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1.
Crit Care Explor ; 2(9): e0202, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-1795075

ABSTRACT

OBJECTIVES: Patients with coronavirus disease 2019 acute respiratory distress syndrome appear to present with at least two distinct phenotypes: severe hypoxemia with relatively well-preserved lung compliance and lung gas volumes (type 1) and a more conventional acute respiratory distress syndrome phenotype, displaying the typical characteristics of the "baby lung" (type 2). We aimed to test plausible hypotheses regarding the pathophysiologic mechanisms underlying coronavirus disease 2019 acute respiratory distress syndrome and to evaluate the resulting implications for ventilatory management. DESIGN: We adapted a high-fidelity computational simulator, previously validated in several studies of acute respiratory distress syndrome, to: 1) develop quantitative insights into the key pathophysiologic differences between the coronavirus disease 2019 acute respiratory distress syndrome and the conventional acute respiratory distress syndrome and 2) assess the impact of different positive end-expiratory pressure, Fio2, and tidal volume settings. SETTING: Interdisciplinary Collaboration in Systems Medicine Research Network. SUBJECTS: The simulator was calibrated to represent coronavirus disease 2019 acute respiratory distress syndrome patients with both normal and elevated body mass indices undergoing invasive mechanical ventilation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: An acute respiratory distress syndrome model implementing disruption of hypoxic pulmonary vasoconstriction and vasodilation leading to hyperperfusion of collapsed lung regions failed to replicate clinical data on type 1 coronavirus disease 2019 acute respiratory distress syndrome patients. Adding mechanisms to reflect disruption of alveolar gas-exchange due to the effects of pneumonitis and heightened vascular resistance due to the emergence of microthrombi produced levels of ventilation perfusion mismatch and hypoxemia consistent with data from type 1 coronavirus disease 2019 acute respiratory distress syndrome patients, while preserving close-to-normal lung compliance and gas volumes. Atypical responses to positive end-expiratory pressure increments between 5 and 15 cm H2O were observed for this type 1 coronavirus disease 2019 acute respiratory distress syndrome model across a range of measures: increasing positive end-expiratory pressure resulted in reduced lung compliance and no improvement in oxygenation, whereas mechanical power, driving pressure, and plateau pressure all increased. Fio2 settings based on acute respiratory distress syndrome network protocols at different positive end-expiratory pressure levels were insufficient to achieve adequate oxygenation. Incrementing tidal volumes from 5 to 10 mL/kg produced similar increases in multiple indicators of ventilator-induced lung injury in the type 1 coronavirus disease 2019 acute respiratory distress syndrome model to those seen in a conventional acute respiratory distress syndrome model. CONCLUSIONS: Our model suggests that use of standard positive end-expiratory pressure/Fio2 tables, higher positive end-expiratory pressure strategies, and higher tidal volumes may all be potentially deleterious in type 1 coronavirus disease 2019 acute respiratory distress syndrome patients, and that a highly personalized approach to treatment is advisable.

2.
Drugs Real World Outcomes ; 8(3): 417-425, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1540320

ABSTRACT

BACKGROUND: Critically ill patients are admitted to intensive care units so they can be comprehensively managed and provided with services not covered in general hospital wards, with the aim to increase their chances of survival. These procedures include invasive mechanical ventilation. OBJECTIVE: The aim of this study was to identify the factors associated with survival in critically ill patients who required invasive mechanical ventilation in an intensive care unit of a tertiary-level hospital in Colombia. METHODS: This was a retrospective follow-up study of a cohort of adult patients who required invasive mechanical ventilation in an intensive care unit in San José de Buga Hospital, between 2017 and 2018. Sociodemographic, clinical, and pharmacological variables were identified. Using Cox regression, variables associated with survival and complications were identified. RESULTS: A total of 357 patients were analyzed. The average age was 64.8 ± 18.9 years, and 52.9% were male. The most frequent diagnoses were sepsis/septic shock (38.4%) and trauma (17.4%). The main factors associated with shorter survival were advanced age (HR 0.97; 95% CI 0.96-0.99), a diagnosis of septic shock (HR 0.29; 95% CI 0.18-0.48) or diabetes mellitus at admission (HR 0.57; 95% CI 0.33-0.98), a healthcare-associated infection (HR 0.51; 95% CI 0.33-0.80), and the need for vasopressors (HR 0.36; 95% CI 0.22-0.59). The administration of systemic corticosteroids was associated with a higher probability of survival (HR 1.93; 95% CI 1.15-3.25). CONCLUSIONS: The use of systemic corticosteroids was associated with a greater probability of survival in critically ill patients who required invasive mechanical ventilation in an intensive care unit. The identification of the variables associated with a higher risk of dying should allow care protocols to be improved, thereby extending the life expectancy of these patients.

3.
J Clin Med ; 10(8)2021 Apr 10.
Article in English | MEDLINE | ID: covidwho-1526831

ABSTRACT

A clinical interpretation of the Randomized Evaluation of COVID-19 Therapy (RECOVERY) study was performed to provide a useful tool to understand whether, when, and to whom dexamethasone should be administered during hospitalization for COVID-19. A post hoc analysis of data published in the preliminary report of the RECOVERY study was performed to calculate the person-based number needed to treat (NNT) and number needed to harm (NNH) of 6 mg dexamethasone once daily for up to 10 days vs. usual care with respect to mortality. At day 28, the NNT of dexamethasone vs. usual care was 36.0 (95%CI 24.9-65.1, p < 0.05) in all patients, 8.3 (95%CI 6.0-13.1, p < 0.05) in patients receiving invasive mechanical ventilation, and 34.6 (95%CI 22.1-79.0, p < 0.05) in patients receiving oxygen only (with or without noninvasive ventilation). Dexamethasone increased mortality compared with usual care in patients not requiring oxygen supplementation, leading to a NNH value of 26.7 (95%CI 18.1-50.9, p < 0.05). NNT of dexamethasone vs. usual care was 17.3 (95%CI 14.9-20.6) in subjects <70 years, 27.0 (95%CI 18.5-49.8) in men, and 16.2 (95%CI 13.2-20.8) in patients in which the onset of symptoms was >7 days. Dexamethasone is effective in male subjects < 70 years that require invasive mechanical ventilation experiencing symptoms from >7 days and those patients receiving oxygen without invasive mechanical ventilation; it should be avoided in patients not requiring respiratory support.

