Effects of Etomidate on Postintubation Hypotension, Inflammatory Markers, and Mortality in Critically Ill Patients with COVID-19: An International, Multicenter, Retrospective Study.

OBJECTIVE: To evaluate the association of etomidate with postintubation hypotension, inflammation, and mortality in critically ill patients with COVID-19. DESIGN: International, multicenter, retrospective study. PARTICIPANTS: Critically ill patients hospitalized specifically for COVID-19 from three major academic institutions in the US and Europe. MAIN OUTCOME AND MEASURES: Patients were allocated into the etomidate (ET) group or another induction agent (OA) group. The primary outcome was postintubation hypotension. Secondary outcomes included postintubation inflammatory status, in-hospital mortality, and mortality at 30 days. RESULTS: 171 patients with a median age of 68 (IQR 58-73) years were included (ET, n = 98; OA, n = 73). Etomidate was associated with lower postintubation mean arterial pressure [74.33 (64-85) mm Hg versus 81.84 (69.75-94.25) mm Hg, p = 0.005] compared to other agents. No statistically significant differences were generally observed in inflammatory markers between the two groups at 7- and 14-days after admission to the intensive care unit. In-hospital mortality [77 (79%) versus 41 (56%), p = 0.003] and mortality at 30-days [78 (80%) versus 43 (59%), p = 0.006] were higher in the ET group. In multivariate logistic regression analysis, only etomidate (p = 0.009) and postintubation mean arterial pressure (p < 0.001) had a statistically significant effect on mortality, in contrast to stress-dose steroids (p = 0.301), after adjusting for creatinine (p = 0.695), blood urea nitrogen (p = 0.153), age (p = 0.055), oxygen saturation of hemoglobin (SpO2) (p = 0.941), and fraction of inspired oxygen (FiO2) (p = 0.712). CONCLUSIONS: Administration of a single-bolus dose of etomidate in critically ill patients with COVID-19 is associated with lower postintubation mean arterial pressure and higher in-hospital and 30-day mortality compared to other induction agents.

Association of vasopressors with mortality in critically ill patients with COVID-19: a systematic review and meta-analysis

Exogenous catecholamines may have pronounced side effects and affect physiological cascades. The aim of this study was to investigate the effect of vasopressors on mortality of critically ill patients with coronavirus disease 2019 (COVID-19). A systematic search of PubMed, Scopus, and ClinicalTrials.gov was conducted for relevant articles until December 2022. Eligibility criteria were randomized controlled and non-randomized trials. The primary outcome was in-hospital and 30-day mortality. The quality of studies was assessed using the Methodological Index for Non-Randomized Studies (MINORS) tool, while paired meta-analysis was used to estimate the pooled risk ratios (RR) along with their 95% Confidence Interval (95% CI). Analyses of 22 studies (n = 8034) revealed that vasopressor use is associated with mortality compared to no vasopressor therapy [RR (95%CI): 4.30 (3.21, 5.75);p < 0.001]. In-hospital and 30-day mortality are significantly higher in patients who receive vasopressors [RR (95%CI): 4.60 (2.47, 8.55);p < 0.001 and RR (95%CI): 2.97 (1.72, 5.14);p < 0.001, respectively]. Also, analyses of data from 10 studies (n = 3519) revealed that vasopressor use is associated with acute kidney injury [RR (95%CI): 3.17 (2.21, 4.54);p < 0.001]. In conclusion, current use of vasopressors in critically ill patients with COVID-19 may be associated with higher in-hospital mortality, 30-day mortality, and incidence rate of acute kidney injury. Further research is required to estimate the correlation of specific vasopressor characteristics (type, timing, dose, combination) with adverse effects and mortality in this population. Graphical Supplementary Information The online version contains supplementary material available at 10.1007/s44254-023-00013-7.

High-flow nasal oxygen versus conventional oxygen therapy in patients with COVID-19 pneumonia and mild hypoxaemia: a randomised controlled trial.

