Coronavirus disease (COVID-19) pandemic: an overview of systematic reviews

Abstract Background Navigating the rapidly growing body of scientific literature on the SARS-CoV-2 pandemic is challenging, and ongoing critical appraisal of this output is essential. We aimed to summarize and critically appraise systematic reviews of coronavirus disease (COVID-19) in humans that were available at the beginning of the pandemic. Methods Nine databases (Medline, EMBASE, Cochrane Library, CINAHL, Web of Sciences, PDQ-Evidence, WHO’s Global Research, LILACS, and Epistemonikos) were searched from December 1, 2019, to March 24, 2020. Systematic reviews analyzing primary studies of COVID-19 were included. Two authors independently undertook screening, selection, extraction (data on clinical symptoms, prevalence, pharmacological and non-pharmacological interventions, diagnostic test assessment, laboratory, and radiological findings), and quality assessment (AMSTAR 2). A meta-analysis was performed of the prevalence of clinical outcomes. Results Eighteen systematic reviews were included; one was empty (did not identify any relevant study). Using AMSTAR 2, confidence in the results of all 18 reviews was rated as “critically low”. Identified symptoms of COVID-19 were (range values of point estimates): fever (82–95%), cough with or without sputum (58–72%), dyspnea (26–59%), myalgia or muscle fatigue (29–51%), sore throat (10–13%), headache (8–12%) and gastrointestinal complaints (5–9%). Severe symptoms were more common in men. Elevated C-reactive protein and lactate dehydrogenase, and slightly elevated aspartate and alanine aminotransferase, were commonly described. Thrombocytopenia and elevated levels of procalcitonin and cardiac troponin I were associated with severe disease. A frequent finding on chest imaging was uni- or bilateral multilobar ground-glass opacity. A single review investigated the impact of medication (chloroquine) but found no verifiable clinical data. All-cause mortality ranged from 0.3 to 13.9%. Conclusions In this overview of systematic reviews, we analyzed evidence from the first 18 systematic reviews that were published after the emergence of COVID-19. However, confidence in the results of all reviews was “critically low”. Thus, systematic reviews that were published early on in the pandemic were of questionable usefulness. Even during public health emergencies, studies and systematic reviews should adhere to established methodological standards.

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Coronavirus Disease (COVID-19) Pandemic: An Overview of Systematic Reviews

10.1101/2020.04.16.20068213 ◽

2020 ◽

Cited By ~ 1

Author(s):

Israel Júnior Borges do Nascimento ◽

Dónal P. O’Mathúna ◽

Thilo Caspar von Groote ◽

Hebatullah Mohamed Abdulazeem ◽

Ishanka Weerasekara ◽

...

Keyword(s):

Systematic Reviews ◽

Troponin I ◽

Clinical Symptoms ◽

Meta Analysis ◽

Severe Disease ◽

Ground Glass Opacity ◽

Open Science ◽

Frequent Pattern ◽

Cochrane Library ◽

The Impact

AbstractBackgroundNavigating the rapidly growing body of scientific literature on the SARS-CoV-2 pandemic is challenging and ongoing critical appraisal of this output is essential. We aimed to collate and summarize all published systematic reviews on the coronavirus disease (COVID-19).MethodsNine databases (Medline, EMBASE, Cochrane Library, CINAHL, Web of Sciences, PDQ-Evidence, WHO’s Global Research, LILACS and Epistemonikos) were searched from December 1, 2019 to March 24, 2020. Systematic reviews analyzing primary studies of COVID-19 were included. Two authors independently undertook screening, selection, extraction (data on clinical symptoms, prevalence, pharmacological and non-pharmacological interventions, diagnostic test assessment, laboratory and radiological findings) and quality assessment (AMSTAR 2). Meta-analysis on prevalence of clinical outcomes was performed.ResultsEighteen systematic reviews were included; one was empty. Using AMSTAR 2, confidence in the results of 13 reviews was rated as “critically low”, one as “low”, one as “moderate” and two as “high”. Symptoms of COVID-19 were (range values of point estimates): fever (82–95%), cough with or without sputum (58–72%), dyspnea (26–59%), myalgia or muscle fatigue (29–51%), sore throat (10–13%), headache (8– 12%) and gastrointestinal complaints (5–9%). Severe symptoms were more common in men. Elevated C-reactive protein (associated with lymphocytopenia) and lactate dehydrogenase, and slightly elevated aspartate and alanine aminotransferase, were commonly described. Thrombocytopenia and elevated levels of procalcitonin and cardiac troponin I were associated with severe disease. Chest imaging described a frequent pattern of uni- or bilateral multilobar ground-glass opacity. Only one review investigated the impact of medication (chloroquine) but found no verifiable clinical data. All-cause mortality ranged from 0.3% to 14%.ConclusionsConfidence in the results of most reviews was “critically low”. Future studies and systematic reviews should adhere to established methodologies. The majority of included systematic reviews were hampered by imprecise search strategy and no previous protocol submission.Protocol registrationThis is an extension of a PROSPERO protocol (CRD42020170623); protocol available on Open Science Framework (https://osf.io/6xtyw).

