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Acta Paediatrica (Oslo, Norway : 1992) Feb 2022Pulmonary haemorrhage (PH) is an acute catastrophic event with low incidence yet high mortality among neonates. We aimed to systematically review the management of PH. (Review)
Review
AIM
Pulmonary haemorrhage (PH) is an acute catastrophic event with low incidence yet high mortality among neonates. We aimed to systematically review the management of PH.
METHODS
A search was carried out of the PubMed, EMBASE and Cochrane databases according to the PRISMA guidelines. Data were extracted on study design and size, patient demographics, primary and adjunctive treatment methods, and treatment outcomes.
RESULTS
Sixteen studies with 385 newborn infants were included and were significantly heterogeneous regarding treatment methods. Primary treatments included surfactant, high-frequency oscillatory ventilation (HFOV), epinephrine, coagulopathy management, intermittent positive pressure ventilation, cocaine and tolazoline. Adjunctive treatment methods included blood products, HFOV, increased positive end-expiratory pressure, vitamin K, surfactant, adrenaline, vasopressors and inotropes. All five studies using surfactant as primary treatment were effective in improving oxygenation index measures and preventing recurrence of PH, and three studies found no association between surfactant and death or long-term disability. Ventilatory support, epinephrine, management of coagulopathy and tolazoline were all found to be effective primary treatments for PH.
CONCLUSION
There are several effective methods of managing PH in neonates. Further understanding of the aetiology of PH and ongoing research will allow future prevention and improvements in management of PH.
Topics: Hemorrhage; High-Frequency Ventilation; Humans; Infant, Newborn; Infant, Premature; Intermittent Positive-Pressure Ventilation; Respiratory Distress Syndrome, Newborn
PubMed: 34582587
DOI: 10.1111/apa.16127 -
Critical Care Medicine Mar 2022Tranexamic acid is proposed as a treatment for gastrointestinal bleeding. The Haemorrhage Alleviation with Tranexamic Acid-Intestinal System trial evaluated extended-use... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Tranexamic acid is proposed as a treatment for gastrointestinal bleeding. The Haemorrhage Alleviation with Tranexamic Acid-Intestinal System trial evaluated extended-use (24 hr) high-dose tranexamic acid, prompting a reappraisal for tranexamic acid in gastrointestinal bleeding.
DATA SOURCES
We conducted a systematic review and meta-analysis of randomized controlled trials comparing tranexamic acid with usual care or placebo in adults with gastrointestinal bleeding. We searched MEDLINE, EMBASE, and CENTRAL (inception to September 2019).
DATA SELECTION
Two reviewers independently screened citations, extracted data, and assessed the risk of bias using the Cochrane risk of bias tool in duplicate. The main outcomes were mortality, bleeding, and adverse events.
DATA EXTRACTION
Studies were analyzed as high-dose IV tranexamic acid versus all other dosing strategies for tranexamic acid using fixed-effects models. We assessed certainty of evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach.
DATA SYNTHESIS
Five randomized controlled trials evaluated extended-use high-dose IV tranexamic acid, seven evaluating low-dose IV or enteral tranexamic acid. Extended-use high-dose IV tranexamic acid did not reduce mortality (relative risk, 0.98%; 95% CI, 0.88-1.09; I2 = 63%; high certainty) or bleeding (relative risk, 0.92; 95% CI, 0.82-1.04; p = 0.17 and absolute risk differences, -0.7%; 95% CI, -1.5 to 0.3; high certainty) but resulted in a small increase in deep venous thrombosis (relative risk, 2.01; 95% CI, 1.08-3.72; I2 = 0%), pulmonary embolism (relative risk, 1.78; 95% CI, 1.06-3.0; I2 = 0%), and seizure (relative risk, 1.73; 95% CI, 1.03-2.93) with high certainty. Low-dose IV/enteral tranexamic acid did not reduce mortality (relative risk, 0.62; 95% CI, 0.36-1.09; I2 = 0%) but did reduce risk of rebleeding (relative risk, 0.5; 95% CI, 0.33-0.75; I2 = 9%) and need for surgery (relative risk, 0.58; 95% CI, 0.38-0.88; I2 = 11%), with moderate certainty.
