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2.
JAMA ; 326(17): 1690-1702, 2021 Nov 02.
Article in English | MEDLINE | ID: covidwho-1525402

ABSTRACT

Importance: The evidence for benefit of convalescent plasma for critically ill patients with COVID-19 is inconclusive. Objective: To determine whether convalescent plasma would improve outcomes for critically ill adults with COVID-19. Design, Setting, and Participants: The ongoing Randomized, Embedded, Multifactorial, Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP) enrolled and randomized 4763 adults with suspected or confirmed COVID-19 between March 9, 2020, and January 18, 2021, within at least 1 domain; 2011 critically ill adults were randomized to open-label interventions in the immunoglobulin domain at 129 sites in 4 countries. Follow-up ended on April 19, 2021. Interventions: The immunoglobulin domain randomized participants to receive 2 units of high-titer, ABO-compatible convalescent plasma (total volume of 550 mL ± 150 mL) within 48 hours of randomization (n = 1084) or no convalescent plasma (n = 916). Main Outcomes and Measures: The primary ordinal end point was organ support-free days (days alive and free of intensive care unit-based organ support) up to day 21 (range, -1 to 21 days; patients who died were assigned -1 day). The primary analysis was an adjusted bayesian cumulative logistic model. Superiority was defined as the posterior probability of an odds ratio (OR) greater than 1 (threshold for trial conclusion of superiority >99%). Futility was defined as the posterior probability of an OR less than 1.2 (threshold for trial conclusion of futility >95%). An OR greater than 1 represented improved survival, more organ support-free days, or both. The prespecified secondary outcomes included in-hospital survival; 28-day survival; 90-day survival; respiratory support-free days; cardiovascular support-free days; progression to invasive mechanical ventilation, extracorporeal mechanical oxygenation, or death; intensive care unit length of stay; hospital length of stay; World Health Organization ordinal scale score at day 14; venous thromboembolic events at 90 days; and serious adverse events. Results: Among the 2011 participants who were randomized (median age, 61 [IQR, 52 to 70] years and 645/1998 [32.3%] women), 1990 (99%) completed the trial. The convalescent plasma intervention was stopped after the prespecified criterion for futility was met. The median number of organ support-free days was 0 (IQR, -1 to 16) in the convalescent plasma group and 3 (IQR, -1 to 16) in the no convalescent plasma group. The in-hospital mortality rate was 37.3% (401/1075) for the convalescent plasma group and 38.4% (347/904) for the no convalescent plasma group and the median number of days alive and free of organ support was 14 (IQR, 3 to 18) and 14 (IQR, 7 to 18), respectively. The median-adjusted OR was 0.97 (95% credible interval, 0.83 to 1.15) and the posterior probability of futility (OR <1.2) was 99.4% for the convalescent plasma group compared with the no convalescent plasma group. The treatment effects were consistent across the primary outcome and the 11 secondary outcomes. Serious adverse events were reported in 3.0% (32/1075) of participants in the convalescent plasma group and in 1.3% (12/905) of participants in the no convalescent plasma group. Conclusions and Relevance: Among critically ill adults with confirmed COVID-19, treatment with 2 units of high-titer, ABO-compatible convalescent plasma had a low likelihood of providing improvement in the number of organ support-free days. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707.


Subject(s)
COVID-19/therapy , ABO Blood-Group System , Adult , Aged , Critical Illness/therapy , Female , Hospital Mortality , Humans , Immunization, Passive , Length of Stay , Logistic Models , Male , Middle Aged , Respiration, Artificial/statistics & numerical data , Treatment Failure , Vasoconstrictor Agents/therapeutic use
3.
J Korean Med Sci ; 36(44): e309, 2021 Nov 15.
Article in English | MEDLINE | ID: covidwho-1526761

ABSTRACT

BACKGROUND: We assessed maternal and neonatal outcomes of critically ill pregnant and puerperal patients in the clinical course of coronavirus disease 2019 (COVID-19). METHODS: Records of pregnant and puerperal women with polymerase chain reaction positive COVID-19 virus who were admitted to our intensive care unit (ICU) from March 2020 to August 2021 were investigated. Demographic, clinical and laboratory data, pharmacotherapy, and neonatal outcomes were analyzed. These outcomes were compared between patients that were discharged from ICU and patients who died in ICU. RESULTS: Nineteen women were included in this study. Additional oxygen was required in all cases (100%). Eight patients (42%) were intubated and mechanically ventilated. All patients that were mechanically ventilated have died. Increased levels of C-reactive protein (CRP) was seen in all patients (100%). D-dimer values increased in 15 patients (78.9%); interleukin-6 (IL-6) increased in 16 cases (84.2%). Sixteen patients used antiviral drugs. Eleven patients were discharged from the ICU and eight patients have died due to complications of COVID-19 showing an ICU mortality rate of 42.1%. Mean number of hospitalized days in ICU was significantly lower in patients that were discharged (P = 0.037). Seventeen patients underwent cesarean-section (C/S) (89.4%). Mean birth week was significantly lower in patients who died in ICU (P = 0.024). Eleven preterm (57.8%) and eight term deliveries (42.1%) occurred. CONCLUSION: High mortality rate was detected among critically ill pregnant/parturient patients followed in the ICU. Main predictors of mortality were the need of invasive mechanical ventilation and higher number of days hospitalized in ICU. Rate of C/S operations and preterm delivery were high. Pleasingly, the rate of neonatal death was low and no neonatal COVID-19 occurred.


