Non-invasive positive pressure ventilation for prevention of complications after pulmonary resection in lung cancer patients

  • Protocol
  • Intervention


  • Maria FS Torres,

    Corresponding author
    1. Universidade Federal de São Paulo, Evidence-based Medicine, São Paulo, Brazil
    • Maria FS Torres, Evidence-based Medicine, Universidade Federal de São Paulo, Martiniano de Carvalho, 669 / Complement 805 - Bela Vista, São Paulo, 04039-001, Brazil.

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  • Alan PV Carvalho,

    1. Universidade Federal de São Paulo, Urgency Medicine, São Paulo, São Paulo, Brazil
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  • Rachel Riera

    1. Centro de Estudos de Medicina Baseada em Evidências e Avaliação Tecnológica em Saúde, Brazilian Cochrane Centre, São Paulo, São Paulo, Brazil
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This is the protocol for a review and there is no abstract. The objectives are as follows:

To assess the effectiveness and safety of NIPPV for prevention of complications in patients who underwent pulmonary resection for lung cancer (SCLC or NSCLC).


Description of the condition

Lung cancer is the most common malignant tumour and accounted for 1.37 million deaths worldwide in 2008 according to World Health Organization (WHO). It is one of the malignant tumours that causes most deaths in the world, being the second most common cancer in men, after prostate, and in women, after breast cancer. In about 87% of cases, smoking is related to the diagnosis and proves to be the main risk factor for disease development. Other risk factors are exposure to ultraviolet and ionising radiation, random gas and asbestos; viral infection and genetic factors (Ferlay 2010; Jemal 2011; NICE 2011).

Symptoms such as haemoptysis, cough, shortness breathing or dyspnoea, chest pain, hoarseness, weight loss, and finger clubbing can be often observed as clinical manifestations and an X-ray or chest computed tomography should be performed. If there is an image suggestive of lung cancer, the patient should be referred promptly to a specialist and more specific tests will be required in order to confirm the diagnosis, identify the type of cancer and the stage of the lesion (Rivera 2007).

There are several different types of lung cancer, but it is usually classified into two major groups: non-small-cell lung carcinoma (NSCLC) and small-cell lung carcinoma (SCLC). The most common treatment with curative intent for NSCLC is surgery. It is indicated for patients with stages I and II disease who are fit to tolerate surgery. An overall risk score, such as Thoracoscore, is used in order to estimate the risk of operative death. The treatment of choice is lobectomy (either open or thoracoscopic) (NICE 2011).

Factors such as the duration of surgery, duration of anaesthesia and mechanical ventilation may contribute to postoperative morbidity and mortality. The type and extent of surgery can reduce these complications. For example video-assisted thoracic surgery is less invasive than open thoracotomy and may result in fewer complications. One retrospective descriptive study conducted at the Siriraj University Hospital, Thailand, between 2006 and 2010 studied 512 patients. The objective was to determine the morbidity and mortality in pulmonary resection surgery using clinical data. About 70% of all patients underwent pulmonary resection for lung cancer and 39.5% experienced morbidity or mortality (Igai 2009; Kutlu 2000; Suksompong 2012).

Mortality and morbidity after lung resection are usually caused by complications during the postoperative period often related to pulmonary complications, such as acute lung injury, acute respiratory distress syndrome and pneumonia. To minimise these postoperative respiratory complications, some authors recommend the use of non-invasive positive pressure ventilation (NIPPV). Using this support may help to expand the lungs, prevent atelectasis, prevent hypoxaemia, and mobilise intrapulmonary secretions thus preventing their accumulation and resultant pneumonia (Brooks-Brunn 1995; Kutlu 2000; Lorut 2005; Perrin 2007).

Description of the intervention

NIPPV can be defined as a technique that provides pressurised gas to the airway, promoting increased transpulmonary pressure, inflating the lungs through a mask or interface, and which does not use an invasive route (e.g. endotracheal tube, oronasal tube or tracheostomy). Physiologically, this technique promotes an increase in functional residual capacity and recruitment of collapsed airways, providing better oxygenation, reducing carbon dioxide (CO2) retention and decreasing the work of breathing (Brochard 2002; Schettino 2007).

