BMJ Open BMJ Open: first published as 10.1136/bmjopen-2015-007842 on 5 January 2016. Downloaded from The efficacy and safety of complete pericardial drainage by means of intrapericardial fibrinolysis in the prevention of complications of pericardial effusion: a systematic review protocol For peer review only Journal: BMJ Open Manuscript ID: bmjopen-2015-007842 Article Type: Protocol Date Submitted by the Author: 08-Feb-2015 Complete List of Authors: Kakia, Aloysious; Walter Sisulu University, Family Medicine and Rural Health Wiysonge, Charles; Stellenbosch University, Centre for Evidence-based Health Care Ochodo, Eleanor; Stellenbosch University, Centre for Evidence-based Health Care Awotedu, Abolade; Walter Sisulu University, Internal Medicine Ristic, Arsen; Belgrade University, Department of Cardiology, Clinical Center of Serbia and Belgrade University School of Medicine Mayosi, Bongani; University of Cape Town, Department of Medicine, Groote Schuur Hospital http://bmjopen.bmj.com/ <b>Primary Subject Cardiovascular medicine Heading</b>: Secondary Subject Heading: Evidence based practice Adult cardiology < CARDIOLOGY, Paediatric cardiology < CARDIOLOGY, Keywords: PREVENTIVE MEDICINE, Cardiology < INTERNAL MEDICINE on September 30, 2021 by guest. Protected copyright. For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 1 of 10 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2015-007842 on 5 January 2016. Downloaded from 1 2 3 4 The efficacy and safety of complete pericardial drainage by means of 5 6 intrapericardial fibrinolysis in the prevention of complications of pericardial 7 8 9 effusion: a systematic review protocol 10 11 12 13 1* 2, 3 2 4 5 14 Aloysious Kakia , Charles S. Wiysonge , Eleanor A. Ochodo , Abolade A. Awotedu , Arsen D. Ristic, 15 Bongani M. MayosiFor6 peer review only 16 17 18 19 20 1 21 Department of Family Medicine and Rural Health, Walter Sisulu University, Mthatha, South 22 23 Africa;2 Centre for Evidence-based Health Care, Stellenbosch University, Cape Town, South 24 25 Africa;3 Division of Community Health, Stellenbosch University, Cape Town, South 26 27 4 28 Africa; Department of Medicine, Nelson Mandela Academic Hospital and Walter Sisulu 29 30 University, Mthatha, South Africa;5Department of Cardiology, Clinical Center of Serbia and 31 32 Belgrade University School of Medicine, Belgrade, Serbia;6Groote Schuur Hospital and 33 34 http://bmjopen.bmj.com/ 35 University of Cape Town, Cape Town, South Africa 36 37 Email addresses: 38 39 40 Aloysious Kakia: [email protected]; Charles Shey Wiysonge: [email protected]; 41 42 Eleanor A. Ochodo: [email protected]; Abolade A. Awotedu: [email protected]; on September 30, 2021 by guest. Protected copyright. 43 44 Arsen Ristic: [email protected]; Bongani M. Mayosi: [email protected] 45 46 47 48 * Corresponding author. 49 50 51 52 53 54 55 56 57 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 2 of 10 BMJ Open: first published as 10.1136/bmjopen-2015-007842 on 5 January 2016. Downloaded from 1 2 3 ABSTRACT: 4 5 6 7 Background: Intrapericardial fibrinolysis has been proposed as a means of preventing 8 9 complications of pericardial effusion such as cardiac tamponade, persistent and recurrent 10 11 12 pericardial effusion, as well as pericardial constriction. There is a need to understand the efficacy 13 14 and safety of this procedure because it shows promise. The purpose of this review therefore is to 15 For peer review only 16 conduct a systematic analysis on the efficacy and safety of intrapericardial fibrinolysis in the 17 18 19 prevention of the complications of pericardial effusion. 20 21 22 Methods: We will include studies that evaluate the efficacy and/or safety of complete pericardial 23 24 fluid drainage by intrapericardial fibrinolysis for preventing complications of pericardial effusion 25 26 27 irrespective of study design, geographical location, language, status of publication, age of 28 29 participants, aetiology of pericardial disease, or types of fibrinolytics used up to 31st December 30 31 32 2014. The primary outcomes will be development of cardiac tamponade, persistent or recurrent 33 34 pericarditis without tamponade, constrictive pericarditis, hospitalization and death, as well as http://bmjopen.bmj.com/ 35 36 adverse events related to the use of intrapericardial fibrinolytics. We shall search PubMed, the 37 38 39 Cochrane Library, African Journals online, Cumulative Index to Nursing and Allied Health 40 41 Literature, Trip database, Clinical trials.gov and the WHO International Clinical Trials Registry 42 on September 30, 2021 by guest. Protected copyright. 43 Platform. Two reviewers will do the search independently, screen the search outputs for 44 45 46 potentially eligible studies, and assess whether the studies meet the inclusion criteria. 