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1.
Crit Care ; 25(1): 344, 2021 09 23.
Article in English | MEDLINE | ID: covidwho-1438302

ABSTRACT

BACKGROUND: The primary aim of this study was to assess the outcome of elderly intensive care unit (ICU) patients treated during the spring and autumn COVID-19 surges in Europe. METHODS: This was a prospective European observational study (the COVIP study) in ICU patients aged 70 years and older admitted with COVID-19 disease from March to December 2020 to 159 ICUs in 14 European countries. An electronic database was used to register a number of parameters including: SOFA score, Clinical Frailty Scale, co-morbidities, usual ICU procedures and survival at 90 days. The study was registered at ClinicalTrials.gov (NCT04321265). RESULTS: In total, 2625 patients were included, 1327 from the first and 1298 from the second surge. Median age was 74 and 75 years in surge 1 and 2, respectively. SOFA score was higher in the first surge (median 6 versus 5, p < 0.0001). The PaO2/FiO2 ratio at admission was higher during surge 1, and more patients received invasive mechanical ventilation (78% versus 68%, p < 0.0001). During the first 15 days of treatment, survival was similar during the first and the second surge. Survival was lower in the second surge after day 15 and differed after 30 days (57% vs 50%) as well as after 90 days (51% vs 40%). CONCLUSION: An unexpected, but significant, decrease in 30-day and 90-day survival was observed during the second surge in our cohort of elderly ICU patients. The reason for this is unclear. Our main concern is whether the widespread changes in practice and treatment of COVID-19 between the two surges have contributed to this increased mortality in elderly patients. Further studies are urgently warranted to provide more evidence for current practice in elderly patients. TRIAL REGISTRATION NUMBER: NCT04321265 , registered March 19th, 2020.


Subject(s)
COVID-19/mortality , Critical Illness/mortality , Pneumonia, Viral/mortality , Aged , Aged, 80 and over , Comorbidity , Europe/epidemiology , Female , Frail Elderly , Humans , Intensive Care Units , Male , Organ Dysfunction Scores , Pandemics , Pneumonia, Viral/virology , Prospective Studies , SARS-CoV-2 , Survival Analysis
2.
Am J Respir Crit Care Med ; 2021 May 26.
Article in English | MEDLINE | ID: covidwho-1416749

ABSTRACT

RATIONALE: Early empirical antimicrobial treatment is frequently prescribed to critically ill patients with COVID-19, based on Surviving Sepsis Campaign guidelines. OBJECTIVE: We aimed to determine the prevalence of early bacterial identification in intubated patients with SARS-CoV-2 pneumonia, as compared to influenza pneumonia, and to characterize its microbiology and impact on outcomes. METHODS: Multicenter retrospective European cohort performed in 36 ICUs. All adult patients receiving invasive mechanical ventilation >48h were eligible if they had SARS-CoV-2 or influenza pneumonia at ICU admission. Bacterial identification was defined by a positive bacterial culture, within 48h after intubation, in endotracheal aspirates, bronchoalveolar lavage, blood cultures, or a positive pneumococcal or legionella urinary antigen test. MEASUREMENTS AND MAIN RESULTS: 1,050 patients were included (568 in SARS-CoV-2 and 482 in influenza groups). The prevalence of bacterial identification was significantly lower in patients with SARS-CoV-2 pneumonia as compared to patients with influenza pneumonia (9.7 vs 33.6%, unadjusted odds ratio (OR) 0.21 (95% confidence interval (CI) 0.15 to 0.30), adjusted OR 0.23 (95% CI 0.16 to 0.33), p<0.0001). Gram-positive cocci were responsible for 58% and 72% of co-infection in patients with SARS-CoV-2 and influenza pneumonia, respectively. Bacterial identification was associated with increased adjusted hazard ratio for 28-day mortality in patients with SARS-CoV-2 pneumonia (1.57 (95% CI 1.01 to 2.44), p=0.043). However, no significant difference was found in heterogeneity of outcomes related to bacterial identification between the two study groups, suggesting that the impact of co-infection on mortality was not different between SARS-CoV-2 and influenza patients. CONCLUSIONS: Bacterial identification within 48h after intubation is significantly less frequent in patients with SARS-CoV-2 pneumonia as compared to patients with influenza pneumonia. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

