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1.
J Crit Care ; 69: 154022, 2022 Mar 24.
Article in English | MEDLINE | ID: covidwho-1768292

ABSTRACT

PURPOSE: We determined the incidence of hypercapnia and associations with outcome in invasively ventilated COVID-19 patients. METHODS: Posthoc analysis of a national, multicenter, observational study in 22 ICUs. Patients were classified as 'hypercapnic' or 'normocapnic' in the first three days of invasive ventilation. Primary endpoint was prevalence of hypercapnia. Secondary endpoints were ventilator parameters, length of stay (LOS) in ICU and hospital, and mortality in ICU, hospital, at day 28 and 90. RESULTS: Of 824 patients, 485 (58.9%) were hypercapnic. Hypercapnic patients had a higher BMI and had COPD, severe ARDS and venous thromboembolic events more often. Hypercapnic patients were ventilated with lower tidal volumes, higher respiratory rates, higher driving pressures, and with more mechanical power of ventilation. Hypercapnic patients had comparable minute volumes but higher ventilatory ratios than normocapnic patients. In hypercapnic patients, ventilation and LOS in ICU and hospital was longer, but mortality was comparable to normocapnic patients. CONCLUSION: Hypercapnia occurs often in invasively ventilated COVID-19 patients. Main differences between hypercapnic and normocapnic patients are severity of ARDS, occurrence of venous thromboembolic events, and a higher ventilation ratio. Hypercapnia has an association with duration of ventilation and LOS in ICU and hospital, but not with mortality.

2.
Alzheimer's & Dementia ; 17(S5):e057841, 2021.
Article in English | Wiley | ID: covidwho-1589190

ABSTRACT

Background COVID-19 is a respiratory disease where neurological sequelae are frequently reported. Neurofilament light (NfL) in plasma is a validated biomarker for neuronal damage. We assessed the trajectory of NfL levels in intensive care unit (ICU) patients diagnosed with COVID-19, and studied its relationship to clinical outcomes and markers of hypothesized pathophysiological mechanisms. Method As part of the Art-Deco study and Amsterdam UMC COVID-biobank, longitudinal samples and clinical data were collected weekly from a cohort of 31 prospectively admitted ICU patients with a minimum of 7 days of ventilation. The mean±sd age was 63±11 years. Admission duration ranged from 14-35 days and 156 samples were collected. We evaluated the NfL trajectory over time, and whether this trajectory differed by 90-day mortality outcome. Due to the non-linear trajectory of NfL, we applied linear mixed models including cubic splines for the time variable. Secondly, we tested whether baseline or peak NfL levels predicted mortality (n=7/31), delirium incidence after detubation (n=18/22), and duration of delirium (6±6 days). Third, we assessed if disease severity (day 7 Sequential Organ Failure Assessment [SOFA] score) and baseline hypoxemia (pAO2 before intubation), inflammation (IL1-b, IL-6, IL-8, TNF-α), and coagulopathy (d-dimer, presence of pulmonary embolism) were predictive of the NfL trajectory. For the latter models, we included an interaction term for the pathophysiological markers in the linear mixed models. All models were adjusted for age. Result NfL increased during ICU admission (p<001), and persisted longer in the non-survivors (p<0.05;Figure 1). Baseline or maximum NfL was not predictive of mortality or delirium incidence. However, maximum NfL correlated to the duration of delirium (r=0.5;p=0.02). From the pathophysiological markers, SOFA scores (p<0.05) and baseline TNF-α (p<0.05) were related to a stronger increase of NfL over time. Conclusion NfL levels increased over time and plateaued after 2-3 weeks in most COVID-19 patients at the ICU. Peak levels of NfL were predictive of delirium persistence. Repeated NfL levels may provide a future method for monitoring neurological outcomes in sedated ICU patients. Disease severity and specific inflammatory components appear important predictors of the NfL trajectory reflecting axonal damage in severe COVID-19 patients.

