Predicting the association of different levels of physical activity on postoperative pulmonary complications using the international physical activity questionnaire in patients undergoing thoracoscopic lung surgery under general anaesthesia: protocol for a prospective cohort study

STRENGTHS AND LIMITATIONS OF THIS STUDY

  • This is a well-designed single-centre, prospective, longitudinal cohort study examining the association between physical activity (PA) levels and postoperative pulmonary complications (PPCs) after thoracoscopic lung surgery.

  • This study uses the International Physical Activity Questionnaire to assess the PA levels of patients due to long-term PA habits.

  • Arterial blood is collected as biological samples and stored for future analysis.

  • A limitation of this study is that the broad and complex definition of PPCs may increase the risk of conflicting results between studies.

  • This study may have limitations that cohort studies may have, such as long follow-up time, prone to loss to follow-up bias.

Introduction

Postoperative pulmonary complications (PPCs) can be defined as a comprehensive outcome measure that includes atelectasis, respiratory failure, pleural effusion, pneumonia, unplanned non-invasive or invasive ventilation, pulmonary congestion, bronchospasm and pneumothorax.1 PPCs are associated with an increase in the length of stay (LOS) (general ward or intensive care unit (ICU)), which is an important indicator of patient prognosis.2 PPCs are also important independent risk factors for high mortality with short-term and long-term.3 4

The incidence of PPCs is common in patients undergoing thoracic surgery, and the incidence can even reach 50%.5 Among them, due to the particularity of characteristics of the surgical site and ventilation mode, patients are more prone to have lung injury after lung surgery, that is, PPCs. As the surgical wound is close to the chest, the risk of infection is relatively high. Moreover, postoperative pain is also reported to affect wound recovery.6–8 Previous studies have suggested that the high concentration of oxygen used during one-lung ventilation in lung surgery can lead to reabsorptive atelectasis, which increases the risk of lung infection and respiratory failure.9 10 In recent years, the widespread use of thoracoscopy in lung surgery has led to a gradual decline in the incidence of PPCs.

The positive impacts of physical activity (PA) on health have been reported for several years. The World Health Organization’s 2020 guidelines on physical activity and sedentary behavior have stated that any PA is meaningful. Adults should be active regularly, replacing sedentary time with PA of any intensity.11 Previous studies have also inspired the positive impacts of high levels of PA on cardiovascular outcomes.12 13 Based on the assessment of the patient’s PA tolerance, anaesthesiologists can preliminarily predict the possibility of postoperative cardiovascular complications to some extent. But whether there is an association between PA levels and PPCs remains unclear at present.

Some studies have implemented specific exercise programmes for patients in the hope that they can achieve a good respiratory prognosis after lung surgery, and most of the primary outcomes predicted are lung function indicators such as maximum ventilatory capacity and maximum oxygen uptake (VO2max).14 15 However, the activity levels caused by these interventions are not a long-term outcome. In this context, anaesthesiologist seems to need an implement to predict the patient’s PA levels that are not instantaneous, but formed by long-term PA habits.

The International Physical Activity Questionnaire (IPAQ) is a tool for the assessment of PA levels based on participants’ recollection of PA (intensity, frequency and duration) within 7 days, which focuses more on PA levels as a result of long-term PA habits.16–18 It is suitable for use in population-based prevalence studies of participation in PA.19 Currently, the IPAQ is mainly used as a public health surveillance indicator in large representative surveys and for comparing PA estimates across borders or regions.20 The IPAQ has been gradually applied in clinical epidemiology to study the relationship between the level of PA and some clinical outcomes, and the level of PA assessed by the IPAQ has been shown to be negatively correlated with health risks such as obesity and cardiovascular disease (CVD) events.21–24

In view of the currently available information, the aim of this study is to (1) investigate the association between PA levels and PPCs after thoracoscopic lung surgery and to prospectively evaluate its prognostic role and (2) investigate whether PA levels are associated with the levels of inflammatory markers, extubation time, postoperative adverse events (PAE), LOS, unplanned ICU admission and short-term postoperative mortality.