3.
Intensive Care Med ; 47(2): 188-198, 2021 02.
Article in English | MEDLINE | ID: covidwho-1384370

ABSTRACT

PURPOSE: Although patients with SARS-CoV-2 infection have several risk factors for ventilator-associated lower respiratory tract infections (VA-LRTI), the reported incidence of hospital-acquired infections is low. We aimed to determine the relationship between SARS-CoV-2 pneumonia, as compared to influenza pneumonia or no viral infection, and the incidence of VA-LRTI. METHODS: Multicenter retrospective European cohort performed in 36 ICUs. All adult patients receiving invasive mechanical ventilation > 48 h were eligible if they had: SARS-CoV-2 pneumonia, influenza pneumonia, or no viral infection at ICU admission. VA-LRTI, including ventilator-associated tracheobronchitis (VAT) and ventilator-associated pneumonia (VAP), were diagnosed using clinical, radiological and quantitative microbiological criteria. All VA-LRTI were prospectively identified, and chest-X rays were analyzed by at least two physicians. Cumulative incidence of first episodes of VA-LRTI was estimated using the Kalbfleisch and Prentice method, and compared using Fine-and Gray models. RESULTS: 1576 patients were included (568 in SARS-CoV-2, 482 in influenza, and 526 in no viral infection groups). VA-LRTI incidence was significantly higher in SARS-CoV-2 patients (287, 50.5%), as compared to influenza patients (146, 30.3%, adjusted sub hazard ratio (sHR) 1.60 (95% confidence interval (CI) 1.26 to 2.04)) or patients with no viral infection (133, 25.3%, adjusted sHR 1.7 (95% CI 1.2 to 2.39)). Gram-negative bacilli were responsible for a large proportion (82% to 89.7%) of VA-LRTI, mainly Pseudomonas aeruginosa, Enterobacter spp., and Klebsiella spp. CONCLUSIONS: The incidence of VA-LRTI is significantly higher in patients with SARS-CoV-2 infection, as compared to patients with influenza pneumonia, or no viral infection after statistical adjustment, but residual confounding may still play a role in the effect estimates.


Subject(s)
COVID-19 , Pneumonia, Ventilator-Associated , Respiratory Tract Infections , Aged , COVID-19/epidemiology , Europe , Female , Humans , Incidence , Influenza, Human/epidemiology , Male , Middle Aged , Pneumonia, Ventilator-Associated/epidemiology , Respiratory Tract Infections/epidemiology , Retrospective Studies , Ventilators, Mechanical
4.
Clin Hemorheol Microcirc ; 2021 Aug 28.
Article in English | MEDLINE | ID: covidwho-1379956

ABSTRACT

PURPOSECritically ill elderly patients who suffer from Sars-CoV-2 disease are at high risk for organ failure. The modified MELD-XI score has not been evaluated for outcome prediction in these most vulnerable patients.METHODSThe Corona Virus disease (COVID19) in Very Elderly Intensive Care Patients study (COVIP, NCT04321265) prospectively recruited patients on intensive care units (ICU), who were = 70 years. Data were collected from March 2020 to February 2021. The MELD-XI score was calculated using the highest serum bilirubin and creatinine on ICU admission. Univariate and multivariable logistic regression analyses were performed to assess associations between the MELD-XI score and mortality. The primary outcome was 30-day-mortality, the secondary outcomes were ICU- and 3-month-mortality.RESULTSIn total, data from 2,993 patients were analyzed. Most patients had a MELD-XI <12 on admission (76%). The patients with MELD-XI = 12 had a significantly higher 30-day-, ICU- and 3-month-mortality (44%vs 64%, and 42%vs. 59%, and 57%vs. 76%, p < 0.001). After adjustment for multiple confounders, MELD-XI = 12 remained significantly associated with 30-day- (aOR 1.572, CI 1.268-1.949, p < 0.001), ICU-, and 3-month-mortality.CONCLUSIONIn critically ill elderly intensive care patients with COVID-19, the MELD-XI score constitutes a valuable tool for an early outcome prediction.