CONCLUSIONS
Extended-use high-dose IV tranexamic acid does not improve mortality or bleeding outcomes and increases adverse events. Low-dose/enteral tranexamic acid may be effective in reducing hemorrhage; more evidence is required to demonstrate its safety.
Topics: Antifibrinolytic Agents; Gastrointestinal Hemorrhage; Humans; Length of Stay; Secondary Prevention; Tranexamic Acid
PubMed: 34709209
DOI: 10.1097/CCM.0000000000005362 -
Pediatric Critical Care Medicine : a... Jan 2022Critically ill children frequently receive plasma and platelet transfusions. We sought to determine evidence-based recommendations, and when evidence was insufficient,...
Executive Summary of Recommendations and Expert Consensus for Plasma and Platelet Transfusion Practice in Critically Ill Children: From the Transfusion and Anemia EXpertise Initiative-Control/Avoidance of Bleeding (TAXI-CAB).
OBJECTIVES
Critically ill children frequently receive plasma and platelet transfusions. We sought to determine evidence-based recommendations, and when evidence was insufficient, we developed expert-based consensus statements about decision-making for plasma and platelet transfusions in critically ill pediatric patients.
DESIGN
Systematic review and consensus conference series involving multidisciplinary international experts in hemostasis, and plasma/platelet transfusion in critically ill infants and children (Transfusion and Anemia EXpertise Initiative-Control/Avoidance of Bleeding [TAXI-CAB]).
SETTING
Not applicable.
PATIENTS
Children admitted to a PICU at risk of bleeding and receipt of plasma and/or platelet transfusions.
INTERVENTIONS
None.
MEASUREMENTS AND MAIN RESULTS
A panel of 29 experts in methodology, transfusion, and implementation science from five countries and nine pediatric subspecialties completed a systematic review and participated in a virtual consensus conference series to develop recommendations. The search included MEDLINE, EMBASE, and Cochrane Library databases, from inception to December 2020, using a combination of subject heading terms and text words for concepts of plasma and platelet transfusion in critically ill children. Four graded recommendations and 49 consensus expert statements were developed using modified Research and Development/UCLA and Grading of Recommendations, Assessment, Development, and Evaluation methodology. We focused on eight subpopulations of critical illness (1, severe trauma, intracranial hemorrhage, or traumatic brain injury; 2, cardiopulmonary bypass surgery; 3, extracorporeal membrane oxygenation; 4, oncologic diagnosis or hematopoietic stem cell transplantation; 5, acute liver failure or liver transplantation; 6, noncardiac surgery; 7, invasive procedures outside the operating room; 8, sepsis and/or disseminated intravascular coagulation) as well as laboratory assays and selection/processing of plasma and platelet components. In total, we came to consensus on four recommendations, five good practice statements, and 44 consensus-based statements. These results were further developed into consensus-based clinical decision trees for plasma and platelet transfusion in critically ill pediatric patients.
CONCLUSIONS
The TAXI-CAB program provides expert-based consensus for pediatric intensivists for the administration of plasma and/or platelet transfusions in critically ill pediatric patients. There is a pressing need for primary research to provide more evidence to guide practitioners.