Subject(s)
COVID-19/mortality , Pregnancy Complications, Infectious/mortality , Puerperal Disorders/mortality , SARS-CoV-2 , Adult , Antiviral Agents/therapeutic use , COVID-19/blood , COVID-19/diagnostic imaging , COVID-19/therapy , Cesarean Section , Combined Modality Therapy , Critical Illness/mortality , Delivery, Obstetric/statistics & numerical data , Female , Hospital Mortality , Humans , Infant, Newborn , Intensive Care Units/statistics & numerical data , Length of Stay/statistics & numerical data , Lung/diagnostic imaging , Oxygen Inhalation Therapy , Pregnancy , Pregnancy Outcome , Respiration, Artificial , Retrospective Studies , Treatment Outcome , Young Adult
4.
Artif Organs ; 45(12): 1522-1532, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1526346

ABSTRACT

Disturbed oxygenation is foremost the leading clinical presentation in COVID-19 patients. However, a small proportion also develop carbon dioxide removal problems. The Advanced Organ Support (ADVOS) therapy (ADVITOS GmbH, Munich, Germany) uses a less invasive approach by combining extracorporeal CO2 -removal and multiple organ support for the liver and the kidneys in a single hemodialysis device. The aim of our study is to evaluate the ADVOS system as treatment option in-COVID-19 patients with multi-organ failure and carbon dioxide removal problems. COVID-19 patients suffering from severe respiratory insufficiency, receiving at least two treatments with the ADVOS multi system (ADVITOS GmbH, Munich, Germany), were eligible for study inclusion. Briefly, these included patients with acute kidney injury (AKI) according to KDIGO guidelines, and moderate or severe ARDS according to the Berlin definition, who were on invasive mechanical ventilation for more than 72 hours. In total, nine COVID-19 patients (137 ADVOS treatment sessions with a median of 10 treatments per patient) with moderate to severe ARDS and carbon dioxide removal problems were analyzed. During the ADVOS treatments, a rapid correction of acid-base balance and a continuous CO2 removal could be observed. We observed a median continuous CO2 removal of 49.2 mL/min (IQR: 26.9-72.3 mL/min) with some treatments achieving up to 160 mL/min. The CO2 removal significantly correlated with blood flow (Pearson 0.421; P < .001), PaCO2 (0.341, P < .001) and HCO 3 - levels (0.568, P < .001) at the start of the treatment. The continuous treatment led to a significant reduction in PaCO2 from baseline to the last ADVOS treatment. In conclusion, it was feasible to remove CO2 using the ADVOS system in our cohort of COVID-19 patients with acute respiratory distress syndrome and multiorgan failure. This efficient removal of CO2 was achieved at blood flows up to 300 mL/min using a conventional hemodialysis catheter and without a membrane lung or a gas phase.


Subject(s)
COVID-19/therapy , Carbon Dioxide/blood , Extracorporeal Circulation/instrumentation , Lung/physiopathology , Multiple Organ Failure/therapy , Renal Dialysis/instrumentation , Respiration, Artificial , Aged , COVID-19/blood , COVID-19/diagnosis , COVID-19/physiopathology , Critical Illness , Extracorporeal Circulation/adverse effects , Female , Humans , Male , Middle Aged , Multiple Organ Failure/blood , Multiple Organ Failure/diagnosis , Multiple Organ Failure/physiopathology , Renal Dialysis/adverse effects , Respiration, Artificial/adverse effects , Time Factors , Treatment Outcome
5.
Front Immunol ; 12: 765330, 2021.
Article in English | MEDLINE | ID: covidwho-1518489

ABSTRACT

Aims: Although the exact factors promoting disease progression in COVID-19 are not fully elucidated, unregulated activation of the complement system (CS) seems to play a crucial role in the pathogenesis of acute lung injury (ALI) induced by SARS-CoV-2. In particular, the lectin pathway (LP) has been implicated in previous autopsy studies. The primary purpose of our study is to investigate the role of the CS in hospitalized COVID-19 patients with varying degrees of disease severity. Methods: In a single-center prospective observational study, 154 hospitalized patients with PCR-confirmed SARS-CoV-2 infection were included. Serum samples on admission to the COVID-19 ward were collected for analysis of CS pathway activities and concentrations of LP proteins [mannose-binding lectin (MBL) and ficolin-3 (FCN-3)] & C1 esterase inhibitor (C1IHN). The primary outcome was mechanical ventilation or in-hospital death. Results: The patients were predominately male and had multiple comorbidities. ICU admission was required in 16% of the patients and death (3%) or mechanical ventilation occurred in 23 patients (15%). There was no significant difference in LP activity, MBL and FCN-3 concentrations according to different peak disease severities. The median alternative pathway (AP) activity was significantly lower (65%, IQR 50-94) in patients with death/invasive ventilation compared to patients without (87%, IQR 68-102, p=0.026). An optimal threshold of <65.5% for AP activity was derived from a ROC curve resulting in increased odds for death or mechanical ventilation (OR 4,93; 95% CI 1.70-14.33, p=0.003) even after adjustment for confounding factors. Classical pathway (CP) activity was slightly lower in patients with more severe disease (median 101% for death/mechanical ventilation vs 109%, p=0.014). C1INH concentration correlated positively with length of stay, inflammatory markers and disease severity on admission but not during follow-up. Conclusion: Our results point to an overactivated AP in critically ill COVID-19 patients in vivo leading to complement consumption and consequently to a significantly reduced AP activity in vitro. The LP does not seem to play a role in the progression to severe COVID-19. Apart from its acute phase reaction the significance of C1INH in COVID-19 requires further studies.


