A multicenter randomized trial to assess the efficacy of CONvalescent plasma therapy in patients with Invasive COVID-19 and acute respiratory failure treated with mechanical ventilation: the CONFIDENT trial protocol

Abstract Background The COVID-19 pandemic reached Europe in early 2020. Convalescent plasma is used without a consistent evidence of efficacy. Our hypothesis is that passive immunization with plasma collected from patients having contracted COVID-19 and developed specific neutralizing antibodies may alleviate symptoms and reduce mortality in patients treated with mechanical ventilation for severe respiratory failure during the evolution of SARS-CoV-2 pneumonia. Methods We plan to include 500 adult patients, hospitalized in 16 Belgian intensive care units between September 2020 and 2022, diagnosed with SARS-CoV-2 pneumonia, under mechanical ventilation for less than 5 days and a clinical frailty scale less than 6. The study treatment will be compared to standard of care and allocated by randomization in a 1 to 1 ratio without blinding. The main endpoint will be mortality at day 28. We will perform an intention to treat analysis. The number of patients to include is based on an expected mortality rate at day 28 of 40 percent and an expected relative reduction with study intervention of 30 percent with α risk of 5 percent and β risk of 20 percent. Discussion This study will assess the efficacy of plasma in the population of mechanically ventilated patients. A stratification on the delay from mechanical ventilation and inclusion will allow to approach the optimal time use. Selecting convalescent plasmas with a high titer of neutralizing antibodies against SARS-CoV-2 will allow a homogeneous study treatment. The inclusion in the study is based on the consent of the patient or his/her legal representative, and the approval of the Investigational Review Board of the University hospital of Liège, Belgium. A data safety monitoring board (DSMB) has been implemented. Interim analyses have been planned at 100, 2002, 300 and 400 inclusions in order to decide whether the trail should be discontinued prematurely for ethical issues. We plan to publish our results in a peer-reviewed journal and to present them at national and international conferences. Funding and registration The trial is funded by the Belgian Health Care Knowledge Center KCE # COV201004 Trial registration Clinicaltrials.gov registration number NCT04558476. Registered 14 September 2020—Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04558476

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APHACHE Score as a Predictive Indices for Weanability from Mechanical Ventilation

Bangladesh Critical Care Journal ◽

10.3329/bccj.v1i1.14360 ◽

2013 ◽

Vol 1 (1) ◽

pp. 18-22 ◽

Cited By ~ 2

Author(s):

Md Sayedul Islam

Keyword(s):

Mechanical Ventilation ◽

Respiratory Failure ◽

Private Hospital ◽

Total Duration ◽

Apache Ii ◽

Apache Ii Score ◽

P Value ◽

Apache Score ◽

Number Of Patients ◽

Weaning Outcome

Objective: To determine the significance of acute physiology and chronic health evaluation (APACHE) score as an important parameter of weaning outcome for mechanical ventilation. Design: prospective, observational. Setting: The medical ICU of a modernized private hospital, Dhaka. Method: The study was carried out during the period of 2008 to 2009 in a specialized private hospital Dhaka. Critical care physicians were asked to filled up the data sheets having detail problem of the patients including the APACHE II score. The APACHE II score is divided into three steps High score>25, Medium score 20-24 and Low score < 20. The clinicians were suggested to predict whether it would take < 3 days or 4to 7days or >8days to wean each patients from mechanical ventilation. The cause of respiratory failure and total duration of weaning were recorded. The significance was set at p<.05. Result: Total number of patients included in this study were 40. Male were 22 (55%) and female were 18 (45%), the mean age of the patients were 51.1±13.9. The most common cause of respiratory failure were COPD 11(24.5%) and next common were pneumonia and ARDS due to sepsis 8 (20%) each. Among the studied population 20 (50%) having low APACHE score (<20), 12 (30%) were medium score (20-24) and 8 (20%) patients were high score (>25). Total 25 (62.5%) of the patients were successfully weaned from mechanical ventilation, 10 (25%) of the patient died and 5 (12.5%) of the patent were shifted to other low cost hospital. The successfully weaned groups 17 (68%) had lower APACHE II score than the unsuccessfully (failure) group which were statistically significant ÷2 =.8546, df =2, p-value >.005. Conclusions: The overall severity of illness as assessed by APACHE II score correlates better with weaning outcome. DOI: http://dx.doi.org/10.3329/bccj.v1i1.14360 Bangladesh Crit Care J March 2013; 1: 18-22