Topics: Anemia; Child; Critical Care; Critical Illness; Erythrocyte Transfusion; Evidence-Based Medicine; Humans; Infant; Platelet Transfusion
PubMed: 34989711
DOI: 10.1097/PCC.0000000000002851 -
Journal of Hypertension Jul 2020The prevalence of hypertensive emergencies and urgencies and of acute hypertension-mediated organ damage (aHMOD) in emergency departments is unknown. Moreover, the... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
The prevalence of hypertensive emergencies and urgencies and of acute hypertension-mediated organ damage (aHMOD) in emergency departments is unknown. Moreover, the predictive value of symptoms, blood pressure (BP) levels and cardiovascular risk factors to suspect the presence of aHMOD is still unclear. The aim of this study was to investigate the prevalence of hypertensive emergencies and hypertensive urgencies in emergency departments and of the relative frequency of subtypes of aHMOD, as well as to assess the clinical variables associated with aHMOD.
METHODS
We conducted a systematic literature search on PubMed, OVID, and Web of Science from their inception to 22 August 2019. Two independent investigators extracted study-level data for a random-effects meta-analysis.
RESULTS
Eight studies were analysed, including 1970 hypertensive emergencies and 4983 hypertensive urgencies. The prevalence of hypertensive emergencies and hypertensive urgencies was 0.3 and 0.9%, respectively [odds ratio for hypertensive urgencies vs. hypertensive emergencies 2.5 (1.4-4.3)]. Pulmonary oedema/heart failure was the most frequent subtype of aHMOD (32%), followed by ischemic stroke (29%), acute coronary syndrome (18%), haemorrhagic stroke (11%), acute aortic syndrome (2%) and hypertensive encephalopathy (2%). No clinically meaningful difference was found for BP levels at presentations. Hypertensive urgency patients were younger than hypertensive emergency patients by 5.4 years and more often complained of nonspecific symptoms and/or headache, whereas specific symptoms were more frequent among hypertensive emergency patients.
CONCLUSION
Hypertensive emergencies and hypertensive urgencies are a frequent cause of access to emergency departments, with hypertensive urgencies being significantly more common. BP levels alone do not reliably predict the presence of aHMOD, which should be suspected according to the presenting signs and symptoms.
Topics: Acute Coronary Syndrome; Antihypertensive Agents; Blood Pressure; Emergency Medicine; Emergency Service, Hospital; Heart Failure; Humans; Hypertension; Hypertension, Malignant; Hypertensive Encephalopathy; Ischemic Stroke; Odds Ratio; Prevalence; Pulmonary Edema; Stroke
PubMed: 32510905
DOI: 10.1097/HJH.0000000000002372 -
The Cochrane Database of Systematic... Oct 2021Stroke is the third leading cause of early death worldwide. Most ischaemic strokes are caused by a blood clot blocking an artery in the brain. Patient outcomes might be... (Review)
Review
BACKGROUND
Stroke is the third leading cause of early death worldwide. Most ischaemic strokes are caused by a blood clot blocking an artery in the brain. Patient outcomes might be improved if they are offered anticoagulants that reduce their risk of developing new blood clots and do not increase the risk of bleeding. This is an update of a Cochrane Review first published in 1995, with updates in 2004, 2008, and 2015.
OBJECTIVES
To assess the effectiveness and safety of early anticoagulation (within the first 14 days of onset) for people with acute presumed or confirmed ischaemic stroke. Our hypotheses were that, compared with a policy of avoiding their use, early anticoagulation would be associated with: • reduced risk of death or dependence in activities of daily living a few months after stroke onset; • reduced risk of early recurrent ischaemic stroke; • increased risk of symptomatic intracranial and extracranial haemorrhage; and • reduced risk of deep vein thrombosis and pulmonary embolism.
SEARCH METHODS
We searched the Cochrane Stroke Group Trials Register (August 2021); the Cochrane Database of Systematic Reviews (CDSR); the Cochrane Central Register of Controlled Trials (CENTRAL; 2021, Issue 7), in the Cochrane Library (searched 5 August 2021); MEDLINE (2014 to 5 August 2021); and Embase (2014 to 5 August 2021). In addition, we searched ongoing trials registries and reference lists of relevant papers. For previous versions of this review, we searched the register of the Antithrombotic Trialists' (ATT) Collaboration, consulted MedStrategy (1995), and contacted relevant drug companies.