Subject(s)
COVID-19/immunology , Complement System Proteins/immunology , SARS-CoV-2 , Adult , Aged , COVID-19/blood , COVID-19/mortality , COVID-19/therapy , Complement C1 Inhibitor Protein/immunology , Critical Illness , Female , Hospital Mortality , Hospitalization , Humans , Lectins/immunology , Male , Middle Aged , Prospective Studies , Respiration, Artificial , Severity of Illness Index
6.
Ann Intern Med ; 174(10): 1409-1419, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1515633

ABSTRACT

BACKGROUND: The COVID-19 pandemic has caused substantial morbidity and mortality. OBJECTIVE: To describe monthly clinical trends among adults hospitalized with COVID-19. DESIGN: Pooled cross-sectional study. SETTING: 99 counties in 14 states participating in the Coronavirus Disease 2019-Associated Hospitalization Surveillance Network (COVID-NET). PATIENTS: U.S. adults (aged ≥18 years) hospitalized with laboratory-confirmed COVID-19 during 1 March to 31 December 2020. MEASUREMENTS: Monthly hospitalizations, intensive care unit (ICU) admissions, and in-hospital death rates per 100 000 persons in the population; monthly trends in weighted percentages of interventions, including ICU admission, mechanical ventilation, and vasopressor use, among an age- and site-stratified random sample of hospitalized case patients. RESULTS: Among 116 743 hospitalized adults with COVID-19, the median age was 62 years, 50.7% were male, and 40.8% were non-Hispanic White. Monthly rates of hospitalization (105.3 per 100 000 persons), ICU admission (20.2 per 100 000 persons), and death (11.7 per 100 000 persons) peaked during December 2020. Rates of all 3 outcomes were highest among adults aged 65 years or older, males, and Hispanic or non-Hispanic Black persons. Among 18 508 sampled hospitalized adults, use of remdesivir and systemic corticosteroids increased from 1.7% and 18.9%, respectively, in March to 53.8% and 74.2%, respectively, in December. Frequency of ICU admission, mechanical ventilation, and vasopressor use decreased from March (37.8%, 27.8%, and 22.7%, respectively) to December (20.5%, 12.3%, and 12.8%, respectively); use of noninvasive respiratory support increased from March to December. LIMITATION: COVID-NET covers approximately 10% of the U.S. population; findings may not be generalizable to the entire country. CONCLUSION: Rates of COVID-19-associated hospitalization, ICU admission, and death were highest in December 2020, corresponding with the third peak of the U.S. pandemic. The frequency of intensive interventions for management of hospitalized patients decreased over time. These data provide a longitudinal assessment of clinical trends among adults hospitalized with COVID-19 before widespread implementation of COVID-19 vaccines. PRIMARY FUNDING SOURCE: Centers for Disease Control and Prevention.


Subject(s)
COVID-19/therapy , Hospitalization/trends , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/therapeutic use , Adolescent , Adrenal Cortex Hormones/therapeutic use , Adult , Age Distribution , Aged , Alanine/analogs & derivatives , Alanine/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/ethnology , COVID-19/mortality , Critical Care/trends , Cross-Sectional Studies , Female , Humans , Intensive Care Units/trends , Length of Stay/trends , Male , Middle Aged , Pandemics , Respiration, Artificial/trends , SARS-CoV-2 , United States/epidemiology , Vasoconstrictor Agents/therapeutic use , Young Adult
7.
JAMA Netw Open ; 4(11): e2134241, 2021 11 01.
Article in English | MEDLINE | ID: covidwho-1508587

ABSTRACT

Importance: The influence of sleep-disordered breathing (SDB) and sleep-related hypoxemia in SARS-CoV-2 viral infection and COVID-19 outcomes remains unknown. Controversy exists regarding whether to continue treatment for SDB with positive airway pressure given concern for aerosolization with limited data to inform professional society recommendations. Objective: To investigate the association of SDB (identified via polysomnogram) and sleep-related hypoxia with (1) SARS-CoV-2 positivity and (2) World Health Organization (WHO)-designated COVID-19 clinical outcomes while accounting for confounding including obesity, underlying cardiopulmonary disease, cancer, and smoking history. Design, Setting, and Participants: This case-control study was conducted within the Cleveland Clinic Health System (Ohio and Florida) and included all patients who were tested for COVID-19 between March 8 and November 30, 2020, and who had an available sleep study record. Sleep indices and SARS-CoV-2 positivity were assessed with overlap propensity score weighting, and COVID-19 clinical outcomes were assessed using the institutional registry. Exposures: Sleep study-identified SDB (defined by frequency of apneas and hypopneas using the Apnea-Hypopnea Index [AHI]) and sleep-related hypoxemia (percentage of total sleep time at <90% oxygen saturation [TST <90]). Main Outcomes and Measures: Outcomes were SARS-CoV-2 infection and WHO-designated COVID-19 clinical outcomes (hospitalization, use of supplemental oxygen, noninvasive ventilation, mechanical ventilation or extracorporeal membrane oxygenation, and death). Results: Of 350 710 individuals tested for SARS-CoV-2, 5402 (mean [SD] age, 56.4 [14.5] years; 3005 women [55.6%]) had a prior sleep study, of whom 1935 (35.8%) tested positive for SARS-CoV-2. Of the 5402 participants, 1696 were Black (31.4%), 3259 were White (60.3%), and 822 were of other race or ethnicity (15.2%). Patients who were positive vs negative for SARS-CoV-2 had a higher AHI score (median, 16.2 events/h [IQR, 6.1-39.5 events/h] vs 13.6 events/h [IQR, 5.5-33.6 events/h]; P < .001) and increased TST <90 (median, 1.8% sleep time [IQR, 0.10%-12.8% sleep time] vs 1.4% sleep time [IQR, 0.10%-10.8% sleep time]; P = .02). After overlap propensity score-weighted logistic regression, no SDB measures were associated with SARS-CoV-2 positivity. Median TST <90 was associated with the WHO-designated COVID-19 ordinal clinical outcome scale (adjusted odds ratio, 1.39; 95% CI, 1.10-1.74; P = .005). Time-to-event analyses showed sleep-related hypoxia associated with a 31% higher rate of hospitalization and mortality (adjusted hazard ratio, 1.31; 95% CI, 1.08-1.57; P = .005). Conclusions and Relevance: In this case-control study, SDB and sleep-related hypoxia were not associated with increased SARS-CoV-2 positivity; however, once patients were infected with SARS-CoV-2, sleep-related hypoxia was an associated risk factor for detrimental COVID-19 outcomes.


