临床试验雷达

• Background: Postoperative pulmonary complications (PPCs) are the most common complications after major upper abdominal surgery. PPCs include respiratory infections, severe atelectasis, pleural effusion, bronchospasm, aspiration pneumonitis, pneumothorax, exacerbation of chronic pulmonary condition, and respiratory failure. Although PPC rates are higher after open liver surgery, PPCs still occur in approximately 12-13% of patients undergoing laparoscopic liver surgery. Preoperative respiratory physiotherapy education reduces PPCs after open major abdominal surgery and after laparoscopic colorectal surgery. The aim of this study is to investigate the impact of enhanced perioperative pulmonary physiotherapy on the incidence of PPCs after laparoscopic liver surgery.
• Methods: A prospective, multicentre, single-blinded, randomized controlled trial will be conducted according to the study protocol at participating centers. A total of 326 patients scheduled for laparoscopic liver surgery will be randomized at a 1:1 ratio into intervention group or standard Enhanced Recovery After Surgery (ERAS) -based perioperative education group. Surgeons/ researchers are blinded to the patient allocation. Patients in the intervention group receive preoperative breathing education in a single session and an educational video to guide pulmonary training at home. Pulmonary training lasts for 7 days prior to surgery and for 7 days postoperatively. The training includes deep breathing, and coughing, pursed lip breathing and positive expiratory pressure (PEP) therapy. Patients receive instructions for conducting exercises along with an individual risk assessment at a preoperative ambulatory visit. The exercise session (10min) is to be performed two times daily for total of 14 days. The control group receives standard perioperative breathing education. Primary outcome is the rate of postoperative pulmonary complications within 14 days of operation. Secondary outcomes include 90-day mortality, Clavien-Dindo classified complications, length of hospital stay, intensive care unit (ICU) stay, and hospital costs.
• Discussion: Little effort is currently put into preventing pulmonary complications after surgery, although PPCs aggravate considerable morbidity and costs to health care system. ERAS Society protocols concentrate mainly on optimizing postoperative recovery. Laparoscopic techniques as such and frequent manipulation of the diaphragm during liver surgery provoke PPCs at a considerable rate. Aim of the study is to present a short-and-easy perioperative pulmonary physiotherapy initiative and evaluate its impact on PPC rate and PPCs ramifications, including direct costs, after laparoscopic liver surgery.

Background: Postoperative pulmonary complications (PPC) are the most common serious complications after major abdominal surgery. PPC rate varies between 10-50% after open abdominal surgery, depending on the definitions used (Miskovic & Lumb, 2017; PROVE Network Investigators for the Clinical Trial Network of the European Society of Anaesthesiology et al., 2014). According to the European Perioperative Clinical Outcome (EPCO) definition, PPCs enclose clinically relevant pulmonary complications including respiratory infection, atelectasis, pleural effusion, respiratory failure, bronchospasm/ exacerbation of chronic pulmonary condition, pulmonary embolism, aspiration pneumonitis and pneumothorax (Table 1) (Jammer et al., 2015). PPCs cause extensive health care costs due to increased length of stay, ICU days, medication costs, and mortality (Miskovic & Lumb, 2017).

Table 1. Definitions of PPCs (Jammer et al., 2015)

PPCs after abdominal surgery result from shallow breathing due to pain, and abdominal distension, bed rest, long duration of surgery, mucociliary clearance disorder, and dysfunction of diaphragm after mechanical ventilation (Miskovic & Lumb, 2017). Laparoscopic surgery and use of modern Enhanced Recovery After Surgery (ERAS) protocols are associated with reduced PPC rates compared to open surgery, and to poor ERAS compliance (Jurt et al., 2018; Milone et al., 2017). However, PPCs still are the most frequent postoperative complications also after laparoscopic liver surgery, occurring in approximately 12-13% of cases (Fuks et al., 2016; Qin et al., 2021). The relatively high incidence is likely due to laparoscopy and pneumoperitoneum as such, since elevated intra-abdominal pressure accelerates atelectasis formation, decreases respiratory compliance, and causes ventilation/perfusion mismatch, leading to PPCs (Lunardi et al., 2013; Park et al., 2016). PPCs are however more common after laparoscopic liver surgery than after e.g. laparoscopic gastrectomy, where PPC rate is commonly only around 7%(Ntutumu et al., 2016). This implies that specific characteristic of liver surgery, such as manipulation of diaphragm, tendency for postoperative fluid collections under the diaphragm and the disease specific susceptibility of cirrhotic patients for developing PPCs, all most likely affect the higher rate of PPCs after liver surgery.