5.
Ann Intensive Care ; 11(1): 128, 2021 Aug 21.
Article in English | MEDLINE | ID: covidwho-1367683

ABSTRACT

PURPOSE: Lactate is an established prognosticator in critical care. However, there still is insufficient evidence about its role in predicting outcome in COVID-19. This is of particular concern in older patients who have been mostly affected during the initial surge in 2020. METHODS: This prospective international observation study (The COVIP study) recruited patients aged 70 years or older (ClinicalTrials.gov ID: NCT04321265) admitted to an intensive care unit (ICU) with COVID-19 disease from March 2020 to February 2021. In addition to serial lactate values (arterial blood gas analysis), we recorded several parameters, including SOFA score, ICU procedures, limitation of care, ICU- and 3-month mortality. A lactate concentration ≥ 2.0 mmol/L on the day of ICU admission (baseline) was defined as abnormal. The primary outcome was ICU-mortality. The secondary outcomes 30-day and 3-month mortality. RESULTS: In total, data from 2860 patients were analyzed. In most patients (68%), serum lactate was lower than 2 mmol/L. Elevated baseline serum lactate was associated with significantly higher ICU- and 3-month mortality (53% vs. 43%, and 71% vs. 57%, respectively, p < 0.001). In the multivariable analysis, the maximum lactate concentration on day 1 was independently associated with ICU mortality (aOR 1.06 95% CI 1.02-1.11; p = 0.007), 30-day mortality (aOR 1.07 95% CI 1.02-1.13; p = 0.005) and 3-month mortality (aOR 1.15 95% CI 1.08-1.24; p < 0.001) after adjustment for age, gender, SOFA score, and frailty. In 826 patients with baseline lactate ≥ 2 mmol/L sufficient data to calculate the difference between maximal levels on days 1 and 2 (∆ serum lactate) were available. A decreasing lactate concentration over time was inversely associated with ICU mortality after multivariate adjustment for SOFA score, age, Clinical Frailty Scale, and gender (aOR 0.60 95% CI 0.42-0.85; p = 0.004). CONCLUSION: In critically ill old intensive care patients suffering from COVID-19, lactate and its kinetics are valuable tools for outcome prediction. TRIAL REGISTRATION NUMBER: NCT04321265.

6.
Crit Care ; 25(1): 177, 2021 05 25.
Article in English | MEDLINE | ID: covidwho-1352667

ABSTRACT

BACKGROUND: Patients with SARS-CoV-2 infection are at higher risk for ventilator-associated pneumonia (VAP). No study has evaluated the relationship between VAP and mortality in this population, or compared this relationship between SARS-CoV-2 patients and other populations. The main objective of our study was to determine the relationship between VAP and mortality in SARS-CoV-2 patients. METHODS: Planned ancillary analysis of a multicenter retrospective European cohort. VAP was diagnosed using clinical, radiological and quantitative microbiological criteria. Univariable and multivariable marginal Cox's regression models, with cause-specific hazard for duration of mechanical ventilation and ICU stay, were used to compare outcomes between study groups. Extubation, and ICU discharge alive were considered as events of interest, and mortality as competing event. FINDINGS: Of 1576 included patients, 568 were SARS-CoV-2 pneumonia, 482 influenza pneumonia, and 526 no evidence of viral infection at ICU admission. VAP was associated with significantly higher risk for 28-day mortality in SARS-CoV-2 (adjusted HR 1.70 (95% CI 1.16-2.47), p = 0.006), and influenza groups (1.75 (1.03-3.02), p = 0.045), but not in the no viral infection group (1.07 (0.64-1.78), p = 0.79). VAP was associated with significantly longer duration of mechanical ventilation in the SARS-CoV-2 group, but not in the influenza or no viral infection groups. VAP was associated with significantly longer duration of ICU stay in the 3 study groups. No significant difference was found in heterogeneity of outcomes related to VAP between the 3 groups, suggesting that the impact of VAP on mortality was not different between study groups. INTERPRETATION: VAP was associated with significantly increased 28-day mortality rate in SARS-CoV-2 patients. However, SARS-CoV-2 pneumonia, as compared to influenza pneumonia or no viral infection, did not significantly modify the relationship between VAP and 28-day mortality. CLINICAL TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov, number NCT04359693.