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Associations Between the Use of Renin–Angiotensin System Inhibitors and the Risks of Severe COVID-19 and Mortality in COVID-19 Patients With Hypertension: A Meta-Analysis of Observational Studies

Frontiers in Cardiovascular Medicine ◽

10.3389/fcvm.2021.609857 ◽

2021 ◽

Vol 8 ◽

Author(s):

Xiao-Ce Dai ◽

Zhuo-Yu An ◽

Zi-Yang Wang ◽

Zi-Zhen Wang ◽

Yi-Ren Wang

Keyword(s):

Angiotensin Converting Enzyme ◽

Observational Studies ◽

Meta Analysis ◽

Severe Disease ◽

Host Cells ◽

Cochrane Library ◽

Converting Enzyme ◽

Significant Difference ◽

Duration Of Hospitalization ◽

The Impact

Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) share a target receptor with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The use of ACEIs/ARBs may cause angiotensin-converting enzyme 2 receptor upregulation, facilitating the entry of SARS-CoV-2 into host cells. There is concern that the use of ACEIs/ARBs could increase the risks of severe COVID-19 and mortality. The impact of discontinuing these drugs in patients with COVID-19 remains uncertain. We aimed to assess the association between the use of ACEIs/ARBs and the risks of mortality and severe disease in patients with COVID-19. A systematic search was performed in PubMed, EMBASE, Cochrane Library, and MedRxiv.org from December 1, 2019, to June 20, 2020. We also identified additional citations by manually searching the reference lists of eligible articles. Forty-two observational studies including 63,893 participants were included. We found that the use of ACEIs/ARBs was not significantly associated with a reduction in the relative risk of all-cause mortality [odds ratio (OR) = 0.87, 95% confidence interval (95% CI) = 0.75–1.00; I2 = 57%, p = 0.05]. We found no significant reduction in the risk of severe disease in the ACEI subgroup (OR = 0.95, 95% CI = 0.88–1.02, I2 = 50%, p = 0.18), the ARB subgroup (OR = 1.03, 95% CI = 0.94–1.13, I2 = 62%, p = 0.48), or the ACEI/ARB subgroup (OR = 0.83, 95% CI = 0.65–1.08, I2 = 67%, p = 0.16). Moreover, seven studies showed no significant difference in the duration of hospitalization between the two groups (mean difference = 0.33, 95% CI = −1.75 to 2.40, p = 0.76). In conclusion, the use of ACEIs/ARBs appears to not have a significant effect on mortality, disease severity, or duration of hospitalization in COVID-19 patients. On the basis of the findings of this meta-analysis, there is no support for the cessation of treatment with ACEIs or ARBs in patients with COVID-19.

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Outcomes of digital biomarker-based interventions: protocol for a systematic review of systematic reviews (Preprint)

10.2196/preprints.28204 ◽

2021 ◽

Author(s):

Hossein Motahari-Nezhad ◽

Márta Péntek ◽

László Gulácsi ◽

Zsombor Zrubka

Keyword(s):