RATIONALE: In patients with COVID-19 pneumonia and mild hypoxaemia, the clinical benefit of high-flow nasal oxygen (HFNO) remains unclear. We aimed to examine whether HFNO compared with conventional oxygen therapy (COT) could prevent escalation of respiratory support in this patient population. METHODS: In this multicentre, randomised, parallel-group, open-label trial, patients with COVID-19 pneumonia and peripheral oxygen saturation (SpO2) ≤92% who required oxygen therapy were randomised to HFNO or COT. The primary outcome was the rate of escalation of respiratory support (ie, continuous positive airway pressure, non-invasive ventilation or invasive mechanical ventilation) within 28 days. Among secondary outcomes, clinical recovery was defined as the improvement in oxygenation (SpO2 ≥96% with fractional inspired oxygen (FiO2) ≤30% or partial pressure of arterial carbon dioxide/FiO2 ratio >300 mm Hg). RESULTS: Among 364 randomised patients, 55 (30.3%) of 181 patients assigned to HFNO and 70 (38.6%) of 181 patients assigned to COT underwent escalation of respiratory support, with no significant difference between groups (absolute risk difference -8.2% (95% CI -18% to +1.4%); RR 0.79 (95% CI 0.59 to 1.05); p=0.09). There was no significant difference in clinical recovery (69.1% vs 60.8%; absolute risk difference 8.2% (95% CI -1.5% to +18.0%), RR 1.14 (95% CI 0.98 to 1.32)), intensive care unit admission (7.7% vs 11.0%, absolute risk difference -3.3% (95% CI -9.3% to +2.6%)), and in hospital length of stay (11 (IQR 8-17) vs 11 (IQR 7-20) days, absolute risk difference -1.0% (95% CI -3.1% to +1.1%)). CONCLUSIONS: Among patients with COVID-19 pneumonia and mild hypoxaemia, the use of HFNO did not significantly reduce the likelihood of escalation of respiratory support. TRIAL REGISTRATION NUMBER: NCT04655638.

Investigation of admission serum creatinine as a predictor of hospital length of stay in triple-vaccinated COVID-19 inpatients.

BACKGROUND: This study assessed the association between admission kidney function and the duration of hospitalization in triple-vaccinated coronavirus disease 2019 (COVID-19) inpatients during the omicron surge in Larissa, central Greece. METHODS: Regression analysis was used to estimate the effect of kidney function biomarkers on hospital length of stay (LoS) within a dataset from a cohort of 51 subjects. RESULTS: Sex- and age-adjusted admission serum creatinine was associated with hospital LoS (p=0.034). CONCLUSIONS: Serum creatinine concentration on admission should be further evaluated as a possible clinical predictor of hospital LoS among triple-vaccinated COVID-19 inpatients both at the country and global level.

Cutting-Edge Approaches in Respiratory and Critical Care Medicine.

The COVID-19 pandemic has affected health care across the world, with respiratory and critical care medicine being affected the most [...].

COVID-19 and the cardiovascular system-current knowledge and future perspectives.

The current coronavirus disease 2019 (COVID-19) pandemic has had devastating impact on populations around the world. The high mortality rates in patients with COVID-19 has been attributed to the influence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), its causative viral agent, on several physiological systems in human body, including the respiratory, cardiovascular, and neurological systems. There is emerging evidence on propensity of this virus to attack cardiovascular system. However, various pathophysiological mechanisms by which SARS-CoV-2 interacts with cardiovascular system and leads to high morbidity and mortality, including cardiovascular complications, are poorly understood. This mini review aims to provide an update on the current knowledge and perspectives on areas of future research.

Neuromuscular Blockade in the Pre- and COVID-19 ARDS Patients.

Acute respiratory distress syndrome (ARDS) accounts for a quarter of mechanically ventilated patients, while during the pandemic, it overwhelmed the capacity of intensive care units (ICUs). Lung protective ventilation (low tidal volume, positive-end expiratory pressure titrated to lung mechanics and oxygenation, permissive hypercapnia) is a non-pharmacological approach that is the gold standard of management. Among the pharmacological treatments, the use of neuromuscular blocking agents (NMBAs), although extensively studied, has not yet been well clarified. The rationale is to minimize the risk for lung damage progression, in the already-injured pulmonary parenchyma. By abolishing rigorous spontaneous efforts, NMBAs may decrease the generation of high transpulmonary pressures that could aggravate patients' self-inflicted lung injury. Moreover, NMBAs can harmonize the patient-ventilator interaction. Recent randomized controlled trials reported contradictory results and changed the clinical practice in a bidirectional way. NMBAs have not been documented to improve long-term survival; thus, the current guidance suggests their use only in patients in whom a lung protective ventilation protocol cannot be applied, due to asynchrony or increased respiratory efforts. In the present review, we discuss the published data and additionally the clinical practice in the "war" conditions of the COVID-19 pandemic, concerning NMBA use in the management of patients with ARDS.

Remdesivir-induced Bradycardia is not Associated with Worse Outcome in Patients with COVID-19: A Retrospective Analysis.