4.
N Engl J Med ; 382(18): 1708-1720, 2020 04 30.
Article in English | MEDLINE | ID: covidwho-1428982

ABSTRACT

BACKGROUND: Since December 2019, when coronavirus disease 2019 (Covid-19) emerged in Wuhan city and rapidly spread throughout China, data have been needed on the clinical characteristics of the affected patients. METHODS: We extracted data regarding 1099 patients with laboratory-confirmed Covid-19 from 552 hospitals in 30 provinces, autonomous regions, and municipalities in mainland China through January 29, 2020. The primary composite end point was admission to an intensive care unit (ICU), the use of mechanical ventilation, or death. RESULTS: The median age of the patients was 47 years; 41.9% of the patients were female. The primary composite end point occurred in 67 patients (6.1%), including 5.0% who were admitted to the ICU, 2.3% who underwent invasive mechanical ventilation, and 1.4% who died. Only 1.9% of the patients had a history of direct contact with wildlife. Among nonresidents of Wuhan, 72.3% had contact with residents of Wuhan, including 31.3% who had visited the city. The most common symptoms were fever (43.8% on admission and 88.7% during hospitalization) and cough (67.8%). Diarrhea was uncommon (3.8%). The median incubation period was 4 days (interquartile range, 2 to 7). On admission, ground-glass opacity was the most common radiologic finding on chest computed tomography (CT) (56.4%). No radiographic or CT abnormality was found in 157 of 877 patients (17.9%) with nonsevere disease and in 5 of 173 patients (2.9%) with severe disease. Lymphocytopenia was present in 83.2% of the patients on admission. CONCLUSIONS: During the first 2 months of the current outbreak, Covid-19 spread rapidly throughout China and caused varying degrees of illness. Patients often presented without fever, and many did not have abnormal radiologic findings. (Funded by the National Health Commission of China and others.).


Subject(s)
Betacoronavirus , Coronavirus Infections , Disease Outbreaks , Pandemics , Pneumonia, Viral , Adolescent , Adult , Aged , COVID-19 , Child , China/epidemiology , Coronavirus Infections/complications , Coronavirus Infections/diagnosis , Coronavirus Infections/epidemiology , Coronavirus Infections/therapy , Female , Fever/etiology , Humans , Male , Middle Aged , Patient Acuity , Pneumonia, Viral/complications , Pneumonia, Viral/diagnosis , Pneumonia, Viral/epidemiology , Pneumonia, Viral/therapy , SARS-CoV-2 , Young Adult
5.
Am J Respir Crit Care Med ; 204(5): 546-556, 2021 09 01.
Article in English | MEDLINE | ID: covidwho-1416749

ABSTRACT

Rationale: Early empirical antimicrobial treatment is frequently prescribed to critically ill patients with coronavirus disease (COVID-19) based on Surviving Sepsis Campaign guidelines.Objectives: We aimed to determine the prevalence of early bacterial identification in intubated patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia, as compared with influenza pneumonia, and to characterize its microbiology and impact on outcomes.Methods: A multicenter retrospective European cohort was performed in 36 ICUs. All adult patients receiving invasive mechanical ventilation >48 hours were eligible if they had SARS-CoV-2 or influenza pneumonia at ICU admission. Bacterial identification was defined by a positive bacterial culture within 48 hours after intubation in endotracheal aspirates, BAL, blood cultures, or a positive pneumococcal or legionella urinary antigen test.Measurements and Main Results: A total of 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 compared with patients with influenza pneumonia (9.7 vs. 33.6%; unadjusted odds ratio, 0.21; 95% confidence interval [CI], 0.15-0.30; adjusted odds ratio, 0.23; 95% CI, 0.16-0.33; P < 0.0001). Gram-positive cocci were responsible for 58% and 72% of coinfection 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, 1.01-2.44; P = 0.043). However, no significant difference was found in the heterogeneity of outcomes related to bacterial identification between the two study groups, suggesting that the impact of coinfection on mortality was not different between patients with SARS-CoV-2 and influenza.Conclusions: Bacterial identification within 48 hours after intubation is significantly less frequent in patients with SARS-CoV-2 pneumonia than patients with influenza pneumonia.Clinical trial registered with www.clinicaltrials.gov (NCT04359693).


