Study registration
This systematic review has been registered with PROSPERO (registration number: CRD 42020207555). This protocol was prepared according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) guidelines. The review will be conducted in accordance with the PRISMA guidelines [37,38]. The study is expected to begin searching in May 2021 and end in November 2021.
Eligibility criteria
Inclusion criteria
Type of studies We will include randomized controlled trials (RCTs) that evaluated the PCV-VG, dual-controlled ventilation or PRVC ventilation for intraoperative mechanical ventilation in adults (aged 18 years old or over). Only studies published in English or Chinese will be included. No time limits will be applied to the searches.
Types of participants Adult Participants (18 years of age or older) undergoing operations requiring intraoperative mechanical ventilation will be included. Intraoperative mechanical ventilation with PCV-VG, PRVC or dual-controlled ventilation will be included. There will be no limits on study participants in terms of gender, ethnicity and types of surgery.
Types of interventions In the intervention group, participants had to have received intraoperative mechanical ventilation with PCV-VG, PRVC or dual-controlled ventilation.
Types of comparators The comparator group will be the participants received intraoperative mechanical ventilation with conventional mechanical ventilation modes (Such as VCV or PCV)
Type of outcome measurements
Primary outcomes The primary outcome will be the incidence of PPCs, expressed as risk ratio (RR). PPCs being defined as the composite of any of respiratory infection, respiratory failure, pleural effusion, atelectasis, or pneumothorax, as defined in the definition of postoperative respiratory complications from European Perioperative Clinical Outcome (EPCO) consensus statement and the recent consensus definitions [39,40].
Secondary outcome The secondary outcomes will be:
- Intraoperative gas exchange parameters: arterial partial pressure of oxygen (PaO2); arterial oxygen saturation (SaO2); arterial partial pressure of carbon dioxide (PaCO2); pressure of end-tidal carbon dioxide (PEtCO2); oxygenation index [PaO2/ fraction of inspiration O2 (FiO2)]; Physiologic Dead-space to Tidal Volume [Dead space volume (VD) /Tidal volume (VT)].
- Intraoperative respiratory parameters: peak inspiratory pressure (Ppeak), mean inspiratory pressure (Pmean), plateau inspiratory pressure (Pplateau), pulmonary dynamic compliance (Cdyn).
- Intraoperative hemodynamic parameters: mean arterial pressure (MAP), heart rate (HR), central venous pressure (CVP).
Exclusion criteria
Studies with the following situations will be excluded: (a) participants undergoing emergency surgery; (b) participants with respiratory complications before surgery; (c) studies with insufficient data or without an effective classification; duplicated data or data that cannot be extracted; (d) crossover trials, cluster-RCTs, quasi-RCTs, uncontrolled trial, animal study, review, comment, case report, case series, non-clinical study.
Databases and search strategy
The following electronic databases will be searched from inception: English database including-PubMed, Web of Science, Cochrane Library, Ovid MEDLINE and Embase; Chinese database including-China National Knowledge Infrastructure (CNKI), Chinese BioMedical Literature, Wanfang database and VIP Database. These electronic databases will be searched from inception to May 2021. In addition, we will scrutinize the list of references, relevant conference literature, dissertations and trial registry database (WHO International Clinical Trials Registry Platform and Clinical Trials.gov) to overcome the publication bias due to identify additional studies.
The search strategy for PubMed (as an example) is shown in table 1. The following search terms will be used singly or as combinations (MeSH terms and free words): pressure-controlled volume guaranteed, PCV-VG, dual controlled ventilation, pressure regulated volume controlled, PRVC, intraoperative and randomized controlled trial. The search terms will be translated into Chinese for study identification in Chinese databases. Prior to final publication, we will perform a new search in the databases to check if any studies were published during the elaboration of the systematic review. The preliminary search strategy of other electronic databases is given in (online supplementary additional file 1).