3.
BMJ Open ; 11(10): e054901, 2021 10 07.
Article in English | MEDLINE | ID: covidwho-1462977

ABSTRACT

INTRODUCTION: Owing to the novelty of COVID-19, there are still large knowledge gaps concerning its effect on the brain and the resulting impact on peoples' lives. This large-scale prospective follow-up study investigates COVID-19-associated brain damage, neuropsychological dysfunction and long-term impact on the well-being of patients and their close ones. It is hypothesised that structural brain damage and cognitive dysfunction primarily occur in severely ill patients, as compared with moderately ill patients. Cognitive complaints, emotional distress and impact on well-being are hypothesised to be less dependent on illness severity. METHODS AND ANALYSIS: For this multicentre study, 200 patients with COVID-19 (100 intensive care unit (ICU) patients and 100 non-ICU patients) formerly hospitalised in one of the six recruiting hospitals during the first European infection wave (ie, March to June 2020) and their close ones will be recruited. At minimally 6 months posthospital discharge, patients will perform a set of neuropsychological tests and are subjected to a 3T MRI scan. Patients and close ones will fill out a set of questionnaires, also at minimally 6 months posthospital discharge and again another 6 months thereafter. Data related to COVID-19 hospitalisation will be extracted from the patients' medical records. MRI abnormalities will ultimately be related to neuropsychological test performance and questionnaire outcomes. ETHICS AND DISSEMINATION: Ethics approval was granted by the medical research ethics committee of Maastricht University Medical Centre and Maastricht University (NL75102.068.20). The project is sponsored by The Brain Foundation Netherlands. Findings will be presented at national and international conferences, as well as published in peer-reviewed scientific journals. TRIAL REGISTRATION NUMBER: NCT04745611.


Subject(s)
COVID-19 , Cohort Studies , Follow-Up Studies , Humans , Intensive Care Units , Multicenter Studies as Topic , Prospective Studies , SARS-CoV-2 , Survivors
4.
J Thorac Imaging ; 36(5): 286-293, 2021 Sep 01.
Article in English | MEDLINE | ID: covidwho-1440700

ABSTRACT

PURPOSE: Patients with novel coronavirus disease (COVID-19) frequently develop acute respiratory distress syndrome (ARDS) and need invasive ventilation. The potential to reaerate consolidated lung tissue in COVID-19-related ARDS is heavily debated. This study assessed the potential to reaerate lung consolidations in patients with COVID-19-related ARDS under invasive ventilation. MATERIALS AND METHODS: This was a retrospective analysis of patients with COVID-19-related ARDS who underwent chest computed tomography (CT) at low positive end-expiratory pressure (PEEP) and after a recruitment maneuver at high PEEP of 20 cm H2O. Lung reaeration, volume, and weight were calculated using both CT scans. CT scans were performed after intubation and start of ventilation (early CT), or after several days of intensive care unit admission (late CT). RESULTS: Twenty-eight patients were analyzed. The median percentages of reaerated and nonaerated lung tissue were 19% [interquartile range, IQR: 10 to 33] and 11% [IQR: 4 to 15] for patients with early and late CT scans, respectively (P=0.049). End-expiratory lung volume showed a median increase of 663 mL [IQR: 483 to 865] and 574 mL [IQR: 292 to 670] after recruitment for patients with early and late CT scans, respectively (P=0.43). The median decrease in lung weight attributed to nonaerated lung tissue was 229 g [IQR: 165 to 376] and 171 g [IQR: 81 to 229] after recruitment for patients with early and late CT scans, respectively (P=0.16). CONCLUSIONS: The majority of patients with COVID-19-related ARDS undergoing invasive ventilation had substantial reaeration of lung consolidations after recruitment and ventilation at high PEEP. Higher PEEP can be considered in patients with reaerated lung consolidations when accompanied by improvement in compliance and gas exchange.


Subject(s)
COVID-19 , Respiratory Distress Syndrome , COVID-19/diagnostic imaging , COVID-19/therapy , Female , Humans , Lung/diagnostic imaging , Male , Middle Aged , Positive-Pressure Respiration , Respiratory Distress Syndrome/diagnostic imaging , Respiratory Distress Syndrome/therapy , Retrospective Studies , Tomography, X-Ray Computed
5.
Ann Transl Med ; 9(9): 813, 2021 May.
Article in English | MEDLINE | ID: covidwho-1257379