Subject(s)
COVID-19 , Coinfection , Influenza, Human , Adult , COVID-19/complications , Humans , Influenza, Human/complications , Influenza, Human/epidemiology , Retrospective Studies , SARS-CoV-2
6.
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
7.
Crit Care Med ; 49(7): 1026-1037, 2021 07 01.
Article in English | MEDLINE | ID: covidwho-1307563

ABSTRACT

OBJECTIVES: Therapies for patients with respiratory failure from coronavirus disease 2019 are urgently needed. Early implementation of prone positioning ventilation improves survival in patients with acute respiratory distress syndrome, but studies examining the effect of proning on survival in patients with coronavirus disease 2019 are lacking. Our objective was to estimate the effect of early proning initiation on survival in patients with coronavirus disease 2019-associated respiratory failure. DESIGN: Data were derived from the Study of the Treatment and Outcomes in Critically Ill Patients with coronavirus disease 2019, a multicenter cohort study of critically ill adults with coronavirus disease 2019 admitted to 68 U.S. hospitals. Using these data, we emulated a target trial of prone positioning ventilation by categorizing mechanically ventilated hypoxemic (ratio of Pao2 over the corresponding Fio2 ≤ 200 mm Hg) patients as having been initiated on proning or not within 2 days of ICU admission. We fit an inverse probability-weighted Cox model to estimate the mortality hazard ratio for early proning versus no early proning. Patients were followed until death, hospital discharge, or end of follow-up. SETTING: ICUs at 68 U.S. sites. PATIENTS: Critically ill adults with laboratory-confirmed coronavirus disease 2019 receiving invasive mechanical ventilation with ratio of Pao2 over the corresponding Fio2 less than or equal to 200 mm Hg. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among 2,338 eligible patients, 702 (30.0%) were proned within the first 2 days of ICU admission. After inverse probability weighting, baseline and severity of illness characteristics were well-balanced between groups. A total of 1,017 (43.5%) of the 2,338 patients were discharged alive, 1,101 (47.1%) died, and 220 (9.4%) were still hospitalized at last follow-up. Patients proned within the first 2 days of ICU admission had a lower adjusted risk of death compared with nonproned patients (hazard ratio, 0.84; 95% CI, 0.73-0.97). CONCLUSIONS: In-hospital mortality was lower in mechanically ventilated hypoxemic patients with coronavirus disease 2019 treated with early proning compared with patients whose treatment did not include early proning.


Subject(s)
COVID-19/complications , Hypoxia/therapy , Patient Positioning , Prone Position , Respiration, Artificial , Respiratory Insufficiency/etiology , Aged , Cohort Studies , Female , Hospital Mortality , Humans , Intensive Care Units , Male , Middle Aged , SARS-CoV-2 , Survival Analysis , Time-to-Treatment , United States/epidemiology
8.
Crit Care Med ; 49(3): 437-448, 2021 03 01.
Article in English | MEDLINE | ID: covidwho-1298993

ABSTRACT

OBJECTIVES: To describe the outcomes of hospitalized patients in a multicenter, international coronavirus disease 2019 registry. DESIGN: Cross-sectional observational study including coronavirus disease 2019 patients hospitalized with laboratory-confirmed severe acute respiratory syndrome coronavirus-2 infection between February 15, 2020, and November 30, 2020, according to age and type of organ support therapies. SETTING: About 168 hospitals in 16 countries within the Society of Critical Care Medicine's Discovery Viral Infection and Respiratory Illness University Study coronavirus disease 2019 registry. PATIENTS: Adult hospitalized coronavirus disease 2019 patients who did and did not require various types and combinations of organ support (mechanical ventilation, renal replacement therapy, vasopressors, and extracorporeal membrane oxygenation). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Primary outcome was hospital mortality. Secondary outcomes were discharge home with or without assistance and hospital length of stay. Risk-adjusted variation in hospital mortality for patients receiving invasive mechanical ventilation was assessed by using multilevel models with hospitals as a random effect, adjusted for age, race/ethnicity, sex, and comorbidities. Among 20,608 patients with coronavirus disease 2019, the mean (± sd) age was 60.5 (±17), 11,1887 (54.3%) were men, 8,745 (42.4%) were admitted to the ICU, and 3,906 (19%) died in the hospital. Hospital mortality was 8.2% for patients receiving no organ support (n = 15,001). The most common organ support therapy was invasive mechanical ventilation (n = 5,005; 24.3%), with a hospital mortality of 49.8%. Mortality ranged from 40.8% among patients receiving only invasive mechanical ventilation (n =1,749) to 71.6% for patients receiving invasive mechanical ventilation, vasoactive drugs, and new renal replacement therapy (n = 655). Mortality was 39% for patients receiving extracorporeal membrane oxygenation (n = 389). Rates of discharge home ranged from 73.5% for patients who did not require organ support therapies to 29.8% for patients who only received invasive mechanical ventilation, and 8.8% for invasive mechanical ventilation, vasoactive drugs, and renal replacement; 10.8% of patients older than 74 years who received invasive mechanical ventilation were discharged home. Median hospital length of stay for patients on mechanical ventilation was 17.1 days (9.7-28 d). Adjusted interhospital variation in mortality among patients receiving invasive mechanical ventilation was large (median odds ratio 1.69). CONCLUSIONS: Coronavirus disease 2019 prognosis varies by age and level of organ support. Interhospital variation in mortality of mechanically ventilated patients was not explained by patient characteristics and requires further evaluation.


Subject(s)
COVID-19/therapy , Critical Care Outcomes , Hospital Mortality , Hospitalization , Patient Discharge/statistics & numerical data , Registries , Adult , Aged , Extracorporeal Membrane Oxygenation , Female , Humans , Length of Stay/statistics & numerical data , Male , Middle Aged , Renal Replacement Therapy , Respiration, Artificial , Vasoconstrictor Agents
9.
Ann Clin Biochem ; 58(5): 520-527, 2021 09.
Article in English | MEDLINE | ID: covidwho-1277833

