Noninvasive Oxygenation Strategies in Immunocompromised Patients With Acute Hypoxemic Respiratory Failure: A Pairwise and Network Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: Acute hypoxemic respiratory failure (AHRF) is a leading cause of intensive care unit (ICU) admission among immunocompromised patients. Invasive mechanical ventilation is associated with increased morbidity and mortality. OBJECTIVE: To evaluate the efficacy of various oxygenation strategies including noninvasive ventilation (NIV), high-flow nasal cannula (HFNC), and conventional oxygen therapy in immunocompromised patients with AHRF. METHODS: Electronic databases including PubMed, Embase, and the Cochrane Library were reviewed from inception to December 2018. We included all randomized controlled trials (RCTs) comparing different modalities of initial oxygenation strategies in immunocompromised patients with AHRF. Our primary outcome was the need for intubation and invasive mechanical ventilation while secondary outcomes were ICU acquired infections and short- and long-term mortality. Data were extracted separately and independently by 2 reviewers. We performed a Bayesian network meta-analysis to calculate odds ratio (OR) and Bayesian 95% credible intervals (CrIs). RESULTS: Nine RCTs were included (1570 patients, mean age 61.1 ± 13.8 years with 64% male). Noninvasive ventilation was associated with a significantly reduced intubation rate compared with standard oxygen therapy (OR: 0.53; 95% CrI: 0.26-0.91). There were no significant reductions of intubation between NIV versus HFNC (OR: 0.83; 95% CrI: 0.35-2.11) or HFNC versus standard oxygen therapy (OR: 0.65; 95% CrI: 0.26-1.24). There were no significant differences between all groups regarding short-term (28-day or ICU) mortality or long-term (90-day or hospital) mortality or ICU-acquired infections (P > 0.05). CONCLUSION: Among immunocompromised patients with AHRF, NIV was associated with a significant reduction of intubation compared with standard oxygen therapy. There were no significant differences among all oxygenation strategies regarding mortality and ICU-acquired infections.

Effect of oxygenation modalities among patients with postoperative respiratory failure: a pairwise and network meta-analysis of randomized controlled trials.

BACKGROUND: Postoperative respiratory failure is associated with increased perioperative complications. Our aim is to compare outcomes between non-invasive ventilation (NIV), high-flow nasal cannula (HFNC), and standard oxygen in patients at high-risk for or with established postoperative respiratory failure. METHODS: Electronic databases including PubMed, Embase, and the Cochrane Library were reviewed from inception to September 2019. We included only randomized controlled trials (RCTs) that compared NIV, HFNC, and standard oxygen in patients at high risk for or with established postoperative respiratory failure. We performed a Bayesian network meta-analysis to calculate the odds ratio (OR) and Bayesian 95% credible intervals (CrIs). RESULTS: Nine RCTs representing 1865 patients were included (the mean age was 61.6 ± 10.2 and 64.4% were males). In comparison with standard oxygen, NIV was associated with a significant reduction in intubation rate (OR 0.23; 95% Cr.I. 0.10-0.46), mortality (OR 0.45; 95% Cr.I. 0.27-0.71), and intensive care unit (ICU)-acquired infections (OR 0.43, 95% Cr.I. 0.25-0.70). Compared to standard oxygen, HFNC was associated with a significant reduction in intubation rate (OR 0.28, 95% Cr.I. 0.08-0.76) and ICU-acquired infections (OR 0.41; 95% Cr.I. 0.20-0.80), but not mortality (OR 0.58; 95% Cr.I. 0.26-1.22). There were no significant differences between HFNC and NIV regarding different outcomes. In a subgroup analysis, we observed a mortality benefit with NIV over standard oxygen in patients undergoing cardiothoracic surgeries but not in abdominal surgeries. Furthermore, in comparison with standard oxygen, NIV and HFNC were associated with lower intubation rates following cardiothoracic surgeries while only NIV reduced the intubation rates following abdominal surgeries. CONCLUSIONS: Among patients with post-operative respiratory failure, HFNC and NIV were associated with significantly reduced rates of intubation and ICU-acquired infections compared with standard oxygen. Moreover, NIV was associated with reduced mortality in comparison with standard oxygen.