ABSTRACT

BACKGROUND: Patients with coronavirus disease 2019 (COVID-19) may need hospitalization for supplemental oxygen, and some need intensive care unit (ICU) admission for escalation of care. Practice of adjunctive and supportive treatments remain uncertain and may vary widely between countries, within countries between hospitals, and possibly even within ICUs. We aim to investigate practice of adjunctive and supportive treatments, and their associations with outcome, in critically ill COVID-19 patients. METHODS: The 'PRactice of Adjunctive Treatments in Intensive Care Unit Patients with Coronavirus Disease 2019' (PRoAcT-COVID) study is a national, observational study to be undertaken in a large set of ICUs in The Netherlands. The PRoAcT-COVID includes consecutive ICU patients, admitted because of COVID-19 to one of the participating ICUs during a 3-month period. Daily follow-up lasts 28 days. The primary endpoint is a combination of adjunctive treatments, including types of oxygen support, ventilation, rescue therapies for hypoxemia refractory to supplementary oxygen or during invasive ventilation, other adjunctive and supportive treatments, and experimental therapies. We will also collect tracheostomy rate, duration of invasive ventilation and ventilator-free days and alive at day 28 (VFD-28), ICU and hospital length of stay, and the mortality rates in the ICU, hospital and at day 90. DISCUSSION: The PRoAcT-COVID study is an observational study combining high density treatment data with relevant clinical outcomes. Information on treatment practices, and their associations with outcomes in COVID-19 patients in highly and urgently needed. The results of the PRoAcT-COVID study will be rapidly available, and circulated through online presentations, such as webinars and electronic conferences, and publications in peer-reviewed journals-findings will also be presented at a dedicated website. At request, and after agreement of the PRoAcT-COVID steering committee, source data will be made available through local, regional and national anonymized datasets. TRIAL REGISTRATION: The PRoAcT-COVID study is registered at clinicaltrials.gov (study identifier NCT04719182).

6.
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
7.
Expert Rev Respir Med ; 15(8): 1013-1023, 2021 08.
Article in English | MEDLINE | ID: covidwho-1180435

ABSTRACT

INTRODUCTION: It is uncertain whether ventilation in patients with acute respiratory failure related to coronavirus disease 2019 (COVID-19) differs from that in patients with acute respiratory distress syndrome (ARDS) from another origin. AREAS COVERED: We undertook two literature searches in PubMed to identify observational studies reporting on ventilation management--one in patients with acute respiratory failure related to COVID-19, and one in patients with ARDS from another origin. The searches identified 14 studies in patients with acute respiratory failure related to COVID-19, and 8 studies in patients with ARDS from another origin. EXPERT OPINION: In patients with acute respiratory failure related to COVID-19, ventilation management seems to be similar to that of patients with ARDS from another origin. The future lies in studies focused on personalized treatment of ARDS of all origins, including COVID-19.


Subject(s)
COVID-19 , Respiratory Distress Syndrome , Respiratory Insufficiency , Humans , Lung , Respiration, Artificial , Respiratory Distress Syndrome/diagnosis , Respiratory Distress Syndrome/therapy , Respiratory Insufficiency/diagnosis , Respiratory Insufficiency/therapy , SARS-CoV-2
8.
Lancet Respir Med ; 9(2): 139-148, 2021 02.
Article in English | MEDLINE | ID: covidwho-1065695

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
9.
Lancet Rheumatol ; 2(12): e764-e773, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-1003183