ABSTRACT

BACKGROUND: The variability of Covid-19 severity between patients has driven efforts to identify prognosticating laboratory markers that could aid clinical decision-making. Procalcitonin is classically used as a diagnostic marker in bacterial infections, but its role in predicting Covid-19 disease severity is emerging. We aimed to identify the association between procalcitonin and Covid-19 disease severity in a critical care setting and whether bacterial co-infection is implicated. METHODS: We retrospectively reviewed Covid-19 patients with procalcitonin concentrations measured in a critical care setting at our institution between February and September 2020. Laboratory markers including peak procalcitonin values and a range of bacterial culture results were analysed. Outcomes were the requirement and duration of invasive mechanical ventilation as well as inpatient mortality. RESULTS: In total, 60 patients were included; 68% required invasive mechanical ventilation and 45% died as inpatient. Univariate analysis identified higher peak procalcitonin concentrations significantly associated with both the requirement for invasive mechanical ventilation (OR: 3.2, 95% CI 1.3-9.0, P = 0.02) and inpatient mortality (OR: 2.6, 95% CI 1.1-6.6, P = 0.03). Higher peak procalcitonin concentrations was an independent predictor of mortality on multivariate analysis (OR 3.7, 95% CI 1.1-12.4, P = 0.03). There was a significant positive correlation between increased peak procalcitonin concentrations and duration on invasive mechanical ventilation. No significant difference was found between peak procalcitonin concentrations of patients with positive and negative bacterial cultures. CONCLUSIONS: Elevated procalcitonin concentrations in Covid-19 patients are associated with respiratory failure requiring prolonged invasive mechanical ventilation and inpatient mortality. This association may be independent of bacterial co-infection.


Subject(s)
Bacterial Infections/blood , Bacterial Infections/complications , COVID-19/blood , COVID-19/complications , Procalcitonin/blood , SARS-CoV-2 , Adult , Aged , Bacterial Infections/diagnosis , Biomarkers/blood , COVID-19/epidemiology , Coinfection/blood , Critical Care , England/epidemiology , Female , Humans , Male , Middle Aged , Multivariate Analysis , Pandemics , Prognosis , Respiration, Artificial , Retrospective Studies , Risk Factors , Severity of Illness Index
10.
Postgrad Med J ; 98(1161): 509-514, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1262407

ABSTRACT

PURPOSE: This systematic review and meta-analysis aimed to evaluate the effect of sofosbuvir/daclatasvir (SOF/DCV) on mortality, the need for intensive care unit (ICU) admission or invasive mechanical ventilation (IMV) and clinical recovery in patients with COVID-19. METHODS: We performed a systematic literature search through the PubMed, Scopus and Embase from the inception of databases until 6 April 2021. The intervention group was SOF/DCV, and the control group was standard of care. The primary outcome was mortality, defined as clinically validated death. The secondary outcomes were (1) the need for ICU admission or IMV and (2) clinical recovery. The pooled effect estimates were reported as risk ratios (RRs). RESULTS: There were four studies with a total of 231 patients in this meta-analysis. Three studies were randomised controlled trial, and one study was non-randomised. SOF/DCV was associated with lower mortality (RR: 0.31 (0.12, 0.78); p=0.013; I2: 0%) and reduced need for ICU admission or IMV (RR: 0.35 (0.18, 0.69); p=0.002; I2: 0%). Clinical recovery was achieved more frequently in the SOF/DCV (RR: 1.20 (1.04, 1.37); p=0.011; I2: 21.1%). There was a moderate certainty of evidence for mortality and need for ICU/IMV outcome, and a low certainty of evidence for clinical recovery. The absolute risk reductions were 140 fewer per 1000 for mortality and 186 fewer per 1000 for the need for ICU/IMV. The increase in clinical recovery was 146 more per 1000. CONCLUSION: SOF/DCV may reduce mortality rate and need for ICU/IMV in patients with COVID-19 while increasing the chance for clinical recovery. PROTOCOL REGISTRATION: PROSPERO: CRD42021247510.


Subject(s)
COVID-19 , Sofosbuvir , COVID-19/drug therapy , Carbamates , Controlled Clinical Trials as Topic , GRADE Approach , Humans , Imidazoles , Pyrrolidines , Sofosbuvir/therapeutic use , Valine/analogs & derivatives
11.
Medicine (Baltimore) ; 100(19): e25917, 2021 May 14.
Article in English | MEDLINE | ID: covidwho-1262274

ABSTRACT

ABSTRACT: The coronavirus disease (COVID-19) has become a global pandemic. Invasive mechanical ventilation is recommended for the management of patients with COVID-19 who have severe respiratory symptoms. However, various complications can develop after its use. The efficient and appropriate management of patients requires the identification of factors associated with an aggravation of COVID-19 respiratory symptoms to a degree where invasive mechanical ventilation becomes necessary, thereby enabling clinicians to prevent such ventilation. This retrospective study included 138 inpatients with COVID-19 at a tertiary hospital. We evaluated the differences in the demographic and clinical data between 27 patients who required invasive mechanical ventilation and 111 patients who did not. Multivariate logistic regression analysis indicated that the duration of fever, national early warning score (NEWS), and lactate dehydrogenase (LDH) levels on admission were significantly associated with invasive mechanical ventilation in this cohort. The optimal cut-off values were: fever duration ≥1 day (sensitivity 100.0%, specificity 54.95%), NEWS ≥7 (sensitivity 72.73%, specificity 92.52%), and LDH >810 mg/dL (sensitivity 56.0%, specificity 90.29%). These findings can assist in the early identification of patients who will require invasive mechanical ventilation. Further studies in larger patient populations are recommended to validate our findings.