There are two types of NIPPV: continuous positive airway pressure (CPAP), where only one pressure level is employed at end-expiration, and bi-level positive airway pressure, which employs two pressure levels (inspiration/end-expiration). The main difference is that the bi-level type can increase the tidal volume and may help during the inspiratory phase (Vital 2008; Schettino 2007).

Some studies have shown benefits from the use of NIPPV in the treatment of acute respiratory failure, the most common postoperative complication following abdominal or thoracic surgery. Other complications which may be avoided by the use of NIPPV include hypercapnia, hypoxaemia, atelectasis, pleural fistula and respiratory muscle dysfunction. (Martin 2000; Auriant 2001).

Published clinical trials have demonstrated that the use of NIPPV can reduce the number of pulmonary complications and mortality. This makes it possible to reduce the length of hospital stay and hospital costs (Nakagawa 2001; Arozullah 2003; Lorut 2005).

How the intervention might work

The use of NIPPV (CPAP or bi-level) promotes increased lung volumes because of recruitment of collapsed airways, leading to a better oxygenation of tissues and increased lung capacity. Atelectasis, lung infections, bronchial congestion and consequent acute respiratory failure can be prevented (Brochard 2002).

Therefore, the intervention aims to minimise the risk of complications, reduce the length of hospital stay and the need for re-intubation.

Why it is important to do this review

In recent years trials have been published focusing on this intervention and therefore it seems to be relevant to objectively review the results.


To assess the effectiveness and safety of NIPPV for prevention of complications in patients who underwent pulmonary resection for lung cancer (SCLC or NSCLC).


Criteria for considering studies for this review

Types of studies

Randomised controlled trials (RCTs) with no restriction regarding intervention and follow-up length. Cross-over trials will not be included.

Types of participants

Patients aged above 18 years of both genders, who underwent any type of lung resection (pneumectomy, lobectomy, segmentectomy) for lung cancer (SCLC or NSCLC), associated or not with chemotherapy or radiotherapy.

Types of interventions

Intervention: NIPPV initiated in the immediate postoperative period, defined as the first 24 hours after the surgery (CPAP mode or bi-level positive airway pressure mode) applied through a nasal or facemask.

Comparison: oxygen therapy in order to obtain pulse oxymetry oxygen saturation (SpO2) ≥ 92% or arterial partial pressure of oxygen (PaO2) ≥ 65 mmHg; chest physiotherapy techniques for removing secretions; breathing exercises; incentive spirometry; no intervention.

Types of outcome measures

All outcomes described below will be analysed if the authors describe the method of assessing the outcome, or a validated and recognised instrument may be replicated.

Primary outcomes
  • Pulmonary complications rate (i.e. pulmonary infections, bronchial congestion, atelectasis, acute lung injury, pleural fistula).

  • Rate of intubations.

  • Mortality.

Secondary outcomes
  • Non-pulmonary complications rate (i.e. sepsis).

  • Postoperative consumption of antibiotics.

  • Length of intensive care unit stay.

  • Length of hospital stay.

  • Adverse effects related to NIPPV (i.e. skin damage, pulmonary aspiration, gastric distension, vomiting, asphyxia, pneumothorax, conjunctivitis, sinusitis, mask discomfort, claustrophobia).

Search methods for identification of studies

Electronic searches

We will search in the databases Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, current Issue), MEDLINE, EMBASE, CINAHL, LILACS and PEDro, to identify potentially eligible trials by using database-specific search strategies. We will not limit our search by language or publication status. A specific filter for clinical trials will be used for each database.

1) Search terms for MEDLINE (accessed via PubMed) (Appendix 1)

Searching other resources

To identify additional information, potential trials will be sought from references of primary studies and review articles.

Conference and abstract proceedings will be checked.

Authors and experts in the field will be contacted to identify published and unpublished trials.

To identify ongoing studies we will access and

RCTs published only as abstracts will also be included and the authors will be contacted for further information on the study.

Data collection and analysis

Selection of studies

Two review authors (Torres MFS; Carvalho APV) will independently assess the titles and abstracts of studies retrieved in the search in order to ascertain whether or not they represent potentially relevant trials. Based on this first assessment, we will obtain the full text of all potentially relevant articles. Any disagreement will be resolved by a third review author (Riera R).