Methods and analysis

Study design and setting

The study will be a longitudinal, prospective cohort study lasting 23 months. It will be conducted between May 2022 and March 2024 at The First Affiliated Hospital of Shandong First Medical University. A total of 204 participants aged between 18 and 80 years undergoing elective thoracoscopic lung surgery will be enrolled. The types of surgery include thoracoscopic wedge resection, thoracoscopic segmentectomy and thoracoscopic lobectomy. Participants who meet the inclusion criteria will have to provide written informed consent prior to inclusion. The expected allocation ratio is 1:1 to investigate the association between PA levels and PPCs after thoracoscopic lung surgery and to prospectively evaluate its prognostic role (figure 1). Recruitment of the first case and data collection were completed on 10 May 2022. This protocol is reported in accordance with the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) statement. The SPIRIT 2013 checklist is included as online supplemental data.

Supplemental material

Figure 1
Figure 1

Flow chart. Group A, adequate physical activity (PA) group; Group I, insufficient PA group; ICU, intensive care unit; IPAQ, International Physical Activity Questionnaire; LOS, length of stay; PAE, postoperative adverse events; PPCs, postoperative pulmonary complications.

Participants

Inclusion criteria

Participants will be eligible for inclusion in the study if they meet the following criteria: (1) men/women aged between 18 and 80 years, (2) American Society of Anaesthesiologists (ASA) physical status I–III, (3) scheduled to undergo elective thoracoscopic lung surgery and (4) provision of written informed consent for surgery.

Exclusion criteria

Participants will be excluded from the study if they meet one or more of the following criteria: (1) moderate or severe chronic obstructive pulmonary disease (global initiative for chronic obstructive lung disease Grade III or IV level grade), (2) severe or uncontrolled bronchial asthma, (3) severe neuromuscular disease or thoracic malformation, (4) severe heart disease (New York Heart Association Class III or IV level grade or acute coronary syndrome or persistent ventricular arrhythmia), (5) cognitive dysfunction, (6) coagulation dysfunction, (7) participation in other clinical trials within the previous 30 days and (8) have received radiotherapy or chemotherapy within 2 months prior to surgery.

Procedures

The day before the surgery, the patients will be assessed for eligibility for inclusion in the study. All eligible patients will sign an informed consent form after receiving an in-depth explanation regarding the study process, potential benefits and risks. All patients will be asked to complete the IPAQ based on their levels of PA. Recall time for patients to answer the questionnaire is set to 1 week prior to admission. The questionnaire can be self-administered or administered by telephone. The patients will be classified into group A, the adequate PA group (≥ 5 days of any combination of walking, moderate-intensity or vigorous-intensity activities achieving a minimum total PA of at least 600 MET-minutes/week), and group I, the insufficient PA group (≥ 5 days of any combination of walking, moderate-intensity or vigorous-intensity activities achieving a maximum total PA lower than 600 MET-minutes/week) according to the International Manual of Physical Activity classification criteria.