Subject(s)
COVID-19/physiopathology , Early Warning Score , Respiration, Artificial/statistics & numerical data , Adult , Age Factors , Aged , Aged, 80 and over , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Female , Fever/physiopathology , Humans , Hydroxychloroquine/therapeutic use , L-Lactate Dehydrogenase/blood , Logistic Models , Male , Middle Aged , Pandemics , Real-Time Polymerase Chain Reaction , Republic of Korea , Retrospective Studies , Risk Assessment , Risk Factors , SARS-CoV-2 , Sex Factors , Socioeconomic Factors , Tertiary Care Centers , Young Adult
12.
PLoS One ; 16(6): e0252760, 2021.
Article in English | MEDLINE | ID: covidwho-1259246

ABSTRACT

BACKGROUND: COVID 19 is the most recent cause of Adult respiratory distress syndrome ARDS. Invasive mechanical ventilation IMV can support gas exchange in patients failing non-invasive ventilation, but its reported outcome is highly variable between countries. We conducted a systematic review and meta-analysis on IMV for COVID-associated ARDS to study its outcome among different countries. METHODS: CENTRAL, MEDLINE/PubMed, Cochrane Library, and Scopus were systematically searched up to August 8, 2020. Studies reporting five or more patients with end point outcome for severe COVID 19 infection treated with IMV were included. The main outcome assessed was mortality. Baseline, procedural, outcome, and validity data were systematically appraised and pooled with random-effect methods. Subgroup analysis for different countries was performed. Meta-regression for the effect of study timing and patient age and were tested. Publication bias was examined. This trial was registered with PROSPERO under registration number CRD42020190365. FINDINGS: Our electronic search retrieved 4770 citations, 103 of which were selected for full-text review. Twenty-one studies with a combined population of 37359 patients with COVID-19 fulfilled the inclusion criteria. From this population, 5800 patients were treated by invasive mechanical ventilation. Out of those, 3301 patients reached an endpoint of ICU discharge or death after invasive mechanical ventilation while the rest were still in the ICU. Mortality from IMV was highly variable among the included studies ranging between 21% and 100%. Random-effect pooled estimates suggested an overall in-hospital mortality risk ratio of 0.70 (95% confidence interval 0.608 to 0.797; I2 = 98%). Subgroup analysis according to country of origin showed homogeneity in the 8 Chinese studies with high pooled mortality risk ratio of 0.97 (I2 = 24%, p = 0.23) (95% CI = 0.94-1.00), similar to Italy with a low pooled mortality risk ratio of 0.26 (95% CI 0.08-0.43) with homogeneity (p = 0.86) while the later larger studies coming from the USA showed pooled estimate mortality risk ratio of 0.60 (95% CI 0.43-0.76) with persistent heterogeneity (I2 = 98%, p<0.001). Meta-regression showed that outcome from IMV improved with time (p<0.001). Age had no statistically significant effect on mortality (p = 0.102). Publication bias was excluded by visualizing the funnel plot of standard error, Egger's test with p = 0.714 and Begg&Mazumdar test with p = 0.334. INTERPRETATION: The study included the largest number of patients with outcome findings of IMV in this current pandemic. Our findings showed that the use of IMV for selected COVID 19 patients with severe ARDS carries a high mortality, but outcome has improved over the last few months and in more recent studies. The results should encourage physicians to use this facility when indicated for severely ill COVID-19 patients.


Subject(s)
COVID-19 , Respiration, Artificial , Respiratory Distress Syndrome , SARS-CoV-2 , COVID-19/mortality , COVID-19/therapy , Humans , Respiratory Distress Syndrome/mortality , Respiratory Distress Syndrome/therapy
13.
BMJ Open ; 11(5): e045041, 2021 05 11.
Article in English | MEDLINE | ID: covidwho-1259009

ABSTRACT

INTRODUCTION: International guidelines include early nutritional support (≤48 hour after admission), 20-25 kcal/kg/day, and 1.2-2 g/kg/day protein at the acute phase of critical illness. Recent data challenge the appropriateness of providing standard amounts of calories and protein during acute critical illness. Restricting calorie and protein intakes seemed beneficial, suggesting a role for metabolic pathways such as autophagy, a potential key mechanism in safeguarding cellular integrity, notably in the muscle, during critical illness. However, the optimal calorie and protein supply at the acute phase of severe critical illness remains unknown. NUTRIREA-3 will be the first trial to compare standard calorie and protein feeding complying with guidelines to low-calorie low-protein feeding. We hypothesised that nutritional support with calorie and protein restriction during acute critical illness decreased day 90 mortality and/or dependency on intensive care unit (ICU) management in mechanically ventilated patients receiving vasoactive amine therapy for shock, compared with standard calorie and protein targets. METHODS AND ANALYSIS: NUTRIREA-3 is a randomised, controlled, multicentre, open-label trial comparing two parallel groups of patients receiving invasive mechanical ventilation and vasoactive amine therapy for shock and given early nutritional support according to one of two strategies: early calorie-protein restriction (6 kcal/kg/day-0.2-0.4 g/kg/day) or standard calorie-protein targets (25 kcal/kg/day, 1.0-1.3 g/kg/day) at the acute phase defined as the first 7 days in the ICU. We will include 3044 patients in 61 French ICUs. Two primary end-points will be evaluated: day 90 mortality and time to ICU discharge readiness. The trial will be considered positive if significant between-group differences are found for one or both alternative primary endpoints. Secondary outcomes include hospital-acquired infections and nutritional, clinical and functional outcomes. ETHICS AND DISSEMINATION: The NUTRIREA-3 study has been approved by the appropriate ethics committee. Patients are included after informed consent. Results will be submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03573739.


