Efficacy and safety of corticosteroids for the treatment of community-acquired pneumonia: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The role of corticosteroids in the treatment of community-acquired pneumonia (CAP) remains uncertain. We conducted an updated meta-analysis to investigate the effectiveness and potential effect modifiers of adjunctive corticosteroids in patients with CAP. METHODS: The protocol of this meta-analysis was registered with PROSPERO (CRD42022354920). We searched MEDLINE, Embase, the Cochrane Library and trial registers from inception till March 2023 to identify randomized controlled trials (RCTs) investigating corticosteroids in adult patients with CAP. Our primary outcome was the risk of all-cause mortality within 30 days after randomization (if not reported at day 30, we extracted the outcome closest to 30 days). Risk ratios (RR) and mean differences (MDs) were pooled under a random-effects model. RESULTS: Fifteen RCTs (n = 3252 patients) were included in this review. Corticosteroids reduced the risk of all-cause mortality in CAP patients (RR: 0.69, 95% CI: 0.53-0.89; high certainty). This significant result was restricted to hydrocortisone therapy and patients with severe CAP. Additionally, younger patients demonstrated a greater reduction in mortality. Corticosteroids reduced the incidence of shock and the need for mechanical ventilation (MV), and decreased the length of hospital and ICU stay (moderate certainty). CONCLUSIONS: Corticosteroids reduce the risk of all-cause mortality, especially in younger patients receiving hydrocortisone, and probably decrease the need for MV, the incidence of shock, and the length of hospital and ICU stay in patients with CAP. Our findings indicate that patients with CAP, especially severe CAP, will benefit from adjunctive corticosteroid therapy.

Short-course versus prolonged-course antibiotic regimens for ventilator-associated pneumonia: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Current guidelines recommend short-duration antibiotic therapy for non-fermenting gram-negative bacilli (NF-GNB) ventilator-associated pneumonia (VAP) which may be associated with a higher recurrence of pneumonia. In this meta-analysis, we aimed to compare short- versus prolonged-course antibiotic regimens for VAP. METHODS: We searched several databases for randomized controlled trials (RCTs) that compared the effectiveness of a short- versus long-course of antibiotic treatment in patients with VAP. Data analysis was performed using RevMan 5.4. RESULTS: Our pooled analysis consisted of six RCTs. For 28-day mortality, no significant difference was found between the prolonged course and the short course. Administration of a short course of antibiotics increased the risk of recurrence of pneumonia in patients with VAP due to NF-GNB (RR 1.73; 95% CI: 1.17-2.54). Secondary outcomes, such as clinical resolution, duration of ICU stay, and duration of mechanical ventilation, revealed no significant difference between the two regimens. The quality of evidence was low for most outcomes. CONCLUSIONS: Low-quality evidence suggests that a short course of antibiotics is associated with a higher recurrence of pneumonia in NF-GNB VAP with no difference in mortality as compared to a prolonged course. For definitive conclusions, large-scale and blinded RCTs are required.

Awake Prone Positioning for Non-Intubated COVID-19 Patients with Acute Respiratory Failure: A Meta-Analysis of Randomised Controlled Trials.

INTRODUCTION: Awake prone positioning (APP) has been widely applied in non-intubated patients with COVID-19-related acute hypoxemic respiratory failure. However, the results from randomised controlled trials (RCTs) are inconsistent. We performed a meta-analysis to assess the efficacy and safety of APP and to identify the subpopulations that may benefit the most from it. METHODS: We searched five electronic databases from inception to August 2022 (PROSPERO registration: CRD42022342426). We included only RCTs comparing APP with supine positioning or standard of care with no prone positioning. Our primary outcomes were the risk of intubation and all-cause mortality. Secondary outcomes included the need for escalating respiratory support, length of ICU and hospital stay, ventilation-free days, and adverse events. RESULTS: We included 11 RCTs and showed that APP reduced the risk of requiring intubation in the overall population (RR 0.84, 95% CI: 0.74-0.95; moderate certainty). Following the subgroup analyses, a greater benefit was observed in two patient cohorts: those receiving a higher level of respiratory support (compared with those receiving conventional oxygen therapy) and those in intensive care unit (ICU) settings (compared to patients in non-ICU settings). APP did not decrease the risk of mortality (RR 0.93, 95% CI: 0.77-1.11; moderate certainty) and did not increase the risk of adverse events. CONCLUSIONS: In patients with COVID-19-related acute hypoxemic respiratory failure, APP likely reduced the risk of requiring intubation, but failed to demonstrate a reduction in overall mortality risk. The benefits of APP are most noticeable in those requiring a higher level of respiratory support in an ICU environment.

Probiotics for the Prevention of Ventilator-Associated Pneumonia: An Updated Systematic Review and Meta-Analysis of Randomised Controlled Trials.

BACKGROUND: Presently, there is conflicting evidence regarding the efficacy of probiotics in the prevention of ventilator-associated pneumonia (VAP). This meta-analysis was conducted to update current clinical evidence and evaluate the efficacy and safety of probiotics for the prevention of VAP. METHODS: We searched three databases and two trial registers to retrieve randomised controlled trials (RCTs) comparing probiotics or synbiotics with placebo or standard treatment for the prevention of VAP in adult patients receiving mechanical ventilation in the intensive care unit (ICU). RESULTS: Our meta-analysis included 18 RCTs involving 4893 patients. Our results showed that probiotics may reduce the incidence of VAP (RR 0.68, 95% CI: 0.55-0.84; low certainty). However, in our subgroup and sensitivity analyses, the effect was not significant in double-blind studies, and in studies with a low risk of bias in the randomisation process. Probiotics reduced the length of ICU stay (MD -2.22 days, 95% CI: -4.17 to -0.28; moderate certainty) and the duration of antibiotic use (MD -1.25 days, 95% CI -1.86 to -0.64; moderate certainty). CONCLUSIONS: Probiotics may reduce the incidence of VAP but due to the low quality of pooled evidence, the use of probiotics warrants caution. Further, large-scale, high-quality RCTs need to be conducted to provide conclusive evidence.

The role of rotational thromboelastometry in understanding the coagulation problems in COVID-19 associated critical illness.

In critically ill patients with COVID-19, concomitant abnormalities of coagulation have been seen with an unusually high incidence, often despite seemingly appropriate prophylactic anti-coagulation. It appears that standard coagulation tests are limited in their ability to accurately reflect the severity of the prothrombotic phenotype observed in severe COVID-19 infections. In this narrative review we consider the role of a global haemostatic assay, rotational thromboelastometry (ROTEM), as a near bedside test allowing a more comprehensive assessment of haemostatic function in the context of COVID-19 infection. A comprehensive literature search was conducted on PubMed using the keywords "COVID-19" OR "SARS-CoV-2" AND "Rotational thromboelastometry". Sixteen original articles were included for analysis and two existing literature reviews were considered. Whilst not the perfect substitute for in vivo coagulation, studies utilising rotational thromboelastometry assays in COVID-19 patients have demonstrated increased maximum clot firmness (consistent with hypercoagulability) and reduced maximum lysis (consistent with "fibrinolytic shutdown"). There is a possible association with disease severity and degree of hypercoagulability and hypofibrinolysis as a possible tool for risk stratification and the potential modulation of fibrinogen-dependent maximum clot firmness with enhanced anticoagulation strategies. Precisely how these coagulation abnormalities can be modified by optimum, individualised medical interventions to improve clinical outcomes, however, remains unclear.