Estimating the Case Fatality Risk of COVID-19 among Mechanically Ventilated Patients.
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ABSTRACT:
SUBMITTER: Angriman F
PROVIDER: S-EPMC7781131 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundSevere coronavirus disease 2019 (COVID-19) can manifest in rapid decompensation and respiratory failure with elevated inflammatory markers, consistent with cytokine release syndrome for which IL-6 blockade is an approved treatment.MethodsWe assessed effectiveness and safety of IL-6 blockade with tocilizumab in a single-center cohort of patients with COVID-19 requiring mechanical ventilation. The primary endpoint was survival probability postintubation; secondary analyses included an ordinal illness severity scale integrating superinfections. Outcomes in patients who received tocilizumab compared with tocilizumab-untreated controls were evaluated using multivariable Cox regression with propensity score inverse probability of treatment weighting (IPTW).Results154 patients were included, of whom 78 received tocilizumab and 76 did not. Median follow-up was 47 days (range, 28-67). Baseline characteristics were similar between groups, although tocilizumab-treated patients were younger (mean: 55 vs 60 years), less likely to have chronic pulmonary disease (10% vs 28%), and had lower D-dimer values at time of intubation (median: 2.4 vs 6.5 mg/dL). In IPTW-adjusted models, tocilizumab was associated with a 45% reduction in hazard of death (HR, .55; 95% CI, .33-.90) and improved status on the ordinal outcome scale [OR per 1-level increase, .58; .36-.94). Although tocilizumab was associated with an increased proportion of patients with superinfections (54% vs 26%; P < .001), there was no difference in 28-day case fatality rate among tocilizumab-treated patients with versus without superinfection (22% vs 15%; P = .42). Staphylococcus aureus accounted for ~50% of bacterial pneumonia.ConclusionsIn this cohort of mechanically ventilated COVID-19 patients, tocilizumab was associated with lower mortality despite higher superinfection occurrence.
| S-EPMC7454462 | biostudies-literature
Project description:ObjectiveTo determine the incidence, predictors, and outcome of pneumothorax (PNX)/pneumomediastinum (PMD) in coronavirus disease 2019 (COVID-19) acute respiratory distress syndrome (ARDS).DesignObservational study.SettingTertiary-care university hospital.ParticipantsOne hundred sixteen consecutive critically ill, invasively ventilated patients with COVID-19 ARDS.InterventionsThe authors collected demographic, mechanical ventilation, imaging, laboratory, and outcome data. Primary outcome was the incidence of PNX/PMD. Multiple logistic regression analyses were performed to identify predictors of PNX/PMD.Measurements and main resultsPNX/PMD occurred in a total of 28 patients (24.1%), with 22 patients developing PNX (19.0%) and 13 developing PMD (11.2%). Mean time to development of PNX/PMD was 14 ± 11 days from intubation. The authors found no significant difference in mechanical ventilation parameters between patients who developed PNX/PMD and those who did not. Mechanical ventilation parameters were within recommended limits for protective ventilation in both groups. Ninety-five percent of patients with PNX/PMD had the Macklin effect (linear collections of air contiguous to the bronchovascular sheaths) on a baseline computed tomography scan, and tended to have a higher lung involvement at intensive care unit (ICU) admission (Radiographic Assessment of Lung Edema score 32.2 ± 13.4 v 18.7 ± 9.8 in patients without PNX/PMD, p = 0.08). Time from symptom onset to intubation and time from total bilirubin on day two after ICU admission were the only independent predictors of PNX/PMD. Mortality was 60.7% in patients who developed PNX/PMD versus 38.6% in those who did not (p = 0.04).ConclusionPNX/PMD occurs frequently in COVID-19 patients with ARDS requiring mechanical ventilation, and is associated with increased mortality. Development of PNX/PMD seems to occur despite use of protective mechanical ventilation and has a radiologic predictor sign.