Subject(s)
COVID-19 , Diet, Protein-Restricted , Adult , Critical Illness , Humans , Respiration, Artificial , SARS-CoV-2
14.
JAMA Otolaryngol Head Neck Surg ; 147(7): 646-655, 2021 07 01.
Article in English | MEDLINE | ID: covidwho-1245338

ABSTRACT

Importance: Approximately 5% to 15% of patients with COVID-19 require invasive mechanical ventilation (IMV) and, at times, tracheostomy. Details regarding the safety and use of tracheostomy in treating COVID-19 continue to evolve. Objective: To evaluate the association of tracheostomy with COVID-19 patient outcomes and the risk of SARS-CoV-2 transmission among health care professionals (HCPs). Data Sources: EMBASE (Ovid), Medline (Ovid), and Web of Science from January 1, 2020, to March 4, 2021. Study Selection: English-language studies investigating patients with COVID-19 who were receiving IMV and undergoing tracheostomy. Observational and randomized clinical trials were eligible (no randomized clinical trials were found in the search). All screening was performed by 2 reviewers (P.S. and M.L.). Overall, 156 studies underwent full-text review. Data Extraction and Synthesis: We performed data extraction in accordance with Meta-analysis of Observational Studies in Epidemiology guidelines. We used a random-effects model, and ROBINS-I was used for the risk-of-bias analysis. Main Outcomes and Measures: SARS-CoV-2 transmission between HCPs and levels of personal protective equipment, in addition to complications, time to decannulation, ventilation weaning, and intensive care unit (ICU) discharge in patients with COVID-19 who underwent tracheostomy. Results: Of the 156 studies that underwent full-text review, only 69 were included in the qualitative synthesis, and 14 of these 69 studies (20.3%) were included in the meta-analysis. A total of 4669 patients were included in the 69 studies, and the mean (range) patient age across studies was 60.7 (49.1-68.8) years (43 studies [62.3%] with 1856 patients). We found that in all studies, 1854 patients (73.8%) were men and 658 (26.2%) were women. We found that 28 studies (40.6%) investigated either surgical tracheostomy or percutaneous dilatational tracheostomy. Overall, 3 of 58 studies (5.17%) identified a small subset of HCPs who developed COVID-19 that was associated with tracheostomy. Studies did not consistently report the number of HCPs involved in tracheostomy. Among the patients, early tracheostomy was associated with faster ICU discharge (mean difference, 6.17 days; 95% CI, -11.30 to -1.30), but no change in IMV weaning (mean difference, -2.99 days; 95% CI, -8.32 to 2.33) or decannulation (mean difference, -3.12 days; 95% CI, -7.35 to 1.12). There was no association between mortality or perioperative complications and type of tracheostomy. A risk-of-bias evaluation that used ROBINS-I demonstrated notable bias in the confounder and patient selection domains because of a lack of randomization and cohort matching. There was notable heterogeneity in study reporting. Conclusions and Relevance: The findings of this systematic review and meta-analysis indicate that enhanced personal protective equipment is associated with low rates of SARS-CoV-2 transmission during tracheostomy. Early tracheostomy in patients with COVID-19 may reduce ICU stay, but this finding is limited by the observational nature of the included studies.


Subject(s)
COVID-19/transmission , Infectious Disease Transmission, Patient-to-Professional , Pneumonia, Viral/transmission , Tracheostomy , COVID-19/prevention & control , Humans , Personal Protective Equipment , Pneumonia, Viral/prevention & control , Pneumonia, Viral/virology , SARS-CoV-2
15.
Minerva Anestesiol ; 87(8): 915-926, 2021 08.
Article in English | MEDLINE | ID: covidwho-1244403

ABSTRACT

INTRODUCTION: To date, a shared international consensus on treatment of Coronavirus disease 2019 (COVID-19) with invasive or non-invasive respiratory support is lacking. Patients' management and outcomes, especially in severe and critical cases, can vary depending on regional standard operating procedures and local guidance. EVIDENCE ACQUISITION: Rapid review methodology was applied to include all the studies published on PubMed and Embase between December 15th, 2019 and February 28th, 2021, reporting in-hospital and respiratory support-related mortality in adult patients hospitalized with COVID-19 that underwent either continuous positive airway pressure (CPAP), non-invasive ventilation (NIV) or invasive mechanical ventilation (IMV). Only English language studies with ≥100 patients and reporting data on respiratory failure were included. Data on comorbidities, ventilatory parameters and hospital-related complications were registered. EVIDENCE SYNTHESIS: Fifty-two studies (287,359 patients; 57.5% males, mean age 64 years, range 24-98 years) from 17 different countries were included in the final analysis. 33.3% of patients were hospitalized in intensive care units. 44.2% had hypertension, 26.1% had diabetes, and 7.1% a chronic respiratory disease. 55% of patients underwent respiratory support (36% IMV, 62% NIV and 2% CPAP). Without considering a study with the highest number of patients treated with NIV (N.=96,729), prevalence of NIV and CPAP use was 12.5% and 13.5% respectively. Globally, invasive and non-invasive approaches were heterogeneously applied. In-hospital mortality was 33.7%, and IMV-related mortality was 72.6% (range: 4.3-99%). Specific mortality in patients treated with CPAP or NIV was available for 53% of studies, and was 29% (range: 7.2-100%). The median length of hospital stay was 13 days (range: 6-63). The most frequent hospital-related complication was acute kidney injury being reported in up to 55.7% of enrolled patients. CONCLUSIONS: Global employment of respiratory supports and related outcomes are very heterogeneous. The most frequent respiratory support in patients with COVID-19 pneumonia is IMV, while NIV and CPAP are less frequently and equally applied, the latter especially in Europe, while data on NIV/CPAP-related mortality is often under-reported. Integrated and comprehensive reporting is desirable and needed to construct evidence-based recommendations.