Subject(s)
COVID-19/mortality , COVID-19/therapy , Pneumonia, Ventilator-Associated/epidemiology , Aged , Europe/epidemiology , Female , Hospital Mortality , Humans , Intensive Care Units , Length of Stay/statistics & numerical data , Male , Middle Aged , Respiration, Artificial/statistics & numerical data , Retrospective Studies
8.
Crit Care ; 25(1): 171, 2021 05 17.
Article in English | MEDLINE | ID: covidwho-1232432

ABSTRACT

BACKGROUND: Estimates for dead space ventilation have been shown to be independently associated with an increased risk of mortality in the acute respiratory distress syndrome and small case series of COVID-19-related ARDS. METHODS: Secondary analysis from the PRoVENT-COVID study. The PRoVENT-COVID is a national, multicenter, retrospective observational study done at 22 intensive care units 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 aim was to quantify the dynamics and determine the prognostic value of surrogate markers of wasted ventilation in patients with COVID-19-related ARDS. RESULTS: A total of 927 consecutive patients admitted with COVID-19-related ARDS were included in this study. Estimations of wasted ventilation such as the estimated dead space fraction (by Harris-Benedict and direct method) and ventilatory ratio were significantly higher in non-survivors than survivors at baseline and during the following days of mechanical ventilation (p < 0.001). The end-tidal-to-arterial PCO2 ratio was lower in non-survivors than in survivors (p < 0.001). As ARDS severity increased, mortality increased with successive tertiles of dead space fraction by Harris-Benedict and by direct estimation, and with an increase in the VR. The same trend was observed with decreased levels in the tertiles for the end-tidal-to-arterial PCO2 ratio. After adjustment for a base risk model that included chronic comorbidities and ventilation- and oxygenation-parameters, none of the dead space estimates measured at the start of ventilation or the following days were significantly associated with 28-day mortality. CONCLUSIONS: There is significant impairment of ventilation in the early course of COVID-19-related ARDS but quantification of this impairment does not add prognostic information when added to a baseline risk model. TRIAL REGISTRATION: ISRCTN04346342. Registered 15 April 2020. Retrospectively registered.


Subject(s)
COVID-19/mortality , Patient Acuity , Respiration, Artificial , Respiratory Dead Space , Respiratory Distress Syndrome/therapy , Adult , Biomarkers , COVID-19/complications , COVID-19/physiopathology , Female , Humans , Intensive Care Units , Male , Prognosis , ROC Curve , Respiratory Distress Syndrome/etiology , Respiratory Function Tests , Respiratory Mechanics , Retrospective Studies
9.
Obesity (Silver Spring) ; 29(9): 1477-1486, 2021 09.
Article in English | MEDLINE | ID: covidwho-1219092

ABSTRACT

OBJECTIVE: Previous studies have unveiled a relationship between the severity of coronavirus disease 2019 (COVID-19) pneumonia and obesity. The aims of this multicenter retrospective cohort study were to disentangle the association of BMI and associated metabolic risk factors (diabetes, hypertension, hyperlipidemia, and current smoking status) in critically ill patients with COVID-19. METHODS: Patients admitted to intensive care units for COVID-19 in 21 centers (in Europe, Israel, and the United States) were enrolled in this study between February 19, 2020, and May 19, 2020. Primary and secondary outcomes were the need for invasive mechanical ventilation (IMV) and 28-day mortality, respectively. RESULTS: A total of 1,461 patients were enrolled; the median (interquartile range) age was 64 years (40.9-72.0); 73.2% of patients were male; the median BMI was 28.1 kg/m2 (25.4-32.3); a total of 1,080 patients (73.9%) required IMV; and the 28-day mortality estimate was 36.1% (95% CI: 33.0-39.5). An adjusted mixed logistic regression model showed a significant linear relationship between BMI and IMV: odds ratio = 1.27 (95% CI: 1.12-1.45) per 5 kg/m2 . An adjusted Cox proportional hazards regression model showed a significant association between BMI and mortality, which was increased only in obesity class III (≥40; hazard ratio = 1.68 [95% CI: 1.06-2.64]). CONCLUSIONS: In critically ill COVID-19 patients, a linear association between BMI and the need for IMV, independent of other metabolic risk factors, and a nonlinear association between BMI and mortality risk were observed.

