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1.
Ann Am Thorac Soc ; 18(9): 1560-1566, 2021 09.
Article in English | MEDLINE | ID: covidwho-1381294

ABSTRACT

The unprecedented public health burdens of coronavirus disease (COVID-19) have intensified the urgency of identifying effective, low-cost treatments that limit the need for advanced life support measures and improve clinical outcomes. However, personal protective equipment and staffing shortages, disease virulence, and infectivity have created significant barriers to traditional clinical trial practices. We present the novel design of a pragmatic, adaptive, multicenter, international, prospective randomized controlled clinical trial evaluating the safety and effectiveness of awake prone positioning in spontaneously breathing patients with COVID-19 (APPEX-19 [Awake Prone Position for Early Hypoxemia in COVID-19]). Key innovations of this trial include 1) a novel smartphone-based communication process that facilitates rapid enrollment and intervention delivery while allowing social distancing and conservation of personal protective equipment, 2) Bayesian response-adaptive randomization to allow preferential assignment to the most effective intervention and expedite trial completion compared with frequentist designs, 3) remote electronic collection of patient-reported outcomes and electronic medical record data, and 4) pragmatic prospective use of patient-reported data and data collected as part of routine clinical care. Clinical trial registered with www.clinicaltrials.gov (NCT04344587).


Subject(s)
COVID-19 , Wakefulness , Bayes Theorem , Humans , Hypoxia , Multicenter Studies as Topic , Prone Position , Prospective Studies , Randomized Controlled Trials as Topic , SARS-CoV-2 , Treatment Outcome
2.
Front Med (Lausanne) ; 8: 638201, 2021.
Article in English | MEDLINE | ID: covidwho-1264342

ABSTRACT

Introduction: Noninvasive ventilation (NIV) has been used to alleviate hypoxemia and dyspnea, but there is no consensus on the application of NIV in patients with coronavirus disease 2019 (COVID-19). Some staff use NIV as the rescue therapy which might lead to the adverse outcomes. This study was to identify early factors associated with intubation to help the medical staff select appropriate patients for receiving NIV treatment. Methods: Patients with laboratory-confirmed COVID-19 who were treated with NIV in emergency department or ICU of the Third People's Hospital (the only designated hospital for treating COVID-19 in Shenzhen) between January 1 and August 31, 2020, were retrospectively analyzed. Results: Thirty-nine patients with COVID-19 treated with NIV were included; of them, 16 (41%) received endotracheal intubation and 3 (8%) died. Significant differences were observed between intubated and non-intubated patients in PaO2/FiO2 before NIV initiation, hospitalization duration, NIV as the rescue therapy, and PaO2/FiO2 of ≤200 mmHg after 1-2 h of NIV initiation. Notably, 1-2 h after NIV initiation, a PaO2/FiO2 of ≤200 mmHg (odds ratio [OR], 9.35; 95% confidence interval [CI], 1.84-47.62; P = 0.007) and NIV as the rescue therapy (OR, 5.43; 95% CI, 1.09-27.12; P = 0.039) were the risk factors for intubation. Conclusions: In patients with COVID-19-related acute hypoxemic respiratory failure receiving NIV, close attention should be paid to PaO2/FiO2 after 1-2 h of NIV initiation. Also, using NIV as rescue therapy should draw our awareness that it might delay escalation of respiratory support and lead to adverse outcomes.

3.
Am J Respir Cell Mol Biol ; 64(6): 677-686, 2021 06.
Article in English | MEDLINE | ID: covidwho-1259048

ABSTRACT

There is an urgent need for new drugs for patients with acute respiratory distress syndrome (ARDS), including those with coronavirus disease (COVID-19). ARDS in influenza-infected mice is associated with reduced concentrations of liponucleotides (essential precursors for de novo phospholipid synthesis) in alveolar type II (ATII) epithelial cells. Because surfactant phospholipid synthesis is a primary function of ATII cells, we hypothesized that disrupting this process could contribute significantly to the pathogenesis of influenza-induced ARDS. The goal of this study was to determine whether parenteral liponucleotide supplementation can attenuate ARDS. C57BL/6 mice inoculated intranasally with 10,000 plaque-forming units/mouse of H1N1 influenza A/WSN/33 virus were treated with CDP (cytidine 5'-diphospho)-choline (100 µg/mouse i.p.) ± CDP -diacylglycerol 16:0/16:0 (10 µg/mouse i.p.) once daily from 1 to 5 days after inoculation (to model postexposure influenza prophylaxis) or as a single dose on Day 5 (to model treatment of patients with ongoing influenza-induced ARDS). Daily postexposure prophylaxis with CDP-choline attenuated influenza-induced hypoxemia, pulmonary edema, alterations in lung mechanics, impairment of alveolar fluid clearance, and pulmonary inflammation without altering viral replication. These effects were not recapitulated by the daily administration of CTP (cytidine triphosphate) and/or choline. Daily coadministration of CDP-diacylglycerol significantly enhanced the beneficial effects of CDP-choline and also modified the ATII cell lipidome, reversing the infection-induced decrease in phosphatidylcholine and increasing concentrations of most other lipid classes in ATII cells. Single-dose treatment with both liponucleotides at 5 days after inoculation also attenuated hypoxemia, altered lung mechanics, and inflammation. Overall, our data show that liponucleotides act rapidly to reduce disease severity in mice with severe influenza-induced ARDS.