Table 1 Search strategy applied in PubMed
#1 (((((((((((((((Pressure controlled volume guaranteed[Title/Abstract]) OR (Pressure-controlled volume-guaranteed[Title/Abstract])) OR (Pressure-controlled Ventilation with Volume Guarantee[Title/Abstract])) OR (Pressure-controlled volume guaranteed[Title/Abstract])) OR (pressure-controlled ventilation-volume guaranteed[Title/Abstract])) OR (pressure-controlled ventilation volume guaranteed[Title/Abstract])) OR (Pressure-controlled ventilation with volume-guarantee[Title/Abstract])) OR (pressure support ventilation with volume guarantee[Title/Abstract])) OR (pressure support ventilation plus volume guarantee[Title/Abstract])) OR (pressure support plus volume guarantee[Title/Abstract])) OR (Volume-guaranteed pressure-support[Title/Abstract])) OR (volume-guaranteed pressure-regulated[Title/Abstract])) OR (PCV-VG[Title/Abstract])) OR (Dual controlled ventilation[Title/Abstract])) OR (Pressure Regulated Volume Controlled[Title/Abstract])) OR (PRVC[Title/Abstract])
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#2 (Surgical Procedures, Operative [MeSH Major Topic]) OR (((((((Operat*) OR (surger*)) OR (surgical)) OR (intraoperat*)) OR (intra-operat*)) OR (Peri-operat*)) OR (Perioperat*))
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#3 ((((((controlled clinical trial [Publication Type]) OR (randomized controlled trial [Publication Type])) OR (randomized [Title/Abstract])) OR (randomized [Title/Abstract])) OR (Placebo [Title/Abstract])) OR (randomly [Title/Abstract])) OR (Clinical trial [Title])
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#4 (animals [MeSH Terms]) NOT ((human [MeSH Terms]) AND (animals [MeSH Terms]))
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#5 #1 and #2 and #3 not #4
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*Represents multiple characters
Study selection
Two authors (JQZ and LD) will independently perform study selection based on pre-designed eligibility criteria. All searched records will be imported into citation management system (Endnote X9), and we will filter and remove all duplicates. First, all studies will be identified by screening titles/abstracts, and irrelevant records will be eliminated. Then, the full text of potential studies will be obtained and checked against all pre-designed inclusion criteria. If divergences occur, a third author will help determine and solve them to reach a final decision about whether the trial meets the eligibility criteria through discussion or consensus meeting.
Two reviewers (JQZ and LD) will be required to screen the retrieved studies independently. We will import the searched records into citation management system (Endnote X9), filter and remove all duplicates. Briefly, they will exclude studies not matching the inclusion criteria by reading title and abstracts. Then they will read the full text of each study to select those meeting the inclusion criteria. Any disagreements will be resolved through discussion with a third reviewer (JW). A fourth reviewer (LZ) will check all procedures before approving the data extraction. The entire study selection process is shown in the flow diagram (figure 1).
Data extraction and management
Two reviewers (JQZ and XQD) will extract data from the included studies independently following a previously designed standard data acquisition excel form. The form will include the basic information (e.g., first author, title, journal, country, year of publication, and sample size), patient characteristics (e.g., age, sex, body mass index, eligibility criteria, surgical type and surgical position), study design and quality (e.g., random sequence generation, allocation concealment and blinding methods), detail information of interventions and controls [e.g., conventional ventilation mode (PCV-VG, VCV or PCV) , ventilation mode (One lung ventilation, two lung ventilation), intra-abdominal pressure during pneumoperitoneum, target value of tidal volume, inspiratory to expiratory ratio (I/E), respiratory rate (RR), FiO2, positive end-expiratory pressure (PEEP), target value of PETCO2], outcome measures, conflicts of interest, and any other relevant information. Third reviewer (GC) will double-check the data to ensure consistency.
If necessary, we will extract numerical data from graphs using Adobe Photoshop as described by Sevda Gheibi [41]. If data are missing or incomplete in any study, we will contact with the authors to obtain the original data. In case it is impossible to obtain the data, to ensure the statistical power and avoid bias, the last observation carried forward imputation method will be used to assume a missing value and then an intent-to-treat analysis and sensitivity analysis will be performed to assess whether that the results are consistent.
For continuous outcome data, the mean differences (MDs) or the standardised mean difference (SMDs) with 95% confidence intervals (CIs) will be used for analysis. For dichotomous data, the RR with 95% CIs will be used for analysis.
Assessment of risk of bias
The risk of bias in the included studies will be determined by two reviewers (JW and LZ) independently using the Cochrane Collaboration tool [42]. The Cochrane Collaboration’s tool covers six aspects, random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, selective reporting and other bias. The risk will be divided into three levels (low risk, unclear and high risk) in accordance with the item in the checklist. If any disagreements, the risk assignment will be settled through arbitration of a third reviewer (GC).
