Prophylactic Penehyclidine Inhalation for Prevention of Postoperative Pulmonary Complications in High-risk Patients: A Double-blind Randomized Trial

• Published in: Anesthesiology (Philadelphia) 2022-04, Vol.136 (4), p.551-566
• Main Authors: Yan, Ting, Liang, Xin-Quan, Wang, Guo-Jun, Wang, Tong, Li, Wei-Ou, Liu, Yang, Wu, Liang-Yu, Yu, Kun-Yao, Zhu, Sai-Nan, Wang, Dong-Xin, Sessler, Daniel I.
• Format: Article
• Language: English
• Subjects: Bronchial Spasm - chemically induced; Bronchial Spasm - complications; Double-Blind Method; Female; Humans; Male; Middle Aged; Postoperative Complications - epidemiology; Postoperative Complications - etiology; Postoperative Complications - prevention & control; Pulmonary Atelectasis - complications; Quinuclidines - adverse effects; Quinuclidines - therapeutic use
• ISSN: 0003-3022; 1528-1175
• DOI: 10.1097/ALN.0000000000004159

Postoperative pulmonary complications are common. Aging and respiratory disease provoke airway hyperresponsiveness, high-risk surgery induces diaphragmatic dysfunction, and general anesthesia contributes to atelectasis and peripheral airway injury. This study therefore tested the hypothesis that inhalation of penehyclidine, a long-acting muscarinic antagonist, reduces the incidence of pulmonary complications in high-risk patients over the initial 30 postoperative days. This single-center double-blind trial enrolled 864 patients age over 50 yr who were scheduled for major upper-abdominal or noncardiac thoracic surgery lasting 2 h or more and who had an Assess Respiratory Risk in Surgical Patients in Catalonia score of 45 or higher. The patients were randomly assigned to placebo or prophylactic penehyclidine inhalation from the night before surgery through postoperative day 2 at 12-h intervals. The primary outcome was the incidence of a composite of pulmonary complications within 30 postoperative days, including respiratory infection, respiratory failure, pleural effusion, atelectasis, pneumothorax, bronchospasm, and aspiration pneumonitis. A total of 826 patients (mean age, 64 yr; 63% male) were included in the intention-to-treat analysis. A composite of pulmonary complications was less common in patients assigned to penehyclidine (18.9% [79 of 417]) than those receiving the placebo (26.4% [108 of 409]; relative risk, 0.72; 95% CI, 0.56 to 0.93; P = 0.010; number needed to treat, 13). Bronchospasm was less common in penehyclidine than placebo patients: 1.4% (6 of 417) versus 4.4% (18 of 409; relative risk, 0.327; 95% CI, 0.131 to 0.82; P = 0.011). None of the other individual pulmonary complications differed significantly. Peak airway pressures greater than 40 cm H2O were also less common in patients given penehyclidine: 1.9% (8 of 432) versus 4.9% (21 of 432; relative risk, 0.381; 95% CI, 0.171 to 0.85; P = 0.014). The incidence of other adverse events, including dry mouth and delirium, that were potentially related to penehyclidine inhalation did not differ between the groups. In high-risk patients having major upper-abdominal or noncardiac thoracic surgery, prophylactic penehyclidine inhalation reduced the incidence of pulmonary complications without provoking complications.