Subject(s)
COVID-19 , Cause of Death , Hospitalization , Severity of Illness Index , Sleep Apnea Syndromes/complications , Aged , COVID-19/complications , COVID-19/mortality , COVID-19/therapy , Case-Control Studies , Continuous Positive Airway Pressure , Delivery of Health Care, Integrated , Extracorporeal Membrane Oxygenation , Female , Florida , Hospital Mortality , Humans , Hypoxia , Logistic Models , Male , Middle Aged , Odds Ratio , Ohio , Respiration, Artificial , Risk Factors , SARS-CoV-2 , Sleep , Sleep Apnea Syndromes/pathology , Sleep Apnea Syndromes/therapy
8.
BMC Cardiovasc Disord ; 21(1): 528, 2021 11 08.
Article in English | MEDLINE | ID: covidwho-1505900

ABSTRACT

BACKGROUND: The value of mechanical circulatory support (MCS) in cardiogenic shock, especially the combination of the ECMELLA approach (Impella combined with ECMO), remains controversial. CASE PRESENTATION: A previously healthy 33-year-old female patient was submitted to a local emergency department with a flu-like infection and febrile temperatures up to 39 °C. The patient was tested positive for type-A influenza, however negative for SARS-CoV-2. Despite escalated invasive ventilation, refractory hypercapnia (paCO2: 22 kPa) with severe respiratory acidosis (pH: 6.9) and a rising norepinephrine rate occurred within a few hours. Due to a Horovitz-Index < 100, out-of-centre veno-venous extracorporeal membrane oxygenation (vv-ECMO)-implantation was performed. A CT-scan done because of anisocoria revealed an extended dissection of the right vertebral artery. While the initial left ventricular function was normal, echocardiography revealed severe global hypokinesia. After angiographic exclusion of coronary artery stenoses, we geared up LV unloading by additional implantation of an Impella CP and expanded the vv-ECMO to a veno-venous-arterial ECMO (vva-ECMO). Clinically relevant bleeding from the punctured femoral arteries resulted in massive transfusion and was treated by vascular surgery later on. Under continued MCS, LVEF increased to approximately 40% 2 days after the initiation of ECMELLA. After weaning, the Impella CP was explanted at day 5 and the vva-ECMO was removed on day 9, respectively. The patient was discharged in an unaffected neurological condition to rehabilitation 25 days after the initial admission. CONCLUSIONS: This exceptional case exemplifies the importance of aggressive MCS in severe cardiogenic shock, which may be especially promising in younger patients with non-ischaemic cardiomyopathy and potentially reversible causes of cardiogenic shock. This case impressively demonstrates that especially young patients may achieve complete neurological restoration, even though the initial prognosis may appear unfavourable.


Subject(s)
Extracorporeal Membrane Oxygenation/methods , Heart-Assist Devices , Influenza A virus/isolation & purification , Influenza, Human , Respiration, Artificial/methods , Respiratory Insufficiency , Ventricular Dysfunction, Left , Adult , COVID-19/diagnosis , Clinical Deterioration , Critical Care/methods , Echocardiography/methods , Female , Heart Failure/physiopathology , Heart Failure/therapy , Humans , Influenza, Human/complications , Influenza, Human/diagnosis , Influenza, Human/physiopathology , Respiratory Insufficiency/etiology , Respiratory Insufficiency/physiopathology , Respiratory Insufficiency/therapy , SARS-CoV-2 , Serologic Tests/methods , Severity of Illness Index , Shock, Cardiogenic/etiology , Shock, Cardiogenic/physiopathology , Shock, Cardiogenic/therapy , Treatment Outcome , Ventricular Dysfunction, Left/etiology , Ventricular Dysfunction, Left/physiopathology , Ventricular Dysfunction, Left/therapy
9.
BMC Infect Dis ; 21(1): 1136, 2021 Nov 04.
Article in English | MEDLINE | ID: covidwho-1504761