Subject(s)
Alveolar Epithelial Cells/metabolism , Cytidine Diphosphate Choline/pharmacology , Cytidine Diphosphate Diglycerides/pharmacology , Influenza A Virus, H1N1 Subtype/metabolism , Orthomyxoviridae Infections/drug therapy , Respiratory Distress Syndrome/prevention & control , Alveolar Epithelial Cells/pathology , Alveolar Epithelial Cells/virology , Animals , COVID-19/drug therapy , COVID-19/pathology , Mice , Orthomyxoviridae Infections/complications , Orthomyxoviridae Infections/metabolism , Orthomyxoviridae Infections/pathology , Respiratory Distress Syndrome/etiology , Respiratory Distress Syndrome/metabolism , Respiratory Distress Syndrome/pathology , SARS-CoV-2/metabolism
4.
Ther Adv Respir Dis ; 15: 17534666211019555, 2021.
Article in English | MEDLINE | ID: covidwho-1247557

ABSTRACT

BACKGROUNDS: High flow nasal cannula (HFNC) is an alternative therapy for acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 (COVID-19). This study aimed first to describe outcomes of patients suffering from COVID-19-related ARDS treated with HFNC; secondly to evaluate safety of HFNC (patients and healthcare workers) and compare patients according to respiratory outcome. METHODS: A retrospective cohort was conducted in French general hospital intensive care unit (ICU). Patients were included if receiving HFNC for hypoxemia (saturation pulse oxygen (SpO2) <92% under oxygen ⩾6 L/min) associated with ARDS and positive SARS-CoV-2 polymerase chain reaction (PCR). Main clinical characteristics and outcomes are described in patients: (a) with do not intubate order (HFNC-DNIO); (b) who did not need intubation (HFNC-only); and (c) eventually intubated (HFNC-intubation). Medians are presented with (1st-3rd) interquartile range. RESULTS: From 26 February to 30 June 2020, 46 patients of median age 75 (70-79) years were included. In the HFNC-DNIO group (n = 11), partial arterial oxygen pressure (PaO2)/inhaled fraction of oxygen (FiO2) ratio median worst PaO2/FiO2 ratio was 109 (102-172) and hospital mortality was 54.5%. Except the HFNC-DNIO patients (n = 35), 20 patients (57%) were eventually intubated (HFNC-intubation group) and 15 were only treated by HFNC (HFNC-only). HFNC-intubation patients presented higher worst respiratory rates per minute in ICU [37 (34-41) versus 33 (24-34) min, p < 0.05] and worsened ICU admission PaO2/FiO2 ratios [121 (103-169) versus 191 (162-219), p < 0.001] compared with HFNC-only patients. Hospital mortality was 35% (n = 7/20) in HFNC-intubation group, 0% in HFNC-only group with a global mortality of these two groups of 20% (n = 7/35). Among tests performed in healthcare workers, 1/12 PCR in symptomatic healthcare workers and 1.8% serologies in asymptomatic healthcare workers were positive. After review of each case, COVID-19 was likely to be acquired outside hospital. CONCLUSIONS: HFNC seems to be useful for COVID-19-related ARDS and safe for healthcare workers. ARDS severity with PaO2/FiO2 <150 associated with respiratory rate >35/min could be regarded as a predictor of intubation.The reviews of this paper are available via the supplemental material section.


Subject(s)
COVID-19/complications , Cannula , Noninvasive Ventilation/instrumentation , Oxygen Inhalation Therapy/instrumentation , Respiratory Distress Syndrome/therapy , Respiratory Distress Syndrome/virology , Aged , COVID-19/mortality , COVID-19/therapy , Critical Care , Female , France , Hospital Mortality , Humans , Male , Respiratory Distress Syndrome/mortality , Retrospective Studies
5.
JAMA ; 325(17): 1731-1743, 2021 05 04.
Article in English | MEDLINE | ID: covidwho-1241490

ABSTRACT

Importance: High-flow nasal oxygen is recommended as initial treatment for acute hypoxemic respiratory failure and is widely applied in patients with COVID-19. Objective: To assess whether helmet noninvasive ventilation can increase the days free of respiratory support in patients with COVID-19 compared with high-flow nasal oxygen alone. Design, Setting, and Participants: Multicenter randomized clinical trial in 4 intensive care units (ICUs) in Italy between October and December 2020, end of follow-up February 11, 2021, including 109 patients with COVID-19 and moderate to severe hypoxemic respiratory failure (ratio of partial pressure of arterial oxygen to fraction of inspired oxygen ≤200). Interventions: Participants were randomly assigned to receive continuous treatment with helmet noninvasive ventilation (positive end-expiratory pressure, 10-12 cm H2O; pressure support, 10-12 cm H2O) for at least 48 hours eventually followed by high-flow nasal oxygen (n = 54) or high-flow oxygen alone (60 L/min) (n = 55). Main Outcomes and Measures: The primary outcome was the number of days free of respiratory support within 28 days after enrollment. Secondary outcomes included the proportion of patients who required endotracheal intubation within 28 days from study enrollment, the number of days free of invasive mechanical ventilation at day 28, the number of days free of invasive mechanical ventilation at day 60, in-ICU mortality, in-hospital mortality, 28-day mortality, 60-day mortality, ICU length of stay, and hospital length of stay. Results: Among 110 patients who were randomized, 109 (99%) completed the trial (median age, 65 years [interquartile range {IQR}, 55-70]; 21 women [19%]). The median days free of respiratory support within 28 days after randomization were 20 (IQR, 0-25) in the helmet group and 18 (IQR, 0-22) in the high-flow nasal oxygen group, a difference that was not statistically significant (mean difference, 2 days [95% CI, -2 to 6]; P = .26). Of 9 prespecified secondary outcomes reported, 7 showed no significant difference. The rate of endotracheal intubation was significantly lower in the helmet group than in the high-flow nasal oxygen group (30% vs 51%; difference, -21% [95% CI, -38% to -3%]; P = .03). The median number of days free of invasive mechanical ventilation within 28 days was significantly higher in the helmet group than in the high-flow nasal oxygen group (28 [IQR, 13-28] vs 25 [IQR 4-28]; mean difference, 3 days [95% CI, 0-7]; P = .04). The rate of in-hospital mortality was 24% in the helmet group and 25% in the high-flow nasal oxygen group (absolute difference, -1% [95% CI, -17% to 15%]; P > .99). Conclusions and Relevance: Among patients with COVID-19 and moderate to severe hypoxemia, treatment with helmet noninvasive ventilation, compared with high-flow nasal oxygen, resulted in no significant difference in the number of days free of respiratory support within 28 days. Further research is warranted to determine effects on other outcomes, including the need for endotracheal intubation. Trial Registration: ClinicalTrials.gov Identifier: NCT04502576.


