Duration of Resuscitation Efforts and Survival after In-hospital Cardiac Arrest: An Observational Study

Comparison of Dopamine and Norepinephrine in the Treatment of Shock

Coronavirus Disease 2019 (COVID-19) is a multi-systemic infection caused by the novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), that has become a pandemic. Although its prevailing symptoms include anosmia, ageusia, dry couch, fever, shortness of brief, arthralgia, myalgia, and fatigue, regional and methodological assessments vary, leading to heterogeneous clinical descriptions of COVID-19. Aging, uncontrolled diabetes, hypertension, obesity, and exposure to androgens have been correlated with worse prognosis in COVID-19. Abnormalities in the renin-angiotensin-aldosterone system (RAAS), angiotensin-converting enzyme-2 (ACE2) and the androgen-driven transmembrane serine protease 2 (TMPRSS2) have been elicited as key modulators of SARS-CoV-2. While safe and effective therapies for COVID-19 lack, the current moment of pandemic urges for therapeutic options. Existing drugs should be preferred over novel ones for clinical testing due to four inherent characteristics: 1. Well-established long-term safety profile, known risks and contraindications; 2. More accurate predictions of clinical effects; 3. Familiarity of clinical management; and 4. Affordable costs for public health systems. In the context of the key modulators of SARS-CoV-2 infectivity, endocrine targets have become central as candidates for COVID-19. The only endocrine or endocrine-related drug class with already existing emerging evidence for COVID-19 is the glucocorticoids, particularly for the use of dexamethasone for severely affected patients. Other drugs that are more likely to present clinical effects despite the lack of specific evidence for COVID-19 include anti-androgens (spironolactone, eplerenone, finasteride and dutasteride), statins, N-acetyl cysteine (NAC), ACE inhibitors (ACEi), angiotensin receptor blockers (ARB), and direct TMPRSS-2 inhibitors (nafamostat and camostat). Several other candidates show less consistent plausibility. In common, except for dexamethasone, all candidates have no evidence for COVID-19, and clinical trials are needed. While dexamethasone may reduce mortality in severely ill patients with COVID-19, in the absence of evidence of any specific drug for mild-to-moderate COVID-19, researchers should consider testing existing drugs due to their favorable safety, familiarity, and cost profile. However, except for dexamethasone in severe COVID-19, drug treatments for COVID-19 patients must be restricted to clinical research studies until efficacy has been extensively proven, with favorable outcomes in terms of reduction in hospitalization, mechanical ventilation, and death.

/pdf/repurposing-existing-drugs-for-covid-19-an-endocrinology-4oefm8bube.pdf

Repurposing existing drugs for COVID-19: an endocrinology perspective.

Oxygen administration is particularly relevant in patients undergoing surgery under general anesthesia and in those who suffer from acute or critical illness. Nevertheless, excess O2, or hyperoxia, is also known to be harmful. Toxicity arises from the enhanced formation of reactive oxygen species (ROS) that, exceeding the antioxidant defense, may generate oxidative stress. Oxidative stress markers are used to quantify ROS toxicity in clinical and non-clinical settings and represent a promising tool to assess the optimal FiO2 in anesthesia and critical care setting. Despite controversial, the guidelines for the regulation of FiO2 in such settings suggest the adoption of high perioperative oxygen levels. However, hyperoxia has also been shown to be an independent mortality risk factor in critically ill patients. In this literature review, we discuss the biochemical mechanisms behind oxidative stress and the available biomarkers for assessing the pro-oxidant vs antioxidant status. Then, we summarize recent knowledge on the hyperoxia-related consequences in the most common anesthesia and critical care settings, such as traumatic brain injury or cardiac arrest. To this purpose, we searched the PubMed database according to the following combination of key words: ("hyperoxia" OR "FiO2" OR "oxygen therapy") AND ("oxidative stress" OR "ROS" OR "RNS" OR "lipid peroxidation") AND ("anesthesia" OR "surgery" OR "intensive care"). We focused in the results from the past 20 years. Available evidence points toward a conservative monitoring and use of oxygen, unless there is solid proof of its efficacy.

/pdf/hyperoxia-and-oxidative-stress-in-anesthesia-and-critical-1x5ek5aim1.pdf

Hyperoxia and oxidative stress in anesthesia and critical care medicine.

Introduction: Pharmacotherapy for the acute respiratory distress syndrome (ARDS) has been tested in preclinical and clinical studies. However, to date, no pharmacological interventions have proven effective. This may be attributed to lack of proper identification of different ARDS phenotypes.Areas covered: We designed inclusive search strings and searched four bibliographic databases (Cochrane Database of Systematic Reviews, PubMed, Web of Science, and clinicaltrials.gov) to identify relevant research. Search results were mainly restricted to papers published from 2009 through 2019. ARDS is a heterogeneous syndrome, and its different phenotypes - defined according to clinical, radiological, and biological parameters - may affect response to therapy. The most promising pharmacological approaches to date have been based on ARDS pathophysiology. They focus on reducing inflammation and pulmonary edema, promoting selective vasodilation, and repairing alveolar epithelial and endothelial cells.Expert opinion: Pharmacotherapeutic approaches targeting ARDS pathophysiology have failed to exert beneficial effects. Personalized medicine targeting the different ARDS phenotypes has emerged as an option to improve survival. Identification of specific ARDS patient phenotypes that respond to specific therapies seems to be the most important challenge for the next decade. Additional research is warranted before personalized medicine approaches can be applied at bedside for ARDS patients.

https://www.tandfonline.com/doi/pdf/10.1080/13543784.2020.1699531

Personalized pharmacological therapy for ARDS: a light at the end of the tunnel.