Initial Noninvasive Oxygenation Strategies in Subjects With De Novo Acute Hypoxemic Respiratory Failure.

BACKGROUND: De novo hypoxemic respiratory failure is defined as significant hypoxemia in the absence of chronic lung disease such as COPD, and excluding respiratory failure occurring in the immediate postoperative or postextubation period. We aimed to evaluate the efficacy of various oxygenation strategies including noninvasive ventilation (NIV), high-flow nasal cannula (HFNC), and conventional oxygen therapy in patients with de novo hypoxemic respiratory failure. METHODS: We performed electronic database searches of PubMed, Cochrane Library, and Embase from inception to December 2018 to include randomized controlled trials that compared various oxygenation strategies in cases of de novo hypoxemic respiratory failure occurring in adult subjects without a preexisting chronic lung disease and excluding respiratory failure in the immediate postoperative or postextubation periods. We performed a Bayesian network meta-analysis to calculate odds ratio (OR) and Bayesian 95% credible intervals (CrI). RESULTS: 16 studies were included, involving 2,180 subjects with a mean age of 61 ± 17 y (66% were male; 46% of the included subjects were treated with conventional oxygen, 27.8% were treated with NIV, and 25.8% were treated with HFNC). Compared to conventional oxygen, NIV was associated with reduced intubation rates (OR 0.42, 95% CrI 0.26-0.62) but no significant reduction in short-term (OR 0.73, 95% CrI 0.47-1.02) or long-term mortality (OR 0.60, 95% CrI 0.29-1.06). There was no significant difference between NIV and HFNC or between HFNC and conventional oxygen regarding all outcomes. In a sensitivity analysis, the results remained consistent after exclusion of studies that included subjects with respiratory failure secondary to cardiogenic pulmonary edema. CONCLUSION: Among subjects with hypoxemic respiratory failure, NIV was associated with a significant reduction in intubation rates but not short- or long-term mortality when compared to conventional oxygen therapy. There was no significant difference between NIV and HFNC or between HFNC and conventional oxygen regarding all outcomes.

Haloperidol for the management of delirium in adult intensive care unit patients: A systematic review and meta-analysis of randomized controlled trials.

PURPOSE: Delirium commonly presents as a complication in critically ill patients. Our aim is to perform a meta-analysis investigating the role of haloperidol versus placebo in management (treatment and prophylaxis), of delirium in intensive care unit (ICU). MATERIALS AND METHODS: Our study is a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing haloperidol versus placebo for treatment and/or prophylaxis of ICU-related delirium. RESULTS: Six RCTs representing 2552 patients. There was no significant difference between haloperidol and placebo-treated patients in short-term all-cause mortality (risk ratio [RR] 0.96; 95% confidence interval [CI] 0.81-1.14; P = 0.67), incidence of delirium (RR 0.93; 95% CI 0.65-1.34; P = 0.70), ICU length of stay (Mean difference [MD] 0.00 days; 95% CI -0.82-0.83; P = 0.99), or delirium/coma-free days (MD 0.09; 95% CI -0.05-0.24; P = 0.21). Haloperidol was not associated with increased risk for serious adverse events (RR 0.65; 95% CI 0.23-1.88; P = 0.43), QTc prolongation (RR 0.87; 95% CI 0.63-1.19; P = 0.38), or extrapyramidal symptoms (RR 0.84; 95% CI 0.57-1.23; P = 0.37). CONCLUSION: Among critically ill patients, haloperidol administration compared with placebo does not significantly affect short-term mortality, incidence of delirium, ICU length of stay, or delirium or coma-free days. Additionally, there was no increased risk of adverse events.