All patients will receive anaesthesia according to the same predefined anaesthesia management plan. Standard monitoring (ECG, non-invasive arterial blood pressure and saturation of pulse oxygen (SPO2)) will be performed after the patient enters the operating room. Subsequently, peripheral venous access and radial artery invasive arterial pressure monitoring will be established. Induction will be performed with midazolam (0.05–0.1 mg/kg), propofol (2.0–3.0 mg/kg), sufentanil (0.3–0.5 ug/kg) and atracurium (0.3–0.6 mg/kg). After 3 minutes of preoxygenation, orotracheal intubation will be performed with a bronchial catheter, and correct placement will be verified with a fibre-optic bronchoscope. The parameters applied during two-lung ventilation will be as follows: volume-controlled ventilation with a tidal volume of 6 mL/kg of the predicted body weight, positive end-expiratory pressure (PEEP) level of 5 cmH2O, fraction of inspired oxygen (FiO2) of 0.4–0.5 and a respiratory rate adjusted to maintain the end-tidal carbon dioxide (ETCO2) between 35 and 45 mm Hg. The values applied during one-lung ventilation will be as follows: tidal volume of 6 mL/kg of the predicted body weight, PEEP level of 5 cmH2O, permissive hypercapnia and FiO2 of 0.8–1.0 to maintain a SpO2 of >95%. Intraoperative anaesthesia will be maintained using propofol (4–10 mg/kg/h), remifentanil (0.1–0.3 ug/kg/min) and atracurium (0.3–0.6 mg/kg/h). The bispectral index (BIS) value will be maintained at 40–60. The following respiratory parameters will be recorded immediately after bronchial intubation, 1.5 hours after the start of surgery and 3 hours after the start of surgery: heart rate, arterial blood pressure, SPO2, BIS, FiO2, tidal volume, minute ventilation, respiratory rate, ETCO2, peak pressure, plateau pressure and end-expiratory pressure. Arterial blood samples will be collected before the induction of anaesthesia, 1.5 hours after the start of the surgery, 3 hours after the start of the surgery and 1 hour after the end of the surgery. The samples will be centrifuged, and the supernatant will be analysed in a specialised laboratory. An ELISA will be used to detect the levels of serum inflammatory indicators (interleukin (IL)-6, IL-8 and tumour necrosis factor (TNF)-α). All arterial blood samples obtained during the procedure will be analysed for blood gases, and the index results will be recorded. At the end of the surgery, the patients will be referred to the post-anaesthesia care unit after assessment. The extubation time will be recorded after removing the bronchial catheter and the recovery of consciousness. Thereafter, the patient will be returned to the ward. Cases with severe complications will be transferred to the ICU after the surgery for further intensive monitoring and treatment.

After the patient returns to the ward, an investigator blinded to the group allocation will evaluate the patient daily for 5 days and record the outcomes, including the incidence of PPCs, number of PPCs and incidence of PAE. One month postoperatively, doctors will re-evaluate the incidence and recovery of PPCs and calculate the mortality of patients. At this time, all patients will undergo chest CT re-examination in the outpatient clinic, which will be a good reference. Investigators will contact patients who were not evaluated in person by telephone if required. Figure 2 illustrates the data table that will be used to record the above-mentioned details.

Figure 2
Figure 2

Participant timeline. Group A, adequate physical activity (PA) group; Group I, insufficient PA group; ICU, intensive care unit; LOS, length of stay; PAE, postoperative adverse events; PPCs, postoperative pulmonary complications; T0, before induction of anaesthesia; T1, immediately after bronchial intubation; T-1, the day before the surgery; T2, 1.5 hours after the start of surgery; T3, 3 hours after the start of surgery; T4, 1 hour after the end of surgery; T5, within postoperative 5 days; T6, 1 month after the surgery.

Outcomes

Primary outcome

The primary outcome of this study is the incidence of PPCs within the first 5 postoperative days. PPCs include eight respiratory events, and the occurrence of any one or more of the following respiratory events will be defined as the occurrence of PPCs.

  1. Atelectasis: atelectasis will be defined as the presence of pulmonary opacities; shift of the mediastinum, hilum and diaphragm towards the affected area; and compensatory overinflation of adjacent non-atelectatic pulmonary tissue.1

  2. Respiratory failure: respiratory failure will be defined as the presence of a postoperative partial pressure of oxygen of <60 mm Hg on room air; a ratio of oxygen partial pressure to inhaled oxygen concentration of <300 mm Hg; or an arterial oxygen saturation of <90% as measured by pulse oximetry, with the requirement of oxygen therapy.1 25

  3. Pleural effusion: pleural effusion will be defined as the presence of a blunted costophrenic angle, displacement of adjacent anatomical structures, loss of the clear contour of the ipsilateral hemidiaphragm in the upright position or vague opacity of the lower hemidiaphragm in the supine position with preserved vascular shadow on a chest radiograph.1 25