10.
Crit Care ; 25(1): 149, 2021 04 19.
Article in English | MEDLINE | ID: covidwho-1191486

ABSTRACT

BACKGROUND: The COVID-19 pandemic has led highly developed healthcare systems to the brink of collapse due to the large numbers of patients being admitted into hospitals. One of the potential prognostic indicators in patients with COVID-19 is frailty. The degree of frailty could be used to assist both the triage into intensive care, and decisions regarding treatment limitations. Our study sought to determine the interaction of frailty and age in elderly COVID-19 ICU patients. METHODS: A prospective multicentre study of COVID-19 patients ≥ 70 years admitted to intensive care in 138 ICUs from 28 countries was conducted. The primary endpoint was 30-day mortality. Frailty was assessed using the clinical frailty scale. Additionally, comorbidities, management strategies and treatment limitations were recorded. RESULTS: The study included 1346 patients (28% female) with a median age of 75 years (IQR 72-78, range 70-96), 16.3% were older than 80 years, and 21% of the patients were frail. The overall survival at 30 days was 59% (95% CI 56-62), with 66% (63-69) in fit, 53% (47-61) in vulnerable and 41% (35-47) in frail patients (p < 0.001). In frail patients, there was no difference in 30-day survival between different age categories. Frailty was linked to an increased use of treatment limitations and less use of mechanical ventilation. In a model controlling for age, disease severity, sex, treatment limitations and comorbidities, frailty was independently associated with lower survival. CONCLUSION: Frailty provides relevant prognostic information in elderly COVID-19 patients in addition to age and comorbidities. Trial registration Clinicaltrials.gov: NCT04321265 , registered 19 March 2020.


Subject(s)
COVID-19/mortality , COVID-19/therapy , Critical Care , Frail Elderly/statistics & numerical data , Frailty/mortality , Aged , Aged, 80 and over , Female , Humans , Male , Prognosis , Prospective Studies , Survival Analysis
11.
Am J Trop Med Hyg ; 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.

12.
Br J Clin Pharmacol ; 87(8): 3075-3091, 2021 08.
Article in English | MEDLINE | ID: covidwho-1035466

ABSTRACT

AIMS: Inhaled nebulised unfractionated heparin (UFH) has a strong scientific and biological rationale that warrants urgent investigation of its therapeutic potential in patients with COVID-19. UFH has antiviral effects and prevents the SARS-CoV-2 virus' entry into mammalian cells. In addition, UFH has significant anti-inflammatory and anticoagulant properties, which limit progression of lung injury and vascular pulmonary thrombosis. METHODS: The INHALEd nebulised unfractionated HEParin for the treatment of hospitalised patients with COVID-19 (INHALE-HEP) metatrial is a prospective individual patient data analysis of on-going randomised controlled trials and early phase studies. Individual studies are being conducted in multiple countries. Participating studies randomise adult patients admitted to the hospital with confirmed SARS-CoV-2 infection, who do not require immediate mechanical ventilation, to inhaled nebulised UFH or standard care. All studies collect a minimum core dataset. The primary outcome for the metatrial is intubation (or death, for patients who died before intubation) at day 28. The secondary outcomes are oxygenation, clinical worsening and mortality, assessed in time-to-event analyses. Individual studies may have additional outcomes. ANALYSIS: We use a Bayesian approach to monitoring, followed by analysing individual patient data, outcomes and adverse events. All analyses will follow the intention-to-treat principle, considering all participants in the treatment group to which they were assigned, except for cases lost to follow-up or withdrawn. TRIAL REGISTRATION, ETHICS AND DISSEMINATION: The metatrial is registered at ClinicalTrials.gov ID NCT04635241. Each contributing study is individually registered and has received approval of the relevant ethics committee or institutional review board. Results of this study will be shared with the World Health Organisation, published in scientific journals and presented at scientific meetings.


Subject(s)
COVID-19 , Heparin , Adult , Bayes Theorem , Humans , Prospective Studies , SARS-CoV-2 , Treatment Outcome
14.
Ann Intensive Care ; 10(1): 110, 2020 Aug 08.
Article in English | MEDLINE | ID: covidwho-704421