Comparison of Coronary Artery Bypass Grafting and Drug-Eluting Stents in Patients with Left Main Coronary Artery Disease and Chronic Kidney Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: Treatment of left main coronary artery disease (LMCAD) in patients with chronic kidney disease (CKD) with either percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) remains controversial. Therefore, we performed a meta-analysis to evaluate the optimal choice of therapy when treating LMCAD in patients with CKD. METHOD: We performed an electronic database search of Pubmed, Embase, and Cochrane Library for all studies that compared PCI with CABG when treating LMCAD in the setting of CKD. Major adverse cardiac and cerebrovascular events (MACCE) were the primary outcome. Secondary outcomes included myocardial infarction (MI), cerebrovascular events, all-cause mortality, and repeat revascularization. RESULTS: Our analysis included 5 studies (2 randomized controlled trial and 3 retrospective) representing a total of 1212 patients. Mean follow up was 3.4 ±â€¯1.3 years. Our study demonstrated a significant reduction in MACCE for patients treated with CABG compared with PCI (odd ratio [OR] 0.72; 95% confidence interval [CI] 0.55-0.95, P = 0.02, I2 = 0%). We also found a significant reduction in both MI (OR 0.55; 95% CI 0.34-0.87; P = 0.01; I2 = 0%) and repeat revascularization (OR 0.22; 95% CI 0.10-0.51; P < 0.001, I2 = 63%) in the CABG group. However, CABG was associated with increased risks of cerebrovascular disease events compared with PCI (OR 2.04; 95% CI 1.02-4.08; P = 0.04, I2 = 0%). CONCLUSION: In patients with CKD requiring LMCAD intervention, CABG is associated with a lower risk of MACCE, MI, and repeat revascularization, however it was associated with an increased risk of cerebrovascular accidents when compared to patients who received PCI therapy. Further RCTs with sufficient power are required to confirm these findings.

Antiarrhythmic Drugs or Catheter Ablation in the Management of Ventricular Tachyarrhythmias in Patients With Implantable Cardioverter-Defibrillators: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: In patients with an implantable cardioverter-defibrillator (ICD), shocks are associated with increased morbidity and mortality. Therefore, we conducted this study to evaluate the efficacy and safety of antiarrhythmic drugs and catheter ablation (CA) in the treatment of ventricular tachyarrhythmias (VT) in patients with an ICD. METHODS: An electronic database search for randomized controlled trials that evaluated antiarrhythmic drugs and CA in patients with ICD was conducted. The primary outcome was recurrent VT. Secondary outcomes were ICD shocks and any deaths. Bayesian and frequentist network meta-analyses were performed to calculate hazard ratios (HRs) and 95% credible intervals (CrIs)/CIs. RESULTS: Twenty-two randomized controlled trials were identified (3828 total patients; age 64.3±11.4; 79% males). The use of amiodarone was associated with a significantly reduced rate of VT recurrence compared with control (HR=0.34 [95% CrI=0.15-0.74]; absolute risk difference=-0.23 [95% CrI=-0.23 to -0.09]; number needed to treat=4). Sotalol was associated with increased risk of VT recurrence compared with amiodarone (HR=2.88 [95% CrI=1.35-6.46]). Compared with control, amiodarone (HR=0.33 [95% CrI=0.15-0.76]; absolute risk difference=-0.17 [95% CrI=-0.32 to -0.06]; number needed to treat=6) and CA (HR=0.52 [95% CrI=0.30-0.89; absolute risk difference=-0.12 [95% CrI=-0.24 to -0.03]; number needed to treat=8) were associated with significantly reduced ICD shocks. Compared with amiodarone, sotalol was associated with significantly increased ICD shocks (HR=2.70 [95% CrI=1.17-6.71]). The rate of death was not significantly different between the competing strategies. The node-splitting method showed no inconsistency. CONCLUSIONS: Among patients with an ICD, amiodarone significantly reduced VT recurrence and ICD shocks, while CA reduced ICD shocks. Sotalol significantly increased VT recurrence and ICD shocks compared with amiodarone. The long-term side effects of amiodarone and early complications of CA should be weighed carefully according to specific patient characteristics.