ABSTRACT

BACKGROUND: Severe COVID-19 is characterised by inflammation and coagulation in the presence of complement system activation. We aimed to explore the potential benefit and safety of selectively blocking the anaphylatoxin and complement protein C5a with the monoclonal antibody IFX-1 (vilobelimab), in patients with severe COVID-19. METHODS: We did an exploratory, open-label, randomised phase 2 trial (part of the adaptive phase 2/3 PANAMO trial) of intravenous IFX-1 in adults with severe COVID-19 at three academic hospitals in the Netherlands. Eligibility criteria were age 18 years or older; severe pneumonia with pulmonary infiltrates consistent with pneumonia, a clinical history of severe shortness of breath within the past 14 days, or a need for non-invasive or invasive ventilation; severe disease defined as a ratio of partial pressure of arterial oxygen to fractional concentration of oxygen in inspired air (PaO2/FiO2) between 100 mm Hg and 250 mm Hg in the supine position; and severe acute respiratory syndrome coronavirus 2 infection confirmed by RT-PCR. Patients were randomly assigned 1:1 to receive IFX-1 (up to seven doses of 800 mg intravenously) plus best supportive care (IFX-1 group) or best supportive care only (control group). The primary outcome was the percentage change in PaO2/FiO2 in the supine position between baseline and day 5. Mortality at 28 days and treatment-emergent and serious adverse events were key secondary outcomes. The primary analysis was done in the intention-to-treat population and safety analyses were done in all patients according to treatment received. This trial is registered at ClinicalTrials.gov (NCT04333420). FINDINGS: Between March 31 and April 24, 2020, 30 patients were enrolled and randomly assigned to the IFX-1 group (n=15) or the control group (n=15). During the study it became clear that several patients could not be assessed regularly in the supine position because of severe hypoxaemia. It was therefore decided to focus on all PaO2/FiO2 assessments (irrespective of position). At day 5 after randomisation, the mean PaO2/FiO2 (irrespective of position) was 158 mm Hg (SD 63; range 84-265) in the IFX-1 group and 189 mm Hg (89; 71-329) in the control group. Analyses of the least squares mean relative change in PaO2/FiO2 at day 5 showed no differences between treatment groups (17% change in the IFX-1 group vs 41% in the control group; difference -24% [95% CI -58 to 9], p=0·15. Kaplan-Meier estimates of mortality by 28 days were 13% (95% CI 0-31) for the IFX-1 group and 27% (4-49) for the control group (adjusted hazard ratio for death 0·65 [95% CI 0·10-4·14]). The frequency of serious adverse events were similar between groups (nine [60%] in the IFX-1 group vs seven [47%] in the control group) and no deaths were considered related to treatment assignment. However, a smaller proportion of patients had pulmonary embolisms classed as serious in the IFX-1 group (two [13%]) than in the control group (six [40%]). Infections classed as serious were reported in three (20%) patients in the IFX-1 group versus five (33%) patients in the control group. INTERPRETATION: In this small exploratory phase 2 part of the PANAMO trial, C5a inhibition with IFX-1 appears to be safe in patients with severe COVID-19. The secondary outcome results in favour of IFX-1 are preliminary because the study was not powered on these endpoints, but they support the investigation of C5a inhibition with IFX-1 in a phase 3 trial using 28-day mortality as the primary endpoint. FUNDING: InflaRx.

10.
Ann Transl Med ; 8(19): 1251, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-994852

ABSTRACT

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic is rapidly expanding across the world, with more than 100,000 new cases each day as of end-June 2020. Healthcare workers are struggling to provide the best care for COVID-19 patients. Approaches for invasive ventilation vary widely between and within countries and new insights are acquired rapidly. We aim to investigate invasive ventilation practices and outcome in COVID-19 patients in the Netherlands. METHODS: PRoVENT-COVID ('study of PRactice of VENTilation in COVID-19') is an investigator-initiated national, multicenter observational study to be undertaken in intensive care units (ICUs) in The Netherlands. Consecutive COVID-19 patients aged 18 years or older, who are receiving invasive ventilation in the participating ICUs, are to be enrolled during a 10-week period, with a daily follow-up of 7 days. The primary outcome is ventilatory management (including tidal volume expressed as mL/kg predicted body weight and positive end-expiratory pressure expressed as cmH2O) during the first 3 days of ventilation. Secondary outcomes include other ventilatory variables, use of rescue therapies for refractory hypoxemia such as prone positioning and extracorporeal membrane oxygenation, use of sedatives, vasopressors and inotropes; daily cumulative fluid balances; acute kidney injury; ventilator-free days and alive at day 28 (VFD-28), duration of ICU and hospital stay, and ICU, hospital and 90-day mortality. DISCUSSION: PRoVENT-COVID will be the largest observational study to date, with high density ventilatory data and major outcomes. There is urgent need for a better understanding of ventilation practices, and the effects of ventilator settings on outcomes in COVID-19 patients. The results of PRoVENT-COVID will be rapidly disseminated through electronic presentations, such as webinars and electronic conferences, and publications in international peer-reviewed journals. Access to source data will be made available through local, regional and national anonymized datasets on request, and after agreement of the PRoVENT-COVID steering committee. TRIAL REGISTRATION: PRoVENT-COVID is registered at clinicaltrials.gov (identifier NCT04346342).

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