Clinical use of Macklin-like radiological sign (Macklin effect): A systematic review

Introduction: Recent studies suggested that Macklin sign is a predictor of barotrauma in patients with acute respiratory distress syndrome (ARDS). We performed a systematic review to further characterize the clinical role of Macklin. Methods: PubMed, Scopus, Cochrane Central Register and Embase were searched for studies reporting data on Macklin. Studies without data on chest CT, pediatric studies, non-human and cadaver studies, case reports and series including <5 patients were excluded. The primary objective was to assess the number of patients with Macklin sign and barotrauma. Secondary objectives were: occurrence of Macklin in different populations, clinical use of Macklin, prognostic impact of Macklin. Results: Seven studies enrolling 979 patients were included. Macklin was present in 4-22% of COVID-19 patients. It was associated with barotrauma in 124/138 (89.8%) of cases. Macklin sign preceded barotrauma in 65/69 cases (94.2%) 3-8 days in advance. Four studies used Macklin as pathophysiological explanation for barotrauma, two studies as a predictor of barotrauma and one as a decision-making tool. Two studies suggested that Macklin is a strong predictor of barotrauma in ARDS patients and one study used Macklin sign to candidate high-risk ARDS patients to awake extracorporeal membrane oxygenation (ECMO). A possible correlation between Macklin and worse prognosis was suggested in two studies on COVID-19 and blunt chest trauma. Conclusions: Increasing evidence suggests that Macklin sign anticipate barotrauma in patients with ARDS and there are initial reports on use of Macklin as a decision-making tool. Further studies investigating the role of Macklin sign in ARDS are justified.