Aspirin Efficacy in Primary Prevention: A Meta-analysis of Randomized Controlled Trials.

INTRODUCTION: The role of aspirin as a means of primary prevention remains controversial. AIM: We have conducted a meta-analysis of all randomized controlled trials (RCTs) to evaluate the role of aspirin in primary prevention. METHODS: Literature search was performed via PubMed, Embase, and the Cochrane Library for all related RCTs. All-cause mortality was the primary endpoint. Secondary endpoints included major adverse cardiovascular events (MACE), myocardial infarction (MI), cardiovascular mortality, cerebrovascular events, and bleeding events. We used a random effects model to report the risk ratios (RRs) with 95% confidence intervals (CIs). RESULTS: Our analysis included 17 RCTs (164,862 patients; 83,309 received aspirin and 81,744 received placebo). Our study did not demonstrate any significant reduction in all-cause mortality for patients treated with aspirin when compared with placebo (RR 0.97; 95% CI 0.93-1.01; P = 0.13). Sensitivity analysis performed by excluding healthy elderly (≥ 65) showed significant reductions in all-cause mortality in the aspirin-treated patients (RR 0.94; 95% CI 0.90-0.99; P = 0.01). There were no significant differences between both groups regarding cardiovascular mortality and cerebrovascular events (P > 0.05). However, aspirin-treated patients significantly reduced MACE and MI events (RR 0.89; 95% CI 0.85-0.93; P < 0.001 and RR 0.88; 95% CI 0.78-0.98; P = 0.02, respectively), respectively. However, aspirin was associated with a significantly higher incidence of bleeding, including major bleeding and intracranial bleeding (P < 0.001). CONCLUSIONS: Aspirin use in primary prevention has resulted in a lower incidence of MACE and MI without significantly effecting cerebrovascular events. However, aspirin was associated with a higher bleeding risk. Use of aspirin as a means of primary prevention should be thoroughly discussed with patients and pursued based on the risk of cardiovascular disease while also considering bleeding risk.

Triple versus dual inhaler therapy in moderate-to-severe COPD: A systematic review and meta-analysis of randomized controlled trials.

INTRODUCTION: Treatment of chronic obstructive pulmonary disease (COPD) is evolving specially with triple inhaler therapy. OBJECTIVES: To perform a meta-analysis to ascertain the safety and efficacy of triple inhaler therapy consisting of an inhaled-glucocorticoid (ICS), long-acting muscarinic antagonist (LAMA) and long-acting beta2-agonist (LABA) when compared with dual therapy (ICS-LABA or LAMA-LABA). METHODS: We performed an electronic database search to include randomized controlled trials (RCTs) comparing between triple and dual inhalers. Pooled rate-ratio (RR) or odds-ratio (OR) for dichotomous data and weighted mean difference (MD) for continuous data were calculated with their corresponding 95% confidence interval (CI). RESULTS: Our study included 12 RCTs totaling 19,322 patients, mean age of 65 ± 8.2 years and 68.2% were male. Pooled analysis demonstrated a significant reduction in moderate-to-severe COPD exacerbations with triple therapy (RR 0.75; 95% CI 0.69-0.83; P < 0.01). Additionally, triple therapy caused significant increase in trough FEV1 (MD 0.09 L; 95% CI 0.07-0.12; P < 0.01), significant reduction in the mean St. George's Respiratory Questionnaire (SGRQ) score (MD -1.67; 95% CI -2.02- -1.31; P < 0.01), and more patients experienced ≥ 4 points reduction of SGRQ score (OR 1.27; 95% CI 1.19-1.35; P < 0.01). Triple therapy was associated with an increased risk of pneumonia when compared to LABA/LAMA (OR 1.25; 95% 1.03-1.97; P = 0.03) but there were no significant differences in other adverse events between triple and dual inhalers. CONCLUSIONS: Among patients with moderate-to-severe COPD, triple inhaler therapy was associated with a reduction of moderate-to-severe COPD exacerbations, improved lung function and improved quality of life when compared to dual inhaler therapy but with an increased pneumonia risk.

