scholarly journals Efficacy and safety of gastrointestinal bleeding prophylaxis in critically ill patients: systematic review and network meta-analysis

BMJ ◽  
2020 ◽  
pp. l6744 ◽  
Author(s):  
Ying Wang ◽  
Zhikang Ye ◽  
Long Ge ◽  
Reed A C Siemieniuk ◽  
Xin Wang ◽  
...  

AbstractObjectiveTo determine, in critically ill patients, the relative impact of proton pump inhibitors (PPIs), histamine-2 receptor antagonists (H2RAs), sucralfate, or no gastrointestinal bleeding prophylaxis (or stress ulcer prophylaxis) on outcomes important to patients.DesignSystematic review and network meta-analysis.Data sourcesMedline, PubMed, Embase, Cochrane Central Register of Controlled Trials, trial registers, and grey literature up to March 2019.Eligibility criteria for selecting studies and methodsWe included randomised controlled trials that compared gastrointestinal bleeding prophylaxis with PPIs, H2RAs, or sucralfate versus one another or placebo or no prophylaxis in adult critically ill patients. Two reviewers independently screened studies for eligibility, extracted data, and assessed risk of bias. A parallel guideline committee (BMJ Rapid Recommendation) provided critical oversight of the systematic review, including identifying outcomes important to patients. We performed random-effects pairwise and network meta-analyses and used GRADE to assess certainty of evidence for each outcome. When results differed between low risk and high risk of bias studies, we used the former as best estimates.ResultsSeventy two trials including 12 660 patients proved eligible. For patients at highest risk (>8%) or high risk (4-8%) of bleeding, both PPIs and H2RAs probably reduce clinically important gastrointestinal bleeding compared with placebo or no prophylaxis (odds ratio for PPIs 0.61 (95% confidence interval 0.42 to 0.89), 3.3% fewer for highest risk and 2.3% fewer for high risk patients, moderate certainty; odds ratio for H2RAs 0.46 (0.27 to 0.79), 4.6% fewer for highest risk and 3.1% fewer for high risk patients, moderate certainty). Both may increase the risk of pneumonia compared with no prophylaxis (odds ratio for PPIs 1.39 (0.98 to 2.10), 5.0% more, low certainty; odds ratio for H2RAs 1.26 (0.89 to 1.85), 3.4% more, low certainty). It is likely that neither affect mortality (PPIs 1.06 (0.90 to 1.28), 1.3% more, moderate certainty; H2RAs 0.96 (0.79 to 1.19), 0.9% fewer, moderate certainty). Otherwise, results provided no support for any affect on mortality, Clostridium difficile infection, length of intensive care stay, length of hospital stay, or duration of mechanical ventilation (varying certainty of evidence).ConclusionsFor higher risk critically ill patients, PPIs and H2RAs likely result in important reductions in gastrointestinal bleeding compared with no prophylaxis; for patients at low risk, the reduction in bleeding may be unimportant. Both PPIs and H2RAs may result in important increases in pneumonia. Variable quality evidence suggested no important effects of interventions on mortality or other in-hospital morbidity outcomes.Systematic review registrationPROSPERO CRD42019126656.

BMJ ◽  
2020 ◽  
pp. l6722 ◽  
Author(s):  
Zhikang Ye ◽  
Annika Reintam Blaser ◽  
Lyubov Lytvyn ◽  
Ying Wang ◽  
Gordon H Guyatt ◽  
...  