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Prone Position after Liberation from Prolonged Mechanical Ventilation in COVID-19 Respiratory Failure

Critical Care Research and Practice ◽

10.1155/2020/6688120 ◽

2020 ◽

Vol 2020 ◽

pp. 1-7

Author(s):

Andrei Karpov ◽

Anish R. Mitra ◽

Sarah Crowe ◽

Gregory Haljan

Keyword(s):

Intensive Care Unit ◽

Mechanical Ventilation ◽

Intensive Care ◽

Respiratory Failure ◽

Respiratory Rate ◽

Prolonged Mechanical Ventilation ◽

Case Series ◽

Prone Positioning ◽

Retrospective Case ◽

Number Of Patients

Objective and Rationale. Prone positioning of nonintubated patients has prevented intubation and mechanical ventilation in patients with respiratory failure from coronavirus disease 2019 (COVID-19). A number of patients in a recently published cohort have undergone postextubation prone positioning (PEPP) following liberation from prolonged mechanical ventilation in attempt to prevent reintubation. The objective of this study is to systematically search the literature for reports of PEPP as well as describe the feasibility and outcomes of PEPP in patients with COVID-19 respiratory failure. Design. This is a retrospective case series describing the feasibility and tolerability of postextubation prone positioning (PEPP) and its impact on physiologic parameters in a tertiary intensive care unit during the COVID-19 pandemic. Setting and Patients. This study was conducted on patients with COVID-19 respiratory failure hospitalized in a tertiary Intensive Care Unit at Surrey Memorial Hospital during the COVID-19 pandemic. Measurements and Results. We did not find prior reports of PEPP following prolonged intubation in the literature. Four patients underwent a total of 13 PEPP sessions following liberation from prolonged mechanical ventilation. Each patient underwent a median of 3 prone sessions (IQR: 2, 4.25) lasting a median of 1.5 hours (IQR: 1.2, 2.1). PEPP sessions were associated with a reduction in median oxygen requirements, patient respiratory rate, and reintubation rate. The sessions were well tolerated by patients, nursing, and the allied health team. Conclusions. The novel practice of PEPP after liberation from prolonged mechanical ventilation in patients with COVID-19 respiratory failure is feasible and well tolerated, and may be associated with favourable clinical outcomes including improvement in oxygenation and respiratory rate and a low rate of reintubation. Larger prospective studies of PEPP are warranted.

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Use of Either Non-invasive Ventilation Immediately Post-extubation or Controlled Mechanical Ventilation for One Hour after Fulfilling Weaning Criteria Decreases Re-intubation of Patients with Post-traumatic ARDS

The Open Anesthesia Journal ◽

10.2174/2589645802115010007 ◽

2021 ◽

Vol 15 (1) ◽

pp. 7-19

Author(s):

Mohamed Gaber Ibrahim Mostafa Allam

Keyword(s):