SELECTION CRITERIA
Randomised trials comparing early anticoagulant therapy (started within two weeks of stroke onset) with control in people with acute presumed or confirmed ischaemic stroke.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected trials for inclusion, assessed trial quality, and extracted data. We assessed the overall certainty of the evidence for each outcome using RoB1 and GRADE methods.
MAIN RESULTS
We included 28 trials involving 24,025 participants. Quality of the trials varied considerably. We considered some studies to be at unclear or high risk of selection, performance, detection, attrition, or reporting bias. Anticoagulants tested were standard unfractionated heparin, low-molecular-weight heparins, heparinoids, oral anticoagulants, and thrombin inhibitors. Over 90% of the evidence is related to effects of anticoagulant therapy initiated within the first 48 hours of onset. No evidence suggests that early anticoagulation reduced the odds of death or dependence at the end of follow-up (odds ratio (OR) 0.98, 95% confidence interval (CI) 0.92 to 1.03; 12 RCTs, 22,428 participants; high-certainty evidence). Similarly, we found no evidence suggesting that anticoagulant therapy started within the first 14 days of stroke onset reduced the odds of death from all causes (OR 0.99, 95% CI 0.90 to 1.09; 22 RCTs, 22,602 participants; low-certainty evidence) during the treatment period. Although early anticoagulant therapy was associated with fewer recurrent ischaemic strokes (OR 0.75, 95% CI 0.65 to 0.88; 12 RCTs, 21,665 participants; moderate-certainty evidence), it was also associated with an increase in symptomatic intracranial haemorrhage (OR 2.47; 95% CI 1.90 to 3.21; 20 RCTs, 23,221 participants; moderate-certainty evidence). Similarly, early anticoagulation reduced the frequency of symptomatic pulmonary emboli (OR 0.60, 95% CI 0.44 to 0.81; 14 RCTs, 22,544 participants; high-certainty evidence), but this benefit was offset by an increase in extracranial haemorrhage (OR 2.99, 95% CI 2.24 to 3.99; 18 RCTs, 22,255 participants; moderate-certainty evidence).
AUTHORS' CONCLUSIONS
Since the last version of this review, four new relevant studies have been published, and conclusions remain consistent. People who have early anticoagulant therapy after acute ischaemic stroke do not demonstrate any net short- or long-term benefit. Treatment with anticoagulants reduced recurrent stroke, deep vein thrombosis, and pulmonary embolism but increased bleeding risk. Data do not support the routine use of any of the currently available anticoagulants for acute ischaemic stroke.
Topics: Activities of Daily Living; Anticoagulants; Brain Ischemia; Heparin; Humans; Ischemic Stroke; Stroke; Systematic Reviews as Topic
PubMed: 34676532
DOI: 10.1002/14651858.CD000024.pub5 -
Journal of the American College of... Jan 2023The efficacy and safety of direct oral anticoagulants (DOACs) for patients with thrombotic antiphospholipid syndrome remain controversial. (Meta-Analysis)
Meta-Analysis
BACKGROUND
The efficacy and safety of direct oral anticoagulants (DOACs) for patients with thrombotic antiphospholipid syndrome remain controversial.
OBJECTIVES
The authors performed a systematic review and meta-analysis of randomized controlled trials that compared DOACs with vitamin K antagonists (VKAs).
METHODS
We searched PubMed, EMBASE, and Cochrane Central Register of Controlled Trials through April 9, 2022. The 2 main efficacy outcomes were a composite of arterial thrombotic events and venous thromboembolic events (VTEs). The main safety outcome was major bleeding. Random effects models with inverse variance were used.