| S-EPMC8054543 | biostudies-literature
Project description:Severe COVID-19 can manifest in rapid decompensation and respiratory failure with elevated inflammatory markers. This presentation is consistent with cytokine release syndrome in chimeric antigen receptor T cell therapy, for which IL-6 blockade is approved treatment. We assessed effectiveness and safety of IL-6 blockade with tocilizumab in a single-center cohort of patients with COVID-19 requiring mechanical ventilation. The primary endpoint was survival probability post-intubation; secondary analyses included an ordinal illness severity scale integrating superinfections. Outcomes in patients who received tocilizumab compared to tocilizumab-untreated controls were evaluated using multivariable Cox regression with propensity score inverse probability weighting (IPTW). 154 patients were included, of whom 78 received tocilizumab and 76 did not. Median follow-up was 47 days (range 28-67). Baseline characteristics were similar between groups, although tocilizumab-treated patients were younger (mean 55 vs. 60 years), less likely to have chronic pulmonary disease (10% vs. 28%), and had lower D-dimer values at time of intubation (median 2.4 vs. 6.5 mg/dL). In IPTW-adjusted models, tocilizumab was associated with a 45% reduction in hazard of death [hazard ratio 0.55 (95% CI 0.33, 0.90)] and improved status on the ordinal outcome scale [odds ratio per 1-level increase: 0.59 (0.36, 0.95)]. Though tocilizumab was associated with an increased proportion of patients with superinfections (54% vs. 26%; p<0.001), there was no difference in 28-day case fatality rate among tocilizumab-treated patients with versus without superinfection [22% vs. 15%; p=0.42]. In this cohort of mechanically ventilated COVID-19 patients, tocilizumab was associated with a decreased likelihood of death despite higher superinfection occurrence. Randomized controlled trials are urgently needed to confirm these findings.
| S-EPMC7302290 | biostudies-literature
Project description:BackgroundSolid data on cardiovascular derangements in critically ill COVID-19 patients remain scarce. The aim of this study is to describe hemodynamic characteristics in a cohort of COVID-19-related critically ill patients.MethodsA retrospective observational cohort study in twenty-eight consecutive mechanically ventilated COVID-19 patients. Pulse contour analysis-derived data were obtained from all patients, using the PiCCO® system.ResultsThe mean arterial pressure increased from 77 ± 10 mmHg on day 1 to 84 ± 9 mmHg on day 21 (p=0.04), in combination with the rapid tapering and cessation of norepinephrine and the gradual use of antihypertensive drugs in the vast majority of patients. The cardiac index increased significantly from 2.8 ± 0.7 L/min/m2 on day 1 to 4.0 ± 0.8 L/min/m2 on day 21 (p < 0.001). Dobutamine was administered in only two patients. Mean markers of left ventricular contractility and peripheral perfusion, as well as lactate levels, remained within the normal range. Despite a constant fluid balance, extravascular lung water index decreased significantly from 17 ± 7 mL/kg on day 1 to 11 ± 4 mL/kg on day 21 (p < 0.001). Simultaneously, intrapulmonary right-to-left shunt fraction (Q s/Q t) decreased significantly from 27 ± 10% in week 1 to 15 ± 9% in week 3 (p=0.007). PaO2/FiO2 ratio improved from 159 ± 53 mmHg to 319 ± 53 mmHg (p < 0.001), but static lung compliance remained unchanged.ConclusionsIn general, this cohort of patients with COVID-19 respiratory failure showed a marked rise in blood pressure over time, not accompanied by distinctive markers of circulatory failure. Characteristically, increased extravascular lung water, vascular permeability, and intrapulmonary shunt diminished over time, concomitant with an improvement in gas exchange.