47 48 Discrepancies between the two reviewers will be resolved through discussion with a third 49 50 reviewer and consensus. Data from the selected studies shall be extracted using a standardised 51 52 53 data collection form which will be piloted before use. The methodological quality of studies will 54 55 be assessed using the Cochrane Collaboration’s tool for assessing risk of bias for experimental 56 57 58 studies and the Scottish Intercollegiate Guidelines Network (SIGN) checklist for other study 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 3 of 10 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2015-007842 on 5 January 2016. Downloaded from 1 2 3 designs. The primary meta-analysis will use random effects models due to expected inter-studies 4 5 6 heterogeneity. Dichotomous data will be analysed using relative risk and continuous data using 7 8 weighted mean differences (or standardised mean differences), both with 95% CIs. 9 10 11 Discussion: This systematic review will shed light on the evidence to date regarding the efficacy 12 13 14 and safety of intrapericardial fibrinolysis in preventing constrictive pericarditis, and guide future 15 For peer review only 16 research on this theme. 17 18 Study strengths: Unbiased selection of many studies conducted in different settings. This will 19 20 21 strengthen the validity of the review results. 22 23 Study limitations: Heterogeneity of the study settings of the low-income, lower-middle-income 24 25 26 and upper-middle-income countries as well as heterogeneity in study designs. 27 28 29 30 Review registration: This review is registered with PROSPERO, registration number 31 32 33 CRD42014015238 34 http://bmjopen.bmj.com/ 35 36 Key words: ‘Pericarditis’, ‘tuberculous pericarditis,’ ‘purulent pericarditis,’ 37 38 ’pericardiocentesis’, ‘therapeutic pericardiocentesis,’ ‘fibrinolytics,’ ‘intrapericardial 39 40 41 fibrinolytics,’ ‘urokinase,’ ‘streptokinase,’ ‘tissue plasminogen activator.’ 42 on September 30, 2021 by guest. Protected copyright. 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 4 of 10 BMJ Open: first published as 10.1136/bmjopen-2015-007842 on 5 January 2016. Downloaded from 1 2 3 BACKGROUND 4 5 6 7 The era of human immune-deficiency virus (HIV) has seen an increase in the incidence of 8 9 pericarditis1. The main cause of pericarditis in Africa is tuberculosis2. Pericarditis may 10 11 complicate to tamponade in the short term, and chronic effusive pericarditis and constrictive 12 13 14 pericarditis in the long term. Cardiac tamponade and constrictive pericarditis lead to death if not 15 For peer review only 16 treated. The definitive management for constrictive pericarditis involves pericardiectomy, which 17 18 is associated with a mortality of up to fourteen percent3, and is an expensive procedure4. Imazio 19 20 5 21 et al have shown that tuberculous and purulent pericarditis are more likely to progress to 22 23 constrictive pericarditis than pericarditis due to other causes. Ntsekhe et al6 found a 10.9 % 24 25 26 incidence of constrictive pericarditis over a six month period in patients with pericardial 27 28 effusions presumed to be tuberculous. These findings highlight the importance of efforts to 29 30 prevent progression of pericarditis to constrictive pericarditis. 31 32 33 34 Various strategies have been used to prevent progression of acute pericarditis to constrictive http://bmjopen.bmj.com/ 35 36 pericarditis. Early diagnosis and prompt treatment of pericarditis, including treating the 37 38 underlying cause and draining effusions, are a major step in this direction. The use of colchicine 39 40 41 as adjunctive treatment to prevent recurrent and persistent pericarditis, and thereby reducing the 42 on September 30, 2021 by guest. Protected copyright. 43 risk of constriction, showed promise in a randomized clinical trial conducted by Imazio et al7. 44 45 Corticosteroids have been found to be useful in several trials; however, the findings of Mayosi et 46 47 8 48 al have shown that corticosteroids could increase the risk of cancers in patients co-infected with 49 50 HIV. 51 52 53 Intra-pericardial fibrinolysis has been proposed as a way of stemming the development of 54 55 56 cardiac tamponade and constriction in patients with effusive pericarditis. The objective of 57 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 5 of 10 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2015-007842 on 5 January 2016. Downloaded from 1 2 3 fibrinolysis is to target fibrin formation, to optimize evacuation of a thick fluid, and therefore to 4 5 9 6 prevent both persistent purulent pericarditis and constrictive pericarditis . The procedure is also 7 8 minimally invasive. A clinical review conducted by Augustine et al9 concluded that 9 10 10 11 intrapericardial fibrinolysis may be useful for prevention of constrictive pericarditis. Cui et al 12 13 investigated the efficacy of intrapericardial fibrinolysis in preventing constrictive pericarditis in 14 15 patients with infectiveFor pericardial peer effusion, review 60 % of which were onlyof tuberculous origin.