ABSTRACT

BACKGROUND: The COVID-19 pandemic has resulted in an unprecedented healthcare crisis with a high prevalence of psychological distress in healthcare providers. We sought to document the prevalence of burnout syndrome amongst intensivists facing the COVID-19 outbreak. METHODS: Cross-sectional survey among intensivists part of the European Society of Intensive Care Medicine. Symptoms of severe burnout, anxiety and depression were collected. Factors independently associated with severe burnout were assessed using Cox model. RESULTS: Response rate was 20% (1001 completed questionnaires were returned, 45 years [39-53], 34% women, from 85 countries, 12 regions, 50% university-affiliated hospitals). The prevalence of symptoms of anxiety and depression or severe burnout was 46.5%, 30.2%, and 51%, respectively, and varied significantly across regions. Rating of the relationship between intensivists and other ICU stakeholders differed significantly according to the presence of anxiety, depression, or burnout. Similar figures were reported for their rating of the ethical climate or the quality of the decision-making. Factors independently associated with anxiety were female gender (HR 1.85 [1.33-2.55]), working in a university-affiliated hospital (HR 0.58 [0.42-0.80]), living in a city of > 1 million inhabitants (HR 1.40 [1.01-1.94]), and clinician's rating of the ethical climate (HR 0.83 [0.77-0.90]). Independent determinants of depression included female gender (HR 1.63 [1.15-2.31]) and clinician's rating of the ethical climate (HR 0.84 [0.78-0.92]). Factors independently associated with symptoms of severe burnout included age (HR 0.98/year [0.97-0.99]) and clinician's rating of the ethical climate (HR 0.76 [0.69-0.82]). CONCLUSIONS: The COVID-19 pandemic has had an overwhelming psychological impact on intensivists. Follow-up, and management are warranted to assess long-term psychological outcomes and alleviate the psychological burden of the pandemic on frontline personnel.

15.
Crit Care ; 24(1): 486, 2020 08 05.
Article in English | MEDLINE | ID: covidwho-695243

ABSTRACT

BACKGROUND: There is little evidence to support the management of severe COVID-19 patients. METHODS: To document this variation in practices, we performed an online survey (April 30-May 25, 2020) on behalf of the European Society of Intensive Care Medicine (ESICM). A case vignette was sent to ESICM members. Questions investigated practices for a previously healthy 39-year-old patient presenting with severe hypoxemia from COVID-19 infection. RESULTS: A total of 1132 ICU specialists (response rate 20%) from 85 countries (12 regions) responded to the survey. The survey provides information on the heterogeneity in patient's management, more particularly regarding the timing of ICU admission, the first line oxygenation strategy, optimization of management, and ventilatory settings in case of refractory hypoxemia. Practices related to antibacterial, antiviral, and anti-inflammatory therapies are also investigated. CONCLUSIONS: There are important practice variations in the management of severe COVID-19 patients, including differences at regional and individual levels. Large outcome studies based on multinational registries are warranted.


Subject(s)
Coronavirus Infections/therapy , Critical Care , Internationality , Pneumonia, Viral/therapy , Practice Patterns, Physicians'/statistics & numerical data , Adult , COVID-19 , Health Care Surveys , Humans , Pandemics , Severity of Illness Index
16.
Crit Care ; 24(1): 454, 2020 07 22.
Article in English | MEDLINE | ID: covidwho-662500

ABSTRACT

Nebulised unfractionated heparin (UFH) has a strong scientific and biological rationale and warrants urgent investigation of its therapeutic potential, for COVID-19-induced acute respiratory distress syndrome (ARDS). COVID-19 ARDS displays the typical features of diffuse alveolar damage with extensive pulmonary coagulation activation resulting in fibrin deposition in the microvasculature and formation of hyaline membranes in the air sacs. Patients infected with SARS-CoV-2 who manifest severe disease have high levels of inflammatory cytokines in plasma and bronchoalveolar lavage fluid and significant coagulopathy. There is a strong association between the extent of the coagulopathy and poor clinical outcomes.The anti-coagulant actions of nebulised UFH limit fibrin deposition and microvascular thrombosis. Trials in patients with acute lung injury and related conditions found inhaled UFH reduced pulmonary dead space, coagulation activation, microvascular thrombosis and clinical deterioration, resulting in increased time free of ventilatory support. In addition, UFH has anti-inflammatory, mucolytic and anti-viral properties and, specifically, has been shown to inactivate the SARS-CoV-2 virus and prevent its entry into mammalian cells, thereby inhibiting pulmonary infection by SARS-CoV-2. Furthermore, clinical studies have shown that inhaled UFH safely improves outcomes in other inflammatory respiratory diseases and also acts as an effective mucolytic in sputum-producing respiratory patients. UFH is widely available and inexpensive, which may make this treatment also accessible for low- and middle-income countries.These potentially important therapeutic properties of nebulised UFH underline the need for expedited large-scale clinical trials to test its potential to reduce mortality in COVID-19 patients.


Subject(s)
Coronavirus Infections/drug therapy , Heparin/administration & dosage , Nebulizers and Vaporizers , Pneumonia, Viral/drug therapy , COVID-19 , Humans , Pandemics , Randomized Controlled Trials as Topic , Treatment Outcome
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