Mechanical Ventilation ◽

Respiratory Failure ◽

Icu Stay ◽

Number Of Patients ◽

Icu Discharge ◽

Significant Difference ◽

Prolonged Ventilation ◽

Group A ◽

Weaning Criteria ◽

Severe Lung

Introduction: Re-intubation and re-ventilation after complete weaning of patients with prolonged ventilation are considered a major problem in ICU. The re-intubation in such patients associated with higher mortalities prolongs the duration of ICU stay. The mortality rate in those patients may exceed 40% in some studies. Aims: The study aimed to compare and evaluate the effect of use of two new maneuvers with control after fulfilling criteria of weaning from prolonged ventilation, either immediate use of NIV post-extubation and every 12 hours for 24 hours or MV for one hour on both re-intubation and ICU discharge of traumatic ARDS patients who ventilated for one week or more. Materials and Methods: It is a prospective double-blind study done on total 300 patients, admitted with respiratory failure ARDS due to severe lung contusion. All of them were selected to be ventilated for > one week. All of them fulfilled the criteria of weaning at the end of the studied period. Patients were randomly allocated in three groups; each group contained 100 patients. Group A was considered the control group. They extubated and followed our routine protocol; patients of group B used our first new maneuver and reconnected to mechanical ventilation before extubation for one hour, while patients of group C used our second new maneuver; patients of this group extubated and immediately connected to NIV with BIPAP mode for 1 hour every 12 hours for 24 hours. Results: There was a significant reduction in the number of patients who experienced deterioration in conscious level throughout the study in patients of both groups B and C compared to group A. Also, a significant reduction was seen in the number of patients who experienced deterioration in clinical parameters of respiration, of both groups B and C compared to group A with regard to high respiratory rate, desaturation and development of hyperdynamic circulation (tachycardia and hypertension). Also, a significant reduction was seen in the number of patients who had multiple quadrant parenchymatous infiltration throughout the study in patients of both groups B and C compared to group A. significant reduction in the number of patients marked limitation to FEV1, FVC and MVV in patients of both groups B and C compared to group A. Conclusion: Use of either immediate NIV every 12 hours for 24 hours or MV for one hour after fulfillment of weaning criteria reduced reintubation, re-ventilation and post-extubation respiratory failure and decreased the ICU stay in prolonged ventilated patients due to ARDS from severe lung trauma with no significant difference between them.

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Level of IL-6 predicts respiratory failure in hospitalized symptomatic COVID-19 patients

10.1101/2020.04.01.20047381 ◽

2020 ◽

Cited By ~ 34

Author(s):

Tobias Herold ◽

Vindi Jurinovic ◽

Chiara Arnreich ◽

Johannes C. Hellmuth ◽

Michael von Bergwelt-Baildon ◽

...

Keyword(s):

Mechanical Ventilation ◽

Intensive Care ◽

Respiratory Failure ◽

Early Stage ◽

Severe Disease ◽

High Accuracy ◽

Emergency Rooms ◽

Laboratory Findings ◽

Number Of Patients ◽

Qsofa Score

The pandemic Coronavirus-disease 19 (COVID-19) is characterized by a heterogeneous clinical course. While most patients experience only mild symptoms, a relevant proportion develop severe disease progression with increasing hypoxia up to acute respiratory distress syndrome. The substantial number of patients with severe disease have strained intensive care capacities to an unprecedented level. Owing to the highly variable course and lack of reliable predictors for deterioration, we aimed to identify variables that allow the prediction of patients with a high risk of respiratory failure and need of mechanical ventilation Patients with PCR proven symptomatic COVID-19 infection hospitalized at our institution from 29th February to 27th March 2020 (n=40) were analyzed for baseline clinical and laboratory findings. Patients requiring mechanical ventilation 13/40 (32.5%) did not differ in age, comorbidities, radiological findings, respiratory rate or qSofa score. However, elevated interleukin-6 (IL-6) was strongly associated with the need for mechanical ventilation (p=1.2.10-5). In addition, the maximal IL-6 level (cutoff 80 pg/ml) for each patient during disease predicted respiratory failure with high accuracy (p=1.7.10-8, AUC=0.98). The risk of respiratory failure for patients with IL-6 levels of >; 80 pg/ml was 22 times higher compared to patients with lower IL-6 levels. In the current situation with overwhelmed intensive care units and overcrowded emergency rooms, correct triage of patients in need of intensive care is crucial. Our study shows that IL-6 is an effective marker that might be able to predict upcoming respiratory failure with high accuracy and help physicians correctly allocate patients at an early stage.

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Predictors of CPAP outcome in hospitalised COVID-19 patients

10.1101/2020.06.14.20130880 ◽

2020 ◽

Author(s):

Y Noeman-Ahmed ◽

S Gokaraju ◽

DJ Powrie ◽

DA Amran ◽

I El Sayed ◽

...