Subject(s)
COVID-19/complications , Intubation, Intratracheal/statistics & numerical data , Noninvasive Ventilation/instrumentation , Oxygen Inhalation Therapy/methods , Respiratory Insufficiency/therapy , Aged , COVID-19/mortality , COVID-19/therapy , Female , Hospital Mortality , Humans , Hypoxia/etiology , Male , Middle Aged , Noninvasive Ventilation/methods , Respiratory Insufficiency/etiology , Treatment Failure
6.
Rev Invest Clin ; 73(3): 190-198, 2021.
Article in English | MEDLINE | ID: covidwho-1239310

ABSTRACT

BACKGROUND: There is no pharmacological intervention on the treatment of hypoxemia and respiratory distress in COVID-19 patients. OBJECTIVE: The objective of the study was to study the effect of the reduced form of methylene blue (MB) on the improvement of oxygen saturation (SpO2) and respiratory rate (RR). METHODS: In an academic medical center, 80 hospitalized patients with severe COVID-19 were randomly assigned to receive either oral MB along with standard of care (SOC) (MB group, n = 40) or SOC only (SOC group, n=40). The primary outcomes were SpO2 and RR on the 3rd and 5th days. The secondary outcomes were hospital stay and mortality within 28 days. RESULTS: In the MB group, a significant improvement in SpO2 and RR was observed on the 3rd day (for both, p < 0.0001) and also the 5th day (for both, p < 0.0001). In the SOC group, there was no significant improvement in SpO2 (p = 0.24) and RR (p = 0.20) on the 3rd day, although there was a significant improvement of SpO2 (p = 0.002) and RR (p = 0.01) on the 5th day. In the MB group in comparison to the SOC group, the rate ratio of increased SpO2 was 13.5 and 2.1 times on the 3rd and 5th days, respectively. In the MB group compared with the SOC group, the rate ratio of RR improvement was 10.1 and 3.7 times on the 3rd and 5th days, respectively. The hospital stay was significantly shortened in the MB group (p = 0.004), and the mortality was 12.5% and 22.5% in the MB and SOC groups, respectively. CONCLUSIONS: The addition of MB to the treatment protocols significantly improved SpO2 and respiratory distress in COVID-19 patients, which resulted in decreased hospital stay and mortality. ClinicalTrials.gov: NCT04370288.


Subject(s)
COVID-19/drug therapy , Methylene Blue/therapeutic use , Adult , Aged , Female , Hospitalization , Humans , Male , Middle Aged
7.
World J Clin Cases ; 9(14): 3385-3393, 2021 May 16.
Article in English | MEDLINE | ID: covidwho-1232704

ABSTRACT

BACKGROUND: Several reports with clinical, histological and imaging data have observed the involvement of lung vascular function to explain the severe hypoxemia in coronavirus disease 2019 (COVID-19) patients. It has been hypothesized that an increased pulmonary blood flow associated with an impairment of hypoxic pulmonary vasoconstriction is responsible for an intrapulmonary shunt. COVID-19 may lead to refractory hypoxemia (PaO2/FiO2 ratio below 100 mmHg) despite mechanical ventilation and prone positioning. We hypothesized that the use of a pulmonary vasoconstrictor may help decrease the shunt and thus enhance oxygenation. CASE SUMMARY: We report our experience with three patients with refractory hypoxemia treated with almitrine to enhance oxygenation. Low dose almitrine (Vectarion®; Servier, Suresnes, France) was started at an infusion rate of 4 µg × kg/min on a central line. The PaO2/FiO2 ratio and total respiratory system compliance during almitrine infusion were measured. For the three patients, the PaO2/FiO2 ratio time-course showed a dramatic increase whereas total respiratory system compliance was unchanged. The three patients were discharged from the intensive care unit. The intensive care unit length of stay for patient 1, patient 2 and patient 3 was 30 d, 32 d and 31 d, respectively. Weaning from mechanical ventilation was performed 13 d, 18 d and 15 d after almitrine infusion for patient 1, 2 and 3, respectively. We found no deleterious effects on the right ventricular function, which was similar to previous studies on almitrine safety. CONCLUSION: Almitrine may be effective and safe to enhance oxygenation in coronavirus disease 2019 patients. Further controlled studies are required.