Clinical Outcomes ◽

Systematic Reviews ◽

Meta Analysis ◽

Cochrane Library ◽

Level Of Evidence ◽

Clinical Benefits ◽

The Cochrane Library ◽

The Impact ◽

Digital Biomarkers

BACKGROUND Digital biomarkers are defined as objective, quantifiable physiological and behavioral data that are collected and measured by means of digital devices such as portables, wearables, implantables or digestibles. For their widespread adoption in publicly financed healthcare systems, it is important to understand how their benefits translate into improved patient outcomes, which is essential for demonstrating their value. OBJECTIVE To assess the quality and strength of evidence of the impact of digital biomarkers on clinical outcomes compared to interventions without digital biomarkers, reported in systematic reviews. METHODS A comprehensive search for 2019-2020 will be conducted in the PubMed and the Cochrane Library using keywords related to digital biomarkers and a filter for systematic reviews. Original full-text English publications of systematic reviews comparing clinical outcomes of interventions with and without digital biomarkers via meta-analysis will be included. The AMSTAR-2 tool will be used to assess the methodological quality of reviews. To assess the quality of evidence, we will evaluate systematic reviews using the GRADE tool. To detect the possible presence of reporting bias, we will record whether the protocol of the systematic reviews was published before the start of the study. A qualitative summary of results by digital biomarker technology and outcome will be provided. RESULTS This protocol was submitted before data collection. The next steps in this review will be initiated after the protocol is accepted for publication. CONCLUSIONS Our study will provide a comprehensive summary of the highest level of evidence available on digital biomarker interventions. Our results will help identify clinical areas where the use of digital biomarkers leads to favorable clinical outcomes. In addition, our findings will highlight areas of evidence gaps where the clinical benefits of digital biomarkers have not yet been demonstrated.

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Management of haemorrhoids: protocol of an umbrella review of systematic reviews and meta-analyses

BMJ Open ◽

10.1136/bmjopen-2019-035287 ◽

2020 ◽

Vol 10 (3) ◽

pp. e035287

Author(s):

Min Chen ◽

Tai-Chun Tang ◽

Tao-Hong He ◽

Yong-Jun Du ◽

Di Qin ◽

...

Keyword(s):

Systematic Reviews ◽

Meta Analysis ◽

Random Effect Model ◽

Current Evidence ◽

Cochrane Library ◽

Final Report ◽

Umbrella Review ◽

Effect Model ◽

Meta Analyses ◽

The Impact

IntroductionThe prevalence of haemorrhoidal diseases was high in general population, and many treatments are proposed for the management of haemorrhoids. The treatments include conservative and surgical interventions; the credibility and strength of current evidence of their effectiveness are not comprehensively evaluated. We aim to evaluate the credibility of systematic reviews and meta-analyses that assess the effectiveness of the treatments for haemorrhoidal diseases through an umbrella review.Methods and analysisWe will search Ovid Medline, Embase, Cochrane library and Web of Science from inception to March 2020 without any language restriction. We will include meta-analyses that examine the effectiveness of treatments in the management of haemorrhoids. Two reviewers will independently screen the titles and abstracts of retrieved articles, and they will extract data from the included meta-analyses. For each meta-analysis, we will estimate the effect size of a treatment through the random-effect model and the fixed-effect model, and we will evaluate between-study heterogeneity (Cochrane’s Q and I2statistics) and small-study effect (Egger’s test); we will also estimate the evidence of excess significance bias. Evidence of each treatment will be graded according to prespecified criteria. Methodological quality of each meta-analysis will be evaluated by using Assessment of Multiple Systematic Reviews 2. The corrected cover area method will be used to assess the impact of overlap in reviews on the findings of the umbrella review.Ethics and disseminationWe will present the results of the umbrella review at conferences and publish the final report in a peer-reviewed journal. The umbrella review does not require ethical approval.PROSPERO registration numberCRD42019140702.

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Effects of Adoptive Transfer of Tolerogenic Dendritic Cells on Allograft Survival in Organ Transplantation Models: An Overview of Systematic Reviews

Journal of Immunology Research ◽

10.1155/2016/5730674 ◽

2016 ◽

Vol 2016 ◽

pp. 1-17 ◽

Cited By ~ 12

Author(s):

Yanni Zhou ◽

Juan Shan ◽

Yingjia Guo ◽

Shengfu Li ◽

Dan Long ◽

...

Keyword(s):

Organ Transplantation ◽

Systematic Reviews ◽

Meta Analysis ◽

Cochrane Library ◽

Allograft Survival ◽

Skin Allografts ◽

Islet Allografts ◽

Tolerogenic Dendritic Cells ◽

Overview Of Systematic Reviews ◽

The Cochrane Library

Objective. To dissect the efficacy of Tol-DC therapy with or without IS in multiple animal models of transplantation.Methods and Results. PubMed, Medline, Embase, and the Cochrane Library were searched for reviews published up to April 2015. Six systematic reviews and a total of 61 articles were finally included. Data were grouped by organ transplantation models and applied to meta-analysis. Our meta-analysis shows that Tol-DC therapy successfully prolonged allograft survival to varying extents in all except the islet transplantation models and with IS drugs further prolonged the survival of heart, skin, and islet allografts in mice, but not of heart allografts in rats. Compared with IS drugs alone, Tol-DC therapy with IS extended islet allograft survival in rats but failed to influence the survival of skin, small intestine, and heart allografts in rats or of heart and skin allografts in mice.Conclusion. Tol-DC therapy significantly prolonged multiple allograft survival and further prolonged survival with IS. However, standardized protocols for modification of Tol-DC should be established before its application in clinic.