Keyword(s):

Mechanical Ventilation ◽

Respiratory Failure ◽

Positive Airway Pressure ◽

Invasive Mechanical Ventilation ◽

University Hospital ◽

High Dependency Unit ◽

Future Studies ◽

High Dependency ◽

Management Protocol ◽

Before And After

AbstractIntroductionThroughout March – April 2020, many patients with COVID-19 presented to Southend University Hospital with Acute Hypoxaemic Respiratory Failure (AHRF). Patients were managed in a Specialist Respiratory High Dependency Unit. We present our experience on the usage of continuous positive airway pressure (CPAP) therapy and possible indicators of its success in this patient group.MethodsData from patients (n=89) requiring mechanical ventilation during the months of March-April 2020, were retrospectively collected and analysed. 37 patients received IMV (Invasive Mechanical Ventilation) without a CPAP trial beforehand. 52 patients underwent a CPAP trial, of which 21 patients successfully avoided intubation and ITU admission.ResultsThe 52 patients, prior to receiving CPAP had significant respiratory failure as evidenced by a low PaO2: FiO2 (PFR) (mean± SD 123 ± 60 mmHg) and mean SpO2:FiO2 (SFR) (mean ± SD: 140 ± 50). The main indicators of CPAP success were: higher SFR before and after CPAP, lower respiratory rate (RR), lower Neutrophil to Lymphocyte ratio (NLR) and higher PFR prior to CPAP.DiscussionCPAP proved successful in 40% of COVID-19 patients presenting with AHRF. SFR, PFR, RR and NLR are predictors of such success. SFR can be used for effective real time monitoring of patients before and after CPAP to identify likelihood of success. Based on our results, we have suggested a modified CPAP management protocol in COVID-19. These findings can guide future studies and will allow improved triage of patients to either CPAP or IMV, in the event of a future COVID peak.

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Impact of early tracheotomy for successful prognosis of patients

Emergency Medical Service ◽

10.36740/emems202004103 ◽

2020 ◽

Vol 7 (4) ◽

pp. 261-266

Author(s):

Mateusz Lech ◽

Paulina Bakier ◽

Sylwia Jabłońska ◽

Rafał Milewski ◽

Emilia Duchnowska ◽

...

Keyword(s):

Mechanical Ventilation ◽

Intensive Care ◽

Respiratory Failure ◽

Prolonged Mechanical Ventilation ◽

Intensive Therapy ◽

University Hospital ◽

Individual Treatment ◽

Clinical Issue ◽

Early Tracheostomy ◽

Risk Of Death

Introduction: Complications associated with intra-hospital infections are an important clinical issue determining the further condition of hospitalized patients. One of the most invasive and of high risk of complications in ICU conditions is the otolaryngological procedure of opening the anterior wall of the trachea, aimed at introducing the tube into the lumen of the respiratory tract, enabling subsequent ventilation. Epidemiological data indicate that in Poland the percentage of patients admitted to the ICU annually, due to respiratory failure, who require the implementation of mechanical ventilation reaches 74%, where 41% is qualified for prolonged ventilation and requires a tracheostomy. The aim: The epidemiological analysis of patients under the care of the Department of Anaesthesiology and Intensive Care of University Hospital in Bialystok. Particular attention was paid to patients who underwent tracheostomy. Material and methods: The study material was collected based on the analysis of the patient’s individual treatment process cards, the results of microbiological tests functioning in the Department of Anaesthesiology and Intensive Therapy of the University Hospital in Bialystok. 115 patients were qualified for the study, including 48 women and 67 men. Results: Retrospective studies were based on medical records of 115 patients treated in the Intensive Care Unit of the Department of Anaesthesiology and Intensive Care, University Hospital in Bialystok in 2017-2018. The analysis involved patients after tracheostomy tube implementation, 48 were women and 67 men. Among the analyzed cases, 53 deaths (46.1%) occurred, and 62 subjects were discharged from the ICU (53.9%). Conclusions: Early tracheostomy significantly improved patients’ prognosis and reduced the risk of death. Cardio-respiratory failure with respiratory arrest may often be associated with the need for prolonged mechanical ventilation applied in patients with the aforementioned disease. Therefore, prevention in the form of early tracheostomy is important.

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Retrospective analysis of high flow nasal therapy in COVID-19-related moderate-to-severe hypoxaemic respiratory failure

BMJ Open Respiratory Research ◽

10.1136/bmjresp-2020-000650 ◽

2020 ◽

Vol 7 (1) ◽

pp. e000650 ◽

Cited By ~ 5

Author(s):

Maulin Patel ◽

Andrew Gangemi ◽

Robert Marron ◽

Junad Chowdhury ◽

Ibraheem Yousef ◽

...