8.
Dtsch Med Wochenschr ; 146(10): 671-676, 2021 05.
Article in German | MEDLINE | ID: covidwho-1217717

ABSTRACT

The COVID-19 pandemic poses new challenges for the healthcare systems world-wide which will go beyond prevention, acute and intensive care treatment of patients with severe illness. A large proportion of "COVID-survivors" - and not only elderly patients - suffers from "post-COVID-syndrome". Risk factors are preexisting somatic multimorbidity, cognitive and cerebral changes together with pneumonia and hypoxemia, intensive care treatment and confusional states during the acute phase of illness. Post-COVID cognitive deficits usually manifest as a frontal dysexecutive syndrome combined with fatigue and dysphoria and/or with attentional and memory deficits. Several pathogenetic mechanisms of COVID encephalopathy are understood, but no specific treatment strategies have been established so far. We assume that general practitioners, psychiatrists, neurologists and social workers will need to take care of the activation, reintegration and expert appraisals of patients with post-COVID fatigue and cognitive deficits during the years to come.


Subject(s)
COVID-19 , Cognitive Dysfunction , Aged , COVID-19/complications , COVID-19/epidemiology , COVID-19/physiopathology , Cognitive Dysfunction/epidemiology , Cognitive Dysfunction/physiopathology , Cognitive Dysfunction/virology , Female , Humans , Male , Middle Aged , Multimorbidity , Pandemics , Risk Factors , SARS-CoV-2
9.
Lancet Respir Med ; 9(2): 139-148, 2021 02.
Article in English | MEDLINE | ID: covidwho-1199179

ABSTRACT

BACKGROUND: Little is known about the practice of ventilation management in patients with COVID-19. We aimed to describe the practice of ventilation management and to establish outcomes in invasively ventilated patients with COVID-19 in a single country during the first month of the outbreak. METHODS: PRoVENT-COVID is a national, multicentre, retrospective observational study done at 18 intensive care units (ICUs) in the Netherlands. Consecutive patients aged at least 18 years were eligible for participation if they had received invasive ventilation for COVID-19 at a participating ICU during the first month of the national outbreak in the Netherlands. The primary outcome was a combination of ventilator variables and parameters over the first 4 calendar days of ventilation: tidal volume, positive end-expiratory pressure (PEEP), respiratory system compliance, and driving pressure. Secondary outcomes included the use of adjunctive treatments for refractory hypoxaemia and ICU complications. Patient-centred outcomes were ventilator-free days at day 28, duration of ventilation, duration of ICU and hospital stay, and mortality. PRoVENT-COVID is registered at ClinicalTrials.gov (NCT04346342). FINDINGS: Between March 1 and April 1, 2020, 553 patients were included in the study. Median tidal volume was 6·3 mL/kg predicted bodyweight (IQR 5·7-7·1), PEEP was 14·0 cm H2O (IQR 11·0-15·0), and driving pressure was 14·0 cm H2O (11·2-16·0). Median respiratory system compliance was 31·9 mL/cm H2O (26·0-39·9). Of the adjunctive treatments for refractory hypoxaemia, prone positioning was most often used in the first 4 days of ventilation (283 [53%] of 530 patients). The median number of ventilator-free days at day 28 was 0 (IQR 0-15); 186 (35%) of 530 patients had died by day 28. Predictors of 28-day mortality were gender, age, tidal volume, respiratory system compliance, arterial pH, and heart rate on the first day of invasive ventilation. INTERPRETATION: In patients with COVID-19 who were invasively ventilated during the first month of the outbreak in the Netherlands, lung-protective ventilation with low tidal volume and low driving pressure was broadly applied and prone positioning was often used. The applied PEEP varied widely, despite an invariably low respiratory system compliance. The findings of this national study provide a basis for new hypotheses and sample size calculations for future trials of invasive ventilation for COVID-19. These data could also help in the interpretation of findings from other studies of ventilation practice and outcomes in invasively ventilated patients with COVID-19. FUNDING: Amsterdam University Medical Centers, location Academic Medical Center.


Subject(s)
COVID-19/therapy , Respiration, Artificial , Aged , Cohort Studies , Female , Humans , Male , Middle Aged , Netherlands , Retrospective Studies , Treatment Outcome
10.
J Med Virol ; 93(3): 1443-1448, 2021 03.
Article in English | MEDLINE | ID: covidwho-1196454

ABSTRACT

Our study intended to longitudinally explore the prediction effect of immunoglobulin A (IgA) on pulmonary exudation progression in COVID-19 patients. The serum IgA was tested with chemiluminescence method. Autoregressive moving average model was used to extrapolate the IgA levels before hospital admission. The positive rate of IgA and IgG in our cohort was 97% and 79.0%, respectively. In this study, the IgA levels peaks within 10-15 days after admission, while the IgG levels peaks at admission. We found that the time difference between their peaks was about 10 days. Viral RNA detection results showed that the positive rate in sputum and feces were the highest. Blood gas analysis showed that deterioration of hypoxia with the enlargement of pulmonary exudation area. And alveolar-arterial oxygen difference and oxygenation index were correlated with IgA and IgG. The results of biopsy showed that the epithelium of lung was exfoliated and the mucosa was edematous. In severe COVID-19 patients, the combination of IgA and IgG can predict the progress of pulmonary lesions and is closely related to hypoxemia and both also play an important defense role in invasion and destruction of bronchial and alveolar epithelium by SARS-CoV-2.