Data extraction and management

We will extract the data and record them by using data extraction forms, based on the standardised form described in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011) and this will be adapted to suit the study. The form will be developed and headed by two review authors (Carvalho APV; Torres MFS) working independently and must contain:

  1. characteristics of the study: design; risk of bias;

  2. participants: inclusion criteria; age; type of lung resection; number enrolled in each group;

  3. intervention: NIPPV (CPAP or bi-level); type of physiotherapy (chest physiotherapy techniques for removing secretions, breathing exercises, incentive spirometry); frequency and duration of therapy; oxygen therapy and co-interventions;

  4. outcomes: types of outcome measures; timing of outcomes; adverse effects.

Full data extraction will be conducted by these two review authors independently and disagreements will be settled by a third review author (Riera R).

Assessment of risk of bias in included studies

Two review authors (Torres MFS; Carvalho APV) will assess the methodological quality of each study independently by using the tool described in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). Appraisal will follow the 'Risk of bias' (RoB) model created by The Cochrane Collaboration (Higgins 2011). For each RoB domain detailed below, the authors will assign either 'low risk of bias', 'high risk of bias' or 'unclear risk of bias'.

1. Random sequence generation

Was the allocation sequence adequately generated?

2. Allocation concealment

Was allocation adequately concealed?

3. Blinding of participants and personnel

We cannot consider blinding of participants, since it is not possible to blind the patients with this type of intervention and there is no possibility of preventing the outcome assessors from becoming aware of the interventions during the studies.

4. Blinding of outcome assessment

Were the evaluators aware of the results of the outcomes of the assigned interventions? This item will be evaluated on the outcome level.

5. Incomplete outcome data

Did the study describe the completeness of outcome data for each main outcome, including attrition and exclusions from the study?

6. Selective reporting

How the possibility of selective outcome reporting was examined by the review authors, and what was found?

7. Other sources of bias

Have important questions about bias not addressed in other areas of the tool been indicated? For example non-standard design (cross-over or cluster-randomised trials) or specific circumstance (interventions are mixed).

Measures of treatment effect

For each outcome, we will calculate summary estimates of treatment effect (with 95% confidence interval (CI)) for each comparison. For continuous outcomes, mean differences (MD) will be present for measures in the same scale, and standardised mean difference (SMD) will be present for measures that used different scales. For dichotomous outcomes, we will use risk ratio (RR) and number needed to treat for an additional beneficial outcome (NNTB) or number needed to treat for an additional harmful outcome (NNTH). However NNTB and NNTH will not be used for meta-analysis.

Unit of analysis issues

The individual patient will be considered as the unit of analysis.

Dealing with missing data

Where data are missing or unsuitable for analysis, we will contact the authors to request further information. Where data are missing to the extent that the study cannot be included in the meta-analysis and attempts to retrieve data have been exhausted, we will present the results in the review and discuss in the context of the findings.

Missing data will be described according to recommendations presented in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011).

Assessment of heterogeneity

We will do a visual inspection of forest plots to assess heterogeneity between studies. We will investigate the following factors as potential causes of heterogeneity in the included studies using the I2 statistic. We will consider as substantial heterogeneity I2 values above 50% (Higgins 2011).

  1. Clinical heterogeneity: will include study location and setting, full characteristics of participants (i.e. age, gender, smoking, type of tumour, type of surgery), co-morbidity (i.e. cardiovascular disease, chronic obstructive pulmonary disease, diabetes, chronic renal disease) and treatments that participants may be receiving on trial entry (i.e. previous or adjuvant chemotherapy, radiotherapy, or a combination). We will consider how outcomes were measured, the definition of outcomes (i.e. mild, moderate, severe; short, middle and long term - both classifications as defined by included studies), and how they were recorded. Depending upon the extent of the clinical diversity, we will either analyse studies separately or present the results using a narrative approach.

  2. Methodological heterogeneity: will include assessment of the randomisation process, study quality and analytical method.

Assessment of reporting biases

We will search for protocols of included trials using PubMed (National Library of Medicine) and through the UK and other trial registries, where possible. We will contact study authors to attempt to establish a full data set or reasons for the non-reporting of certain outcomes.