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Improved couple satisfaction and communication with marriage and relationship programs: are there gender differences?—a systematic review and meta-analysis

Systematic Reviews ◽

10.1186/s13643-021-01719-0 ◽

2021 ◽

Vol 10 (1) ◽

Author(s):

Zeinab Javadivala ◽

Hamid Allahverdipour ◽

Mohammad Asghari Jafarabadi ◽

Somaye Azimi ◽

Neda Gilani ◽

...

Keyword(s):

Mental Health ◽

Systematic Review ◽

Gender Differences ◽

Mental Health Professionals ◽

Systematic Reviews ◽

Meta Analysis ◽

Medium Effect ◽

Cochrane Library ◽

Relationship Communication ◽

The Impact

Abstract Background The aspects of marriage and relationship and their effect on couples’ satisfaction are essential and critical aspects to be explored in this globalized and contemporary world. Since there are no reported meta-analysis and systematic reviews conducted in the last two decades in this area, we aimed to investigate the effect of marriage and relationship programs (MRP) on couples’ relationship satisfaction (CRS) and couples’ relationship communication (CRC) and also to determine the gender differences if any. Method In this systematic review and meta-analysis, the randomized clinical trials (RCTs) published between 2000 and July 26, 2019, were retrieved from several online electronic databases such as Medline, Embase, ProQuest, and Cochrane Library. Inclusion and exclusion criteria were developed using the PICO (Population, Intervention, Comparison, Outcome) framework of PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). The mean differences (MDs) and 95% confidence intervals (CIs) were calculated. The reported summary statistics were calculated as random effects models based on the heterogeneity between the studies model. Funnel plots and the Egger regression test was used to confirm the presence of any publication bias. Results Of the total 12 intervention studies included, five (5) are education/communication skills programs, three (3) enrichment programs, and four (4) therapy programs. The impact of these programs was investigated on CRS and CRC. Therapy programs had a larger effect than other programs (pooled MD: 0.53 (95% CI = 0.35 to 0.71, I2 = 71.5% p = 0.0001) and had a larger effect size on wives (pooled MD: 0.53 (95% CI 0.25 to 0.80, I2 = 74.1% p = 0.0001) than husbands RS (pooled MD: 0.26 (95% CI 0.25 to 0.76, I2 = 72.4% p = 0.0001). In RC (relationship communication) area, the Enhancement programs showed the small to large effect on CRC (pooled MD: 1.31 (95% CI = 0.13 to 2.50, I2 = 94.7% p = 0.0001)) and educational programs showed small to medium effect (pooled MD: 0.32 (95% CI = 0.13 to 0.50, I2 = 74.5% p = 0.0001) on women and no effect on men. Conclusion Due to the high effect of the therapy programs on CRS and enhancement program on CRC in the current meta-analysis, the priority of their utilizations in interventions, especially by psychologists and mental health professionals, should be emphasized. Therefore, mental health planning in communities to develop MRP and care for couples’ health should be given special attention to men’s health. Due to the high heterogeneity of the results and with scanty literature in this specific domain, we are uncertain about their actual effect. However, well-designed RCTs with a larger sample size would be beneficial in closely examining the effect of MRPs on CRS and CRC.

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Beneficiary effect of a-lipoic acid supplementation on C-reactive protein level among adults

Nutrition & Food Science ◽

10.1108/nfs-03-2018-0082 ◽

2018 ◽

Vol 48 (6) ◽

pp. 1003-1019 ◽

Cited By ~ 3

Author(s):

Somaye Fatahi ◽

Hamed Kord Varkaneh ◽

Alireza Teymouri ◽

Leila Azadbakht

Keyword(s):