Subject(s)
COVID-19/pathology , COVID-19/virology , Immunoglobulin A/blood , Immunoglobulin G/blood , Sputum/virology , Aged , Alveolar Epithelial Cells/metabolism , Alveolar Epithelial Cells/virology , Antibodies, Viral/blood , Bronchi/metabolism , Bronchi/virology , COVID-19/blood , COVID-19/metabolism , Female , Humans , Hypoxia/blood , Hypoxia/metabolism , Male , Middle Aged , Mucous Membrane/metabolism , Mucous Membrane/virology , Oxygen/metabolism , Pulmonary Alveoli/metabolism , Pulmonary Alveoli/virology , RNA, Viral/genetics , SARS-CoV-2/genetics
11.
Ann Surg ; 274(1): 40-44, 2021 07 01.
Article in English | MEDLINE | ID: covidwho-1177358

ABSTRACT

OBJECTIVE: This study analyzed the outcomes of COVID-19 patients with ARDS who were managed with extracorporeal membrane oxygenation (ECMO) across 155 US academic centers. SUMMARY BACKGROUND DATA: ECMO has been utilized in COVID-19 patients with acute respiratory distress syndrome (ARDS) and refractory hypoxemia. Early case series with the use of ECMO in these patients reported high mortality exceeding 90%. METHODS: Using ICD-10 codes, data of patients with COVID-19 with ARDS, managed with ECMO between April and September 2020, were analyzed using the Vizient clinical database. Outcomes measured included in-hospital mortality, hospital and ICU length of stay, and direct cost. For comparative purposes, the outcome of a subset of COVID-19 patients aged between 18 and 64 years and managed with versus without ECMO were examined. RESULTS: 1,182 patients with COVID-19 and ARDS received ECMO. In-hospital mortality was 45.9%, mean length of stay was 36.8 ±â€Š24.9 days, and mean ICU stay was 29.1 ±â€Š17.3 days. In-hospital mortality according to age group was 25.2% for 1 to 30 years; 42.2% for 31 to 50 years; 53.2% for 51 to 64 years; and 73.7% for ≥65 years. A subset analysis of COVID-19 patients, aged 18 to 64 years with ARDS requiring mechanical ventilation and managed with (n = 1113) vs without (n = 16,343) ECMO, showed relatively high in-hospital mortality for both groups (44.6% with ECMO vs 37.9% without ECMO). CONCLUSIONS: In this large US study of patients with COVID-19 and ARDS managed with ECMO, the in-hospital mortality is high but much lower than initial reports. Future research is needed to evaluate which patients with COVID-19 and ARDS would benefit from ECMO.


Subject(s)
Academic Medical Centers , COVID-19/complications , COVID-19/therapy , Extracorporeal Membrane Oxygenation , Respiratory Distress Syndrome/therapy , Adolescent , Adult , Aged , COVID-19/mortality , Child , Child, Preschool , Hospital Mortality , Hospitalization , Humans , Infant , Middle Aged , Outcome Assessment, Health Care , Respiratory Distress Syndrome/mortality , Respiratory Distress Syndrome/virology , Retrospective Studies , United States , Young Adult
12.
JAMA ; 325(17): 1731-1743, 2021 05 04.
Article in English | MEDLINE | ID: covidwho-1148761

ABSTRACT

Importance: High-flow nasal oxygen is recommended as initial treatment for acute hypoxemic respiratory failure and is widely applied in patients with COVID-19. Objective: To assess whether helmet noninvasive ventilation can increase the days free of respiratory support in patients with COVID-19 compared with high-flow nasal oxygen alone. Design, Setting, and Participants: Multicenter randomized clinical trial in 4 intensive care units (ICUs) in Italy between October and December 2020, end of follow-up February 11, 2021, including 109 patients with COVID-19 and moderate to severe hypoxemic respiratory failure (ratio of partial pressure of arterial oxygen to fraction of inspired oxygen ≤200). Interventions: Participants were randomly assigned to receive continuous treatment with helmet noninvasive ventilation (positive end-expiratory pressure, 10-12 cm H2O; pressure support, 10-12 cm H2O) for at least 48 hours eventually followed by high-flow nasal oxygen (n = 54) or high-flow oxygen alone (60 L/min) (n = 55). Main Outcomes and Measures: The primary outcome was the number of days free of respiratory support within 28 days after enrollment. Secondary outcomes included the proportion of patients who required endotracheal intubation within 28 days from study enrollment, the number of days free of invasive mechanical ventilation at day 28, the number of days free of invasive mechanical ventilation at day 60, in-ICU mortality, in-hospital mortality, 28-day mortality, 60-day mortality, ICU length of stay, and hospital length of stay. Results: Among 110 patients who were randomized, 109 (99%) completed the trial (median age, 65 years [interquartile range {IQR}, 55-70]; 21 women [19%]). The median days free of respiratory support within 28 days after randomization were 20 (IQR, 0-25) in the helmet group and 18 (IQR, 0-22) in the high-flow nasal oxygen group, a difference that was not statistically significant (mean difference, 2 days [95% CI, -2 to 6]; P = .26). Of 9 prespecified secondary outcomes reported, 7 showed no significant difference. The rate of endotracheal intubation was significantly lower in the helmet group than in the high-flow nasal oxygen group (30% vs 51%; difference, -21% [95% CI, -38% to -3%]; P = .03). The median number of days free of invasive mechanical ventilation within 28 days was significantly higher in the helmet group than in the high-flow nasal oxygen group (28 [IQR, 13-28] vs 25 [IQR 4-28]; mean difference, 3 days [95% CI, 0-7]; P = .04). The rate of in-hospital mortality was 24% in the helmet group and 25% in the high-flow nasal oxygen group (absolute difference, -1% [95% CI, -17% to 15%]; P > .99). Conclusions and Relevance: Among patients with COVID-19 and moderate to severe hypoxemia, treatment with helmet noninvasive ventilation, compared with high-flow nasal oxygen, resulted in no significant difference in the number of days free of respiratory support within 28 days. Further research is warranted to determine effects on other outcomes, including the need for endotracheal intubation. Trial Registration: ClinicalTrials.gov Identifier: NCT04502576.


