scholarly journals Effect of early treatment with polyvalent immunoglobulin on acute respiratory distress syndrome associated with SARS-CoV-2 infections (ICAR trial): study protocol for a randomized controlled trial

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Aurélien Mazeraud ◽  
Bruno Gonçalves ◽  
Philippe Aegerter ◽  
Letizia Mancusi ◽  
Christine Rieu ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Organ Failure ◽  
Daily Living ◽  
Distress Syndrome ◽  
Phase Iii ◽  
Link Type ◽  
Polyvalent Immunoglobulin

Abstract Background As of mid-June 2020, 7,500,000 people were infected with SARS-CoV-2 worldwide and 420,000 people died, mainly from coronavirus disease 2019 (COVID-19)-related acute respiratory distress syndrome (ARDS). COVID-19-related ARDS is subject to a mortality rate of 50% and prolonged period of mechanical ventilation, with no specific pharmacological treatment currently available (Infection au nouveau Coronavirus (SARS-CoV-2), COVID-19, France et Monde. https://www.santepubliquefrance.fr/dossiers/coronavirus-covid-19). Because of its immunomodulatory action, we propose to evaluate the efficacy and safety of intravenous immunoglobulin (IVIG) administration in patients developing COVID-19-related ARDS. Methods The trial is a phase III double-blind, randomized, multicenter, parallel group, concurrent, controlled study in hospitalized participants with COVID-19 requiring mechanical ventilation using a sequential design. Participants in the treatment group will receive infusions of polyvalent immunoglobulin for 4 consecutive days, and the placebo group will receive an equivalent volume of sodium chloride 0.9% for the same duration. The primary outcome is the number of ventilator-free days up to the 28th day. Secondary objectives are to evaluate the effect of IVIG on (1) organ failure according to the Sequential Organ Failure Assessment (SOFA) score at 14 and 28 days, (2) lung injury score at 14 and 28 days, (3) the occurrence of grade 3 or 4 adverse events of IVIG, (4) length of intensive care unit (ICU) stay, (5) length of hospital stay, (6) functional outcomes at day 90 defined by the activities of daily living and instrumental activities of the daily living scales, and (7) 90-day survival. One hundred thirty-eight subjects will be randomized in a 1:1 ratio to IVIG or placebo groups (69 in each group), considering 90% power, alpha level 0.05 (two sides), and 0.67 effect size level. Discussion The ICAR trial investigates the effect of IVIG in COVID-19-related ARDS. We expect an increase in the survival rate and a reduction in the duration of mechanical ventilation, which is associated with significant morbidity. Trial registration EudraCT 2020-001570-30. ClinicalTrials.gov NCT04350580. Registered on 17 April 2020

A Ventilator-associated Pneumonia Prediction Model in Patients With Acute Respiratory Distress Syndrome

2020 ◽  
Vol 71 (Supplement_4) ◽  
pp. S400-S408
Author(s):  
Zongsheng Wu ◽  
Yao Liu ◽  
Jingyuan Xu ◽  
Jianfeng Xie ◽  
Shi Zhang ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Distress Syndrome ◽  
Neuromuscular Blocking ◽  
Calibration Plot ◽  
Binary Logistic Regression Analysis ◽  
Ventilator Associated Pneumonia ◽  
Mechanical Ventilation Duration

Abstract Background Mechanical ventilation is crucial for acute respiratory distress syndrome (ARDS) patients and diagnosis of ventilator-associated pneumonia (VAP) in ARDS patients is challenging. Hence, an effective model to predict VAP in ARDS is urgently needed. Methods We performed a secondary analysis of patient-level data from the Early versus Delayed Enteral Nutrition (EDEN) of ARDSNet randomized controlled trials. Multivariate binary logistic regression analysis established a predictive model, incorporating characteristics selected by systematic review and univariate analyses. The model’s discrimination, calibration, and clinical usefulness were assessed using the C-index, calibration plot, and decision curve analysis (DCA). Results Of the 1000 unique patients enrolled in the EDEN trials, 70 (7%) had ARDS complicated with VAP. Mechanical ventilation duration and intensive care unit (ICU) stay were significantly longer in the VAP group than non-VAP group (P < .001 for both) but the 60-day mortality was comparable. Use of neuromuscular blocking agents, severe ARDS, admission for unscheduled surgery, and trauma as primary ARDS causes were independent risk factors for VAP. The area under the curve of the model was .744, and model fit was acceptable (Hosmer-Lemeshow P = .185). The calibration curve indicated that the model had proper discrimination and good calibration. DCA showed that the VAP prediction nomogram was clinically useful when an intervention was decided at a VAP probability threshold between 1% and 61%. Conclusions The prediction nomogram for VAP development in ARDS patients can be applied after ICU admission, using available variables. Potential clinical benefits of using this model deserve further assessment.