AbstractClinical questionWhat is the role of gastrointestinal bleeding prophylaxis (stress ulcer prophylaxis) in critically ill patients? This guideline was prompted by the publication of a new large randomised controlled trial.Current practiceGastric acid suppression with proton pump inhibitors (PPIs) or histamine-2 receptor antagonists (H2RAs) is commonly done to prevent gastrointestinal bleeding in critically ill patients. Existing guidelines vary in their recommendations of which population to treat and which agent to use.RecommendationsThis guideline panel makes a weak recommendation for using gastrointestinal bleeding prophylaxis in critically ill patients at high risk (>4%) of clinically important gastrointestinal bleeding, and a weak recommendation for not using prophylaxis in patients at lower risk of clinically important bleeding (≤4%). The panel identified risk categories based on evidence, with variable certainty regarding risk factors. The panel suggests using a PPI rather than a H2RA (weak recommendation) and recommends against using sucralfate (strong recommendation).How this guideline was createdA guideline panel including patients, clinicians, and methodologists produced these recommendations using standards for trustworthy guidelines and the GRADE approach. The recommendations are based on a linked systematic review and network meta-analysis. A weak recommendation means that both options are reasonable.The evidenceThe linked systematic review and network meta-analysis estimated the benefit and harm of these medications in 12 660 critically ill patients in 72 trials. Both PPIs and H2RAs reduce the risk of clinically important bleeding. The effect is larger in patients at higher bleeding risk (those with a coagulopathy, chronic liver disease, or receiving mechanical ventilation but not enteral nutrition or two or more of mechanical ventilation with enteral nutrition, acute kidney injury, sepsis, and shock) (moderate certainty). PPIs and H2RAs might increase the risk of pneumonia (low certainty). They probably do not have an effect on mortality (moderate certainty), length of hospital stay, or any other important outcomes. PPIs probably reduce the risk of bleeding more than H2RAs (moderate certainty).Understanding the recommendationIn most critically ill patients, the reduction in clinically important gastrointestinal bleeding from gastric acid suppressants is closely balanced with the possibility of pneumonia. Clinicians should consider individual patient values, risk of bleeding, and other factors such as medication availability when deciding whether to use gastrointestinal bleeding prophylaxis. Visual overviews provide the relative and absolute benefits and harms of the options in multilayered evidence summaries and decision aids available on MAGICapp.


2021 ◽  
Vol 8 ◽  
Author(s):  
Johannes Gratz ◽  
Marion Wiegele ◽  
Mathias Maleczek ◽  
Harald Herkner ◽  
Herbert Schöchl ◽  
...  

Background: Early during the course of the ongoing COVID-19 pandemic, reports suggested alarmingly high incidences for thromboembolic events in critically ill patients with COVID-19. However, the clinical relevance of these events was not reported in several studies. Additionally, more recent research showed contradictory results and suggested substantially lower rates of venous thromboembolism. Thus, the aim of the present study was to summarize evidence on the incidence of clinically relevant venous thromboembolism (VTE)—defined as VTE excluding isolated subsegmental pulmonary embolism (PE) and distal deep vein thrombosis (DVT)—in adult critically ill patients with COVID-19.Methods: We performed a systematic review of studies reporting the incidence of clinically relevant PE and/or DVT in critically ill patients with COVID-19. Scientific reports published in the English language between January and October 2020 were included. We conducted a random-effects model meta-analysis to calculate incidence estimates of clinically relevant VTE and bleeding events. We also performed exploratory meta-regression and subgroup analyses of different diagnostic approaches and additional factors that possibly influenced the incidence of these outcomes.Results: Fifty-four articles (5,400 patients) fulfilled the predefined inclusion criteria, of which 41 had a high risk of bias. The majority of included patients were male, > 60 years, and overweight. Twenty-one studies reported the use of prophylactic doses of heparin. Pooled incidences for clinically relevant PE were estimated at 8% (95% CI, 4–11%), for proximal DVT at 14% (95% CI, 9–20%), and—after exclusion of studies with a high risk of bias—for the composite outcome of VTE at 18% (95% CI, 13–24%). Clinically relevant bleeding occurred at a rate of 6% (95% CI, 2–9%).Conclusions: We summarized currently available data on the rate of clinically relevant VTE in critically ill patients with COVID-19. Pooled incidence estimates were lower than those reported by previous review articles. In the absence of evidence-based anticoagulation guidelines for critically ill patients with COVID-19, the results of our study provide clinically important information for an individual risk-benefit assessment in this context.Registration: The study protocol was prospectively registered in PROSPERO on June 22, 2020 (CRD42020193353; https://www.crd.york.ac.uk/prospero).


2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Shiren Sun ◽  
Wei Zhang ◽  
Ming Bai ◽  
Lijuan Zhao ◽  
Xiaolan Chen ◽  
...  