Subject(s)
COVID-19 , Noninvasive Ventilation , Pneumonia , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Respiration, Artificial , SARS-CoV-2 , Young Adult
16.
Respir Care ; 66(9): 1406-1415, 2021 09.
Article in English | MEDLINE | ID: covidwho-1244287

ABSTRACT

BACKGROUND: ARDS in patients with coronavirus disease 2019 (COVID-19) is characterized by microcirculatory alterations in the pulmonary vascular bed, which could increase dead-space ventilation more than in non-COVID-19 ARDS. We aimed to establish if dead-space ventilation is different in patients with COVID-19 ARDS when compared with patients with non-COVID-19 ARDS. METHODS: A total of 187 subjects with COVID-19 ARDS and 178 subjects with non-COVID-19 ARDS who were undergoing invasive mechanical ventilation were included in the study. The association between the ARDS types and dead-space ventilation, compliance of the respiratory system, subjects' characteristics, organ failures, and mechanical ventilation was evaluated by using data collected in the first 24 h of mechanical ventilation. RESULTS: Corrected minute ventilation (V˙E), a dead-space ventilation surrogate, was higher in the subjects with COVID-19 ARDS versus in those with non-COVID-19 ARDS (median [interquartile range] 12.6 [10.2-15.8] L/min vs 9.4 [7.5-11.6] L/min; P < .001). Increased corrected V˙E was independently associated with COVID-19 ARDS (odds ratio 1.24, 95% CI 1.07-1.47; P = .007). The best compliance of the respiratory system, obtained after testing different PEEPs, was similar between the subjects with COVID-19 ARDS and the subjects with non-COVID-19 ARDS (mean ± SD 38 ± 11 mL/cm H2O vs 37 ± 11 mL/cm H2O, respectively; P = .61). The subjects with COVID-19 ARDS received higher median (interquartile range) PEEP (12 [10-14] cm H2O vs 8 [5-9] cm H2O; P < .001) and lower median (interquartile range) tidal volume (5.8 [5.5-6.3] mL/kg vs 6.6 [6.1-7.3] mL/kg; P < .001) than the subjects with non-COVID-19 ARDS, being these differences maintained at multivariable analysis. In the multivariable analysis, the subjects with COVID-19 ARDS showed a lower risk of anamnestic arterial hypertension (odds ratio 0.18, 95% CI 0.07-0.45; P < .001) and lower neurologic sequential organ failure assessment score (odds ratio 0.16, 95% CI 0.09-0.27; P < .001) than the subjects with non-COVID-19 ARDS. CONCLUSIONS: Indirect measurements of dead space were higher in subjects with COVID-19 ARDS compared with subjects with non-COVID-19 ARDS. The best compliance of the respiratory system was similar in both ARDS forms provided that different PEEPs were applied. A wide range of compliance is present in every ARDS type; therefore, the setting of mechanical ventilation should be individualized patient by patient and not based on the etiology of ARDS.


Subject(s)
COVID-19 , Respiratory Distress Syndrome , Humans , Microcirculation , Respiratory Distress Syndrome/therapy , SARS-CoV-2 , Tidal Volume
17.
Heart Lung ; 50(5): 654-659, 2021.
Article in English | MEDLINE | ID: covidwho-1243007

ABSTRACT

BACKGROUND: Invasive mechanical ventilation is the treatment of choice in COVID-19 patients when hypoxemia persists, despite maximum conventional oxygen administration. Some frail patients with severe hypoxemic respiratory failure are deemed not eligible for invasive mechanical ventilation. OBJECTIVES: To investigate whether High-flow nasal cannula (HFNC) in the wards could serve as a rescue therapy in these frail patients. METHODS: This retrospective cohort study included frail COVID-19 patients admitted to the hospital between March 9th and May 1st 2020. HFNC therapy was started in the wards. The primary endpoint was the survival rate at hospital discharge. RESULTS: Thirty-two patients with a median age of 79.0 years (74.5-83.0) and a Clinical Frailty Score of 4 out of 9 (3-6) were included. Only 6% reported HFNC tolerability issues. The overall survival rate was 25% at hospital discharge. CONCLUSIONS: This study suggests that, when preferred, HFNC in the wards could be a potential rescue therapy for respiratory failure in vulnerable COVID-19 patients.


Subject(s)
COVID-19 , Noninvasive Ventilation , Respiratory Insufficiency , Aged , Cannula , Hospitals , Humans , Oxygen Inhalation Therapy , Respiratory Insufficiency/therapy , Retrospective Studies , SARS-CoV-2
18.
Medicine (Baltimore) ; 100(21): e26023, 2021 May 28.
Article in English | MEDLINE | ID: covidwho-1242120

ABSTRACT

ABSTRACT: To assess tocilizumab (TCZ) efficacy associated to standard of care (SOC) compared to SOC alone in severe coronavirus associated disease 2019 (COVID-19) patients. In a matched case-control study from 3 French Hospital COVID-19 Departments, 27 patients with severe COVID-19 treated with TCZ and SOC were matched for baseline epidemiological and clinical features and compared to 27 severe COVID-19 patients treated with SOC alone. Baseline characteristics of the study population were comparable between groups. Eleven patients (20%) died. TCZ was not associated with clinical improvement as compared to SOC regarding oxygen-free status (44% vs 63%) and death (18.5% vs 22%), despite a higher decrease of the C-reactive protein at Day 7 (10.7 vs 52 mg/L; P < 10-3). Compared to the 43 patients alive at the end-of follow-up, patients who died were older (78 vs 64 years; P < 10-3), with 82% of them older than 72 years vs only 23% of live patients (P < 10-3). Age (OR = 1.15; 95%CI = 1.04-1.3; P = .008) and age over 72 years (OR) = 14.85; 95%CI = 2.7-80; P = .002) were independently associated with mortality. TCZ in addition to SOC for severe COVID-19 patients did not reduce mortality, subsequent need for invasive mechanical ventilation nor did it shorten the time of oxygen support, despite better control of the inflammatory response. More powerful and randomized controlled trials are warranted to determine if TCZ is effective in the management of COVID-19.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19/drug therapy , COVID-19/therapy , Respiration, Artificial/statistics & numerical data , Standard of Care/statistics & numerical data , Age Factors , Aged , COVID-19/diagnosis , COVID-19/mortality , COVID-19/virology , Case-Control Studies , Female , Follow-Up Studies , France/epidemiology , Hospital Mortality , Humans , Male , Middle Aged , Oxygen/administration & dosage , Retrospective Studies , Risk Factors , SARS-CoV-2/isolation & purification , Severity of Illness Index , Treatment Outcome
19.
Sci Rep ; 11(1): 10727, 2021 05 21.
Article in English | MEDLINE | ID: covidwho-1238019