ABSTRACT

BACKGROUND: The impact of biometric covariates on risk for adverse outcomes of COVID-19 disease was assessed by numerous observational studies on unstratified cohorts, which show great heterogeneity. However, multilevel evaluations to find possible complex, e.g. non-monotonic multi-variate patterns reflecting mutual interference of parameters are missing. We used a more detailed, computational analysis to investigate the influence of biometric differences on mortality and disease evolution among severely ill COVID-19 patients. METHODS: We analyzed a group of COVID-19 patients requiring Intensive care unit (ICU) treatment. For further analysis, the study group was segmented into six subgroups according to Body mass index (BMI) and age. To link the BMI/age derived subgroups with risk factors, we performed an enrichment analysis of diagnostic parameters and comorbidities. To suppress spurious patterns, multiple segmentations were analyzed and integrated into a consensus score for each analysis step. RESULTS: We analyzed 81 COVID-19 patients, of whom 67 required mechanical ventilation (MV). Mean mortality was 35.8%. We found a complex, non-monotonic interaction between age, BMI and mortality. A subcohort of patients with younger age and intermediate BMI exhibited a strongly reduced mortality risk (p < 0.001), while differences in all other groups were not significant. Univariate impacts of BMI or age on mortality were missing. Comparing MV with non-MV patients, we found an enrichment of baseline CRP, PCT and D-Dimers within the MV group, but not when comparing survivors vs. non-survivors within the MV patient group. CONCLUSIONS: The aim of this study was to get a more detailed insight into the influence of biometric covariates on the outcome of COVID-19 patients with high degree of severity. We found that survival in MV is affected by complex interactions of covariates differing to the reported covariates, which are hidden in generic, non-stratified studies on risk factors. Hence, our study suggests that a detailed, multivariate pattern analysis on larger patient cohorts reflecting the specific disease stages might reveal more specific patterns of risk factors supporting individually adapted treatment strategies.


Subject(s)
COVID-19 , Comorbidity , Humans , Intensive Care Units , Respiration, Artificial , SARS-CoV-2
10.
Acta Biomed ; 92(5): e2021365, 2021 11 03.
Article in English | MEDLINE | ID: covidwho-1503645

ABSTRACT

BACKGROUND AND AIM: During the first wave of the Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) pandemic, we faced a massive clinical and organizational challenge having to manage critically ill patients outside the Intensive Care Unit (ICU). This was due to the significant imbalance between ICU bed availability and the number of patients presenting Acute Hypoxemic Respiratory Failure caused by SARS-CoV-2-related interstitial pneumonia. We therefore needed to perform Non-Invasive Ventilation (NIV) in non-intensive wards to assist these patients and relieve pressure on the ICUs and subsequently implemented a new organizational and clinical model. This study was aimed at evaluating its effectiveness and feasibility. METHODS: We recorded the anamnestic, clinical and biochemical data of patients undergoing non-invasive mechanical ventilation while hospitalized in non-intensive CoronaVirus Disease 19 (COVID-19) wards. Data were registered on admission, during anesthesiologist counseling, and when NIV was started and suspended. We retrospectively registered the available results from routine arterial blood gas and laboratory analyses for each time point. RESULTS: We retrospectively enrolled 231 patients. Based on our criteria, we identified 46 patients as NIV responders, representing 19.9% ​​of the general study population and 29.3% of the patients that spent their entire hospital stay in non-ICU wards. Overall mortality was 56.2%, with no significant differences between patients in non-intensive wards (57.3%) and those later admitted to the ICU (54%) Conclusions: NIV is safe and manageable in an emergency situation and could become part of an integrated clinical and organizational model.


Subject(s)
COVID-19 , Noninvasive Ventilation , Respiratory Insufficiency , Humans , Intensive Care Units , Pandemics , Respiration, Artificial , Respiratory Insufficiency/therapy , SARS-CoV-2
11.
BMJ Open ; 11(10): e052013, 2021 10 28.
Article in English | MEDLINE | ID: covidwho-1501717

ABSTRACT

INTRODUCTION: Mechanical ventilation of intensive care unit (ICU) patients universally involves titration of the fraction of inspired oxygen to maintain arterial oxygen saturation (SpO2). However, the optimal SpO2 target remains unknown. METHODS AND ANALYSIS: The Pragmatic Investigation of optimaL Oxygen Targets (PILOT) trial is a prospective, unblinded, pragmatic, cluster-crossover trial being conducted in the emergency department (ED) and medical ICU at Vanderbilt University Medical Center in Nashville, Tennessee, USA. PILOT compares use of a lower SpO2 target (target 90% and goal range: 88%-92%), an intermediate SpO2 target (target 94% and goal range: 92%-96%) and a higher SpO2 target (target 98% and goal range: 96%-100%). The study units are assigned to a single SpO2 target (cluster-level allocation) for each 2-month study block, and the assigned SpO2 target switches every 2 months in a randomly generated sequence (cluster-level crossover). The primary outcome is ventilator-free days (VFDs) to study day 28, defined as the number of days alive and free of invasive mechanical ventilation from the final receipt of invasive mechanical ventilation through 28 days after enrolment. ETHICS AND DISSEMINATION: The trial was approved by the Vanderbilt Institutional Review Board. The results will be submitted for publication in a peer-reviewed journal and presented at one or more scientific conferences. TRIAL REGISTRATION NUMBER: The trial protocol was registered with ClinicalTrials.gov on 25 May 2018 prior to initiation of patient enrolment (ClinicalTrials.gov identifier: NCT03537937).