Keyword(s):

Mechanical Ventilation ◽

Respiratory Failure ◽

Retrospective Analysis ◽

Invasive Mechanical Ventilation ◽

Alternative Therapy ◽

High Flow ◽

University Hospital ◽

Temple University ◽

Chest X Ray ◽

Overall Mortality

Invasive mechanical has been associated with high mortality in COVID-19. Alternative therapy of high flow nasal therapy (HFNT) has been greatly debated around the world for use in COVID-19 pandemic due to concern for increased healthcare worker transmission.This was a retrospective analysis of consecutive patients admitted to Temple University Hospital in Philadelphia, Pennsylvania, from 10 March 2020 to 24 April 2020 with moderate-to-severe respiratory failure treated with HFNT. Primary outcome was prevention of intubation. Of the 445 patients with COVID-19, 104 met our inclusion criteria. The average age was 60.66 (+13.50) years, 49 (47.12 %) were female, 53 (50.96%) were African-American, 23 (22.12%) Hispanic. Forty-three patients (43.43%) were smokers. Saturation to fraction ratio and chest X-ray scores had a statistically significant improvement from day 1 to day 7. 67 of 104 (64.42%) were able to avoid invasive mechanical ventilation in our cohort. Incidence of hospital-associated/ventilator-associated pneumonia was 2.9%. Overall, mortality was 14.44% (n=15) in our cohort with 13 (34.4%) in the progressed to intubation group and 2 (2.9%) in the non-intubation group. Mortality and incidence of pneumonia was statistically higher in the progressed to intubation group.ConclusionHFNT use is associated with a reduction in the rate of invasive mechanical ventilation and overall mortality in patients with COVID-19 infection.

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Antibodies Elicited in Response to a Single Cycle Glycoprotein D Deletion Viral Vaccine Candidate Bind C1q and Activate Complement Mediated Neutralization and Cytolysis

Viruses ◽

10.3390/v13071284 ◽

2021 ◽

Vol 13 (7) ◽

pp. 1284

Author(s):

Maria Luisa Visciano ◽

Aakash Mahant Mahant ◽

Carl Pierce ◽

Richard Hunte ◽

Betsy C. Herold

Keyword(s):

Neutralizing Antibodies ◽

High Titer ◽

Passive Immunization ◽

Immune Serum ◽

Effective Vaccine ◽

Glycoprotein D ◽

Single Cycle ◽

Viral Vaccine ◽

Trial Outcomes ◽

Simplex Virus

Herpes simplex virus (HSV) prevention is a global health priority but, despite decades of research, there is no effective vaccine. Prior efforts focused on generating glycoprotein D (gD) neutralizing antibodies, but clinical trial outcomes were disappointing. The deletion of gD yields a single-cycle candidate vaccine (∆gD-2) that elicits high titer polyantigenic non-gD antibodies that exhibit little complement-independent neutralization but mediate antibody-dependent cellular cytotoxicity (ADCC) and phagocytosis (ADCP). Active or passive immunization with ΔgD-2 completely protects mice from lethal disease and latency following challenge with clinical isolates of either serotype. The current studies evaluated the role of complement in vaccine-elicited protection. The immune serum from the ΔgD-2 vaccinated mice exhibited significantly greater C1q binding compared to the serum from the gD protein vaccinated mice with infected cell lysates from either serotype as capture antigens. The C1q-binding antibodies recognized glycoprotein B. This resulted in significantly greater antibody-mediated complement-dependent cytolysis and neutralization. Notably, complete protection was preserved when the ΔgD-2 immune serum was passively transferred into C1q knockout mice, suggesting that ADCC and ADCP are sufficient in mice. We speculate that the polyfunctional responses elicited by ΔgD-2 may prove more effective in preventing HSV, compared to the more restrictive responses elicited by adjuvanted gD protein vaccines.