RESULTS
Our search retrieved 253 studies. Four open-label randomized controlled trials involving 472 patients were included (mean control-arm time-in-therapeutic-range 60%). All had proper random sequence generation and adequate allocation concealment. Overall, the use of DOACs compared with VKAs was associated with increased odds of subsequent arterial thrombotic events (OR: 5.43; 95% CI: 1.87-15.75; P < 0.001, I = 0%), especially stroke, and the composite of arterial thrombotic events or VTE (OR: 4.46; 95% CI: 1.12-17.84; P = 0.03, I = 0%). The odds of subsequent VTE (OR: 1.20; 95% CI: 0.31-4.55; P = 0.79, I = 0%), or major bleeding (OR: 1.02; 95% CI: 0.42-2.47; P = 0.97; I = 0%) were not significantly different between the 2 groups. Most findings were consistent within subgroups.
CONCLUSIONS
Patients with thrombotic antiphospholipid syndrome randomized to DOACs compared with VKAs appear to have increased risk for arterial thrombosis. No significant differences were observed between patients randomized to DOACs vs VKAs in the risk of subsequent VTE or major bleeding.
Topics: Humans; Administration, Oral; Anticoagulants; Antiphospholipid Syndrome; Fibrinolytic Agents; Hemorrhage; Randomized Controlled Trials as Topic; Thrombosis; Venous Thromboembolism; Vitamin K
PubMed: 36328154
DOI: 10.1016/j.jacc.2022.10.008 -
The Lancet. Oncology Mar 2023Survivors of childhood, adolescent, and young adult cancer, previously treated with anthracycline chemotherapy (including mitoxantrone) or radiotherapy in which the... (Review)
Review
Systematic review and updated recommendations for cardiomyopathy surveillance for survivors of childhood, adolescent, and young adult cancer from the International Late Effects of Childhood Cancer Guideline Harmonization Group.
Survivors of childhood, adolescent, and young adult cancer, previously treated with anthracycline chemotherapy (including mitoxantrone) or radiotherapy in which the heart was exposed, are at increased risk of cardiomyopathy. Symptomatic cardiomyopathy is typically preceded by a series of gradually progressive, asymptomatic changes in structure and function of the heart that can be ameliorated with treatment, prompting specialist organisations to endorse guidelines on cardiac surveillance in at-risk survivors of cancer. In 2015, the International Late Effects of Childhood Cancer Guideline Harmonization Group compiled these guidelines into a uniform set of recommendations applicable to a broad spectrum of clinical environments with varying resource availabilities. Since then, additional studies have provided insight into dose thresholds associated with a risk of asymptomatic and symptomatic cardiomyopathy, have characterised risk over time, and have established the cost-effectiveness of different surveillance strategies. This systematic Review and guideline provides updated recommendations based on the evidence published up to September, 2020.
Topics: Child; Humans; Adolescent; Young Adult; Neoplasms; Survivors; Antibiotics, Antineoplastic; Cardiomyopathies; Mitoxantrone
PubMed: 37052966
DOI: 10.1016/S1470-2045(23)00012-8 -
The Cochrane Database of Systematic... Apr 2023Deep vein thrombosis (DVT) is a condition in which a clot forms in the deep veins, most commonly of the leg. It occurs in approximately one in 1000 people. If left... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Deep vein thrombosis (DVT) is a condition in which a clot forms in the deep veins, most commonly of the leg. It occurs in approximately one in 1000 people. If left untreated, the clot can travel up to the lungs and cause a potentially life-threatening pulmonary embolism (PE). Previously, a DVT was treated with the anticoagulants heparin and vitamin K antagonists. However, two forms of direct oral anticoagulants (DOACs) have been developed: oral direct thrombin inhibitors (DTIs) and oral factor Xa inhibitors, which have characteristics that may be favourable compared to conventional treatment, including oral administration, a predictable effect, lack of frequent monitoring or dose adjustment and few known drug interactions. DOACs are now commonly being used for treating DVT: recent guidelines recommended DOACs over conventional anticoagulants for both DVT and PE treatment. This Cochrane Review was first published in 2015. It was the first systematic review to measure the effectiveness and safety of these drugs in the treatment of DVT. This is an update of the 2015 review. OBJECTIVES: To assess the effectiveness and safety of oral DTIs and oral factor Xa inhibitors versus conventional anticoagulants for the long-term treatment of DVT.