Lipoic Acid ◽

Fixed Effects ◽

Weighted Mean Difference ◽

Meta Analysis ◽

Cochrane Library ◽

Significant Heterogeneity ◽

C Reactive Protein ◽

Content Type ◽

Reactive Protein ◽

The Impact

PurposeClinical evidence has suggested that alpha-lipoic acid (ALA), a potent antioxidant, seems to have some effects on inflammatory process. However, these results are equivocal. The purpose of this paper is to investigate the nature of association between ALA and serum C-reactive protein (CRP) level by pooling the results from clinical trial studies.Design/methodology/approachRelevant studies were identified by systematic literature search of PubMed/MEDLINE, Scopus, Web of Sciences and Cochrane library up to September 2016 for randomized controlled trials (RCTs) evaluating the impact of ALA supplementation on CRP. The pooled data were summarized as weighted mean difference (WMD) and 95 per cent confidence interval (CI). Effect sizes of eligible studies were pooled using random- or fixed-effects (the DerSimonian–Laird estimator) depending on the results of heterogeneity tests.FindingsOf 212 papers, 15 were eligible RCTs according to inclusion criteria. The selected studies comprised 1,408 cases and 457 controls. The dose of ALA supplement ranged from 300 to 1,200 mg, and the duration of follow-up was from 1 to 48 weeks. ALA supplementation significantly reduced the levels of circulating CRP (WMD: −0.088, 95 per cent CI: −0.131, −0.045,p< 0.001) with significant heterogeneity (I2= 73.4 per cent,p< 0.001). Populations with age younger than 50 years (PMD: −0.060 mg/dl), receiving doses less than 600 mg/day (PMD: −0.057 mg/dl), having cardiovascular disease (PMD: −0.105 mg/dl), hemodialysis (PMD: −0.209 mg/dl), diabetes (PMD: −0.021 mg/dl) and otherwise healthy subjects (PMD: −0.045 mg/dl) were sources of heterogeneity.Originality/ValueThis meta-analysis of RCTs suggests that ALA supplementation seems to significantly reduce circulating CRP level.

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What Is the Impact of Different Glucose-lowering Agents for Atrial Fibrillation Risk: A Systematic Review and a Network Meta-analysis

10.21203/rs.3.rs-123781/v1 ◽

2020 ◽

Author(s):

Wence Shi ◽

Zhang Wenchang ◽

Gao Lihua ◽

Ding Chunhua

Keyword(s):

Atrial Fibrillation ◽

Systematic Reviews ◽

Meta Analysis ◽

Cochrane Library ◽

Glucose Lowering ◽

Dipeptidyl Peptidase 4 ◽

Clinical Endpoints ◽

Meta Analyses ◽

The Impact ◽

Diabetes Patients

Abstract Background: The emergence of new glucose-lowering agents has brought revolutionary changes to the treatment of cardiovascular diseases. Diabetes is associated with atrial fibrillation (AF) and atrial flutter (AFL) progression, while whether or not glucose-lowering agents would bring a reduction of AF/AFL is not clear. We therefore evaluate the effect of different glucose-lowering agents on AF/AFL and made this network meta-analysis to identify the optimal treatment for diabetes patients to reduce AF/AFL events.Methods: We searched PubMed, Embase, and the Cochrane Library until September 30 2020, and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used in this network meta-analysis. The primary endpoint for our study was AF or AFL events. Only studies with a follow-up period of at least 12 months and reporting AF/AFL as clinical endpoints were included. Results from trials were presented as odds ratios (ORs) with 95% confidence intervals (CIs) and were pooled using a bayesian random-effects model.Results: 5 eligible studies (9 glucose-lowering agents were analyzed including thiazolidinedione[TZD], metformin[Met], sulfonylurea[SU], insulin[Insu], dipeptidyl peptidase-4 inhibitor[DPP-4i], glucagon-like peptide-1 receptor agonist[GLP-1RA], sodium-glucose cotransporter 2 inhibitor[SGLT2i], alpha glucosidase inhibitor[AGI], and non-sulfonylurea[nSU]) consisting of 263583 patients with type 2 diabetes mellitus were included. Pooled results show that GLP1-RA, when compared to Met (OR 0.17, 95% CI 0.04-0.61), SU (OR 0.23, 95% CI 0.07-0.73), Insu (OR 0.20, 95% CI 0.07-0.86), and nSU (OR 0.18, 95% CI 0.04-0.66) significantly reduce AF/AFL events. In addition, DPP-4i could also reduce AF/AFL events when compared with nSU (OR 0.33, 95% CI 0.12-0.92).Conclusion: The finding of our study indicated that GLP1-RA could be optimal glucose-lowering agent for diabetes patients to prevents AF/AFL. Met and insulin-providing therapy (insulin, sulfonylurea, or non- sulfonylurea) should be avoided to patients with high risk of AF/AFL.Trial registration: We have registered in PROSPERO (international prospective register of systematic reviews (CRD42020212994) for this network meta-analysis

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Clinical characterization and chest CT findings in laboratory-confirmed COVID-19: a systematic review and meta-analysis

10.1101/2020.03.05.20031518 ◽

2020 ◽

Cited By ~ 2

Author(s):

Golnaz Vaseghi ◽

Marjan Mansourian ◽

Raheleh Karimi ◽

Kiyan Heshmat-Ghahdarijani ◽

Sadegh Baradaran Mahdavi ◽

...