Subject(s)
COVID-19 , Humans , Oxygen , Prospective Studies , Respiration, Artificial , SARS-CoV-2
12.
Sci Rep ; 11(1): 21522, 2021 11 02.
Article in English | MEDLINE | ID: covidwho-1500507

ABSTRACT

There is controversy whether IL-6 (receptor) antagonists are beneficial in treating COVID-19 patients. We therefore update our systematic review to answer the following research questions: (1) Do patients hospitalized for COVID-19 treated with IL-6 (receptor) antagonists have lower mortality compared to standard of care? (2) Do patients hospitalized for COVID-19 treated with IL-6 (receptor) antagonists have more side effects compared to standard of care? The following databases were search up to December 1st 2020: PubMed, PMC PubMed Central, MEDLINE, WHO COVID-19 Database, Embase, Web-of-Science, COCHRANE LIBRARY, Emcare and Academic Search Premier. In order to pool the risk ratio (RR) and risk difference of individual studies we used random effects meta-analysis. The search strategy retrieved 2975 unique titles of which 71 studies (9 RCTs and 62 observational) studies comprising 29,495 patients were included. Mortality (RR 0.75) and mechanical ventilation (RR 0.78) were lower and the risk of neutropenia (RR 7.3), impaired liver function (RR 1.67) and secondary infections (RR 1.26) were higher for patients treated with IL-6 (receptor) antagonists compared to patients not treated with treated with IL-6 (receptor) antagonists. Our results showed that IL-6 (receptor) antagonists are effective in reducing mortality in COVID-19 patients, while the risk of side effects was higher. The baseline risk of mortality was an important effect modifier: IL-6 (receptor) antagonists were effective when the baseline mortality risk was high (e.g. ICU setting), while they could be harmful when the baseline mortality risk was low.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19/drug therapy , Receptors, Interleukin-6/antagonists & inhibitors , Antibodies, Monoclonal, Humanized/adverse effects , Antibodies, Monoclonal, Humanized/immunology , COVID-19/mortality , COVID-19/virology , Humans , Odds Ratio , Respiration, Artificial , SARS-CoV-2/isolation & purification , Survival Rate
13.
Saudi Med J ; 42(11): 1217-1222, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1502889

ABSTRACT

OBJECTIVES: To evaluate coronavirus disease 2019 (COVID-19) patient tracheostomy outcomes. METHODS: All COVID-19 patients at the National Guard Hospital, Riyadh, Saudi Arabia, were retrospectively recruited. Those who had tracheostomies between April and December 2020 were included. RESULTS: The population was 45 patients, of which 30 (66.7%) were males, 15 (33.3%) were females and the mean age was 66.76±12.74 years. The tracheostomy indications were anticipated prolonged weaning in 40 (88.9%) and failed extubation in 5 (11.1%) of the patients. The mean intubation to tracheostomy duration was 20.62±7.21 days. Mortalities were high, with most attributed to COVID-19. Mortality and a pre-tracheostomy C-reactive protein (CRP) uptrend were significantly related (p=0.039). Mortality and intubation to tracheostomy duration were not significantly related. The mean post-tracheostomy time to death was 10.64±6.9 days. Among the survivors, 20 (44.4%) males and 11 (24.4%) females were weaned off mechanical ventilation; 9 (20%) remained on ventilation during the study. The mean ventilation weaning time was 27.92±20 days. CONCLUSION: The high mortality rate was attributed to COVID-19. Mortality and a pre-tracheostomy CRP uptrend were significantly related; uptrend patients experienced far more mortalities than downtrend patients. Unlike previous findings, mortality and intubation to tracheostomy duration were not significantly related.


Subject(s)
COVID-19 , Tracheostomy , Aged , Female , Humans , Male , Middle Aged , Respiration, Artificial , Retrospective Studies , SARS-CoV-2 , Saudi Arabia/epidemiology
15.
Front Immunol ; 12: 726283, 2021.
Article in English | MEDLINE | ID: covidwho-1497074

ABSTRACT

Severe status of coronavirus disease 2019 (COVID-19) is extremely associated to cytokine release. Moreover, it has been suggested that blood group is also associated with the prevalence and severity of this disease. However, the relationship between the cytokine profile and blood group remains unclear in COVID-19 patients. In this sense, we prospectively recruited 108 COVID-19 patients between March and April 2020 and divided according to ABO blood group. For the analysis of 45 cytokines, plasma samples were collected in the time of admission to hospital ward or intensive care unit and at the sixth day after hospital admission. The results show that there was a risk of more than two times lower of mechanical ventilation or death in patients with blood group O (log rank: p = 0.042). At first time, all statistically significant cytokine levels, except from hepatocyte growth factor, were higher in O blood group patients meanwhile the second time showed a significant drop, between 20% and 40%. In contrast, A/B/AB group presented a maintenance of cytokine levels during time. Hepatocyte growth factor showed a significant association with intubation or mortality risk in non-O blood group patients (OR: 4.229, 95% CI (2.064-8.665), p < 0.001) and also was the only one bad prognosis biomarker in O blood group patients (OR: 8.852, 95% CI (1.540-50.878), p = 0.015). Therefore, higher cytokine levels in O blood group are associated with a better outcome than A/B/AB group in COVID-19 patients.