SEARCH METHODS
The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase and CINAHL databases and the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 1 March 2022.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) in which people with a DVT, confirmed by standard imaging techniques, were allocated to receive an oral DTI or an oral factor Xa inhibitor compared with conventional anticoagulation or compared with each other for the treatment of DVT. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were recurrent venous thromboembolism (VTE), recurrent DVT and PE. Secondary outcomes included all-cause mortality, major bleeding, post-thrombotic syndrome (PTS) and quality of life (QoL). We used GRADE to assess the certainty of evidence for each outcome.
MAIN RESULTS
We identified 10 new studies with 2950 participants for this update. In total, we included 21 RCTs involving 30,895 participants. Three studies investigated oral DTIs (two dabigatran and one ximelagatran), 17 investigated oral factor Xa inhibitors (eight rivaroxaban, five apixaban and four edoxaban) and one three-arm trial investigated both a DTI (dabigatran) and factor Xa inhibitor (rivaroxaban). Overall, the studies were of good methodological quality. Meta-analysis comparing DTIs to conventional anticoagulation showed no clear difference in the rate of recurrent VTE (odds ratio (OR) 1.17, 95% confidence interval (CI) 0.83 to 1.65; 3 studies, 5994 participants; moderate-certainty evidence), recurrent DVT (OR 1.11, 95% CI 0.74 to 1.66; 3 studies, 5994 participants; moderate-certainty evidence), fatal PE (OR 1.32, 95% CI 0.29 to 6.02; 3 studies, 5994 participants; moderate-certainty evidence), non-fatal PE (OR 1.29, 95% CI 0.64 to 2.59; 3 studies, 5994 participants; moderate-certainty evidence) or all-cause mortality (OR 0.66, 95% CI 0.41 to 1.08; 1 study, 2489 participants; moderate-certainty evidence). DTIs reduced the rate of major bleeding (OR 0.58, 95% CI 0.38 to 0.89; 3 studies, 5994 participants; high-certainty evidence). For oral factor Xa inhibitors compared with conventional anticoagulation, meta-analysis demonstrated no clear difference in recurrent VTE (OR 0.85, 95% CI 0.71 to 1.01; 13 studies, 17,505 participants; moderate-certainty evidence), recurrent DVT (OR 0.70, 95% CI 0.49 to 1.01; 9 studies, 16,439 participants; moderate-certainty evidence), fatal PE (OR 1.18, 95% CI 0.69 to 2.02; 6 studies, 15,082 participants; moderate-certainty evidence), non-fatal PE (OR 0.93, 95% CI 0.68 to 1.27; 7 studies, 15,166 participants; moderate-certainty evidence) or all-cause mortality (OR 0.87, 95% CI 0.67 to 1.14; 9 studies, 10,770 participants; moderate-certainty evidence). Meta-analysis showed a reduced rate of major bleeding with oral factor Xa inhibitors compared with conventional anticoagulation (OR 0.63, 95% CI 0.45 to 0.89; 17 studies, 18,066 participants; high-certainty evidence). AUTHORS' CONCLUSIONS: The current review suggests that DOACs may be superior to conventional therapy in terms of safety (major bleeding), and are probably equivalent in terms of efficacy. There is probably little or no difference between DOACs and conventional anticoagulation in the prevention of recurrent VTE, recurrent DVT, pulmonary embolism and all-cause mortality. DOACs reduced the rate of major bleeding compared to conventional anticoagulation. The certainty of evidence was moderate or high.