If we find at least 10 studies we will examine the funnel plot for the primary outcome to try to identify publication bias.

Data synthesis

We will synthesise data using Review Manager (RevMan 2011) through the forest plot graphics using a fixed-effect model. Where a substantial heterogeneity exists, a random-effects model will be applied. Where data aggregation is not possible, the results of individual studies will be presented in tables or graphics and discussed.

Subgroup analysis and investigation of heterogeneity

The following subgroups will be considered when possible:

  • smoking;

  • type of resection (segmentectomy, lobectomy, pneumectomy);

  • length of the NIPPV;

  • intermittent or continuous NIPPV approach;

  • ventilatory mode (CPAP or bi-level).

Sensitivity analysis

We will conduct sensitivity analyses excluding trials with high risk of bias (Higgins 2011). We will consider and discuss the results of these analyses in comparison to the overall findings.


We appreciate the help that the Cochrane Lung Cancer Group gave us during the implementation of the protocol, in particular Sera Tort, Ivan Solà, Ramon Rami, Mia Schmidt-Hansen, Tajender Vasu, Marta Roqué and Desiree West (Consumer). We also thank the Cochrane Center of Brazil for their support.


Appendix 1. MEDLINE search strategy

#1 Positive-Pressure Respiration[MeSH]

#2 positive pressure ventilation[tiab]

#3 pressure support ventilation[tiab]

#4 noninvasive ventilatory support[tiab]

#5 non invasive ventilatory support[tiab]

#6 NIVS[tiab]

#7 NPPV[tiab]

#8 NIPSV[tiab]

#9 #1 OR #2 OR #3 OR #4 OR #5 OR #6 OR #7 OR #8

#10 Pneumonectomy[MeSH]

#11 lung resection*[tiab]

#12 lobectom*[tiab]

#13 pneumonectom*[tiab]

#14 #10 OR #11 OR #12 OR #13

#15 #9 AND #14

#16 (randomized controlled trial[pt] OR controlled clinical trial[pt] OR randomized[tiab] OR placebo[tiab] OR drug therapy[sh] OR randomly[tiab] OR trial[tiab] OR groups[tiab]) NOT (animals[mh] NOT (humans[mh] AND animals[mh]))

#17 #15 AND #16

Contributions of authors

  • Conceiving the review: Maria FS Torres (Torres MFS); Alan PV Carvalho (Carvalho APV); Rachel Riera (Riera R).

  • Designing the review: Torres MFS, Riera R.

  • Co-ordinating the review: Riera R.

  • Data collection for the review: Torres MFS, Carvalho APV.

  • Designing search strategies: Torres MFS.

  • Undertaking searches: Torres MFS, Carvalho APV.

  • Screening search results: Torres MFS, Carvalho APV.

  • Organising retrieval of papers: Torres MFS, Carvalho APV.

  • Screening retrieved papers against eligibility criteria: Torres MFS, Carvalho APV.

  • Appraising quality of papers: Torres MFS, Carvalho APV.

  • Extracting data from papers: Torres MFS, Carvalho APV.

  • Writing to authors of papers for additional information: Torres MFS, Carvalho APV, Riera R.

  • Providing additional data about papers: Torres MFS, Carvalho APV, Riera R.

  • Obtaining and screening data on unpublished studies: Torres MFS, Carvalho APV, Riera R.

  • Data management for the review: Torres MFS.

  • Entering data into RevMan: Torres MFS.

  • Analysis of data: Torres MFS, Carvalho APV.

  • Interpretation of data: Torres MFS, Carvalho APV.

  • Providing a methodological perspective: Torres MFS.

  • Providing a clinical perspective: Torres MFS.

  • Providing a policy perspective: Torres MFS.

  • Providing a consumer perspective: Torres MFS.

  • Writing the review (or protocol): Torres MFS.

  • Providing general advice on the review: Torres MFS.

  • Securing funding for the review: Torres MFS.

  • Performing previous work that was the foundation of the current review: Torres MFS.

Declarations of interest

There is no conflict of interest.

Sources of support

Internal sources

  • Brazilian Cochrane Center, Brazil.

External sources

  • There are no sources of support, Brazil.