Subject(s)
COVID-19/complications , Intubation, Intratracheal/statistics & numerical data , Noninvasive Ventilation/instrumentation , Oxygen Inhalation Therapy/methods , Respiratory Insufficiency/therapy , Aged , COVID-19/mortality , COVID-19/therapy , Female , Hospital Mortality , Humans , Hypoxia/etiology , Male , Middle Aged , Noninvasive Ventilation/methods , Respiratory Insufficiency/etiology , Treatment Failure
13.
Crit Care ; 25(1): 115, 2021 03 20.
Article in English | MEDLINE | ID: covidwho-1143244

ABSTRACT

BACKGROUND: The mortality of critically ill patients with COVID-19 is high, particularly among those receiving mechanical ventilation (MV). Despite the high number of patients treated worldwide, data on respiratory mechanics are currently scarce and the optimal setting of MV remains to be defined. This scoping review aims to provide an overview of available data about respiratory mechanics, gas exchange and MV settings in patients admitted to intensive care units (ICUs) for COVID-19-associated acute respiratory failure, and to identify knowledge gaps. MAIN TEXT: PubMed, EMBASE, and MEDLINE databases were searched from inception to October 30, 2020 for studies providing at least one ventilatory parameter collected within 24 h from the ICU admission. The quality of the studies was independently assessed using the Newcastle-Ottawa Quality Assessment Form for Cohort Studies. A total of 26 studies were included for a total of 14,075 patients. At ICU admission, positive end expiratory pressure (PEEP) values ranged from 9 to 16.5 cm of water (cmH2O), suggesting that high levels of PEEP were commonly used for setting MV for these patients. Patients with COVID-19 are severely hypoxemic at ICU admission and show a median ratio of partial pressure of arterial oxygen to fraction of inspired oxygen (PaO2/FiO2) ranging from 102 to 198 mmHg. Static respiratory system compliance (Crs) values at ICU admission were highly heterogenous, ranging between 24 and 49 ml/cmH2O. Prone positioning and neuromuscular blocking agents were widely used, ranging from 17 to 81 and 22 to 88%, respectively; both rates were higher than previously reported in patients with "classical" acute respiratory distress syndrome (ARDS). CONCLUSIONS: Available data show that, in mechanically ventilated patients with COVID-19, respiratory mechanics and MV settings within 24 h from ICU admission are heterogeneous but similar to those reported for "classical" ARDS. However, to date, complete data regarding mechanical properties of respiratory system, optimal setting of MV and the role of rescue treatments for refractory hypoxemia are still lacking in the medical literature.


Subject(s)
COVID-19/physiopathology , COVID-19/therapy , Respiration, Artificial , COVID-19/complications , Critical Illness , Humans , Intensive Care Units , Respiratory Distress Syndrome/physiopathology , Respiratory Distress Syndrome/therapy , Respiratory Distress Syndrome/virology , Respiratory Mechanics
14.
ERJ Open Res ; 7(1)2021 Jan.
Article in English | MEDLINE | ID: covidwho-1133579

ABSTRACT

RATIONALE AND OBJECTIVES: Prone positioning as a complement to oxygen therapy to treat hypoxaemia in coronavirus disease 2019 (COVID-19) pneumonia in spontaneously breathing patients has been widely adopted, despite a lack of evidence for its benefit. We tested the hypothesis that a simple incentive to self-prone for a maximum of 12 h per day would decrease oxygen needs in patients admitted to the ward for COVID-19 pneumonia on low-flow oxygen therapy. METHODS: 27 patients with confirmed COVID-19 pneumonia admitted to Geneva University Hospitals were included in the study. 10 patients were randomised to self-prone positioning and 17 to usual care. MEASUREMENTS AND MAIN RESULTS: Oxygen needs assessed by oxygen flow on nasal cannula at inclusion were similar between groups. 24 h after starting the intervention, the median (interquartile range (IQR)) oxygen flow was 1.0 (0.1-2.9) L·min-1 in the prone position group and 2.0 (0.5-3.0) L·min-1 in the control group (p=0.507). Median (IQR) oxygen saturation/fraction of inspired oxygen ratio was 390 (300-432) in the prone position group and 336 (294-422) in the control group (p=0.633). One patient from the intervention group who did not self-prone was transferred to the high-dependency unit. Self-prone positioning was easy to implement. The intervention was well tolerated and only mild side-effects were reported. CONCLUSIONS: Self-prone positioning in patients with COVID-19 pneumonia requiring low-flow oxygen therapy resulted in a clinically meaningful reduction of oxygen flow, but without reaching statistical significance.

