The effect of Pressure- or Volume- controlled ventilation on inammatory factors of patients undergoing surgery with the novel coronavirus (COVID-19) pneumonia: protocol for a systematic review and meta-analysis

Objective During the COVID-19 pandemic, some patients with novel coronavirus pneumonia may have concurrent disease that must be accepted surgery. However, the extensive inammatory response existed in this population, especially in the lungs. And various ventilation could affect the inammation of lungs. Therefore, how to choose the ventilation mode to reduce the effect of mechanical ventilation on inammation is an important clinical practice. We aim to investigate the effect of different ventilation modes on inammatory factor levels of patients undergoing surgery with COVID-19 through this systematic review and meta-analysis. Methods and analysis This systematic review and meta-analysis have been registered in the International Prospective Register of Systematic Reviews (PROSPERO). The PubMed, Embase via Ovid, Chinese Biological Medical Database (CBM), China National Knowledge Infrastructure (CNKI), the Cochrane Central Register of Controlled Trials (CENTRAL) will be searched from inception to date to nd relevant studies. In addition, the relevant literature was also hand-searched. Two searchers independently selected the studies, extracted data and assessed the quality of studies included. The Review Manager 5.4 software (The Cochrane library,Oxford,England) will be used for data synthesis and meta-analysis. Continuous variables were embodied by Weight Mean Differences with 95% condence intervals (CI). Dichotomous outcomes were embodied by Odds ratio with 95%CI. Ethics and dissemination Ethical approval is not required because the data was collected from the published studies. Finally, the results of this systematic review will be published in a peer-reviewed journal.


Introduction
From the end of December 2019 to now, more and more patients have been diagnosed with novel coronavirus (COVID-19) pneumonia, and this epidemic was not limited in the place, Wuhan, China, and caused a global pandemic [1,2]. Till November 2020, there were more than 8 million cases in India, and it has become one of the countries which had the fastest increasing speed of COVID-19 infection for the terrible prevention and control strategy [3,4]. Therefore, it is a challenge for all countries, especially the poor, to manage and control the COVID-19 infection, because of the shortage of medical resources [5].
Patients with novel coronavirus pneumonia would present various clinical manifestations such as fever, cough, dyspnea, and pain, et. al [6]. And in this population, they had an apparent in ammatory reaction.
For example, IL-1β, IL-6, IL-8 was high, but the IL-10 is low [7]. In patients who suffered from acute respiratory distress syndrome, in ammation seriously increases the injury of different organs, especially the lungs [8]. The COVID-19 infection was a massive hit to people's health, and simultaneously these patients might also suffer from another acute disease that needs to be treated by surgery, such as acute surgical abdomen, and it could be a considerable challenge to manage [9]. In the perioperative period, anesthesiologists were among the most critical roles to manage patients undergoing surgery, and the management of the respiratory is the most critical step [10]. The previous studies had found that the mode of ventilation would affect the concentration of in ammatory factors, and pressure-control ventilation might decrease the level of tumor necrosis factor (TNF)-α and interleukin (IL)-6 and also increase the level of IL-10 compared with volume-controlled ventilation [11]. However, another study revealed no difference in in ammatory factor levels between volume-and pressure-controlled ventilation.
So, it is unclear whether the mode of ventilation could in uence the level of in ammatory marker.
However, these factor levels are important for surgical patients' recovery, especially the persons with novel coronavirus pneumonia who have a high level of in ammation. Therefore, to the anesthesiologists' best to minimize the in uence of anesthesiology on the in ammatory level is signi cantly essential. So, it is signi cant to investigate the effect of various ventilation modes on in ammatory factors of surgical patients with COVID-19. Additionally, till now, no systematic review and meta-analysis are examining the in uence of the ventilation approach on in ammatory marker levels of patients undergoing surgery with COVID-19. Therefore, we will qualitatively and quantitatively investigate the effects of pressure-or volume-controlled ventilation on patients' in ammatory factors with novel coronavirus pneumonia in this systematic review and meta-analysis.

Methods
This protocol of systematic review and meta-analysis was conducted in line with the Preferred Reporting Items for Systematic Reviews and Meta-analyses Protocols (the PRISMA-P) [12]. The PROSPERO registration number is CRD42021251937. For the nature of this article, no informed consent of patients was needed.