Subject(s)
COVID-19/immunology , Cytokines/blood , SARS-CoV-2/physiology , ABO Blood-Group System , Aged , Biomarkers , COVID-19/diagnosis , COVID-19/mortality , Disease Progression , Female , Hepatocyte Growth Factor/blood , Hospitalization , Humans , Male , Middle Aged , Prognosis , Prospective Studies , Respiration, Artificial , Severity of Illness Index , Survival Analysis
16.
PLoS One ; 16(10): e0258918, 2021.
Article in English | MEDLINE | ID: covidwho-1496517

ABSTRACT

The objective was to describe the clinical characteristics and outcomes of hospitalized COVID-19 patients during the two different epidemic periods. Prospective, observational, cohort study of hospitalized COVID-19. A total of 421 consecutive patients were included, 188 during the first period (March-May 2020) and 233 in the second wave (July-December 2020). Clinical, epidemiological, prognostic and therapeutic data were compared. Patients of the first outbreak were older and more comorbid, presented worse PaO2/FiO2 ratio and an increased creatinine and D-dimer levels at hospital admission. The hospital stay was shorter (14.5[8;29] vs 8[6;14] days, p<0.001), ICU admissions (31.9% vs 13.3%, p<0.001) and the number of patients who required mechanical ventilation (OR = 0.12 [0.05-10.26]; p<0.001) were reduced. There were no significant differences in hospital and 30-day after discharge mortality (adjusted HR = 1.56; p = 0.1056) or hospital readmissions. New treatments and clinical strategies appear to improve hospital length, ICU admissions and the requirement for mechanical ventilation. However, we did not observe differences in mortality or readmissions.


Subject(s)
COVID-19/epidemiology , COVID-19/mortality , COVID-19/therapy , Adult , Aged , Aged, 80 and over , Cohort Studies , Epidemics/statistics & numerical data , Female , Hospital Mortality/trends , Hospitalization/statistics & numerical data , Hospitalization/trends , Humans , Intensive Care Units/statistics & numerical data , Male , Middle Aged , Prognosis , Prospective Studies , Respiration, Artificial/mortality , Risk Factors , SARS-CoV-2/pathogenicity , Spain/epidemiology , Treatment Outcome
17.
BMJ Open ; 11(9): e048591, 2021 09 14.
Article in English | MEDLINE | ID: covidwho-1495462

ABSTRACT

INTRODUCTION: Pre-emptive inhaled antibiotics may be effective to reduce the occurrence of ventilator-associated pneumonia among critically ill patients. Meta-analysis of small sample size trials showed a favourable signal. Inhaled antibiotics are associated with a reduced emergence of antibiotic resistant bacteria. The aim of this trial is to evaluate the benefit of a 3-day course of inhaled antibiotics among patients undergoing invasive mechanical ventilation for more than 3 days on the occurrence of ventilator-associated pneumonia. METHODS AND ANALYSIS: Academic, investigator-initiated, parallel two group arms, double-blind, multicentre superiority randomised controlled trial. Patients invasively ventilated more than 3 days will be randomised to receive 20 mg/kg inhaled amikacin daily for 3 days or inhaled placebo (0.9% Sodium Chloride). Occurrence of ventilator-associated pneumonia will be recorded based on a standardised diagnostic framework from randomisation to day 28 and adjudicated by a centralised blinded committee. ETHICS AND DISSEMINATION: The protocol and amendments have been approved by the regional ethics review board and French competent authorities (Comité de protection des personnes Ouest I, No.2016-R29). All patients will be included after informed consent according to French law. Results will be disseminated in international scientific journals. TRIAL REGISTRATION NUMBERS: EudraCT 2016-001054-17 and NCT03149640.


Subject(s)
Amikacin , Pneumonia, Ventilator-Associated , Administration, Inhalation , Amikacin/administration & dosage , Double-Blind Method , Humans , Multicenter Studies as Topic , Pneumonia, Ventilator-Associated/prevention & control , Randomized Controlled Trials as Topic , Respiration, Artificial/adverse effects , Treatment Outcome
18.
Crit Care Med ; 49(7): 1058-1067, 2021 07 01.
Article in English | MEDLINE | ID: covidwho-1494030