ABSTRACT

Corticosteroids use in coronavirus disease 2019 (COVID-19) is controversial, especially in mild to severe patients who do not require invasive/noninvasive ventilation. Moreover, many factors remain unclear regarding the appropriate use of corticosteroids for COVID-19. In this context, this multicenter, retrospective, propensity score-matched study was launched to evaluate the efficacy of systemic corticosteroid administration for hospitalized patients with COVID-19 ranging in the degree of severity from mild to critically-ill disease. This multicenter, retrospective study enrolled consecutive hospitalized COVID-19 patients diagnosed January-April 2020 across 30 institutions in Japan. Clinical outcomes were compared for COVID-19 patients who received or did not receive corticosteroids, after adjusting for propensity scores. The primary endpoint was the odds ratio (OR) for improvement on a 7-point ordinal score on Day 15. Of 1092 COVID-19 patients analyzed, 118 patients were assigned to either the corticosteroid and non-corticosteroid group, after propensity score matching. At baseline, most patients did not require invasive/noninvasive ventilation (85.6% corticosteroid group vs. 89.8% non-corticosteroid group). The odds of improvement in a 7-point ordinal score on Day 15 was significantly lower for the corticosteroid versus non-corticosteroid group (OR, 0.611; 95% confidence interval [CI], 0.388-0.962; p = 0.034). The time to improvement in radiological findings was significantly shorter in the corticosteroid versus non-corticosteroid group (hazard ratio [HR], 1.758; 95% CI, 1.323-2.337; p < 0.001), regardless of baseline clinical status. The duration of invasive mechanical ventilation was shorter in corticosteroid versus non-corticosteroid group (HR, 1.466; 95% CI, 0.841-2.554; p = 0.177). Of the 106 patients who received methylprednisolone, the duration of invasive mechanical ventilation was significantly shorter in the pulse/semi-pulse versus standard dose group (HR, 2.831; 95% CI, 1.347-5.950; p = 0.006). In conclusion, corticosteroids for hospitalized patients with COVID-19 did not improve clinical status on Day 15, but reduced the time to improvement in radiological findings for all patients regardless of disease severity and also reduced the duration of invasive mechanical ventilation in patients who required intubation.Trial registration: This study was registered in the University hospital Medical Information Network Clinical Trials Registry on April 21, 2020 (ID: UMIN000040211).


Subject(s)
Adrenal Cortex Hormones/administration & dosage , COVID-19/therapy , Hospitalization , Respiration, Artificial , SARS-CoV-2 , COVID-19/diagnostic imaging , COVID-19/pathology , Critical Illness , Female , Humans , Male , Middle Aged , Retrospective Studies
20.
Rheumatology (Oxford) ; 60(12): 5527-5537, 2021 12 01.
Article in English | MEDLINE | ID: covidwho-1231045

ABSTRACT

OBJECTIVES: Acute respiratory distress syndrome and cytokine release syndrome are the major complications of coronavirus disease 2019 (COVID-19) associated with increased mortality risk. We performed a meta-analysis to assess the efficacy and safety of anakinra in adult hospitalized non-intubated patients with COVID-19. METHODS: Relevant trials were identified by searching literature until 24 April 2021 using the following terms: anakinra, IL-1, coronavirus, COVID-19, SARS-CoV-2. Trials evaluating the effect of anakinra on the need for invasive mechanical ventilation and mortality in hospitalized non-intubated patients with COVID-19 were included. RESULTS: Nine studies (n = 1119) were eligible for inclusion in the present meta-analysis. Their bias risk with reference to the assessed parameters was high. In pooled analyses, anakinra reduced the need for invasive mechanical ventilation (odds ratio (OR): 0.38, 95% CI: 0.17-0.85, P = 0.02, I2 = 67%; six studies, n = 587) and mortality risk (OR: 0.32, 95% CI: 0.23-0.45, P < 0.00001, I2 = 0%; nine studies, n = 1119) compared with standard of care therapy. There were no differences regarding the risk of adverse events, including liver dysfunction (OR: 0.75, 95% CI: 0.48-1.16, P > 0.05, I2 = 28%; five studies, n = 591) and bacteraemia (OR: 1.07, 95% CI: 0.42-2.73, P > 0.05, I2 = 71%; six studies, n = 727). CONCLUSIONS: Available evidence shows that treatment with anakinra reduces both the need for invasive mechanical ventilation and mortality risk of hospitalized non-intubated patients with COVID-19 without increasing the risk of adverse events. Confirmation of efficacy and safety requires randomized placebo-controlled trials.


Subject(s)
COVID-19/drug therapy , Interleukin 1 Receptor Antagonist Protein/therapeutic use , Receptors, Interleukin-1/antagonists & inhibitors , Humans , Treatment Outcome
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