Different types of interventions have been suggested for preventing PPCs. Preoperative pulmonary physiotherapy education has been shown to reduce PPCs after open major upper abdominal surgery by Boden at al. (Boden et al., 2018). In their RCT of 441 patients, intervention was a single preoperative physiotherapy session, during which the investigators informed the patient about PPCs in general, directed the postoperative physiotherapy exercises, and assessed each patients' individual risk for PPC. The high-quality study showed that this type of small-scale intervention halved the rate of PPCs after open upper abdominal surgery. Cochrane analysis by do Nascimento et al. assessed the effect of incentive spirometry on PPCs compared to no therapy or pulmonary physiotherapy, and found no significant benefit (do Nascimento et al., 2014). Usefulness of perioperative physiotherapy in reducing PPCs after laparoscopic surgery has been studied in two Chinese randomized trials, which both found almost 75% decrease in PPCs in the intervention group (Chen et al., 2022; Qin et al., 2021). The trials were conducted with nearly identical protocols, and by the same research group with patients undergoing laparoscopic colorectal surgery (Qin et al., Chen et al. Clin Rehab 2022). The intervention involved a strenuous, and expensive in-hospital physiotherapy for five days prior to surgery and home-bound pulmonary training for 90 postoperative days.

Prehabilitation programs are recognized as potentially beneficial in avoiding postoperative complications and reducing health care costs (Sliwinski et al., 2023). Protocols in prevention of PPCs are however highly heterogeneous and complex programs and generate a need for extra staff for execution in clinical practice. Research concerning prehabilitation has been criticized for discrepant outcome and methodology measures (Sliwinski et al., 2023), and this also concerns PPC prevention studies. At the moment, no evidence exists on prevention measures to reduce PPCs after any type of laparoscopic upper abdominal surgery. Previous studies on the prevention of PPCs after laparoscopic colorectal surgery present programs that cannot be reasonably integrated to current practices.

Objectives:

The objective of our study is to investigate the effect of a short, perioperative pulmonary physiotherapy (7+7 days) on the incidence of PPCs after laparoscopic liver surgery, in a randomized setting. The control group will receive standard ERAS -protocol based treatment.

Trial design:

The study is a multicenter, randomized controlled trial conducted at five Nordic university hospitals in Finland (Oulu, Tampere, Kuopio) and Sweden (Linköping, Lund). Enrolled subjects will undergo assessments at the following intervals: pre-operative, discharge, and 30 days.

Eligibility criteria:

Inclusion criteria

• Patients who undergo elective, laparoscopic surgery of liver
• Patients able to provide an informed written consent
• Patients capable of completing questionnaires at the time of consent
• Patients compliant in taking in preoperative pulmonary counseling and conducting the exercises

Exclusion criteria

• Age <18 years
• Emergency surgery
• Planned open surgery
• Unwillingness to participate in the follow-up assessment
• No informed consent

Additional consent provisions for collection and use of participant data Data collected within the PREPULCION trial is used only for the purposes determined in the protocol. All modifications to protocol will be communicated with Oulu University Hospital Ethics committee by amendments.

Interventions :

Explanation for the choice of comparators

The main goal in designing the intervention was the direct integrability to current clinical practice, providing the intervention will be shown beneficial. Thus, the intervention followed the crude preoperative path of a patient prepared for major HPB laparoscopy at the Finnish university hospitals. According to current preoperative protocol, patients are scheduled either a visit or a remote appointment at a preoperative outpatient clinic 1-4 weeks prior to surgery. The preoperative clinic visit includes appointments with the surgeon, anesthesiologist, when necessary, preoperative nurse, nutritionist if Nutrition Risk Screening 2002 (NRS2002) score is over 5/13, but no preoperative physiotherapy counseling.

Intervention description

The pulmonary physiotherapy program in the intervention group 7 days pre- and 7 days postoperatively:

I: Thoracic expansion exercises/ diaphragmatic breathing x 10 II: Sustained maximal inspiration, and pursed lip breathing x 10 III: PEP training for 2-3 minutes

IV: Video explaining the pathophysiology of PPCs and instructing all the exercises. preoperatively, at the ward, and after discharge

Hyperlink to the video:

https://api.screen9.com/preview/lSnL3Md0uxXWhO6Xs4A\_xVJFomNBwU6TidIydmn\_ezjV7iNJtXdRwrpdUyTRu0BO

Criteria for discontinuing or modifying allocated interventions Not applicable.

Strategies to improve adherence to interventions

1. An individual risk assessment (Scholes et al., 2009) can be conducted for each recruited patient during the preoperative outpatient visit if need to improve compliance.

2. A reporting template, where the conducted exercises will be marked pre- and postoperatively, will be provided to patients in the intervention group

   Relevant concomitant care permitted or prohibited during the trial The current perioperative practice at the Finnish university hospitals includes preoperative counseling according to the ERAS recommendations for liver surgery (ERAS Society). ERAS protocols recommend physical prehabilitation, adjusting nutritional status and correcting anemia preoperatively. Pulmonary prehabilitation is not included in the ERAS Societys's recommendations for any gastrointestinal procedures.

   Outcomes

   Primary Outcomes:

   Primary outcome is the incidence of PPCs. PPC is diagnosed according to the study by Scholes et al. (Scholes et al., 2009):

   PPC is diagnosed when four or more of the following criteria were present:

   • Chest radiograph re...