Anti-atherosclerotic effect of incretin mimetics: a meta-analysis of randomized controlled trials.

Background: Diabetes is a very common cause of cardiovascular disease, and metformin remains the first-line treatment of diabetes. Many trials were conducted to prove the efficacy and safety of other antidiabetic medication as the best add-on medication. Objectives: We aimed to evaluate the atherosclerotic effect of incretin mimetics in patients with diabetes.Methods: We searched in PubMed, clinicaltrials.gov and Cochrane Library for randomized controlled trials (RCTs) comparing incretin mimetic with conventional treatment. The primary outcome was the change in carotid intima-media thickness (CIMT) at the end of the trials.Results: Five RCTs (n = 1241), the mean age of patients included in the trials is 64.3 ± 11.4. The primary outcome was statistically significant for CIMT improvement in terms of long-term follow-up analysis between the incretin mimetic group and conventional group (mean difference [MD] -0.031; 95% Confidence interval [CI] -0.049 to 0.012; P = 0.001), whereas at short-term follow-up it wasn't (MD -0.004; 95% CI -0.024 to 0.016; P = 0.7) in the overall group of study participants. Additionally, the mean change in body mass index (BMI) (MD 0.064; 95% CI -0.54 to 0.67; P = 0.8), and mean change in systolic blood pressure (MD -0.42; 95% CI -3.2 to 2.3; P = 0.8) or diastolic blood pressure (MD 0.25; 95% CI -1.18 to 1.68; P = 0.7) were not significant.Conclusion: Long-term use of incretin mimetic medication results in significant improvement of atherosclerosis, which leads to fewer vascular events, with no apparent effect on blood pressure or BMI. Further dedicated trials are required to show the superiority of adding these medications to conventional treatment versus placebo.

Balanced crystalloids versus isotonic saline in critically ill patients: systematic review and meta-analysis.

OBJECTIVES: Intravenous fluids are one of the most used medical therapy for patients, especially critically ill patients. We conducted a meta-analysis comparing between balanced crystalloids and normal saline in critically ill patients and its effect on various clinical outcomes. DESIGN: Meta-analysis and systematic review of randomized clinical trials (RCTs). METHODS AND DATA SOURCE: Electronic search was performed using PubMed, Cochrane library, and clinical trials.gov from inception through March 1, 2018, with inclusion of prospective studies that investigated one of the primary outcomes which were acute kidney injury (AKI) and in-hospital mortality while secondary outcomes were intensive care unit (ICU) mortality and new renal replacement therapy (RRT). RESULTS: Six RCTs were included. Total of 19,332 patients were included in the final analysis. There was no significant difference in in-hospital mortality (11.5% vs 12.2%; OR 0.92; 95% CI 0.85-1.01; P = 0.09; I2 = 0%), incidence of AKI (12% vs 12.7%, OR 0.92; 95% CI 0.84-1.01; P = 0.1; I2 = 0), overall ICU mortality (OR 0.9, 95% CI 0.81-1.01, P = 0.08, I2 = 0%), or need for new RRT (OR 0.92, 95% CI 0.67-1.28, P = 0.65, I2 = 38%) between balanced crystalloids and isotonic saline in critically ill patients. CONCLUSION: Balanced crystalloids and isotonic saline have no difference on various clinical outcomes including in-hospital mortality, AKI, overall ICU mortality, and new RRT. Further powerful clinical trials are required to determine the relationship between crystalloid fluid type and clinical outcomes.