Keyword(s):

Fixed Effects ◽

Clinical Symptoms ◽

Meta Analysis ◽

Random Effect ◽

Random Effect Model ◽

Ground Glass Opacity ◽

Ground Glass ◽

Cochrane Library ◽

Analysis Model ◽

Ct Findings

AbstractBackgroundImagery techniques have been used as essential parts of diagnostic workup for patients suspected for 2019-nCoV infection, Multiple studies have reported the features of chest computed tomography (CT) scans among a number of 2019-nCoV patients.MethodStudy Identification was carried out in databases (PubMed, Embase and Cochrane Library) to identify published studies examining the diagnosis, the 2019 novel coronavirus (2019-nCoV). Heterogeneity among reported prevalence was assessed by computing p-values of Cochrane Q-test and I2 -statics. The pooled prevalence of treatment failure was carried out with a fixed effects meta-analysis model, generating the pooled 95% confidence interval. A random-effect model was used to pool the results since this model could incorporate the heterogeneity of the studies and therefore proved a more generalized result.ResultsAccording to the combined results of meta-analysis, the total 55% of corona patients were males. The mean age of the patients was 41.31 (34.14, 48.47). Two prevalent clinical symptoms between patients were fever, cough with prevalence of 85%, and 62%, respectively. Either Ground Glass Opacity GGO or consolidation was seen in 86% but 14% had NO GGO or consolidation.The other rare CT symptoms were pericardial effusion, and pleural effusion with 4, 5, 7% prevalence, respectively. The most prevalent event was Either GGO or consolidation in 85% of patients.ConclusionThe most CT-scan abnormality is Either Ground Glass Opacity GGO or consolidation however in few patients none of them might be observed, so trusting in just CT findings will lead to miss some patients.

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The impact of exogenous nitric oxide during cardiopulmonary bypass for cardiac surgery

Perfusion ◽

10.1177/02676591211014821 ◽

2021 ◽

pp. 026765912110148

Author(s):

Joseph Mc Loughlin ◽

Lorraine Browne ◽

John Hinchion

Keyword(s):

Nitric Oxide ◽

Systematic Review ◽

Cardiac Surgery ◽

Cardiopulmonary Bypass ◽

Troponin I ◽

Length Of Hospital Stay ◽

Cochrane Library ◽

High Quality Research ◽

Low Cardiac Output Syndrome ◽

The Impact

Objectives: Cardiac surgery using cardiopulmonary bypass frequently provokes a systemic inflammatory response syndrome. This can lead to the development of low cardiac output syndrome (LCOS). Both of these can affect morbidity and mortality. This study is a systematic review of the impact of gaseous nitric oxide (gNO), delivered via the cardiopulmonary bypass (CPB) circuit during cardiac surgery, on post-operative outcomes. It aims to summarise the evidence available, to assess the effectiveness of gNO via the CPB circuit on outcomes, and highlight areas of further research needed to develop this hypothesis. Methods: A comprehensive search of Pubmed, Embase, Web of Science and the Cochrane Library was performed in May 2020. Only randomised control trials (RCTs) were considered. Results: Three studies were identified with a total of 274 patients. There was variation in the outcomes measures used across the studies. These studies demonstrate there is evidence that this intervention may contribute towards cardioprotection. Significant reductions in cardiac troponin I (cTnI) levels and lower vasoactive inotrope scores were seen in intervention groups. A high degree of heterogeneity between the studies exists. Meta-analysis of the duration of mechanical ventilation, length of ICU stay and length of hospital stay showed no significant differences. Conclusion: This systematic review explored the findings of three pilot RCTs. Overall the hypothesis that NO delivered via the CPB circuit can provide cardioprotection has been supported by this study. There remains a significant gap in the evidence, further high-quality research is required in both the adult and paediatric populations.

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