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Use of High Flow Nasal Therapy to Treat Moderate to Severe Hypoxemic Respiratory Failure in COVID-19

10.1101/2020.05.22.20109355 ◽

2020 ◽

Cited By ~ 2

Author(s):

Maulin Patel ◽

Andrew Gangemi ◽

Robert Marron ◽

Junad Chowdhury ◽

Ibraheem Yousef ◽

...

Keyword(s):

Mechanical Ventilation ◽

Respiratory Failure ◽

Retrospective Analysis ◽

Invasive Mechanical Ventilation ◽

Alternative Therapy ◽

High Flow ◽

University Hospital ◽

Bottom Line ◽

Hypoxemic Respiratory Failure ◽

Overall Mortality

AbstractInvasive mechanical has been associated with high mortality in COVID-19. Alternative therapy of High flow nasal therapy (HFNT) has been greatly debated around the world for use in COVID-19 pandemic due to concern for increased healthcare worker transmission.MethodsThis was a retrospective analysis of consecutive patients admitted to Temple University Hospital in Philadelphia, Pennsylvania, from March 10, 2020, to April 24, 2020 with moderate to severe respiratory failure treated with High Flow nasal therapy (HFNT). Primary outcome was prevention of intubation.ResultsOf the 445 patients with COVID-19, 104 met our inclusion criteria. The average age was 60.66 (±13.50) years, 49 (47.12 %) were female, 53 (50.96%) were African American, 23 (22.12%) Hispanic. Forty-three patients (43.43%) were smokers. SF and chest Xray scores had a statistically significant improvement from day 1 to day 7. 67 of 104 (64.42%) were able to avoid invasive mechanical ventilation in our cohort. Incidence of hospital/ventilator associated pneumonia was 2.9%. Overall, mortality was 14.44% (n=15) in our cohort with 13 (34.4%) in the progressed to intubation group and 2 (2.9%) in the non-intubation group. Mortality and incidence of VAP/HAP was statistically higher in the progressed to intubation group.ConclusionHFNT use is associated with a reduction in the rate of Invasive mechanical ventilation and overall mortality in patients with COVID-19 infection.Key PointsKey QuestionWhat is the utility of High Flow Nasal Therapy (HFNT) in COVID-19 related Hypoxemic Respiratory Failure?Bottom LineIn this retrospective analysis of moderate to severe hypoxic respiratory failure for COVID 19 patients, 67 patients (65.4%) were able to avoid intubation despite severely low SF ratio (Mean 121.9).Why Read onHFNT has a significant role in COVID-19 for reducing rate of intubations and associated mortality

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Mechanical Ventilation during Extracorporeal Membrane Oxygenation in Patients with Acute Severe Respiratory Failure

Canadian Respiratory Journal ◽

10.1155/2017/1783857 ◽

2017 ◽

Vol 2017 ◽

pp. 1-10 ◽

Cited By ~ 15

Author(s):

Zhongheng Zhang ◽

Wan-Jie Gu ◽

Kun Chen ◽

Hongying Ni

Keyword(s):

Mechanical Ventilation ◽

Respiratory Failure ◽

Extracorporeal Membrane Oxygenation ◽

Large Body ◽

Conventional Mechanical Ventilation ◽

Protective Ventilation ◽

Severe Respiratory Failure ◽

Membrane Oxygenation ◽

Number Of Patients ◽

Protective Ventilation Strategy

Conventionally, a substantial number of patients with acute respiratory failure require mechanical ventilation (MV) to avert catastrophe of hypoxemia and hypercapnia. However, mechanical ventilation per se can cause lung injury, accelerating the disease progression. Extracorporeal membrane oxygenation (ECMO) provides an alternative to rescue patients with severe respiratory failure that conventional mechanical ventilation fails to maintain adequate gas exchange. The physiology behind ECMO and its interaction with MV were reviewed. Next, we discussed the timing of ECMO initiation based on the risks and benefits of ECMO. During the running of ECMO, the protective ventilation strategy can be employed without worrying about catastrophic hypoxemia and carbon dioxide retention. There is a large body of evidence showing that protective ventilation with low tidal volume, high positive end-expiratory pressure, and prone positioning can provide benefits on mortality outcome. More recently, there is an increasing popularity on the use of awake and spontaneous breathing for patients undergoing ECMO, which is thought to be beneficial in terms of rehabilitation.

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