15.
Am J Trop Med Hyg ; 104(5): 1676-1686, 2021 Mar 11.
Article in English | MEDLINE | ID: covidwho-1128113

ABSTRACT

Non-intubated patients with acute respiratory failure due to COVID-19 could benefit from awake proning. Awake proning is an attractive intervention in settings with limited resources, as it comes with no additional costs. However, awake proning remains poorly used probably because of unfamiliarity and uncertainties regarding potential benefits and practical application. To summarize evidence for benefit and to develop a set of pragmatic recommendations for awake proning in patients with COVID-19 pneumonia, focusing on settings where resources are limited, international healthcare professionals from high and low- and middle-income countries (LMICs) with known expertise in awake proning were invited to contribute expert advice. A growing number of observational studies describe the effects of awake proning in patients with COVID-19 pneumonia in whom hypoxemia is refractory to simple measures of supplementary oxygen. Awake proning improves oxygenation in most patients, usually within minutes, and reduces dyspnea and work of breathing. The effects are maintained for up to 1 hour after turning back to supine, and mostly disappear after 6-12 hours. In available studies, awake proning was not associated with a reduction in the rate of intubation for invasive ventilation. Awake proning comes with little complications if properly implemented and monitored. Pragmatic recommendations including indications and contraindications were formulated and adjusted for resource-limited settings. Awake proning, an adjunctive treatment for hypoxemia refractory to supplemental oxygen, seems safe in non-intubated patients with COVID-19 acute respiratory failure. We provide pragmatic recommendations including indications and contraindications for the use of awake proning in LMICs.


Subject(s)
COVID-19/complications , Hypoxia/therapy , Prone Position/physiology , Respiratory Insufficiency/therapy , SARS-CoV-2 , Acute Disease , Continuous Positive Airway Pressure , Health Personnel , Humans , Wakefulness
16.
J Clin Med ; 10(6)2021 03 11.
Article in English | MEDLINE | ID: covidwho-1125931

ABSTRACT

We describe the practice of ventilation and mortality rates in invasively ventilated normal-weight (18.5 ≤ BMI ≤ 24.9 kg/m2), overweight (25.0 ≤ BMI ≤ 29.9 kg/m2), and obese (BMI > 30 kg/m2) COVID-19 ARDS patients in a national, multicenter observational study, performed at 22 intensive care units in the Netherlands. The primary outcome was a combination of ventilation variables and parameters over the first four calendar days of ventilation, including tidal volume, positive end-expiratory pressure (PEEP), respiratory system compliance, and driving pressure in normal-weight, overweight, and obese patients. Secondary outcomes included the use of adjunctive treatments for refractory hypoxaemia and mortality rates. Between 1 March 2020 and 1 June 2020, 1122 patients were included in the study: 244 (21.3%) normal-weight patients, 531 (47.3%) overweight patients, and 324 (28.8%) obese patients. Most patients received a tidal volume < 8 mL/kg PBW; only on the first day was the tidal volume higher in obese patients. PEEP and driving pressure were higher, and compliance of the respiratory system was lower in obese patients on all four days. Adjunctive therapies for refractory hypoxemia were used equally in the three BMI groups. Adjusted mortality rates were not different between BMI categories. The findings of this study suggest that lung-protective ventilation with a lower tidal volume and prone positioning is similarly feasible in normal-weight, overweight, and obese patients with ARDS related to COVID-19. A patient's BMI should not be used in decisions to forgo or proceed with invasive ventilation.

17.
Monaldi Arch Chest Dis ; 91(2)2021 03 05.
Article in English | MEDLINE | ID: covidwho-1119586

ABSTRACT

There is limited evidence on the efficacy of awake prone positioning (PP) in non-ventilated patients with COVID-19 who have hypoxemia. We, therefore, aim to describe our experience with the use of early proning in awake, non-intubated patients with confirmed COVID-19. In our retrospective observational study, 23 patients with confirmed positive PCR test results for Severe Acute respiratory Syndrome Coronavirus-2 (SARS-CoV-2) and hypoxemia that required oxygen therapy with or without non-invasive ventilation were treated with PP. Patients were classified into mild, moderate and severe COVID-19 disease. There were no targeted number of hours for proning per day and patients were kept in prone position according to their tolerance. The primary outcome measure was the avoidance of intubation and secondary outcomes were in-hospital mortality, length of hospital stays and complications related to PP. The mean (standard deviation) age of our cohort was 54.5 (11.7) years, and the majority were males (21/23, 91.3%). Sixty-one per cent (14/23) of the patients were suffering from severe disease and 82.6% (19/23) had bilateral lung involvement with interstitial infiltrates. Majority of the patients were prone positioned for a median of 6 days (IQR 4 - 8). Only one patient required transfer to ICU for mechanical ventilation and subsequently died due to severe ARDS. All 22 patients showed progressive improvement in oxygen requirement and PF ratio, mostly after 3-5 days of proning. The mean length of hospital stay was 12 days. All patients, except one, were discharged in stable conditions, on room air or on a minimal oxygen requirement of 1-2 liters. No major complication of PP was recorded. Awake prone positioning is a valuable and safe therapeutic adjunct that can be applied in patients with moderate-to-severe COVID-19. It can also be included in the home-based management protocols of COVID-19 to improve patient outcomes and mitigate the burden on health care facilities.


Subject(s)
COVID-19/therapy , Developing Countries , Patient Positioning , Prone Position , Adult , COVID-19/diagnosis , COVID-19/mortality , Female , Hospital Mortality , Humans , Male , Middle Aged , Oxygen Inhalation Therapy , Pakistan , Respiration, Artificial , Retrospective Studies , Treatment Outcome , Wakefulness
18.
Ann Intensive Care ; 11(1): 36, 2021 Feb 18.
Article in English | MEDLINE | ID: covidwho-1090614