Studies investigating the role of hyperoxia in critically ill patients have reported conflicting results. We did this analysis to reveal the effect of hyperoxia in the patients admitted to the intensive care unit (ICU). Electronic databases were searched for all the studies exploring the role of hyperoxia in adult patients admitted to ICU. The primary outcome was mortality. Random-effect model was used for quantitative synthesis of the adjusted odds ratio (aOR). We identified 24 trials in our final analysis. Statistical heterogeneity was found between hyperoxia and normoxia groups in patients with mechanical ventilation (I2 = 92%, P < 0.01), cardiac arrest(I2 = 63%, P = 0.01), traumatic brain injury (I2 = 85%, P < 0.01) and post cardiac surgery (I2 = 80%, P = 0.03). Compared with normoxia, hyperoxia was associated with higher mortality in overall patients (OR 1.22, 95% CI 1.12~1.33), as well as in the subgroups of cardiac arrest (OR 1.30, 95% CI 1.08~1.57) and extracorporeal life support (ELS) (OR 1.44, 95% CI 1.03~2.02). Hyperoxia would lead to higher mortality in critically ill patients especially in the patients with cardiac arrest and ELS.

/pdf/the-effect-of-hyperoxia-on-mortality-in-critically-ill-12uca83bwi.pdf

The Effect of Hyperoxia on Mortality in Critically Ill Patients: A Systematic Review and Meta Analysis

Background The effects of aspirin in preventing the occurrence of acute respiratory distress syndrome (ARDS)/acute lung injury (ALI) among adult patients are controversial. We aimed to further determine the effectiveness of aspirin in reducing the rate of ARDS/ALI. Methods The Pubmed, Embase, Medline, ClinicalTrials.gov , Cochrane Central Register of Controlled Trials (CENTRAL) as well as the Information Sciences Institute (ISI) Web of Science were searched for all controlled studies that research the role of aspirin in adult patients who have the risk of ARDS/ALI. The outcomes were the ARDS/ALI rate and the mortality. Cochrane systematic review software, Review Manager (RevMan), the R software for statistical computing version 3.2.0, and the metafor package were used to test the hypothesis by Mann-Whitney U test. The heterogeneity test and sensitivity analyses were conducted, and random-effects or fixed-effects model was applied to calculate odds ratio (OR) and mean difference (MD) for dichotomous and continuous data, respectively. Results Six trials involving 6562 patients were pooled in our final study. No significant heterogeneity was found in outcome measures. Aspirin could reduce the rate of ARDS/ALI (OR 0.71, 95% confidence interval (CI) 0.58–0.86) but not the mortality (OR 0.87, 95% CI 0.71–1.07). Conclusions In patients with risk of ARDS/ALI, aspirin could provide protective effect on the rate of ARDS/ALI, but it could not reduce the mortality.

The effect of aspirin in preventing the acute respiratory distress syndrome/acute lung injury: A meta-analysis.

Ghrelin is the only known orexigenic gut hormone, and its synthesis, secretion and degradation are affected by different metabolic statuses. This meta-analysis aimed to investigate the potential differences in plasma acyl ghrelin (AG) and des-acyl ghrelin (DAG) concentrations between normal weight and obese adults. Systematic literature searches of PubMed, Embase and Web of Science through October 2021 were conducted for articles reporting AG or DAG levels in obesity and normal weight, and 34 studies with 1863 participants who met the eligibility criteria were identified. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated to evaluate group differences in circulating AG and DAG levels. Pooled effect size showed significantly lower levels of baseline AG (SMD: - 0.85; 95% CI: - 1.13 to - 0.57; PSMD < 0.001) and DAG (SMD: - 1.06; 95% CI: - 1.43 to - 0.69; PSMD < 0.001) in obese groups compared with healthy controls, and similar results were observed when subgroup analyses were stratified by the assay technique or storage procedure. Postprandial AG levels in obese subjects were significantly lower than those in controls when stratified by different time points (SMD 30 min: - 0.85, 95% CI: - 1.18 to - 0.53, PSMD < 0.001; SMD 60 min: - 1.00, 95% CI: - 1.37 to - 0.63, PSMD < 0.001; SMD 120 min: - 1.21, 95% CI: - 1.59 to - 0.83, PSMD < 0.001). In healthy subjects, a postprandial decline in AG was observed at 120 min (SMD: - 0.42; 95% CI: - 0.77 to - 0.06; PSMD = 0.021) but not in obese subjects (SMD: - 0.28; 95% CI: - 0.60 to 0.03; PSMD = 0.074). The mean change in AG concentration was similar in both the obese and lean health groups at each time point (ΔSMD30min: 0.31, 95% CI: - 0.35 to 0.97, PSMD = 0.359; ΔSMD60min: 0.17, 95% CI: - 0.12 to 0.46, PSMD = 0.246; ΔSMD120min: 0.21, 95% CI: - 0.13 to 0.54, PSMD = 0.224). This meta-analysis strengthens the clinical evidence supporting the following: lower baseline levels of circulating AG and DAG in obese individuals; declines in postprandial circulating AG levels, both for the healthy and obese individuals; a shorter duration of AG suppression in obese subjects after meal intake. These conclusions have significance for follow-up studies to elucidate the role of various ghrelin forms in energy homeostasis. 

/pdf/circulating-acyl-and-des-acyl-ghrelin-levels-in-obese-adults-669lpmq7.pdf

Yan-mei Wang

Papers

The Effect of Hyperoxia on Mortality in Critically Ill Patients: A Systematic Review and Meta Analysis

The effect of aspirin in preventing the acute respiratory distress syndrome/acute lung injury: A meta-analysis.

Circulating acyl and des-acyl ghrelin levels in obese adults: a systematic review and meta-analysis