citations were screened with 14 meeting inclusion criteria. 1032 acute episodes (888 patients) of respiratory failure were managed with NPV, with 234 receiving PPV as a comparator. The majority (n=845, 66.7%) were treated for an acute exacerbation of COPD. 417 patients from four studies were included in the meta-analysis. The effect of NPV on PaCO2, pH and PaO2/FiO2 was similar to PPV with a mean difference -0.39kPa (95% confidence interval (CI): -0.95, 0.18), 0.01 (95% CI: 0.00, 0.02), and -0.16 (95% CI: -1.98, 1.66) respectively. Of those studies not included in the meta-analysis six showed a statistically significantly increase in PaO2 with the use of NPV and 5 showed a statistically significant improvement in PaCO2. Rates of complications were similar with NPV in those studies that compared it to PPV, and NPV appeared to be well tolerated by patients. This systematic review study was limited by a wide range of study designs. Conclusions: NPV appears to be a safe and effective alternative to PPV in the management of acute exacerbation of COPD. Evidence for its use in other forms of respiratory failure is limited but warrants further investigation.