Abstract Background and Aims Continuous renal replacement therapy (CRRT) has been widely used in the critical care setting and anticoagulation is usually necessitated. However, critically ill patients are commonly at incremental risk of bleeding, which contributed to the hesitation of anticoagulant use for CRRT in clinical practice. The current guideline recommended CRRT proceed without anticoagulation in patients with contraindication to citrate and increased bleeding risk. Nevertheless, the efficacy of anticoagulation-free CRRT remains inconsistent. Therefore, the purpose of our present systematic review is to evaluate the efficacy and safety of anticoagulant-free CRRT based on the current literatures. Method We conducted a comprehensive search of PubMed (US National Library of Medicine, Bethesda, MD, USA), Cochrane Library databases and EMBASE from database inception to January 12, 2019 for potential candidate studies. Studies included adult critically ill (age > 18 years) patients with increased bleeding risk, and underwent CRRT without anticoagulation were considered for the inclusion. Results Finally, 17 observational studies and 3 randomized controlled trials with 1615 patients were included in our present meta-analysis. There was no significant difference in filter lifespan between the anticoagulation-free and systemic heparin group. The filter lifespan was significantly prolonged in the citrate (WMD -23.01, 95%CI [-28.62, -17.39], P < 0.001; I2 = 0%, P = 0.53) and nafamostat (WMD -8.4, 95%CI [-9.9, -6.9], P < 0.001; I2 = 33.7%, P = 0.21) groups, compared with anticoagulation-free group. The averaged filter lifespan of the anticoagulation-free CRRT ranged from 10.2 to 52.5 hours. Conclusion The filter lifespan in anticoagulation-free patients with increased bleeding risk was comparable to that in patients without increased bleeding risk underwent systemic heparin anticoagulation CRRT. Nafamostat was not recommended for CRRT anticoagulation due to its drawbacks. Currently, the optimal choice of anticoagulation strategy for critically ill patients without citrate contraindications at high risk of bleeding should be regional citrate anticoagulation. Further studies should focus on the special cut-off value of activated partial thromboplastin time (APTT), international normalized ratio (INR) and platelet (PLT) count, at which the anticoagulation-free CRRT would be beneficial.


2019 ◽  
Author(s):  
Wei Zhang ◽  
Ming Bai ◽  
Yan Yu ◽  
Xiaolan Chen ◽  
Lijuan Zhao ◽  
...  

Abstract Abstract Background: Continuous renal replacement therapy (CRRT) has been widely used in the critical care setting and anticoagulation is usually necessitated. However, critically ill patients are commonly at incremental risk of bleeding, which contributed to the hesitation of anticoagulant use for CRRT in clinical practice. The current guideline recommended CRRT proceed without anticoagulation in patients with contraindication to citrate and increased bleeding risk. Nevertheless, the efficacy of anticoagulation-free CRRT remains inconsistent. Therefore, the purpose of our present systematic review is to evaluate the efficacy and safety of anticoagulant-free CRRT based on the current literatures. Methods: We conducted a comprehensive search of PubMed (US National Library of Medicine, Bethesda, MD, USA), Cochrane Library databases and EMBASE from database inception to January 12, 2019 for potential candidate studies. Studies included adult critically ill (age > 18 years) patients with increased bleeding risk, and underwent CRRT without anticoagulation were considered for the inclusion. Results: Finally, 17 observational studies and 3 randomized controlled trials with 1615 patients were included in our present meta-analysis. There was no significant difference in filter lifespan between the anticoagulation-free and systemic heparin group. The filter lifespan was significantly prolonged in the citrate (WMD -23.01, 95%CI [-28.62, -17.39], P < 0.001; I 2 = 0%, P = 0.53) and nafamostat (WMD -8.4, 95%CI [-9.9, -6.9], P < 0.001; I 2 = 33.7%, P = 0.21) groups, compared with anticoagulation-free group. The averaged filter lifespan of the anticoagulation-free CRRT ranged from 10.2 to 52.5 hours. Conclusion: The filter lifespan in anticoagulation-free patients with increased bleeding risk was comparable to that in patients without increased bleeding risk underwent systemic heparin anticoagulation CRRT. Nafamostat was not recommended for CRRT anticoagulation due to its drawbacks. Currently, the optimal choice of anticoagulation strategy for critically ill patients without citrate contraindications at high risk of bleeding should be regional citrate anticoagulation. Further studies should focus on the special cut-off value of activated partial thromboplastin time (APTT), international normalized ratio (INR) and platelet (PLT) count, at which the anticoagulation-free CRRT would be beneficial. Key words: Anticoagulation, critically ill patients, continuous renal replacement therapy, filter failure, bleeding