BACKGROUND: COVID-19, is primarily a respiratory illness but is known to cause extrapulmonary manifestations, especially on the cardiovascular system. Bradycardia is commonly reported in COVID-19 patients despite no prior history of occurrence, and many studies have shown an association with increased mortality. Multiple case reports have been published showcasing remdesivir potentially causing bradycardia. Our aim was to investigate the incidence of bradycardia in patients receiving remdesivir and examine the association with disease severity and survival outcomes. METHODS: A retrospective study was performed including 160 COVID-19 patients receiving remdesivir for 5 days. Patients' demographics, comorbidities, medication, vital signs, laboratory tests and outcome were recorded. Bradycardia was defined as a heart rate < 60 beats/min and severe bradycardia < 50 beats/min. RESULTS: One hundred eighteen (73.8%) patients experienced at least one episode of bradycardia during hospitalisation. Bradycardia was present in 12 (7.5%) patients before treatment with remdesivir. The rate of bradycardia increased up to the 6th day of hospitalisation (40.6%) and subsequently diminished and normalised within 5 days after the last remdesivir dose (5% at Day 10). Severe bradycardia was observed in 13 (7.5%) patients. No difference was observed in ICU admission between groups (bradycardia vs no bradycardia). When we stratified patients according to the outcome of hospitalisation, no significant difference was observed in the occurrence of bradycardia between groups (alive vs dead) [p = 0.853]. CONCLUSIONS: Treatment with remdesivir may be associated with new-onset bradycardia in hospitalised patients with COVID-19. However, bradycardia is transient and is not associated with ICU admission and mortality.

Do the Kinetics of Antibody Responses Predict Clinical Outcome in Hospitalized Patients With Moderate-to-Severe COVID-19?

BACKGROUND/AIM: The relationship between the kinetics of antibody responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the severity of Coronavirus Disease 2019 (COVID-19) is poorly understood. The aim of the present study was to investigate whether serum SARS-CoV-2 antibody kinetics serve as an early predictor of clinical deterioration or recovery in hospitalized patients with COVID-19. PATIENTS AND METHODS: In this prospective observational study, 102 consecutive patients (median age: 60 years, 58% males) with symptomatic COVID-19 infection diagnosed by real-time polymerase chain reaction assay, hospitalized in two tertiary hospitals, were included. Rapid test for qualitative detection of immunoglobulin M (IgM) and immunoglobulin G (IgG) SARS-CoV-2 antibodies was performed at pre-defined time intervals during hospitalization (days: 0, 3, 7, 10, 14, 21 and 28). RESULTS: During a 3-month follow-up period after COVID-19 disease onset, a total of 87 patients were discharged, 12 patients were intubated and entered the Intensive Care Unit, and three patients died. The median time for seroconversion was 10 days for IgM and 12 days for IgG post onset of symptoms. Univariate logistic regression analysis found no associations between IgM or IgG positivity and clinical outcomes or complications during hospitalization for COVID-19 infection. Diabetes and dyslipidemia were the only clinical risk factors predictive of COVID-19-related complications during hospitalization. CONCLUSION: SARS-CoV-2 antibody responses do not predict clinical outcome in hospitalized patients with moderate-to-severe COVID-19 infection.

Watch Out for Burnout in COVID-19: A Greek Health Care Personnel Study.

The aim of the current study was to examine the mental well-being of healthcare personnel (HCP) working in COVID-19 units in Greece and to calculate the prevalence of burnout (BO) amongst them. A questionnaire based on the Maslach Burnout Inventory for Medical Personnel was utilized between February 21st, 2021 and March 5th, 2021. A total of 190 HCP responded to the questionnaire, of which 73.7% were nurses and midwives. The mean age of the participants was 38.3 (8.4) years. Overall, 71.6% of the participants had a high BO score, while 20.5% had a moderate and 7.9% had a low BO score. Night shifts in COVID-19 wards and job dissatisfaction were significantly associated with a high BO score (P = .03 and P < .0001, respectively). The majority of HCP working in COVID-19 wards in Greece is experiencing high levels of overall BO and emotional exhaustion.

Circulating suPAR associates with severity and in-hospital progression of COVID-19.

BACKGROUND: COVID-19 disease progression is characterized by hyperinflammation and risk stratification may aid in early aggressive treatment and advanced planning. The aim of this study was to assess whether suPAR and other markers measured at hospital admission can predict the severity of COVID-19. METHODS: The primary outcome measure in this international, multi-centre, prospective, observational study with adult patients hospitalized primarily for COVID-19 was the association of WHO Clinical Progression Scale (WHO-CPS) with suPAR, ferritin, CRP, albumin, LDH, eGFR, age, procalcitonin, and interleukin-6. Admission plasma suPAR levels were determined using the suPARnostic® ELISA and suPARnostic® Turbilatex assays. RESULTS: Seven hundred and sixty-seven patients, 440 (57.4%) males and 327 (42.6%) females, were included with a median age of 64 years. Log-suPAR levels significantly correlated with WHO-CPS score, with each doubling of suPAR increasing the score by one point (p < .001). All the other markers were also correlated with WHO-CPS score. Admission suPAR levels were significantly lower in survivors (7.10 vs. 9.63, 95% CI 1.47-3.59, p < .001). A linear model (SALGA) including suPAR, serum albumin, serum lactate dehydrogenase, eGFR, and age can best estimate the WHO-CPS score and survival. Combining all five parameters in the SALGA model can improve the accuracy of discrimination with an AUC of 0.80 (95% CI: 0.759-0.836). CONCLUSIONS: suPAR levels significantly correlated with WHO-CPS score, with each doubling of suPAR increasing the score by one point. The SALGA model may serve as a quick tool for predicting disease severity and survival at admission.