ABSTRACT

SARS-CoV-2, the causative agent of coronavirus disease 2019 (COVID-19), is responsible for the largest pandemic facing humanity since the Spanish flu pandemic in the early twentieth century. Since there is no specific antiviral treatment, optimized support is the most relevant factor in the patient's prognosis. In the hospital setting, the identification of high-risk patients for clinical deterioration is essential to ensure access to intensive treatment of severe conditions in a timely manner. The initial management of hypoxemia includes conventional oxygen therapy, high-flow nasal canula oxygen, and non-invasive ventilation. For patients requiring invasive mechanical ventilation, lung-protective ventilation with low tidal volumes and plateau pressure is recommended. Cardiovascular complications are frequent and include myocardial injury, thrombotic events, myocarditis, and cardiogenic shock. Acute renal failure is a common complication and is a marker of poor prognosis, with significant impact in costs and resources allocation. Regarding promising therapies for COVID-19, the most promising drugs until now are remdesivir and corticosteroids although further studies may be needed to confirm their effectiveness. Other therapies such as, tocilizumab, anakinra, other anti-cytokine drugs, and heparin are being tested in clinical trials. Thousands of physicians are living a scenario that none of us have ever seen: demand for hospital exceed capacity in most countries. Until now, the certainty we have is that we should try to decrease the number of infected patients and that an optimized critical care support is the best strategy to improve patient's survival.

19.
Artif Organs ; 45(5): 495-505, 2021 May.
Article in English | MEDLINE | ID: covidwho-1085292

ABSTRACT

Extracorporeal life support (ECLS) is a means to support patients with acute respiratory failure. Initially, recommendations to treat severe cases of pandemic coronavirus disease 2019 (COVID-19) with ECLS have been restrained. In the meantime, ECLS has been shown to produce similar outcomes in patients with severe COVID-19 compared to existing data on ARDS mortality. We performed an international email survey to assess how ECLS providers worldwide have previously used ECLS during the treatment of critically ill patients with COVID-19. A questionnaire with 45 questions (covering, e.g., indication, technical aspects, benefit, and reasons for treatment discontinuation), mostly multiple choice, was distributed by email to ECLS centers. The survey was approved by the European branch of the Extracorporeal Life Support Organization (ELSO); 276 ECMO professionals from 98 centers in 30 different countries on four continents reported that they employed ECMO for very severe COVID-19 cases, mostly in veno-venous configuration (87%). The most common reason to establish ECLS was isolated hypoxemic respiratory failure (50%), followed by a combination of hypoxemia and hypercapnia (39%). Only a small fraction of patients required veno-arterial cannulation due to heart failure (3%). Time on ECLS varied between less than 2 and more than 4 weeks. The main reason to discontinue ECLS treatment prior to patient's recovery was lack of clinical improvement (53%), followed by major bleeding, mostly intracranially (13%). Only 4% of respondents reported that triage situations, lack of staff or lack of oxygenators, were responsible for discontinuation of ECLS support. Most ECLS physicians (51%, IQR 30%) agreed that patients with COVID-19-induced ARDS (CARDS) benefitted from ECLS. Overall mortality of COVID-19 patients on ECLS was estimated to be about 55%. ECLS has been utilized successfully during the COVID-19 pandemic to stabilize CARDS patients in hypoxemic or hypercapnic lung failure. Age and multimorbidity limited the use of ECLS. Triage situations were rarely a concern. ECLS providers stated that patients with severe COVID-19 benefitted from ECLS.


Subject(s)
COVID-19/therapy , Extracorporeal Membrane Oxygenation , Practice Patterns, Physicians'/statistics & numerical data , Respiratory Distress Syndrome/therapy , Respiratory Insufficiency/therapy , Critical Illness , Humans , Internationality , Respiratory Distress Syndrome/virology , Respiratory Insufficiency/virology , SARS-CoV-2 , Surveys and Questionnaires
20.
J Intensive Care ; 9(1): 17, 2021 Feb 06.
Article in English | MEDLINE | ID: covidwho-1068611

ABSTRACT

Acute respiratory distress syndrome (ARDS) is a fatal condition with insufficiently clarified etiology. Supportive care for severe hypoxemia remains the mainstay of essential interventions for ARDS. In recent years, adequate ventilation to prevent ventilator-induced lung injury (VILI) and patient self-inflicted lung injury (P-SILI) as well as lung-protective mechanical ventilation has an increasing attention in ARDS.Ventilation-perfusion mismatch may augment severe hypoxemia and inspiratory drive and consequently induce P-SILI. Respiratory drive and effort must also be carefully monitored to prevent P-SILI. Airway occlusion pressure (P0.1) and airway pressure deflection during an end-expiratory airway occlusion (Pocc) could be easy indicators to evaluate the respiratory drive and effort. Patient-ventilator dyssynchrony is a time mismatching between patient's effort and ventilator drive. Although it is frequently unrecognized, dyssynchrony can be associated with poor clinical outcomes. Dyssynchrony includes trigger asynchrony, cycling asynchrony, and flow delivery mismatch. Ventilator-induced diaphragm dysfunction (VIDD) is a form of iatrogenic injury from inadequate use of mechanical ventilation. Excessive spontaneous breathing can lead to P-SILI, while excessive rest can lead to VIDD. Optimal balance between these two manifestations is probably associated with the etiology and severity of the underlying pulmonary disease.High-flow nasal cannula (HFNC) and non-invasive positive pressure ventilation (NPPV) are non-invasive techniques for supporting hypoxemia. While they are beneficial as respiratory supports in mild ARDS, there can be a risk of delaying needed intubation. Mechanical ventilation and ECMO are applied for more severe ARDS. However, as with HFNC/NPPV, inappropriate assessment of breathing workload potentially has a risk of delaying the timing of shifting from ventilator to ECMO. Various methods of oxygen administration in ARDS are important. However, it is also important to evaluate whether they adequately reduce the breathing workload and help to improve ARDS.

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