Topics: Humans; Anticoagulants; Antithrombins; Factor Xa Inhibitors; Rivaroxaban; Dabigatran; Venous Thromboembolism; Neoplasm Recurrence, Local; Venous Thrombosis; Pulmonary Embolism; Hemorrhage
PubMed: 37058421
DOI: 10.1002/14651858.CD010956.pub3 -
Canadian Journal of Anaesthesia =... Dec 2022To compare the relative efficacy of supportive therapies (inotropes, vasopressors, and mechanical circulatory support [MCS]) for adult patients with cardiogenic shock... (Meta-Analysis)
Meta-Analysis Review
Inotropes, vasopressors, and mechanical circulatory support for treatment of cardiogenic shock complicating myocardial infarction: a systematic review and network meta-analysis.
PURPOSE
To compare the relative efficacy of supportive therapies (inotropes, vasopressors, and mechanical circulatory support [MCS]) for adult patients with cardiogenic shock complicating acute myocardial infarction.
SOURCE
We conducted a systematic review and network meta-analysis and searched six databases from inception to December 2021 for randomized clinical trials (RCTs). We evaluated inotropes, vasopressors, and MCS in separate networks. Two reviewers performed screening, full-text review, and extraction. We used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework to rate the certainty in findings. The critical outcome of interest was 30-day all-cause mortality.
PRINCIPAL FINDINGS
We included 17 RCTs. Among inotropes (seven RCTs, 1,145 patients), levosimendan probably reduces mortality compared with placebo (odds ratio [OR], 0.53; 95% confidence interval [CI], 0.33 to 0.87; moderate certainty), but primarily in lower severity shock. Milrinone (OR, 0.52; 95% CI, 0.19 to 1.39; low certainty) and dobutamine (OR, 0.67, 95% CI, 0.30 to 1.49; low certainty) may have no effect on mortality compared with placebo. With regard to MCS (eight RCTs, 856 patients), there may be no effect on mortality with an intra-aortic balloon pump (IABP) (OR, 0.94; 95% CI, 0.69 to 1.28; low certainty) or percutaneous MCS (pMCS) (OR, 0.96; 95% CI, 0.47 to 1.98; low certainty), compared with a strategy involving no MCS. Intra-aortic balloon pump use was associated with less major bleeding compared with pMCS. We found only two RCTs evaluating vasopressors, yielding insufficient data for meta-analysis.
CONCLUSION
The results of this systematic review and network meta-analysis indicate that levosimendan reduces mortality compared with placebo among patients with low severity cardiogenic shock. Intra-aortic balloon pump and pMCS had no effect on mortality compared with a strategy of no MCS, but pMCS was associated with higher rates of major bleeding.
STUDY REGISTRATION
Center for Open Science ( https://osf.io/ky2gr ); registered 10 November 2020.
Topics: Adult; Humans; Shock, Cardiogenic; Network Meta-Analysis; Simendan; Intra-Aortic Balloon Pumping; Myocardial Infarction; Hemorrhage; Treatment Outcome
PubMed: 36195825
DOI: 10.1007/s12630-022-02337-7 -
The Cochrane Database of Systematic... Apr 2021Thrombolytic therapy is usually reserved for people with clinically serious or massive pulmonary embolism (PE). Evidence suggests that thrombolytic agents may dissolve... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Thrombolytic therapy is usually reserved for people with clinically serious or massive pulmonary embolism (PE). Evidence suggests that thrombolytic agents may dissolve blood clots more rapidly than heparin and may reduce the death rate associated with PE. However, there are still concerns about the possible risk of adverse effects of thrombolytic therapy, such as major or minor haemorrhage. This is the fourth update of the Cochrane review first published in 2006.
OBJECTIVES
To assess the effects of thrombolytic therapy for acute pulmonary embolism.
SEARCH METHODS
The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, and CINAHL databases and the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 17 August 2020. We undertook reference checking to identify additional studies.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) that compared thrombolytic therapy followed by heparin versus heparin alone, heparin plus placebo, or surgical intervention for people with acute PE (massive/submassive). We did not include trials comparing two different thrombolytic agents or different doses of the same thrombolytic drug.