  4. Pneumonia: according to the Centers for Disease Control and Prevention, pneumonia will be defined as follows26:

    Two or more serial chest radiographs showing at least one of the following:

    (1) Infiltration, (2) consolidation and (3) cavitation

    At least one of the following:

    1. Fever (> 38°C) of unknown origin;

    2. Leucopenia (white blood cell count < 4 × 109/L) or leucocytosis (white blood cell count > 12 × 109/mm3);

    3. Unexplained altered mental status in an adult over 70 years of age.

    At least two of the following:

    1. New purulent sputum or change in sputum quality, increased respiratory secretions or increased need for sputum suction;

    2. New or aggravated cough, shortness of breath or dyspnoea;

    3. Rales or bronchial breath sounds;

    4. Worsening of gas exchange (hypoxemia, increased oxygen demand or increased ventilator demand).

  5. Unplanned non-invasive or invasive ventilation.

  6. Pulmonary congestion: in 2015, the European Society of Cardiology recommended a chest ultrasound as a first-line imaging modality for the assessment of pulmonary congestion.27 B-lines are one or more vertical, comet-like lines that fan out from the pleural line observed under ultrasonography. The total number of B-lines in the anterolateral chest scan is referred to as the B-line score (table 1). Under normal conditions, a maximum of two B-lines per single intercostal space and five B-lines are observed on the comprehensive anterolateral chest scan, and these are more commonly present in the laterobasal areas.28

  7. Bronchospasm: newly detected expiratory wheezing treated with bronchodilators.25

  8. Pneumothorax: air in the pleural space with no vascular bed surrounding the visceral pleura.25

Table 1

Scoring of B-lines

The diagnosis of atelectasis, pleural effusion and pneumothorax will be made based on the findings observed on chest radiographs.1

Secondary outcomes

  1. The number of PPCs

  2. The incidence of PPCs 1 month postoperatively

  3. The arterial blood levels of inflammatory markers (IL-6, IL-8 and TNF-α)

  4. Extubation time

  5. The incidence of PAE within the first 5 postoperative days, including the following:

    1. Arrhythmia

    2. Acute CVD (myocardial infarction and heart failure)

    3. Acute cerebrovascular disease (cerebral infarction and cerebral haemorrhage)

    4. Acute postoperative psychiatric disorder (delirium, somnolence and coma)

    5. Shock

  6. Postoperative LOS

  7. Unplanned admission to the ICU

  8. Mortality 1 month postoperatively

The arterial blood gas analysis and partial preoperative and postoperative test results will also be recorded as these data are of significance for the diagnosis of systemic complications in the patients.

Sample size estimation

We set the statistical power to 0.90 and the two-sided type I error to 0.05. Based on the literature review, we assumed that the incidence of PPCs would be 26.0% and 50.0% in groups A and I, respectively.5 29 Based on these data, we calculated that the sample size should be 81 cases for each group. Allowing for a 20% loss to follow-up and rejection of follow-up, we determined that 102 patients must be enrolled in each group, resulting in a final total of 204 patients.

Statistical analysis

Continuous variables will be described by mean ± SD or median (IQR), and normality will be assessed using the Kolmogorov-Smirnov test. Comparison of quantitative variables will be conducted using Student’s t-test or the Mann-Whitney U-test. Categorical variables will be expressed as a number of cases and percentage, and compared among two or more groups using the χ2 test or Fisher’s exact test.

Multiple logistic regression analysis of factors with statistically significant differences using univariate comparisons will be performed to identify the risk factors for PPCs, and adjusted ORs and 95% CIs will be calculated. A univariate analysis model will be constructed including age, sex, the ASA physical status, body mass index, duration of surgery, smoking status, preoperative anaemia (haemoglobin ≤ 100 g/L), type of postoperative analgesia, type of surgery, chronic obstructive pulmonary disease, hypertension, diabetes and coronary heart disease as independent variables. These variables have been preselected based on the prior literature review and clinical sensitivity. The statistical analysis will be performed using SPSS V. 26.0, and P-values < 0.05 will be considered statistically significant.

