Prophylactic penehyclidine inhalation for prevention of postoperative pulmonary complications in high-risk patients: study protocol of a randomized controlled trial

Abstract

Background: Postoperative pulmonary complications (PPCs) are major causes of morbidity, mortality, and prolonged hospital stay in patients after surgery. Using effective strategies to prevent its occurrence is essential to improve outcome. However, despite various efforts, the incidence of PPCs remains elevated in high-risk patients. Anticholinergic inhalation is used to reduce high airway resistance and improve pulmonary function; it may be helpful to decrease the risk of PPCs. Penehyclidine is a long-acting anticholinergic agent which selectively blocks M1 and M3 receptors. We hypothesize that, in high-risk patients, prophylactic penehyclidine inhalation may decrease the incidence of PPCs.

Methods: This is a randomized, double-blind, placebo-controlled trial with two parallel arms. A total of 864 patients at high risk of PPCs will be enrolled and randomized to receive prophylactic inhalation of either penehyclidine or placebo (water for injection). Study drug inhalation will be administered from the night (7 pm) before surgery until the second day after surgery, in an interval of every 12 hours. The primary outcome is the incidence of PPCs within 30 days after surgery. Secondary outcomes include the time to onset of PPCs (from end of surgery to first diagnosis of PPCs), the number of PPCs (indicates the number of diagnosed individual PPCs), the incidence of postoperative extrapulmonary complications, the length of stay in hospital after surgery, and the 30-day all-cause mortality.

Discussion: Results of the present study will provide evidence to guide clinical practice in using prophylactic inhalation of an anticholinergic to prevent PPCs in high-risk patients.

Trial registration: The study was registered prospectively in Chinese Clinical Trial Registry ( www.chictr.org.cn , ChiCTR-IPC-15006603 ) on 14 May 2015 and retrospectively in ClinicalTrials.gov ( NCT02644876 ) on 30 December 2015.

Keywords: Administration; Cholinergic antagonists; Penehyclidine; Postoperative complications; Pre-exposure prophylaxis; inhalation.

Conflict of interest statement

Ethics approval and consent to participate

The first version protocol was approved by the Clinical Study Ethics Committee of Peking University First Hospital (2015[06]) on 15 April 2015. The second version protocol reduced the study drug dose from 1 mg to 0.5 mg, which was approved by the local Ethics Committee on 13 May 2015 before the start of patient recruitment. The third version of the protocol added an inclusion criterion, i.e., “for patients who are scheduled to undergo thoracoscopic or laparoscopic surgery (with duration ≥ 2 hours), the expected length of incision must be 5 centimeters or more”, and was approved by the local Ethics Committee on 29 March 2016. Further protocol modification will also be sent to and approved by the local Ethics Committee before it can be executed. The study has been registered at Chinese Clinical Trial Registry (ChiCTR-IPC-15006603) and ClinicalTrial.gov (NCT02644876, Additional file 4). Written informed consent will be obtained from each patient or, if the patient cannot provide informed consent, from the surrogate of the patient.

Consent for publication

By providing the written informed consents, the participants agreed that their data will be analyzed and published in the form of scientific papers; however, their individual details (including age, gender, etc.) will be kept confidential. The consent forms are held by both the participants and the first author (YT), and are available for review by the Editor-in-Chief.

Competing interests

The authors declare that they have no competing interests.

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Figures

Fig. 1

Flowchart of the study

Fig. 2

SPIRIT diagram