Surfactant therapy in combination treatment of COVID-19 related acute respiratory distress syndrome

2021 ◽  
pp. 50-56
Author(s):  
Renat R. Gubaidullin ◽  
◽  
Aleksandr P. Kuzin ◽  
Vladimir V. Kulakov ◽  
◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Acute Respiratory Distress Syndrome ◽  
Respiratory Failure ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Standard Therapy ◽  
Distress Syndrome ◽  
Severe Pneumonia ◽  
Lung Ventilation ◽  
Surfactant Therapy

ntroduction. The COVID-19 pandemic caused an outbreak of viral lung infections with severe acute respiratory syndrome complicated with acute respiratory failure. Despite the fact that the pandemic has a lengthened run, none of the therapeutic approaches have proved to be sufficiently effective according to the evidence-based criteria. We consider the use of surfactant therapy in patients with severe viral pneumonia and acute respiratory distress syndrome (ARDS) as one of the possible methods for treating COVID-19 related pneumonia. Objective. To prove the clinical efficacy and safety of orally inhaled Surfactant-BL, an authorized drug, in the combination therapy of COVID-19 related ARDS. Materials and methods. A total of 38 patients with COVID-19 related severe pneumonia and ARDS were enrolled in the study. Of these, 20 patients received the standard therapy in accordance with the temporary guidelines for the prevention, diagnosis and treatment of the novel coronavirus infection (COVID-19) of the Ministry of Health of the Russian Federation, version 9. And 18 patients received the surfactant therapy in addition to the standard therapy. Surfactant-BL was used in accordance with the instructions on how to administer the drug for the indication – prevention of the development of acute respiratory distress syndrome. A step-by-step approach to the build-up of the respiratory therapy aggressiveness was used to manage hypoxia. We used oxygen inhalation via a face mask with an oxygen inflow of 5–15 l/min, highflow oxygen therapy via nasal cannulas using Airvo 2 devices, non-invasive lung ventilation, invasive lung ventilation in accordance with the principles of protective mechanical ventilation. Results and discussion. Significant differences in the frequency of transfers to mechanical ventilation, mortality, Intensive Care Unit (ICU) and hospitalization length of stay (p <0.05) were found between the groups. Patients receiving surfactant therapy who required a transfer to mechanical ventilation accounted for 22% of cases, and the mortality rate was 16%. In the group of patients receiving standard therapy without surfactant inhalation 45% were transferred to mechanical ventilation, and 35% died. For patients receiving surfactant therapy, the hospital stay was reduced by 20% on average, and ICU stay by 30%. Conclusion. The inclusion of surfactant therapy in the treatment of COVID-19 related severe pneumonia and ARDS can reduce the progression of respiratory failure, avoid the use of mechanical ventilation, shorten the ICU and hospitalization length of stay, and improve the survival rate of this patient cohort.

An Evidence-Based Protocol for Manual Prone Positioning of Patients With ARDS

2021 ◽  
Vol 41 (6) ◽  
pp. 55-60
Author(s):  
Patrick Ryan ◽  
Cynthia Fine ◽  
Christine DeForge
Keyword(s):  
Mechanical Ventilation ◽  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Distress Syndrome ◽  
Medical Center ◽  
Academic Medical Center ◽  
Prone Positioning ◽  
Hypoxemic Respiratory Failure ◽  
Unplanned Extubations

Background Manual prone positioning has been shown to reduce mortality among patients with moderate to severe acute respiratory distress syndrome, but it is associated with a high incidence of pressure injuries and unplanned extubations. This study investigated the feasibility of safely implementing a manual prone positioning protocol that uses a dedicated device. Review of Evidence A search of CINAHL and Medline identified multiple randomized controlled trials and meta-analyses that demonstrated both the reduction of mortality when prone positioning is used for more than 12 hours per day in patients with acute respiratory distress syndrome and the most common complications of this treatment. Implementation An existing safe patient-handling device was modified to enable staff to safely perform manual prone positioning with few complications for patients receiving mechanical ventilation. All staff received training on the protocol and use of the device before implementation. Evaluation This study included 36 consecutive patients who were admitted to the medical intensive care unit at a large academic medical center because of hypoxemic respiratory failure/acute respiratory distress syndrome and received mechanical ventilation and prone positioning. Data were collected on clinical presentation, interventions, and complications. Sustainability Using the robust protocol and the low-cost device, staff can safely perform a low-volume, high-risk maneuver. This method provides cost savings compared with other prone positioning methods. Conclusions Implementing a prone positioning protocol with a dedicated device is feasible, with fewer complications and lower costs than anticipated.

Lung volumes and alveolar expansion pattern in immature rabbits treated with serum-diluted surfactant

2004 ◽  
Vol 97 (4) ◽  
pp. 1408-1413 ◽  
Author(s):  
Yongmei Xu ◽  
Tsutomu Kobayashi ◽  
Xiaoguang Cui ◽  
Keisuke Ohta ◽  
Chiharu Kabata ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Distress Syndrome ◽  
Ringer Solution ◽  
Natural Surfactant ◽  
Volume Curve ◽  
Pressure Volume Curve ◽  
Expansion Pattern

In acute respiratory distress syndrome, mechanical ventilation often induces alveolar overdistension aggravating the primary insult. To examine the mechanism of overdistension, surfactant-deficient immature rabbits were anesthetized with pentobarbital sodium, and their lungs were treated with serum-diluted modified natural surfactant (porcine lung extract; 2 mg/ml, 10 ml/kg). By mechanical ventilation with a peak inspiration pressure of 22.5 cmH2O, the animals had a tidal volume of 14.7 ml/kg (mean), when 2.5 cmH2O positive end-expiratory pressure was added. This volume was similar to that in animals treated with nondiluted modified natural surfactant (24 mg/ml in Ringer solution, 10 ml/kg). However, the lungs fixed at 10 cmH2O on the deflation limbs of the pressure-volume curve had the largest alveolar/alveolar duct profiles (≥48,000 μm2), accounting for 38% of the terminal air spaces, and the smallest (<6,000 μm2), accounting for 31%. These values were higher than those in animals treated with nondiluted modified natural surfactant ( P < 0.05). We conclude that administration of serum-diluted surfactant to immature neonatal lungs leads to patchy overdistension of terminal air spaces, similar to the expansion pattern that may be seen after dilution of endogenous surfactant with proteinaceous edema fluid in acute respiratory distress syndrome.

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