Literature search
The PubMed, Web of Science, Embase via Ovid, Chinese Biological Medical Database(CBM), China National Knowledge Infrastructure(CNKI), the Cochrane Central Register of Controlled Trials (CENTRAL) will be searched by two reviewers independently to full access to relevant research from inception to date.
In addition, the relevant pieces of literature were also hand-searched. Studies concerning the effects of ventilation mode for patients' in ammatory factor levels with COVID-19 in the surgery period will be brought into this meta-analysis, including randomized controlled trials (RCTs), controlled clinical trials (CCTs), prospective and retrospective comparative cohort studies, cross-sectional researches and observational researches. The search terms included 'pressure-controlled ventilation' and 'volumecontrolled ventilation' and 'COVID-19' or 'novel coronavirus pneumonia' or 'SARS-CoV-2', and 'in ammation', and the detailed search strategy of PubMed is presented in Table 1. There are no language restrictions. Eligibility Criteria

Type of study design
All relevant studies, such as RCTs, CCTs, prospective and retrospective comparative cohort studies, crosssectional researches, and observational researches, will be covered in this meta-analysis. Due to the de ciency of original trials, we try our best to nd out as many relevant studies as possible.

Participants
The patients with COVID-19 who have been controlled breathing through pressure-or volume-controlled mode in the surgery will be involved. Because the number of concerning studies is relatively small, we do not restrict the population's age. Adult and pediatric patients will be included in this meta-analysis. The studies from various countries will be included in the world.

Interventions
The interventions will be various ventilation modes, including Pressure-controlled ventilation and Volumecontrolled ventilation during the surgery period.

Outcomes
The primary outcome is the in ammatory factor levels in 3h,6h,12h, and 24h after surgery, including IL-6, IL-8, TNF-α, and IL-10. And the secondary outcomes are as follows: postoperative oxygenation index, blood oxygen saturation, serum creatinine concentration, incision infection rate, and hospitalization time.

Study Selection And Data Collection
Two searchers will independently select the studies. If some discrepancies exist between the searchers, further discussion will be done with a senior reviewer to solve this problem. After removing the duplicates, we will assess the preliminary quality of studies according to the title and abstract. And then, we will do the nal assessment by reading the full text. The selection ow gram is presented in Fig. 1. A standard collection form will be adopted to extract the data by two reviewers independently. Any discrepancies will be solved by another senior reviewer. The extracted data including rst author, date of publication, sample size, patient characteristics, ASA physical status, type of surgery, type of study, ventilation mode, surgery and anesthesia time, postoperative laboratory results, inhaled oxygen concentration after surgery, patients' number of incision infection, and length of hospitalization. For the missing data, we will contact the author to get it.

Risk-of-bias Assessment And Quality Assessed
Two tools would be used to evaluate the quality of studies included. The randomized controlled trials were evaluated by Cochrane's risk-of-bias tool according to the following domains: bias arising from the randomization process, bias due to deviations from intended interventions,bias owing to missing outcome data, bias from the measurement of the outcome, bias from the selection of the reported result [13]. And for the non-randomized studies, we will use the Newcastle-Ottawa Scale (NOS) to evaluate the bias, including subjects selection, study comparability, and outcome measurement [14]. According to the tool of assessing the risk of bias, the decisions could be 'Low', or 'High' risk of bias, or express 'Some concerns'. The risk of bias would be assessed by two searchers independently. And the quality of evidence about the studies included was evaluated with the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) criteria [15].
Data synthesis and statistical analysis

Ethics And Dissemination
Ethical approval is not required for the reason that the data was collected from the published reports. Finally, the results of this systematic review will be published in a peer-reviewed journal.

Discussion
As far as we know, this is the rst meta-analysis to examine the effects of Pressure-or Volume-controlled ventilation on patients' in ammatory factor levels with novel coronavirus pneumonia who have experienced surgery. It is crucial for patients who have undergone surgery with COVID-19 to select a proper ventilation mode during the anesthesia period [19]. In this population, the extensive in ammatory response is a signi cant feature, especially the location of the lungs, so it is vital to reduce this response by using a t ventilation method. However, it is uncertain whether ventilation mode could in uence the in ammatory marker levels in patients undergoing surgery with coronavirus pneumonia due to limited original searches. This is the signi cant problem which we concern. And also, there is the main limitation in our meta-analysis for the insu ciency of RCTs, which may reduce the strength of evidence.

Declarations
Ethics approval and consent to participate Not applicable The ow diagram of literature search and selection

Supplementary Files
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