| S-EPMC7783514 | biostudies-literature
Project description:PurposeThe outcomes of patients requiring invasive mechanical ventilation for COVID-19 remain poorly defined. We sought to determine clinical characteristics and outcomes of patients with COVID-19 managed with invasive mechanical ventilation in an appropriately resourced US health care system.MethodsOutcomes of COVID-19 infected patients requiring mechanical ventilation treated within the Inova Health System between March 5, 2020 and April 26, 2020 were evaluated through an electronic medical record review.Results1023 COVID-19 positive patients were admitted to the Inova Health System during the study period. Of these, 164 (16.0%) were managed with invasive mechanical ventilation. All patients were followed to definitive disposition. 70/164 patients (42.7%) had died and 94/164 (57.3%) were still alive. Deceased patients were older (median age of 66 vs. 55, p <0.0001) and had a higher initial d-dimer (2.22 vs. 1.31, p = 0.005) and peak ferritin levels (2998 vs. 2077, p = 0.016) compared to survivors. 84.3% of patients over 70 years old died in the hospital. Conversely, 67.4% of patients age 70 or younger survived to hospital discharge. Younger age, non-Caucasian race and treatment at a tertiary care center were all associated with survivor status.ConclusionMortality of patients with COVID-19 requiring invasive mechanical ventilation is high, with particularly daunting mortality seen in patients of advanced age, even in a well-resourced health care system. A substantial proportion of patients requiring invasive mechanical ventilation were not of advanced age, and this group had a reasonable chance for recovery.
| S-EPMC7682899 | biostudies-literature
Project description:BackgroundNutrition therapy is essential in critically ill adults. Little is known about appropriate nutrition therapy in patients with severe coronavirus disease 2019 (COVID-19) infection.MethodsThis was a retrospective, observational study in adult patients with confirmed COVID-19 infection receiving mechanical ventilation. Data regarding patient demographics and nutrition therapy were collected. Patients that received enteral nutrition within 24 hours of starting mechanical ventilation were compared with patients starting enteral nutrition later. The primary outcome was inpatient length of stay. Propensity score matching was conducted to control for baseline differences in patient groups.ResultsOne hundred fifty-five patients were included in final analysis. Patients who received enteral nutrition within 24 hours received a significantly greater daily amount of calories (17.5 vs 15.2 kcal/kg, P = .015) and protein (1.04 vs 0.85 g/kg, P = .003). There was no difference in length of stay (18.5 vs 23.5 days, P = .37). The propensity score analysis included 100 patients. Following propensity scoring, significant differences in daily calorie (17.7 [4.6] vs 15.1 [5.1] kcal/kg/d, P = .009) and protein (1.03 [0.35] vs 0.86 [0.38] g/kg/d, P = .014) provision remained. No differences in length of stay or other outcomes were noted in the propensity score analysis.ConclusionInitiation of enteral nutrition within 24 hours was not associated with improved outcomes in mechanically ventilated adults with COVID-19. No harm was detected either. Future research should seek to clarify optimal timing of enteral nutrition initiation in patients with COVID-19 who require mechanical ventilation.
| S-EPMC8014144 | biostudies-literature
Project description:The prone position (PP) is increasingly used in mechanically ventilated coronavirus disease 2019 (COVID-19) acute respiratory distress syndrome (ARDS) patients. However, studies investigating the influence of the PP are currently lacking in these patients. This is the first study to investigate the influence of the PP on the oxygenation and decarboxylation in COVID-19 patients. A prospective bicentric study design was used, and in mechanically ventilated COVID-19 patients, PP was indicated from a partial pressure of oxygen in arterial blood (PaO2)/fraction of inspired oxygen (FIO2) ratio of <200. Patients were left prone for 16 h each. Pressure levels, FIO2, were adjusted to ensure a PaO2 greater than 60 mmHg. Blood gas analyses were performed before (baseline 0.5 h), during (1/2/5.5/9.5/13 h), and after being in the PP (1 h), the circulatory/ventilation parameters were continuously monitored, and lung compliance (LC) was roughly calculated. Responders were defined compared to the baseline value (PaO2/FIO2 ratio increase of ≥15%; partial pressure of carbon dioxide (PaCO2) decrease of ≥2%). 13 patients were included and 36 PP sessions were conducted. Overall, PaO2/FIO2 increased significantly in the PP (p < 0.001). Most PaO2/FIO2 responders (29/36 PP sessions, 77%) were identified 9.5 h after turning prone (14% slow responders), while most PaCO2 responders (15/36 PP sessions, 42%) were identified 13 h after turning prone. A subgroup of patients (interval intubation to PP ≥3 days) showed less PaO2/FIO2 responders (16% vs. 77%). An increase in PaCO2 and minute ventilation in the PP showed a significant negative correlation (p < 0.001). LC (median before the PP = 38 mL/cm H2O; two patients with LC >80 mL/cm H2O) showed a significant positive correlation with the 28 day survival of patients (p = 0.01). The PP significantly improves oxygenation in COVID-19 ARDS patients. The data suggest that they also benefit most from an early PP. A decrease in minute ventilation may result in fewer PaCO2 responders. LC may be a predictive outcome parameter in COVID-19 patients. Retrospectively registered.