Data collection and management

The investigators will use an electronic medical record system to record basic patient information in a case report form (CRF). Data on anaesthesia during surgery will be collected via the anaesthesia record sheet. Patients will be followed up after the surgery by another member of the research team, and the results will be recorded in the CRF. All data will be recorded and entered synchronously into the electronic CRF. The personal information of the patients will be maintained confidential. The consent forms and CRF will be stored in a locked research cabinet. At the end of the study, all data will be consolidated and exported to a secure database for further analysis, and the results will be stored therein for at least 10 years. Only the researchers involved in this study will have the right to obtain study data.

Patient and public involvement

No patients or members of the public will be involved in study recruitment or development of the study design and outcome measures.

Discussion

The objective of this single-centre, prospective, longitudinal cohort study is to investigate the association between PA and the incidence of PPCs after undergoing thoracoscopic lung surgery. The use of the IPAQ in this study will strengthen the feasibility and reliability of this questionnaire for clinical risk assessment.

There are several potential advantages to the current study. We will conduct this well-designed cohort study in a single centre to ensure strict consistency in the implementation of the study. Additionally, extrapulmonary complications and haematologic parameters will also be examined to capture an accurate picture of patient outcomes. Some current studies have analysed the predictors of morbidity and mortality in patients undergoing lung surgery. However, inflammatory markers were not been included in these studies.30 31 Our clinical study will measure the levels of inflammatory markers in arterial blood and verify the predictive properties of these markers for postoperative complications.

However, there are several limitations to this study. The current age range for use of the IPAQ is 15–69 years. Thus, older patients aged over 70 years will be excluded. Nevertheless, the available literature suggests that patients aged over 65 years of age in the criteria for the IPAQ is necessary and feasible, but care must be taken to prevent excessive errors. In addition, although the specific content of the questionnaire will be explained to patients to the best of the investigators’ ability, it is inevitable that patients will have doubts regarding some of the questions. Moreover, the importance that patients attach to their state of illness and their financial situation affects their decision to visit the outpatient clinic of the hospital at which they undergo the surgery, after discharge. This aspect should also be taken into account.32 Patients’ hospitalisations for their condition may lower their current PA levels, and PA habits that may protect them over a longer period of time may not be captured by the IPAQ. So we will ask patients to respond to the questionnaire with a recall time set to 1 week before admission to minimise the effect of this bias. The study may also have limitations that other cohort studies may have, such as long follow-up time, prone to loss to follow-up bias, difficulty in data collection and implementation, and the introduction of unknown variables during follow-up may affect the outcomes and complicate the analysis.

Furthermore, the study plan does not include obtaining measurements of the level of inflammatory markers in the bronchial alveolar fluids. However, considering that this study mainly aims to observe the general postoperative complications in patients, assessing local inflammatory responses may be beyond the scope of the study.30

There are several limitations with reference to PPCs. First, there are some differences in the definition of PPCs, and there is no uniform standard in clinical practice. Second, although many current studies point to risk factors that may contribute to PPCs, many other factors may be involved, and it is difficult to identify these independent factors.33 34 Therefore, this may need that we further research.

Ethics and dissemination

The study was approved by the ethics committee of The First Affiliated Hospital of Shandong First Medical University on 31 March 2022 (YXLL-KY-2022(014)) and registered at ClinicalTrials.gov. The study will be implemented after obtaining informed consent from the participating patients, and participation will be completely voluntary. All participants will provide written consent for the publication of their data and findings before joining the study. The results of this study will be disseminated at national and international scientific conferences. We also plan to publish these data in a peer-reviewed international scientific journal.

Ethics statements

Patient consent for publication

Acknowledgments

We would like to thank the staff at the Center for Big Data Research in Health and Medicine, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, for their valuable contribution. We also thank all the collaborators and participants for their support during this study.

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