ABSTRACT

OBJECTIVES: To assess the impact of percutaneous dilational tracheostomy in coronavirus disease 2019 patients requiring mechanical ventilation and the risk for healthcare providers. DESIGN: Prospective cohort study; patients were enrolled between March 11, and April 29, 2020. The date of final follow-up was July 30, 2020. We used a propensity score matching approach to compare outcomes. Study outcomes were formulated before data collection and analysis. SETTING: Critical care units at two large metropolitan hospitals in New York City. PATIENTS: Five-hundred forty-one patients with confirmed severe coronavirus disease 2019 respiratory failure requiring mechanical ventilation. INTERVENTIONS: Bedside percutaneous dilational tracheostomy with modified visualization and ventilation. MEASUREMENTS AND MAIN RESULTS: Required time for discontinuation off mechanical ventilation, total length of hospitalization, and overall patient survival. Of the 541 patients, 394 patients were eligible for a tracheostomy. One-hundred sixteen were early percutaneous dilational tracheostomies with median time of 9 days after initiation of mechanical ventilation (interquartile range, 7-12 d), whereas 89 were late percutaneous dilational tracheostomies with a median time of 19 days after initiation of mechanical ventilation (interquartile range, 16-24 d). Compared with patients with no tracheostomy, patients with an early percutaneous dilational tracheostomy had a higher probability of discontinuation from mechanical ventilation (absolute difference, 30%; p < 0.001; hazard ratio for successful discontinuation, 2.8; 95% CI, 1.34-5.84; p = 0.006) and a lower mortality (absolute difference, 34%, p < 0.001; hazard ratio for death, 0.11; 95% CI, 0.06-0.22; p < 0.001). Compared with patients with late percutaneous dilational tracheostomy, patients with early percutaneous dilational tracheostomy had higher discontinuation rates from mechanical ventilation (absolute difference 7%; p < 0.35; hazard ratio for successful discontinuation, 1.53; 95% CI, 1.01-2.3; p = 0.04) and had a shorter median duration of mechanical ventilation in survivors (absolute difference, -15 d; p < 0.001). None of the healthcare providers who performed all the percutaneous dilational tracheostomies procedures had clinical symptoms or any positive laboratory test for severe acute respiratory syndrome coronavirus 2 infection. CONCLUSIONS: In coronavirus disease 2019 patients on mechanical ventilation, an early modified percutaneous dilational tracheostomy was safe for patients and healthcare providers and associated with improved clinical outcomes.


Subject(s)
COVID-19/therapy , Respiration, Artificial , Tracheostomy/methods , Aged , Cohort Studies , Critical Care , Dilatation/methods , Female , Humans , Male , Middle Aged , New York City/epidemiology , SARS-CoV-2 , Time Factors
19.
Crit Care Med ; 49(7): 1149-1158, 2021 07 01.
Article in English | MEDLINE | ID: covidwho-1494026

ABSTRACT

OBJECTIVES: Circulating nucleosomes and their component histones have been implicated as pathogenic in sepsis and acute respiratory distress syndrome in adults. However, their role in pediatric acute respiratory distress syndrome is unknown. DESIGN: We performed a prospective cohort study in children with acute respiratory distress syndrome, with plasma collection within 24 hours of acute respiratory distress syndrome onset. We associated nucleosome levels with severity of acute respiratory distress syndrome and with nonpulmonary organ failures and tested for association of nucleosomes with PICU mortality and ventilator-free days at 28 days in univariate and multivariable analyses. We also performed proteomics of DNA-bound plasma proteins in a matched case-control study of septic children with and without acute respiratory distress syndrome in order to identify specific histone proteins elevated in acute respiratory distress syndrome. SETTING: Large academic tertiary-care PICU. PATIENTS: Intubated children meeting Berlin criteria for acute respiratory distress syndrome. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We enrolled 333 children with acute respiratory distress syndrome, with 69 nonsurvivors (21%). Plasma nucleosomes were correlated with acute respiratory distress syndrome severity and with the number of nonpulmonary organ failures at acute respiratory distress syndrome onset. Nucleosomes were higher (p < 0.001) in nonsurvivors (0.40 [interquartile range, 0.20-0.71] arbitrary units) relative to survivors (0.10 [interquartile range, 0.04-0.25] arbitrary units). Nucleosomes were associated with PICU mortality in multivariable analysis (adjusted odds ratio 1.84 per 1 sd increase; 95% CI, 1.38-2.45; p < 0.001). Nucleosomes were also associated with a lower probability of being extubated alive by day 28 after multivariable adjustment (adjusted subdistribution hazard ratio, 0.74; 95% CI, 0.63-0.88; p = 0.001). Proteomic analysis demonstrated higher levels of the core nucleosome histones H2A, H2B, H3, and H4 in septic children with acute respiratory distress syndrome, relative to septic children without acute respiratory distress syndrome. CONCLUSIONS: Plasma nucleosomes are associated with acute respiratory distress syndrome severity, nonpulmonary organ failures, and worse outcomes in pediatric acute respiratory distress syndrome.


Subject(s)
Histones/blood , Nucleosomes/metabolism , Respiratory Distress Syndrome/blood , Respiratory Distress Syndrome/mortality , Adolescent , Airway Extubation , Case-Control Studies , Child , Child, Preschool , DNA/blood , Female , Hospital Mortality , Humans , Intensive Care Units, Pediatric , Male , Multiple Organ Failure/mortality , Prognosis , Prospective Studies , Proteomics , Respiration, Artificial , Respiratory Distress Syndrome/complications , Sepsis/blood , Sepsis/complications , Severity of Illness Index , Survival Rate
20.
Anesthesiol Clin ; 39(3): 415-440, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1491667

ABSTRACT

Today's management of the ventilated patient still relies on the measurement of old parameters such as airway pressures and flow. Graphical presentations reveal the intricacies of patient-ventilator interactions in times of supporting the patient on the ventilator instead of fully ventilating the heavily sedated patient. This opens a new pathway for several bedside technologies based on basic physiologic knowledge; however, it may increase the complexity of measurements. The spread of the COVID-19 infection has confronted the anesthesiologist and intensivist with one of the most severe pulmonary pathologies of the last decades. Optimizing the patient at the bedside is an old and newly required skill for all physicians in the intensive care unit, supported by mobile technologies such as lung ultrasound and electrical impedance tomography. This review summarizes old knowledge and presents a brief insight into extended monitoring options.


Subject(s)
Respiration, Artificial , Respiratory Mechanics , COVID-19 , Humans , Intensive Care Units
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