Predictors of SARS-CoV-2 IgG Spike Antibody Responses on Admission and Clinical Outcomes of COVID-19 Disease in Fully Vaccinated Inpatients: The CoVax Study.

BACKGROUND: SARS-CoV-2 vaccines have shown high efficacy in protecting against COVID-19, although the determinants of vaccine effectiveness and breakthrough rates are yet to be determined. We aimed at investigating several factors affecting the SARS-CoV-2 IgG Spike (S) antibody responses on admission and clinical outcomes of COVID-19 disease in fully vaccinated, hospitalized patients. METHODS: 102 subjects were enrolled in the study. Blood serum samples were collected from each patient upon admission for the semiquantitative determination of the SARS-CoV-2 IgG S levels with lateral flow assays. Factors influencing vaccine responses were documented. RESULTS: 27 subjects had a negative antibody test upon hospital admission. Out of the 102 patients admitted to the hospital, 88 were discharged and 14 died. Both the absence of anti-S SARS-CoV-2 antibodies and poor clinical outcomes of COVID-19 disease were associated with older age, lower Ct values, and a shorter period between symptom onset and hospital admission. Ct values and time between symptom onset and hospitalization were independently associated with SARS-CoV-2 IgG S responses upon admission. The PaO2/FiO2 ratio was identified as an independent predictor of in-hospital mortality. CONCLUSIONS: Host- and disease-associated factors can predict SARS-CoV-2 IgG S responses and mortality in hospitalized patients with breakthrough SARS-CoV-2 Infection.

Therapeutic Vitamin D Supplementation Following COVID-19 Diagnosis: Where Do We Stand?-A Systematic Review.

Vitamin D has known immunomodulatory activity and multiple indications exist supporting its potential use against SARS-CoV-2 infection in the setting of the current pandemic. The purpose of this systematic review is to examine the efficacy of vitamin D administered to adult patients following COVID-19 diagnosis in terms of length of hospital stay, intubation, ICU admission and mortality rates. Therefore, PubMed and Scopus databases were searched for original articles referring to the aforementioned parameters. Of the 1376 identified studies, eleven were finally included. Vitamin D supplements, and especially calcifediol, were shown to be useful in significantly reducing ICU admissions and/or mortality in four of the studies, but not in diminishing the duration of hospitalization of COVID-19 patients. Due to the large variation in vitamin D supplementation schemes no absolute conclusions can be drawn until larger randomized controlled trials are completed. However, calcifediol administered to COVID-19 patients upon diagnosis represents by far the most promising agent and should be the focus of upcoming research efforts.

Hydropneumothorax With Persistent Air Leak in a Patient With Mild COVID-19 Disease.

COVID-19 is a pandemic viral disease with a catastrophic global impact. The severity of COVID-19 symptoms ranges from very mild to severe and affects mainly the respiratory system. Spontaneous pneumothorax and pleural effusion are rarely seen in spontaneously breathing COVID-19 patients. We herein report a case of a patient with mild COVID-19 disease presenting to the emergency department with hydropneumothorax. Due to persistent air leak, the patient was managed with video-assisted thoracoscopic surgery (VATS) bullectomy and talc pleurodesis. Clinicians managing these patients should be alert to early diagnose this complication.

COVID-19 Smart Diagnosis in the Emergency Department: all-in in Practice.

INTRODUCTION: Coronavirus Disease 19 (COVID-19) diagnosis has been a major problem in most Emergency Departments (EDs) and other senior care facilities. Various clinical manifestations, and the several radiologic and laboratory data combined with the misleading test results to identify the virus, are responsible for certain misdiagnoses, especially in suspected cases needing urgent management and treatment. Although emergency and other front-line physicians struggle to manage COVID-19 patients, still existent cases with ambiguous diagnosis trammel the ED safety and responsibility. AREAS COVERED: This review article summarizes on a large scale the common information for the medical history, clinical examinations, radiology and laboratory data for SARS-CoV-2. We summarize the available literature using the PubMed, Science Direct and EMBASE databases published until December 2021 on the general information for COVID-19 diagnosis, and, finally, we propose algorithms for a precise and on-the-spot diagnosis the disease. EXPERT OPINION: COVID-19 diagnosis has appeared to be such ambiguous, and physicians need to correlate medical history, medical examination, potential extrapulmonary manifestations, along with laboratory and radiologic data, for a prompt COVID-19 diagnosis.