DATA COLLECTION AND ANALYSIS
Two review authors (ZZ, QH) assessed the eligibility and risk of bias of trials and extracted data. We calculated effect estimates using the odds ratio (OR) with a 95% confidence interval (CI) or the mean difference (MD) with a 95% CI. The primary outcomes of interest were death, recurrence of PE and haemorrhagic events. We assessed the certainty of the evidence using GRADE criteria.
MAIN RESULTS
We identified three new studies for inclusion in this update. We included 21 trials in the review, with a total of 2401 participants. No studies compared thrombolytics versus surgical intervention. We were not able to include one study in the meta-analysis because it provided no extractable data. Most studies carried a high or unclear risk of bias related to randomisation and blinding. Meta-analysis showed that, compared to control (heparin alone or heparin plus placebo), thrombolytics plus heparin probably reduce both the odds of death (OR 0.58, 95% CI 0.38 to 0.88; 19 studies, 2319 participants; low-certainty evidence), and recurrence of PE (OR 0.54, 95% CI 0.32 to 0.91; 12 studies, 2050 participants; low-certainty evidence). Effects on mortality weakened when six studies at high risk of bias were excluded from analysis (OR 0.71, 95% CI 0.45 to 1.13; 13 studies, 2046 participants) and in the analysis of submassive PE participants (OR 0.61, 95% CI 0.37 to 1.02; 1993 participants). Effects on recurrence of PE also weakened after removing one study at high risk of bias for sensitivity analysis (OR 0.60, 95% CI 0.35 to 1.04; 11 studies, 1949 participants). We downgraded the certainty of evidence to low because of 'Risk of bias' concerns. Major haemorrhagic events were probably more common in the thrombolytics group than in the control group (OR 2.84, 95% CI 1.92 to 4.20; 15 studies, 2101 participants; moderate-certainty evidence), as were minor haemorrhagic events (OR 2.97, 95% CI 1.66 to 5.30; 13 studies,1757 participants; low-certainty evidence). We downgraded the certainty of the evidence to moderate or low because of 'Risk of bias' concerns and inconsistency. Haemorrhagic stroke may occur more often in the thrombolytics group than in the control group (OR 7.59, 95% CI 1.38 to 41.72; 2 studies, 1091 participants). Limited data indicated that thrombolytics may benefit haemodynamic outcomes, perfusion lung scanning, pulmonary angiogram assessment, echocardiograms, pulmonary hypertension, coagulation parameters, composite clinical outcomes, need for escalation and survival time to a greater extent than heparin alone. However, the heterogeneity of the studies and the small number of participants involved warrant caution when interpreting results. The length of hospital stay was shorter in the thrombolytics group than in the control group (mean difference (MD) -1.40 days, 95% CI -2.69 to -0.11; 5 studies, 368 participants). Haemodynamic decompensation may occur less in the thrombolytics group than in the control group (OR 0.36, 95% CI 0.20 to 0.66; 3 studies, 1157 participants). Quality of life was similar between the two treatment groups. None of the included studies provided data on post-thrombotic syndrome or on cost comparison.
AUTHORS' CONCLUSIONS
Low-certainty evidence suggests that thrombolytics may reduce death following acute pulmonary embolism compared with heparin (the effectiveness was mainly driven by one trial with massive PE). Thrombolytic therapy may be helpful in reducing the recurrence of pulmonary emboli but may cause more major and minor haemorrhagic events, including haemorrhagic stroke. More studies of high methodological quality are needed to assess safety and cost effectiveness of thrombolytic therapy for people with pulmonary embolism.
Topics: Acute Disease; Bias; Cause of Death; Fibrinolytic Agents; Hemorrhage; Heparin; Humans; Pulmonary Embolism; Randomized Controlled Trials as Topic; Recurrence; Thrombolytic Therapy
PubMed: 33857326
DOI: 10.1002/14651858.CD004437.pub6