Quality of evidence
The modified Jadad scale will be applied to assess the quality of literatures [43,44]. The overall quality of included studies will be conducted in eight Items: randomization (with score 0-2), allocation concealment (with score 0-2), blinding (with score 0-2), withdrawals and dropouts (with score 0-1) adverse effects (with score 0-1), and statistical analysis (with score 0-1) (Table 2). Scale scores for each study could range from 0 to 8 points, with higher scores indicating better quality. Studies with a score less than 4 are defined as low-quality, while 4-8 are considered as high-quality.
Table 2 The modified Jaded Scale
Items
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Score
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1. Was the study described as randomized?
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Yes
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1
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No
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0
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2. Was the method of randomization appropriate?
|
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Yes
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1
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No
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-1
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Not described
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0
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3. Was the study described as blinded?
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Yes (Double-blind)
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1
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Yes (Single-blind)
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0.5
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No
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0
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4. Was the method of blinding appropriate?
|
|
Yes
|
1
|
No
|
-1
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Not described
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0
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5. Was there a description of withdrawals and dropouts?
|
|
Yes
|
1
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No
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0
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6. Was there a clear description of the inclusion and exclusion criteria?
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|
Yes
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1
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No
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0
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7. Was the method used to assess adverse effects described?
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|
Yes
|
1
|
No
|
0
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8. Was the method of statistical analysis described?
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|
Yes
|
1
|
No
|
0
|
Data analysis
Heterogeneity analyses will be performed by Review Manager version 5.4 (Rev Man, Cochrane Collaboration, Oxford, UK). Statistical heterogeneity will be assessed by standard χ2 test (α=0.1) and Ι2 test. if the p≥0.1, and if Ι2≤50%, the fixed-effects model will be used. if the p<0.1 or the Ι2>50%, the random-effects models will be applied. When the heterogeneity is statistically significant, we will conduct a subgroup analysis to investigate the possible sources of heterogeneity according to the patient characteristics and the classification of surgery. If the Ι2>75%, a meta-analysis will not be performed and a narrative, qualitative summary will be provided.
Subgroup analysis
If data are available, subgroup analysis will be performed to assess the heterogeneity according to the conventional mechanical ventilation mode and types of surgery. To explore significant heterogeneity, if a sufficient number of trials are available, we will conduct the following prespecified subgroup analyses separately (hypothesised direction of effect in parentheses): (a) Type of conventional mechanical ventilation mode (PCV-VG is more effective in surgery as compared with PCV or VCV mode). (b) Type of surgery (PCV-VG is more effective in thoracic surgery with one-lung ventilation or laparoscopic gynecologic surgery with carbon dioxide pneumoperitoneum as compared with conventional mechanical ventilation modes).
Trial Sequential Analysis
Trial Sequential Analysis (TSA) will be conducted to control the risks of type I errors and type II errors [45-47]. The required information size (RIS: the number of participants needed in a meta-analysis to detect or reject a certain intervention effect) and the cumulative Z-curve’s breach of relevant trial sequential to monitor boundaries will be calculated for all outcomes [48-49]. For continuous outcomes, we will use the observed SD, a mean difference of the observed SD/2, an alpha of 2.5% and a beta of 10% for outcomes in the TSA [50]. For dichotomous outcomes, we will use the proportion of participants with an outcome in the control group, a relative risk reduction of 20%, and an alpha of 2.5% and a beta of 10% in the TSA [51]. TSA will be performed using the TSA program version 0.9.5.10 Beta (http://www.ctu.dk/tsa) [52].
Sensitivity analysis
If possible, sensitivity analysis will be used to evaluate how uncertain assumptions of data and usage affect the robustness of the combined results. We will exclude low quality studies, re-analyse the included studies, and assess whether there are significant differences between the combined effects. If necessary, we will remove the included studies one by one from the pooled analyses.
Assessment of reporting biases
The potential publication bias will be statistically analysed using funnel plots analysis and Egger’s regression test when more than 10 studies are involved for an outcome [53]. In the presence of plot asymmetry for a given analysis (e.g., publication bias), trim-and-fill method will be used to determine the impact of removing smaller studies on the overall estimate and provide adjusted results [54]. Reporting biases will be performed by Stata/MP 16.0 (Stata Corp, College Station, TX, USA).