| S-EPMC7959453 | biostudies-literature
Project description: Not available
| S-EPMC7301734 | biostudies-literature
Project description:BACKGROUND:Mechanically ventilated patients with COVID-19 have a mortality of 24-53%, in part due to distal mucopurulent secretions interfering with ventilation. DNA from neutrophil extracellular traps (NETs) contribute to the viscosity of mucopurulent secretions and NETs are found in the serum of COVID-19 patients. Dornase alfa is recombinant human DNase 1 and is used to digest DNA in mucoid sputum. Here, we report a single-center case series where dornase alfa was co-administered with albuterol through an in-line nebulizer system. METHODS:Demographic and clinical data were collected from the electronic medical records of five mechanically ventilated patients with COVID-19-including three requiring veno-venous extracorporeal membrane oxygenation-treated with nebulized in-line endotracheal dornase alfa and albuterol, between March 31 and April 24, 2020. Data on tolerability and response were analyzed. RESULTS:The fraction of inspired oxygen requirements was reduced for all five patients after initiating dornase alfa administration. All patients were successfully extubated, discharged from hospital and remain alive. No drug-associated toxicities were identified. CONCLUSIONS:Results suggest that dornase alfa will be well-tolerated by patients with severe COVID-19. Clinical trials are required to formally test the dosing, safety, and efficacy of dornase alfa in COVID-19, and several have been recently registered.
| S-EPMC7522910 | biostudies-literature
Project description:Background Mechanically ventilated patients with coronavirus disease 2019 (COVID-19) have a mortality of 24-53%, in part due to distal mucopurulent secretions interfering with ventilation. Dornase alfa is recombinant human DNase 1 and digests DNA in mucoid sputum. Nebulized dornase alfa is FDA-approved for cystic fibrosis treatment. DNA from neutrophil extracellular traps (NETs) contributes to the viscosity of mucopurulent secretions. NETs are found in the serum of patients with severe COVID-19, and targeting NETs reduces mortality in animal models of acute respiratory distress syndrome (ARDS). Thus, dornase alfa may be beneficial to patients with severe COVID-19, acting as a mucolytic and targeting NETs. However, delivery of nebulized drugs can aerosolize SARS-CoV-2, which causes COVID-19, increasing the infection risk for staff. Here, we report a single center case series where dornase alfa was administered through an in-line nebulizer system to minimize risk of virus aerosolization. Methods Demographic, clinical data, and outcomes were collected from the electronic medical records of five mechanically ventilated patients with COVID-19, including three requiring veno-venous extracorporeal membrane oxygenation (VV-ECMO), treated with nebulized in-line endotracheal dornase alfa co-administered with albuterol (used to increase delivery to the alveoli), between March 31 and April 24, 2020. Data on tolerability and responses, including longitudinal values capturing respiratory function and inflammatory status, were analyzed. Results Following nebulized in-line administration of dornase alfa with albuterol, the fraction of inspired oxygen requirements was reduced for all five patients. All patients remain alive and two patients have been discharged from the intensive care unit. No drug associated toxicities were identified. Conclusions The results presented in this case series suggest that dornase alfa will be well-tolerated by critically ill patients with COVID-19. Clinical trials are required to formally test the dosing, safety, and efficacy of dornase alfa in COVID-19, and two have recently been registered ( NCT04359654 and NCT04355364 ). With this case series, we hope to contribute to the development of management approaches for critically ill patients with COVID-19.
| S-EPMC7273282 | biostudies-literature