Optimal Intrathoracic Pressure Setting Level of a Digital Thoracic Drainage System for Managing Air Leakage After Anatomical Pulmonary Resection: The Thop-Air Multicenter Randomized Controlled Trial

K. Funai¹, K. Takamochi², M. Endo³, T. Haruki⁴, Y. Kitamura⁵, M. Tsuboi⁶, M. Okada⁷, S. Oh⁸, N. Okumura⁹, H. Ito¹⁰, T. Ueno¹¹, S. Nagasaka¹², H. Suzuki¹³, N. Ikeda¹⁴, H. Iwata¹⁵, T. Okamoto¹⁶, T. Banno¹⁷, H. Saji¹⁸, N. Kanauchi¹⁹, Y. Ohtaki²⁰, S. Nojiri²¹, K. Suzuki^22
1First Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka ²Department of General Thoracic Surgery, Juntendo University School of Medicine, Bunkyo, Tokyo ³Department of Thoracic Surgery, Yamagata Prefectural Central Hospital, Yamagata, Yamagata ⁴Division of General Thoracic Surgery, Department of Surgery, Faculty of Medicine, Tottori University, Tottori, Tottori ⁵Division of Chest Surgery, Hyogo Cancer Center, Akashi, Hyogo ⁶Department of Thoracic Surgery and Oncology, National Cancer Center Hospital East, Kashiwa, Chiba ⁷Department of Surgical Oncology, Hiroshima University, Hiroshima, Hiroshima ⁸General Thoracic Surgery, Juntendo University Urayasu Hospital, Urayasu, Chiba ⁹Department of Thoracic Surgery, Kurashiki Central Hospital, Kurashiki, Okayama ¹⁰Department of Thoracic Surgery, Kanagawa Cancer Center, Yokohama, Kanagawa ¹¹Department of Thoracic Surgery, National Hospital Organization Shikoku Cancer Center, Matsuyama, Ehime ¹²Department of Thoracic Surgery, Center Hospital of the National Center for Global Health and Medicine, Shinjyuku, Tokyo ¹³Department of Chest Surgery, Fukushima Medical University, Fukushima, Fukushima ¹⁴Department of Surgery, Tokyo Medical University, Shinjyuku, Tokyo ¹⁵Department of General Thoracic Surgery, Gifu University Hospital, Gifu, Gifu ¹⁶Department of Thoracic Oncology, NHO Kyushu Cancer Center, Fukuoka, Fukuoka ¹⁷General Thoracic Surgery, Juntendo University Nerima Hospital, Nerima, Tokyo ¹⁸Department of Thoracic Surgery, St. Marianna University School of Medicine, Kawasaki, Kanagawa ¹⁹Department of Thoracic Surgery, Nihonkai General Hospital, Sakata, Yamagata ²⁰Division of General Thoracic Surgery, Integrative Center of General Surgery, Gunma University Hospital, Maebashi, Gumma ²¹Juntendo Clinical Research and Trial Center, Juntendo University School of Medicine, Bunkyo, Tokyo ²²Department of General Thoracic Surgery, Juntendo University School of Medicine, Bunkyo-ku, Tokyo

Purpose: We conducted a multicenter, prospective, randomized, controlled trial (Thop-air trial) to clarify the optimal intrathoracic pressure setting (physiological or negative pressure) in digital pleural drainage systems for early healing of air leakage in patients with moderate air leakage after anatomical pulmonary resection.

Methods: Patients scheduled for segmentectomy or lobectomy were primarily registered preoperatively. Patients with moderate air leakage, 100-1000 mL/min on the digital pleural drainage systems set to -15 cmH2O intrathoracic pressure on prospective day 1 (POD 1), were secondary-registered and randomized to group A (set to -8 cmH2O [physiological pressure]) or group B (maintained to -15 cmH2O [negative pressure]). The primary endpoint was the frequency of prolonged air leak (PAL). PAL was defined as a case that corresponded to any of the following in this trial: (1) persistent air leakage after POD 5 and (2) any of the invasive procedures such as an additional chest tube insertion, pleurodesis, or reoperation required before POD 4 due to air leakage. The key secondary endpoints were duration of air leakage, chest tube placement, postoperative hospital stay, frequency of respiratory-related adverse events, and postoperative changes in respiratory function.

Results: Between April 2019 and February 2023, 2379 patients were primarily registered and 175 patients were secondarily registered and assigned to either group A (N = 98) or group B (N = 112) on POD 1. Five patients in group A and six patients in group B were excluded from the study. Therefore, 93 patients in group A and 106 in group B underwent the assigned protocol treatment. No significant difference in the frequency of PAL was found between groups A and B (67.7% [63/93] vs. 60.4% [64/106]; P = 0.303). The duration of air leakage, chest tube placement, and postoperative hospital stay were not significantly different between groups A and B (median, 6 vs. 5 days, P = 0.419; median, 7 vs. 7 days, P = 0.568; and median, 9 vs. 9.5 days; P = 0.550, respectively). The frequency of respiratory-related adverse events (grade 2 or higher based on the Clavien–Dindo classification) was numerically higher in group B than in group A (1 [1.1%] and 7 [6.6%]; P = 0.070). Postoperative reduction in forced expiratory volume in one second (FEV1) in the lobectomy group was significantly greater in group B (-440mL) than in group A (-330mL, P = 0.006).

Conclusion: The frequency of PAL did not differ regardless of the intrathoracic pressure setting. The frequency of respiratory-related adverse events was higher in group B than in group A. Therefore, we recommend the physiological pressure mode (-8 cmH2O) in patients with moderate air leakage after anatomical pulmonary resection.

Identify the source of the funding for this research project: The authors did not receive support from any organization for the submitted work.