2021 ◽  
pp. 1286-1305
Author(s):  
Amogh Rajeev Nadkarni ◽  
Swapna C. Vijayakumaran ◽  
Sudeep Gupta ◽  
Jigeeshu V. Divatia

PURPOSE There are scarce data to aid in prognostication of the outcome of critically ill cancer patients with COVID-19. In this systematic review and meta-analysis, we investigated the mortality of critically ill cancer patients with COVID-19. METHODS We searched online databases and manually searched for studies in English that reported on outcomes of adult cancer patients with COVID-19 admitted to an intensive care unit (ICU) or those with severe COVID-19 between December 2019 and October 2020. Risk of bias was assessed by the Modified Newcastle-Ottawa Scale. The primary outcome was all-cause mortality. We also determined the odds of death for cancer patients versus noncancer patients, as also outcomes by cancer subtypes, presence of recent anticancer therapy, and presence of one or more comorbidities. Random-effects modeling was used. RESULTS In 28 studies (1,276 patients), pooled mortality in cancer patients with COVID-19 admitted to an ICU was 60.2% (95% CI, 53.6 to 6.7; I2 = 80.27%), with four studies (7,259 patients) showing higher odds of dying in cancer versus noncancer patients (odds ratio 1.924; 95% CI, 1.596 to 2.320). In four studies (106 patients) of patients with cancer and severe COVID-19, pooled mortality was 59.4% (95% CI, –39.4 to 77.5; I2 = 72.28%); in one study, presence of hematologic malignancy was associated with significantly higher mortality compared with nonhematologic cancers (odds ratio 1.878; 95% CI, 1.171 to 3.012). Risk of bias was low. CONCLUSION Most studies were reported before the results of trials suggesting the benefit of dexamethasone and tocilizumab, potentially overestimating mortality. The observed mortality of 60% in cancer patients with COVID-19 admitted to the ICU is not prohibitively high, and admission to the ICU should be considered for selected patients (registered with PROSPERO, CRD42020207209).


BMJ Open ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. e037591
Author(s):  
Brian Johnston ◽  
Alexandra Nelson ◽  
Alicia C Waite ◽  
Gedeon Lemma ◽  
Ingeborg Welters

IntroductionAtrial fibrillation (AF) is the most common cardiac arrhythmia in critically ill patients and is associated with an increased risk of thromboembolic events and mortality. Oral anticoagulation for thromboembolism prophylaxis is a key component of managing AF in the general population and is recommended by National Institute for Health and Care Excellence guidelines. However, assessment tools used to aid decision making about anticoagulation have not yet been validated in the critical care setting. There is a paucity of data assessing the impact of anticoagulation strategies on clinical outcomes in critically ill patients with AF. We present a protocol for a systematic review and meta-analysis to evaluate the effectiveness of anticoagulation strategies for AF used specifically in critical care.Methods and analysisWe will conduct a systematic review of the literature by searching MEDLINE, EMBASE, CENTRAL and PubMed databases for articles published from January 1990 to October 2019. Studies reporting anticoagulation strategies for AF in adults (>18 years) admitted to a general critical care setting will be assessed for inclusion. Outcomes of interest will include (1) percentage of patients started on anticoagulation in critical care for AF, (2) incidence of thromboembolism, (3) incidence of bleeding events, (4) intensive care unit (ICU) mortality, (5) hospital mortality, (6) ICU length of stay and (7) hospital length of stay. We will conduct a meta-analysis of trials. Risk of bias will be assessed using the Cochrane Risk of Bias tool for randomised trials or the Newcastle-Ottawa Risk of Bias assessment tool for non-randomised studies. This protocol and subsequent systematic review will be reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist.Ethics and disseminationThis proposed systematic review will include data extracted from published studies; therefore, ethical approval is not required. The results of this review will be published in clinical specialty journals and presented at international meetings and conferences.Trial registration numberCRD42020158237.


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